COVID-19 resources: Articles/publications

Abstract
Background: The COVID-19 pandemic has greatly affected access to elective surgery, largely because of concerns for patients and healthcare workers. A return to normal surgery workflow depends on the prevalence and transmission of coronavirus in elective surgical patients. The aim of this study was to determine the prevalence of active SARS-coronavirus-2 infection during a second wave among patients admitted to hospital for elective surgery in Victoria.

Methods: Prospective cohort study across eight hospitals in Victoria during July-August 2020 was conducted enrolling adults and children admitted to hospital for elective surgery or interventional procedure requiring general anaesthesia. Study outcomes included a positive polymerase chain reaction (PCR) test for SARS-CoV-2 in the preoperative period (primary outcome), and for those with a negative test preoperatively, the incidence of a positive PCR test for SARS-CoV-2 in the post-operative period.

Results: We enrolled 4965 elective adult and paediatric surgical patients from 15 July to 31 August 2020. Four patients screened negative on questionnaire but had a positive PCR test for coronavirus, resulting in a Bayesian estimated prevalence of 0.12% (95% probability interval 0-0.26%). There were no reports of healthcare worker infections linked to elective surgery during and up to 2 weeks after the study period.

Conclusion: The prevalence of SARS-CoV-2 in asymptomatic elective surgical patients during a second wave was approximately 1 in 833. Given the very low likelihood of coronavirus transmission, and with existing current hospital capacity, recommencement of elective surgery should be considered. A coronavirus screening checklist should be mandated for surgical patients.

Abstract
Background: The study aimed to estimate the prevalence of active or previous SARS-CoV-2 infection in asymptomatic adults admitted for elective surgery in Australian hospitals. This surveillance activity was established as part of the National Pandemic Health Intelligence Plan.

Methods: Participants (n = 3037) were recruited from 11 public and private hospitals in four states (NSW, Vic, SA and WA) between 2 June and 17 July 2020, with an overall 66% participation rate. Presence of SARS-CoV-2 viral RNA was assessed by Reverse Transcriptase - Polymerase Chain Reaction (RT-PCR) analysis of nasopharyngeal swabs taken after induction of anaesthesia. Presence of anti-SARS-CoV-2 antibodies was assessed by analysis of serum collected at the same time using a novel dual-antigen ELISA assay.

Results: No patient (0/3010) returned a positive RT-PCR result. The Bayesian estimated prevalence of active infection of 0.02% (95% probability interval 0.00-0.11%), with the upper endpoint being 1 in 918. Positive serology (IgG) was observed in 15 of 2991 patients, with a strong positive in five of those individuals (Bayesian estimated seroprevalence 0.16%; 95% probability interval 0.00-0.47%).

Conclusion: These results confirm that during periods of low community prevalence of SARS-CoV-2 elective surgery patients without fever or respiratory symptoms had a very low prevalence of active SARS-CoV-2 infection.

Abstract
The risk of COVID-19 in those with chronic pain is unknown. We investigated whether self-reported chronic pain was associated with COVID-19 hospitalisation or mortality. UK Biobank recruited 502,624 participants aged 37 to 73 years between 2006 and 2010. Baseline exposure data, including chronic pain (>3 months, in at least 1 of 7 prespecified body sites) and chronic widespread pain (>3 months, all over body), were linked to COVID-19 hospitalisations or mortality. Univariable or multivariable Poisson regression analyses were performed on the association between chronic pain and COVID-19 hospitalisation and Cox regression analyses of the associations with COVID-19 mortality. Multivariable analyses adjusted incrementally for sociodemographic confounders, then lifestyle risk factors, and finally long-term condition count. Of 441,403 UK Biobank participants with complete data, 3180 (0.7%) were hospitalised for COVID-19 and 1040 (0.2%) died from COVID-19. Chronic pain was associated with hospital admission for COVID-19 even after adjustment for all covariates (incidence rate ratio 1.16; 95% confidence interval [CI] 1.08-1.24; P < 0.001), as was chronic widespread pain (incidence rate ratio 1.33; 95% CI 1.06-1.66; P = 0.012). There was clear evidence of a dose-response relationship with number of pain sites (fully adjusted global P -value < 0.001). After adjustment for all covariates, there was no association between chronic pain (HR 1.01; 95% CI 0.89-1.15; P = 0.834) but attenuated association with chronic widespread pain (HR 1.50, 95% CI 1.04-2.16, P -value = 0.032) and COVID-19 mortality. Chronic pain is associated with higher risk of hospitalisation for COVID-19, but the association with mortality is unclear. Future research is required to investigate these findings further and determine whether pain is associated with long COVID.

Abstract
Introduction: The global COVID-19 pandemic highlighted the importance of protecting frontline healthcare workers from novel respiratory infections while also exposing the limited instruction that medical students receive on proper donning of personal protective equipment (PPE) and more importantly the safe doffing of contaminated PPE to minimize their risk of nosocomial infection. The best methods of providing this kind of instruction have not yet been determined.

Methods: Anesthesiology interns and CA-1 residents were trained on proper PPE donning and doffing for AGPs using a methodology based on Miller's pyramid and following a "knows-knows how-shows-does" progression. Participants donned PPE without instruction and were sprayed with Glo Germ® to identify areas of contamination, after which they received both video and in-person instruction on best practices for donning and doffing PPE for AGPs. Following instruction, they again donned PPE and were sprayed with Glo Germ® to identify areas of contamination.

Results: 54 participants completed the study. Before training, overall donning compliance was 60% and overall doffing compliance was 48%. Overall, 70% were contaminated after PPE doffing, with 46% having multiple sites of contamination. After training, donning compliance increased by nearly 30% (P < 0.001), doffing compliance increased by over 20% (P < 0.001), and overall contamination decreased by nearly 30% (P = 0.029), with multiple-site contamination decreasing to only 6% (P = 0.013).

Discussion: While best methods for providing instruction regarding topics such as PPE donning and doffing have not yet been determined, we have demonstrated that the underlying knowledge base from medical school regarding proper donning and doffing for respiratory isolation is insufficient for preventing self-contamination, and that Miller's pyramid-based training using both video and in-person instruction combined with task execution by learners can improve compliance with PPE donning and doffing protocols and more importantly decrease skin contamination among a group of early training anesthesiology residents.

Abstract
Purpose: The aim of this study was to determine the changes in the physical, mental, and social conditions of operating room nurses and their personal experiences during the COVID-19 pandemic.

Design: The study applied a qualitative research design that included the content analysis method.

Methods: Face-to-face interviews were conducted online with 26 operating room nurses. Analysis of the data was completed in six steps using the content analysis method.

Findings: Four main themes emerged from the interviews: physical effect of the COVID-19 pandemic on operating room nurses, psychological effect of the COVID-19 pandemic on operating room nurses, operating room nurses' perceptions on the training given to them during the COVID-19 pandemic, and effects of the COVID-19 pandemic on health care worker and patient safety and nursing care.

Conclusions: This study contributes new findings on the experiences of operating nurses during the COVID-19 pandemic to the relevant literature. The results of the study indicated that the nurses were negatively affected both physically and psychologically during this period, and that this directly affected patient care.

Abstract
Background: Intensive care unit (ICU) patients with Coronavirus disease 2019 (COVID-19) have an increased risk of thromboembolic complications. We describe the occurrence of thromboembolic and bleeding events in all ICU patients with COVID-19 in Denmark during the first and second waves of the pandemic.

Methods: This was a sub-study of the Danish Intensive Care Covid database, in which all patients with SARS-CoV-2 admitted to Danish ICUs from 10th March 2020 to 30th June 2021 were included. We registered coagulation variables at admission, and all thromboembolic and bleeding events, and the use of heparins during ICU stay. Variables associated with thrombosis and bleeding and any association with 90-day mortality were estimated using Cox regression analyses.

Results: We included 1369 patients in this sub-study; 158 (12%, 95% confidence interval 10-13) had a thromboembolic event in ICU and 309 (23%, 20-25) had a bleeding event, among whom 81 patients (6%, 4.8-7.3) had major bleeding. We found that mechanical ventilation and increased D-dimer were associated with thrombosis and mechanical ventilation, low platelet count and presence of haematological malignancy were associated with bleeding. Most patients (76%) received increased doses of thromboprophylaxis during their ICU stay. Thromboembolic events were not associated with mortality in adjusted analysis (hazard ratio 1.35 [0.91-2.01, p = .14], whereas bleeding events were 1.55 [1.18-2.05, p = .002]).

Conclusions: Both thromboembolic and bleeding events frequently occurred in ICU patients with COVID-19. Based on these data, it is not apparent that increased doses of thromboprophylaxis were beneficial.

Abstract
Background: Under the hypothesis that mechanical power ratio could identify the spontaneously breathing patients with higher risk of respiratory failure, we assessed lung mechanics in non-intubated patients with COVID-19 pneumonia aimed at: 1) describe their characteristics; 2) compare lung mechanics between patients who received respiratory treatment escalation and those who did not; 3) identify variables associated with the need for respiratory treatment escalation.

Methods: Secondary analysis of prospectively enrolled cohort involving 111 consecutive spontaneously breathing adults receiving continuous positive airway pressure, enrolled from September 2020 to December 2021. Lung mechanics, other previously reported predictive indices were calculated, as well as a novel variable: the mechanical power ratio (the ratio between the actual and the expected baseline mechanical power). Patients were grouped according to the outcome: 1) no-treatment escalation (patient supported in continuous positive airway pressure until improvement); 2) treatment escalation (escalation of the respiratory support to non-invasive or invasive mechanical ventilation); and the association between lung mechanics/predictive scores and outcome was assessed.

Results: At day 1, patients undergoing treatment escalation had similar spontaneous tidal volume than patients who did not (7.1 ± 1.9 vs 7.1 ± 1.4 mL/KgIBW; p=0.990). In contrast, they showed higher respiratory rate (20 ± 5 vs 18 ± 5 bpm; p=0.028), minute ventilation (9.2 ± 3.0 vs 7.9 ± 2.4 L/min; p=0.011), tidal pleural pressure (8.1 ± 3.7 vs 6.0 ± 3.1 cmH2O; p=0.003), mechanical power ratio (2.4 ± 1.4 vs 1.7 ± 1.5; p=0.042) and lower PaO2/FiO2 (174 ± 64 vs 220 ± 95; p=0.007). Mechanical power (AUC 0.738 [95%CI 0.636-0.839] p<0.001), the mechanical power ratio (AUC 0.734 [95%CI 0.625-0.844] p <0.001) and the pressure-rate index (AUC 0.733 [95%CI 0.631-0.835] p <0.001) showed the highest AUC.

Conclusions: In this COVID-19 cohort, tidal volume was similar in patients undergoing treatment escalation and in patients who did not; mechanical power, its ratio, and pressure-rate index were the variables presenting the highest association with the clinical outcome.

Abstract
Introduction: COVID-19 is associated with severe respiratory distress and high mortality. We investigated the evolution of the respiratory mechanics in COVID-19 acute respiratory distress syndrome (ARDS) and the occurrence of a restrictive respiratory pattern.

Material and methods: A retrospective, single-centre study including patients admitted to the ICU during the first wave of the pandemic (March-April 2020).

Results: A total of 141 consecutive patients were included. Many patients developed a restrictive pattern of respiratory mechanics during the course of the disease. Fifty-two patients died in the hospital (36.8%). In 29 cases (58% of the deceased) death was associated with a pattern of pulmonary mechanics, indicating a restrictive evolution of ARDS. Other diagnoses related to death were pulmonary embolism (n = 7, 14%), septic shock (n = 17, 33%), and other causes (n = 10, 20%), with some patients combining at least 2 of these diagnoses. In a multivariate analysis, age (OR = 1.06; 95% CI: 1.01-1.12; P = 0.029) and the administration of steroid pulses (OR = 2.7; 95% CI: 1.1-6.8; P = 0.03) were associated with the development of a restrictive pulmonary pattern and a higher level of plasmatic interleukin-6.

Conclusions: COVID-19 ARDS is associated with high mortality associated with a specific pattern of respiratory mechanics and sustained activation of innate immunological response. Age and administration of high-dose steroid pulses are associated with this clinical picture.

Abstract
Objectives: To determine in patients with acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) whether reducing driving pressure (ΔP) would decrease plasma biomarkers of inflammation and lung injury (interleukin-6 [IL-6], IL-8, and the soluble receptor for advanced glycation end-products sRAGE).

Design: A single-center prospective physiologic study.

Setting: At a single university medical center.

Participants: Adult patients with severe COVID-19 ARDS on VV ECMO.

Interventions: Participants on VV ECMO had the following biomarkers measured: (1) pre-ECMO with low-tidal-volume ventilation (LTVV), (2) post-ECMO with LTVV, (3) during low-driving-pressure ventilation (LDPV), (4) after 2 hours of very low driving-pressure ventilation (V-LDPV, main intervention ΔP = 1 cmH2O), and (5) 2 hours after returning to LDPV.

Main measurements and results: Twenty-six participants were enrolled; 21 underwent V-LDPV. There was no significant change in IL-6, IL-8, and sRAGE from LDPV to V-LDPV and from V-LDPV to LDPV. Only participants (9 of 21) with nonspontaneous breaths had significant change (p < 0.001) in their tidal volumes (Vt) (mean ± SD), 1.9 ± 0.5, 0.1 ± 0.2, and 2.0 ± 0.7 mL/kg predicted body weight (PBW). Participants with spontaneous breathing, Vt were unchanged-4.5 ± 3.1, 4.7 ± 3.1, and 5.6 ± 2.9 mL/kg PBW (p = 0.481 and p = 0.065, respectively). There was no relationship found when accounting for Vt changes and biomarkers.

Conclusions: Biomarkers did not significantly change with decreased ΔPs or Vt changes during the first 24 hours post-ECMO. Despite deep sedation, reductions in Vt during V-LDPV were not reliably achieved due to spontaneous breaths. Thus, patients on VV ECMO for ARDS may have higher Vt (ie, transpulmonary pressure) than desired despite low ΔPs or Vt.

Abstract
Background: Chronic pain symptoms are distressing conditions that necessitate regular visits to pain therapists and may require interventions, however, the COVID-19 pandemic has caused patients and their therapists to limit both visits and interventions with the transition to telehealth, with little or no preparation or training. This has resulted in the extensive use of over-the counter analgesia and corticosteroids.

Objectives: Our study aimed to evaluate the effect of the COVID-19 pandemic on the rates of counseling and interventional pain management therapies (IPMT), and determine the effects of implementing an infection control program (ICP) and mandating personal protective equipment (PPE) on these rates.

Study design: Prospective multicenter survey, based on an online self-assessed questionnaire.

Setting: Departments of Anesthesia, Pain, Intensive Care Unit, Physical Medicine, Rheumatology, and Rehabilitation at Egyptian University hospitals.

Methods: A self-assessed questionnaire was uploaded on Google forms and links were sent to enrolled therapists with an identification number to allow self-administration and privacy. Feedback was analyzed by 2 authors who were blinded to the identity of the responders.

Results: A total of 57.9% of responders increased their patients' contact by phone and video conference. Within 1-4 months after the outbreak began, 59% stopped in-person contact and 38.2% stopped their IPM practice. Prescriptions of analgesics and oral steroids increased by about 50%. The majority of responders complained of a shortage of ventilation appliances in their workplaces. About 50% of them always use ICP, 85% use surgical masks, 61% use gloves, and 45% wear gowns when meeting with patients. After the application of PPE, 45.5% of responders increased their consultation rate and 40% increased their rate of IPMT.

Limitations: This study is limited to being a national study, and so lacked comparative data.

Conclusion: The COVID-19 outbreak seriously affected the rates of in-person consultations and IPMT for patients with chronic pain and increased the rates of consumption of analgesia and oral steroids. Most responders reported a shortage of PPE especially ventilation appliances in workplaces. A high percentage of responders lack interest in ICP and PPE, despite the positive effects of its application on consultation and IPMT rates.

Abstract
Background and aim: The COVID pandemic necessitated the use of masks to reduce the propagation of coronavirus by airborne transmission. This research was conducted in healthy volunteers to assess the changes in noninvasive measurable physiological variables over 45 min at rest.

Methods: This was a prospective randomized controlled crossover trial. Twenty-one healthy volunteers were monitored for pulse rate (PR), peripheral oxygen saturation (SpO2), systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), inspired carbon dioxide and expired carbon dioxide (ECO2), inspired (FiO2) and expired oxygen (FeO2), every 15 min for 45 minute (min) with N95 respirator, N95 respirator with surgical mask (SM), N95 with SM and visor (V), SM with N95, and N95 respirator with visor.

Results: Repeated measures analysis of variance (ANOVA) of PR, RR, SpO2, SBP, and DBP over time within the group and intragroup was calculated and found statistically insignificant. P value for comparison of mean value within the group was calculated by paired t-test with Bonferroni correction. There was a significant rise in ECO2 in the N95 group over time, and repeated measures ANOVA showed P = 0.04 at 30 min between the N95 + V group and the N95 + SM + V group. Inspired CO2 was statistically significant over time in the N95 + SM + V with P = 0.02.

Conclusion: N95 alone or in combination with a SM and visor does not cause any clinically significant measurable physiological derangements. The inspired CO2 may be implicated in the symptoms manifested by individuals.

Abstract
Background/aim: Given the current severe acute respiratory syndrome coronavirus 2 pandemic, coughing at the time of extubation is at risk of creating aerosolisation. This may place health care workers at risk of nosocomial infection during the perioperative period. This study aims to summarise the current pharmacologic methods to minimise cough at the time of extubation, and to determine whether some strategies could be more beneficial than others.

Methods: This is a summary of systematic reviews. A comprehensive search through MEDLINE was performed. Thirty-three publications were screened for eligibility. Only the manuscripts discussing pharmacologic methods to minimise coughing on extubation were included in this review.

Findings: Many pharmacological agents have been proposed to decrease the incidence of cough at the time of extubation. Of these, intravenous administration of dexmedetomidine (relative risk 0.4; 95% CI: 0.4-0.5) or remifentanil (RR 0.4; 95% CI: 0.4-0.5) seems to have the largest effect to reduce cough on extubation.

Conclusion: The available data in the current literature is sparse. Yet, dexmedetomidine and remifentanil seem to be the most efficient agents to decrease the incidence of emergence coughing.

Abstract
Introduction: COVID-19 is associated with severe respiratory distress and high mortality. We investigated the evolution of the respiratory mechanics in COVID-19 acute respiratory distress syndrome (ARDS) and the occurrence of a restrictive respiratory pattern.

Material and methods: A retrospective, single-centre study including patients admitted to the ICU during the first wave of the pandemic (March-April 2020).

Results: A total of 141 consecutive patients were included. Many patients developed a restrictive pattern of respiratory mechanics during the course of the disease. Fifty-two patients died in the hospital (36.8%). In 29 cases (58% of the deceased) death was associated with a pattern of pulmonary mechanics, indicating a restrictive evolution of ARDS. Other diagnoses related to death were pulmonary embolism (n = 7, 14%), septic shock (n = 17, 33%), and other causes (n = 10, 20%), with some patients combining at least 2 of these diagnoses. In a multivariate analysis, age (OR = 1.06; 95% CI: 1.01-1.12; P = 0.029) and the administration of steroid pulses (OR = 2.7; 95% CI: 1.1-6.8; P = 0.03) were associated with the development of a restrictive pulmonary pattern and a higher level of plasmatic interleukin-6.

Conclusions: COVID-19 ARDS is associated with high mortality associated with a specific pattern of respiratory mechanics and sustained activation of innate immunological response. Age and administration of high-dose steroid pulses are associated with this clinical picture.

Abstract
Background and aims: Individuals with opioid use disorder (OUD) suffer disproportionately from COVID-19. To inform clinical management of OUD patients, research is needed to identify characteristics associated with COVID-19 progression and death among this population. We aimed to investigate the role of OUD and specific comorbidities on COVID-19 progression among hospitalized OUD patients.

Design: Retrospective cohort study of merged electronic health records (EHR) from five large private health systems SETTING: New York City, New York, USA, 2011-2021 PARTICIPANTS: Adults with a COVID-19 encounter and OUD or opioid overdose diagnosis between March 2020-February 2021 MEASUREMENTS: Primary exposure included diagnosis of OUD/opioid overdose. Risk factors included age, sex, race/ethnicity and common medical, substance use and psychiatric co-morbidities known to be associated with COVID-19 severity. Outcomes included COVID-19 hospitalization and subsequent intubation, acute kidney failure, severe sepsis and death.

Findings: Of 110,917 COVID-19+ adults, 1.17% were ever diagnosed with OUD/opioid overdose. OUD patients had higher risk of COVID-19 hospitalization (adjusted risk ratio [aRR]: 1.40 [95% confidence interval (CI) 1.33, 1.47]), intubation (adjusted aood ratio [aOR]: 2.05 [95% CI 1.74, 2.42]), kidney failure (aRR: 1.51 [95% CI 1.34, 1.70)), sepsis (aRR: 2.30 [95% CI 1.88, 2.81]), and death (aRR: 2.10 [95% CI 1.84, 2.40)]. Among hospitalized OUD patients, risks for COVID-19 outcomes included being male; older; of a race/ethnicity other than white, Black or Hispanic; and having co-morbid chronic kidney disease, diabetes, obesity or cancer. Protective factors included having asthma, hepatitis-C, and chronic pain.

Conclusions: Opioid use disorder patients appears to have a substantial risk for COVID-19-associated morbidity and mortality, with particular comorbidities and treatments potentially moderating this risk.

Abstract
Genome-wide association studies (GWASs) show that genetic factors contribute to the risk of severe coronavirus disease 2019 (COVID-19) and blood analyte levels. Here, we utilize GWAS summary statistics to study the shared genetic influences (pleiotropy) between severe COVID-19 and 344 blood analytes at the genome, gene, and single-nucleotide polymorphism (SNP) levels. Our pleiotropy analyses genetically link blood levels of 71 analytes to severe COVID-19 in at least one of the three levels of investigation-suggesting shared biological mechanisms or causal relationships. Six analytes (alanine aminotransferase, alkaline phosphatase, apolipoprotein B, C-reactive protein, triglycerides, and urate) display evidence of pleiotropy with severe COVID-19 at all three levels. Causality analyses indicate that higher triglycerides levels causally increase the risk of severe COVID-19, thereby providing important support for the use of lipid-lowering drugs such as statins and fibrates to prevent severe COVID-19.

Abstract
The COVID-19 pandemic is ongoing as of September 2022. Since January 2020 when the first case was reported in Japan, the medical community faced a variety of problems both domestically and internationally. It is meaningful to review the impact of COVID-19 from an anesthesiologist's perspective to clarify our policy for future infectious disease outbreaks. In this year's Journal of Anesthesia (JA) symposium, five experts who were deeply involved in the COVID-19 response reviewed the past 2.5 years and made recommendations for potential future pandemics. Anesthesiologists are specialists in airway management and their role in intubating patients with COVID-19 has received much attention. However, they have also played an important backup role in intensive care as critical care physicians and must be more involved in critical care in regular (non-pandemic) times to properly fulfill this role. It is especially important for the Japan Society of Anesthesiologists and JA to quickly disseminate accurate information on unknown infectious diseases to the medical community and wider society. Therefore, it is important to promptly publish papers that are quality-assured through peer review.

Abstract
Background: The epidemiology of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be different worldwide. Despite similarities in medicine quality and formation, there are also significant differences concerning healthcare and ICU organisation, staffing, financial resources and population compliance and adherence. Large cohort data of critically ill patients from Central and Eastern Europe are also lacking.

Objectives: The study objectives were to describe the clinical characteristics of patients admitted to Romanian ICUs with SARS-CoV-2 infection and to identify the factors associated with ICU mortality.

Design: Prospective, cohort, observational study.

Setting: National recruitment, multicentre study, between March 2020 to March 2021.

Patients: All patients with SARS-CoV-2 infection admitted to Romanian ICUs were eligible. There were no exclusion criteria.

Intervention: None.

Main outcome measure: ICU mortality.

Results: The statistical analysis included 9058 patients with definitive ICU outcome. The multivariable mixed effects logistic regression model found that age [odds ratio (OR) 1.27; 95% confidence interval (CI), 1.23 to 1.31], male gender (OR 1.21; 95% CI 1.05 to 1.4), medical history of neoplasia (OR 1.74; 95% CI, 1.36 to 2.22), chronic kidney disease (OR 1.54; 95% CI, 1.27 to 1.88), type II diabetes (OR 1.23; 95% CI, 1.06 to 1.43), chronic heart failure (OR 1.24; 95% CI, 1.03 to 1.49), dyspnoea (OR 1.3; 95% CI, 1.1 to 1.5), SpO2 less than 90% (OR 3; 95% CI, 2.5 to 3.5), admission SOFA score (OR 1.07; 95% CI, 1.05 to 1.09), acute respiratory distress syndrome (ARDS) on ICU admission (OR 1.35; 95% CI, 1.1 to 1.63) and the need for noninvasive (OR 1.8, 95% CI, 1.5 to 1.22) or invasive ventilation (OR 28; 95% CI, 22 to 35) and neuromuscular blockade (OR 3.5; 95% CI, 2.6 to 4.8), were associated with larger ICU mortality.Higher GCS on admission (OR 0.81; 95% CI, 0.79 to 0.83), treatment with hydroxychloroquine (OR 0.78; 95% CI, 0.64 to 0.95) and tocilizumab (OR 0.58; 95% CI, 0.48 to 0.71) were inversely associated with ICU mortality.

Conclusion: The SARS-CoV-2 critically ill Romanian patients share common personal and clinical characteristics with published European cohorts. Public health measures and vaccination campaign should focus on patients at risk.

Abstract
Background: Providers performing endotracheal intubation are at high risk of contracting SARS-CoV-2. The objective was to assess various demographic, exposure and institutional preparedness factors affecting intubators' comfort and fear level during COVID-19 intubations.

Methods: We conducted a cross-sectional, survey-based study during the COVID-19 pandemic from September 2020 to January 2021 at a single academic medical centre in Washington, DC, USA. Inclusion criteria were healthcare providers who had an experience in intubating patients confirmed with or suspected of COVID-19. The survey assessed various factors related to the providers' comfort with intubation and fear during COVID-19 intubations.

Results: A total of 329 surveys from 55 hospitals were analysed. Of the respondents, 173 (52.6%) were from emergency medicine providers. Factors that were associated with a higher comfort level of intubating patients with COVID-19 included attending physician position (adjusted OR (aOR)=2.6, 95% CI 1.4 to 4.8; p=0.003), performing more than 20 COVID-19 intubations (aOR=3.3, 95% CI 1.5 to 6.6; p=0.002), participation in an intubation team (aOR=1.6, 95% CI 1.1 to 2.7; p=0.031) and adequate levels of personal protective equipment (PPE) (aOR=4.3, 95% CI 2.0 to 8.8; p<0.0005). Compared with emergency physicians, anaesthesiology providers had higher fear levels of contracting SARS-CoV-2 during both first and subsequent SARS-CoV-2 intubations (first: OR=1.7, 95% CI 1.1 to 2.6, p=0.006; subsequent: OR=2.0, 95% CI 1.4 to3.2, p<0.0005).

Conclusion: A higher degree of comfort in intubating patients suspected of or confirmed with COVID-19 was demonstrated in more senior physicians, members of intubation teams, providers who performed a higher number of intubations and providers who reported adequate PPE. These findings highlight potential targets for improving the experience of providers in this setting.

Abstract
Background: Corticosteroids improve outcomes in patients with severe COVID-19. In the COVID STEROID 2 randomised clinical trial, we found high probabilities of benefit with dexamethasone 12 mg vs. 6 mg daily. While no statistically significant heterogeneity in treatment effects (HTE) was found in the conventional, dichotomous subgroup analyses, these analyses have limitations, and HTE could still exist.

Methods: We assessed whether HTE were present for days alive without life support and mortality at day 90 in the trial according to baseline age, weight, number of comorbidities, category of respiratory failure (type of respiratory support system and oxygen requirements), and predicted risk of mortality using an internal prediction model. We used flexible models for continuous variables and logistic regressions for categorical variables without dichotomisation of the baseline variables of interest. HTE was assessed both visually and with P- and S-values from likelihood ratio tests.

Results: There was no strong evidence for substantial HTE on either outcome according to any of the baseline variables assessed with all P-values >0.37 (and all S-values <1.43) in the planned analyses and no convincingly strong visual indications of HTE.

Conclusions: We found no strong evidence for HTE with 12 vs. 6 mg dexamethasone daily on days alive without life support or mortality at day 90 in patients with COVID-19 and severe hypoxaemia, although these results cannot rule out HTE either. This article is protected by copyright. All rights reserved.

Abstract
Purpose: In response to the surgical backlog created by the COVID-19 pandemic and to spare valuable hospital resources, we developed and implemented a continuous adductor canal catheter (CACC) program for total knee arthroplasty (TKA) patients. CACC's offer superior analgesia, decrease opioid use, and increase patient satisfaction while simultaneously promoting a decreased length of hospital stay and even same day discharges. The implementation of analgesia protocols using continuous peripheral nerve catheters and isometric pumps has been described for other surgical procedures and populations; however, the role of the Acute Pain Service Nurse (APS RN) in the implementation of such a program has not been described.

Design: An best practice initiative for TKA patients receiving CACC was developed and implemented for patients recovering both in the hospital and at home.

Methods: We describe the development and implementation of a CACC program for TKA patients in response to the surgical backlog created by the COVID-19 pandemic from the perspective of the APS RN. We provide a detailed narrative description of our postoperative assessment and experience, and offer practical insights for the postoperative care of these patients. We share the educational resources and assessment tools we developed to ensure consistent, safe, and effective clinical management of CACC patients in the hospital and at home.

Findings: CACCs via elastomeric pumps have been shown to offer significant advances to pain control following TKA, decrease opioid use, enable earlier discharge, and improve patient satisfaction, all of which we observed unequivocally in our patients. In our experience, implementation of a daily telephone follow up by an APS RN for discharged TKA patients with a CACC was crucial for patient safety, patient satisfaction, and reducing emergency phone calls and emergency room visits.

Conclusions: We anticipate this description will provide an invaluable educational resource for other Acute Pain Service programs as similar outpatient peripheral nerve catheter programs are developed in response to the pandemic.

Abstract
Background: The new type of corona virus has a wide range of symptoms. Some people who have COVID-19 can experience long-term effects from their infection, known as post-COVID conditions. The authors aimed to investigate prolonged musculoskeletal pain as a symptom of the post-COVID-19 condition.

Methods: This is a descriptive study on the patients who were diagnosed with COVID-19 in a university hospital, between March 2020 and March 2021. Patient records and an extensive questionnaire were used to obtain relevant demographic and clinical characteristics, including hospitalization history, comorbidities, smoking history, duration of the pain, the area of pain, and the presence of accompanying neuropathic symptoms.

Results: Of the diagnosed patients, 501 agreed to participate in the study. Among the participants, 318 had musculoskeletal pain during COVID-19 infection, and 69 of them reported prolonged pain symptoms as part of their a post-COVID condition which could not be attributed to any other cause. The mean duration of pain was 4.38 ± 1.73 months, and the mean pain level was 7.2 ± 4.3. Neuropathic pain symptoms such as burning sensation (n = 16, 23.2%), numbness (n = 15, 21.7%), tingling (n = 10, 14.5%), stinging (n = 4, 5.8%), freezing (n = 1, 1.4%) were accompanied in patients with prolonged musculoskeletal pain.

Conclusions: Patients with COVID-19 may develop prolonged musculoskeletal pain. In some patients, neuropathic pain accompanies it. Awareness of prolonged post-COVID-19 pain is crucial for its early detection and management.

Abstract
Background: Patients with coronavirus disease 2019 (COVID-19) can present with severe respiratory distress requiring intensive care unit (ICU)-level care. Such care often requires placement of an arterial line for monitoring of pulmonary disease progression, hemodynamics, and laboratory tests. During the first wave of the COVID-19 pandemic in March 2020, experienced physicians anecdotally reported multiple attempts, decreased insertion durations, and greater need for replacement of arterial lines in patients with COVID-19 due to persistent thrombosis. Because invasive procedures in patients with COVID-19 may increase the risk for caregiver infection, better defining difficulties in maintaining arterial lines in COVID-19 patients is important. We sought to explore the association between COVID-19 infection and arterial line thrombosis in critically ill patients.

Methods: In this primary exploratory analysis, a multivariable Fine-Gray subdistribution hazard model was used to retrospectively estimate the association between critically ill COVID-19 (versus sepsis/acute respiratory distress syndrome [ARDS]) patients and the risk of arterial line removal for thrombosis (with arterial line removal for any other reason treated as a competing risk). As a sensitivity analysis, we compared the number of arterial line clots per 1000 arterial line days between critically ill COVID-19 and sepsis/ARDS patients using multivariable negative binomial regression.

Results: We retrospectively identified 119 patients and 200 arterial line insertions in patients with COVID-19 and 54 patients and 68 arterial line insertions with non-COVID ARDS. Using a Fine-Gray subdistribution hazard model, we found the adjusted subdistribution hazard ratio (95% confidence interval [CI]) for arterial line clot to be 2.18 (1.06-4.46) for arterial lines placed in COVID-19 patients versus non-COVID-19 sepsis/ARDS patients (P = .034). Patients with COVID-19 had 36.3 arterial line clots per 1000 arterial line days compared to 19.1 arterial line clots per 1000 arterial line days in patients without COVID-19 (adjusted incidence rate ratio [IRR] [95% CI], 1.78 [0.94-3.39]; P = .078).

Conclusions: Our study suggests that arterial line complications due to thrombosis are more likely in COVID-19 patients and supports the need for further research on the association between COVID-19 and arterial line dysfunction requiring replacement.

Abstract
Background: We performed a systematic review of mechanically ventilated patients with COVID-19, which analysed the effect of tracheostomy timing and technique (surgical vs percutaneous) on mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS), decannulation from tracheostomy, duration of mechanical ventilation, and complications.

Methods: Four databases were screened between January 1, 2020 and January 10, 2022 (PubMed, Embase, Scopus, and Cochrane). Papers were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Population or Problem, Intervention or exposure, Comparison, and Outcome (PICO) guidelines. Meta-analysis and meta-regression for main outcomes were performed.

Results: The search yielded 9024 potentially relevant studies, of which 47 (n=5268 patients) were included. High levels of between-study heterogeneity were observed across study outcomes. The pooled mean tracheostomy timing was 16.5 days (95% confidence interval [CI]: 14.7-18.4; I2=99.6%). Pooled mortality was 22.1% (95% CI: 18.7-25.5; I2=89.0%). Meta-regression did not show significant associations between mortality and tracheostomy timing, mechanical ventilation duration, time to decannulation, and tracheostomy technique. Pooled mean estimates for ICU and hospital LOS were 29.6 (95% CI: 24.0-35.2; I2=98.6%) and 38.8 (95% CI: 32.1-45.6; I2=95.7%) days, both associated with mechanical ventilation duration (coefficient 0.8 [95% CI: 0.2-1.4], P=0.02 and 0.9 [95% CI: 0.4-1.4], P=0.01, respectively) but not tracheostomy timing. Data were insufficient to assess tracheostomy technique on LOS. Duration of mechanical ventilation was 23.4 days (95% CI: 19.2-27.7; I2=99.3%), not associated with tracheostomy timing. Data were insufficient to assess the effect of tracheostomy technique on mechanical ventilation duration. Time to decannulation was 23.8 days (95% CI: 19.7-27.8; I2=98.7%), not influenced by tracheostomy timing or technique. The most common complications were stoma infection, ulcers or necrosis, and bleeding.

Conclusions: In patients with COVID-19 requiring tracheostomy, the timing and technique of tracheostomy did not clearly impact on patient outcomes.

Highlights
- Precautions to be taken during aerosol generating procedures (AGPs).
- Aerosol generating procedures are all associated with increased risk of COVID transmission.
- Wear N95 masks or a Powered Air-Purifying Respirator (PAPR) when performing AGPs.
- The number of persons present in the room should be minimized and specific to those needed to adequately care for the patient.
- Plan for proper disposal of intubation equipment and clean and disinfect procedure room surfaces promptly.

Abstract
Background: During the COVID-19 first wave in France, the capacity of intensive care unit (ICU) beds almost doubled, mainly because of the opening of temporary ICUs with staff and equipment from anaesthesia.

Objectives: We aim to investigate if the initial management in temporary ICU is associated with a change in ICU mortality and short-term prognosis.

Design: Retrospective single-centre cohort study.

Setting: Surgical ICU of the Bichat Claude Bernard University Hospital during the COVID-19 "first wave" (from 18 March to 10 April 2020).

Patients: All consecutive patients older than 18 years of age with laboratory-confirmed SARS-CoV-2 infection and/or typical radiological patterns were included during their first stay in the ICU for COVID-19.

Intervention: Patients were admitted to a temporary ICU if no room was available in the classical ICU and if they needed invasive mechanical ventilation but no renal replacement therapy or Extracorporeal Membrane Oxygenation (ECMO) in the short term. The temporary ICUs were managed by mixed teams (from the ICU and anaesthesiology departments) following a common protocol and staff meetings.

Main outcome measure: ICU mortality RESULTS: Among the 59 patients admitted, 37 (62.7%) patients had initial management in the temporary ICU. They had the same characteristics on admission and the same medical management as patients admitted to the classical ICU. ICU mortality was similar in the 2 groups (32.4% in temporary ICUs versus 40.9% in classical ICUs; p=0.58). SAPS-II and ECMO use were associated with mortality in multivariate analysis but not admission to the temporary ICU.

Conclusion: In an overload context of the ICU of a geographical area, our temporary ICU model allowed access to intensive care for all patients requiring it without endangering them.

Abstract
COVID-19 is a novel virus spread via airborne particles. Given the inherent risk to the anesthesia provider, intubation and airway management guidelines have been recently established. Various studies have been published advocating and detailing the results of different intubation devices designed to decrease the number of airborne particles. Currently, little literature exists regarding devices designed to mitigate the spread of COVID-19 airborne particles during extubation. The purpose of this prospective in situ simulated manikin study was to measure the effectiveness of an aerosolized containment device during passive (deep) and forced (simulated coughing) extubation. Airborne particles were measured at the 0.3, 0.5, 1, 2, 5, 10-micron level. Statistically significant decreases were seen with the use of a barrier device during both passive and forced extubation.

Abstract
Background: To determine the predictive value of mid-regional pro-adrenomedullin (MR-proADM) compared to routine clinical and laboratory parameters in patients with COVID-19.

Methods: A total of 135 adult patients hospitalized with COVID-19 were included in a prospective single-centre study. In addition to routine parameters, the levels of MR-proADM in blood plasma were measured on the day of hospitalization. The patients were divided into 2 groups: those who survived and were discharged (n = 115, 85%) and those who did not survive (n = 20, 15%). Data are presented as median and interquartile range.

Results: The non-survivors had a statistically significantly greater age (73.4 [63.5-84.8] vs. 62.2 [50.3-71.4] years, P = 0.001), a lower level of haemoglobin oxygen saturation (91 [87-92] vs. 92 [92-93]%, P < 0.001), lower lymphocyte level (13 [7-30] vs. 21 [15-27]%, P = 0.03), higher lactate dehydrogenase (338 [273-480] vs. 280 [233-383] EU L-1, P = 0.04) and aspartate aminotransferase levels (49 [28-72] vs. 33 [23-47] EU L-1, P = 0.03), a higher National Early Warning (NEWS) score (7 [7- 8] vs. 6 [5-7] points, P < 0.001), and higher procalcitonin (0.16 [0.11-0.32] vs. 0.1 [0.07-0.18] ng mL-1, P = 0.006) and MR-proADM levels (1.288 [0.886-1.847] vs. 0.769 [0.6-0.955] nmol L-1, P < 0.001). MR-proADM had the highest predictive value for death during hospital stay (cut-off: 0.895 nmol L-1, AUC ROC 0.78 [95% CI: 0.66-0.90], sensitivity 75%, specificity 69%, OR 6.58 [95% CI: 2.22-19.51]).

Conclusions: Compared with other indicators, MR-proADM has the highest predictive value for in-hospital mortality in patients with COVID-19.

Abstract
During the COVID-19 pandemic, ICU bed shortages sparked a discussion about resource allocation. We aimed to analyse the value of ICU treatment of COVID-19 from a patient-centred health economic perspective. We prospectively included 49 patients with severe COVID-19 and calculated direct medical treatment costs. Quality of life was converted into aggregated quality-adjusted life years using the statistical remaining life expectancy. Costs for non-treatment as the comparator were estimated using the value of statistical life year approach. We used multivariable linear or logistic regression to identify predictors of treatment costs, quality of life and survival. Mean (SD) direct medical treatment costs were higher in patients in ICU with COVID-19 compared with those without (£60,866 (£42,533) vs. £8282 (£14,870), respectively; p < 0.001). This was not solely attributable to prolonged ICU length of stay, as costs per day were also higher (£3115 (£1374) vs. £1490 (£713), respectively; p < 0.001), independent of overall disease severity. We observed a beneficial cost-utility value of £7511 per quality-adjusted life-year gained, even with a more pessimistic assumption towards the remaining life expectancy. Extracorporeal membrane oxygenation therapy provided no additional quality-adjusted life-year benefit. Compared with non-treatment (costs per lost life year, £106,085), ICU treatment (costs per quality-adjusted life-year, £7511) was economically preferable, even with a pessimistic interpretation of patient preferences for survival (sensitivity analysis of the value of statistical life year, £48,848). Length of ICU stay was a positive and extracorporeal membrane oxygenation a negative predictor for quality of life, whereas costs per day were a positive predictor for mortality. These data suggest that despite high costs, ICU treatment for severe COVID-19 may be cost-effective for quality-adjusted life-years gained.

Abstract
Airway management during the COVID-19 pandemic has been one of the most challenging aspects of care that anesthesiologists and intensivists face. This study was conducted to evaluate the management of tracheal intubation in patients with suspected or confirmed COVID-19 infection. This is a cross-sectional and international multicenter study based on a 37-item questionnaire. The survey was available to physicians who had performed intubations and tracheostomies in patients with suspected or confirmed COVID-19 and had provided informed consent to participate. The primary outcome is the preference to use a specific device for tracheal intubation. Secondary outcomes are clinical practice variables, use of video laryngoscopes, difficult airway management, and safety features to prevent cross-infection. This study included 2411 physicians who performed an average of 11.90 and 20.67 tracheal intubations in patients diagnosed or suspected of having COVID-19 disease, respectively. Physicians were mainly from the specialties of Anesthesiology (61.2%) and Intensive Care (7.4%). COVID-19 infection diagnosed by positive PCR or serology in physicians participating in intubation in this study was 15.1%. Respondents considered preoxygenation for more than three minutes very useful (75.7%). The preferred device for tracheal intubation was the video laryngoscope (64.8%). However, the direct laryngoscope (57.9%) was the most commonly used, followed by the video laryngoscope (37.5%). The preferred device to facilitate intubation was the Eschmann guide (34.2%). Percutaneous tracheostomy was the preferred technique (39.5%) over the open tracheostomy (22%). The predicted or unpredicted difficult airway management in these patients was preferably performed with a video laryngoscope (61.7% or 63.7, respectively). Intubation was mostly performed by two or more expert airway physicians (61.6%). The use of personal protective equipment increased the practitioners' discomfort during intubation maneuvers. The video laryngoscope is the preferred device for intubating patients with COVID-19, combined with the Eschmann guide, flexible stylet within the endotracheal tube, or Frova guide to facilitate intubation. The sub-analysis of the two groups of physicians by the level of intubation experience showed a higher use of the video laryngoscope (63.4%) in the experts group and no significant differences between the two groups in terms of cross-infection rates in physicians, in their preference for the use of the video laryngoscope or in the number of intubations performed in confirmed or suspected COVID-19 patients.

Abstract
Introduction: COVID-19 has disturbed the functioning of Polish healthcare for the past two years. Due to the high proportion of patients requiring admission to the intensive care unit (ICU), these wards are particularly overwhelmed and are considered the bottleneck of the healthcare system. The aim of this study was to describe clinical outcomes of critically ill patients treated in a single tertiary ICU in Poland, assess factors associated with mortality and compare outcomes of patients treated during the 2nd and 3rd waves of the pandemic.

Material and methods: This is a retrospective single-centre study including patients admitted to the ICU between October 2020 and May 2021 (the 3rd wave) with confirmed SARS-CoV-2 infection. Patients were followed up until death or 90 days after ICU admission. The co-primary endpoints of this study included ICU, 30-day and 90-day mortality.

Results: We enrolled 108 patients at a mean age of 64.3 (SD = 12) years, the majority of whom were male (63.9%). Mortality in the ICU, after 30 days and 90 days was 44.4% (48/108), 50.0% (54/108), and 57.9% (62/108), respectively. Mortality at 90 days was associated with increasing age (OR = 3.97, 95% CI: 1.87-8.41) and was significantly higher during the 2nd wave (65.6 vs. 46.5%, log-rank P = 0.043) compared to the 3rd wave of the pandemic.

Conclusions: This retrospective single-centre study confirms the high mortality rate among critically ill patients with COVID-19. Moreover, it suggests a significant association between 90-day mortality and increasing age as well as differences in mortality between the 2nd and 3rd waves of the pandemic in Poland.

Abstract
In today's applicant landscape, the SARS-COV-2 pandemic has drastically altered the traditional model of in-person interviews shifting it to an online format often conducted by web-based applications. Fellowship programs and naturally fellowship program directors face a new challenge of standardizing information to be distributed to prospective fellowship applicants through American Society of Regional Anesthesia and Pain Medicine (ASRA) common application. Here we describe a set of 11 criteria recommended by other similar studies selected for evaluation of online program training platforms, where only 13.3% of the acute and regional pain fellowship program online platforms met 75% of the criteria with limited presence in areas of research, rotation schedules, list of fellows, alumni, and life in the area. Additional considerations pertaining to the types of procedures performed, evaluation, mentorship, academic involvement, and teaching should be undertaken by the programs.

Abstract
This multicenter cohort study investigated the prevalence of musculoskeletal post-COVID pain during the first year after the infection with mosaic plots and an exponential bar plot model and its associated risk factors. Patients hospitalized because of COVID-19 in 5 hospitals of Madrid (Spain) were scheduled for a telephone interview at 2 follow-up periods after hospitalization for collecting data about musculoskeletal post-COVID pain. Hospitalization and clinical data were collected from hospital medical records. From 2000 patients initially recruited, 1593 (44.6% women, age: 61 +/- 15 years) were assessed at T0 (hospital admission), T1 (mean: 8.0 +/- 1.5 months after discharge), and T2 (mean: 13.2 +/- 1.5 months after discharge). The prevalence of musculoskeletal pain (myalgia) was 30.3% (n = 483) at T0, increased to 43.4% (n = 692) at T1, and decreased to 37.8% (n = 603) at T2. The trajectory curve revealed a decreasing prevalence trend of musculoskeletal post-COVID pain the following years after hospitalization. According to the presence of pre-existing pain symptoms, the prevalence of new-onset post-COVID pain was 75.9%. Female sex (odds ratio [OR] 1.593, 95% confidence interval [CI] 1.148-2.211), history of musculoskeletal pain (OR 1.591, 95% CI 1.211-2.07), the presence of myalgia (OR 1.371, 95% CI 1.032-1.821) or headache (OR 2.278, 95% CI 1.622-3.199) at hospitalization, the days of hospitalization (OR 1.013, 95% CI 1.000-1.025), and the presence of post-COVID pain at T1 (OR 11.02, 95% CI 8.493-14.305) were factors associated with musculoskeletal post-COVID pain 1 year after hospitalization. In conclusion, musculoskeletal post-COVID pain remains highly prevalent 1 year after hospitalization. Female sex, previous history of pain symptoms, pain symptoms at onset, and days at hospital were factors associated with musculoskeletal post-COVID pain 1 year after hospitalization.

Abstract
Background: The COVID-19 pandemic brought many changes to medical training, including in-person education platforms being disbanded and replaced with virtual education. At our institution, dedicated obstetric anesthesiology teaching for residents and fellows occurs daily and is highly valued and rated. In March 2020 due to the COVID-19 pandemic, we changed the teaching platform from in-person to virtual teaching (via video communication). We subsequently surveyed residents, fellows, and attendings to determine the impact of virtual compared with in-person teaching.

Methods: To assess the impact of this change, an electronic survey was sent to 10 anesthesiology residents on their 2nd obstetric anesthesiology rotation, and 10 residents on their 1st rotation, respectively. The electronic survey was also sent to three fellows and eight obstetric anesthesiology attendings. Answers were based on a 5-point Likert scale (1 = strongly disagree, 5 = strongly agree).

Results: The results for 1st rotation residents were higher in all domains compared with 2nd rotation residents and fellows, where "quality" achieved statistical significance (p=0.009) between 1st and 2nd rotation residents. "Engagement" was overall the most impacted domain for trainees. Attendings did not feel that virtual teaching impacted their ability to provide adequate education, however, learner engagement was again the lowest rated domain, and teachers strongly favored resuming in-person teaching.

Conclusions: Virtual teaching is an appropriate alternative when in-person teaching is not possible. Future initiatives are needed to improve engagement and better facilitate virtual teaching.

Abstract
Introduction: The dissemination of the COVID-19 pandemic in Europe, namely in Portugal, demanded an organizational and clinical reaction from the Portuguese National Health Service. With the unpredictable impact of COVID-19 infected patients redefining hospital logistics, reducing non-priority elective care and extending the hospital capacity for critical care patients made mobilizing a significant part of human resources a priority. We conducted a national survey to monitor the contribution and the role of anaesthesiologists belonging to the 53 Portuguese National Health Service hospitals in the first wave fight against the pandemic.

Material and methods: This prospective cross-sectional observational study used a weekly survey sent to the Directors of the Anaesthesiology Departments of all Portuguese National Health Service hospitals, between the period of 13th April and 21st June 2020. Directors were asked about human resources, hospital logistics, anaesthetic activity and residency programs in their departments as well as contingency plans facing the impact of the pandemic growth in the PNHS.

Results: Contingency strategy for all Portuguese National Health Service hospitals planned for a total of 1524 level III critical care beds during the initial phases of the pandemic, an increase of 151% from the existing 607 level III critical care beds in Portugal in January 2020. This re-configuration effort of the Portuguese National Health Service was only possible due to the partial or total suspension of non-urgent elective activity that reached over 90% of these institutions in the first pandemic months (March and April) and the deployment of anaesthesiologists from their normal activities to the treatment of critical care patients. During the peak of the first pandemic wave, 209 anaesthesiology specialists and 170 trainees (22.9% of the total anaesthesiologist's staff in the Portuguese National Health Service) were deployed in critical care. There was an almost complete interruption of the residency program rotation in 70.4% of hospitals with anaesthesiology residents, between March and April 2020.

Conclusion: During the first pandemic wave there was an effective and fast reorganisation of the Portuguese National Health Service in order to increase level III critical care beds, which might have contributed to the low mortality rates in Portugal. We believe that this could have also been a result of the contribution given by all public anaesthesiology departments.

Abstract
Background and aims: Aerosol protection equipment aim at protecting the anaesthesiologist, from aerosol-borne infections, namely, severe acute respiratory syndrome corona virus-2.

Methods: We improvised the first-generation intubation box (IB) by increasing its dimensions, including heat and moisture exchanger with filter, suction catheter, and attaching arm sleeves to make a modified intubation box (MIB). The impact of IB, MIB and transparent sheets (TS) on the patient outcomes during airway management was evaluated.

Results: A significant difference in median (interquartile range in minutes) was observed in time to intubate between IB (4 [4-5]); TS (0.5 [0.3-0.5]) and MIB (0.3 [0.3-1.5]): P = 0.004); and airway devices; McCoy (0.5 [0.3-2]), CMac (0.5 [0.3-1.5]): P = 0.004. First-pass success was 100% with the TS, whereas more than three attempts were required with IB 66.7% and 5.2% with MIB. Video laryngoscope was associated with less airway-related adverse events (ARAEs). The need for mask ventilation (and hence possible aerosolisation) was maximum with IB. All the ARAEs resolved uneventfully. No breach of personal protective equipment was observed; none of the health-care professionals involved in patient care developed any symptoms suggestive of COVID-19.

Conclusion: Video laryngoscope is favourable for managing airway in COVID-19 times. In view of the ongoing pandemic and added protection that it offers, it is worthwhile to include the MIB in the armamentarium for managing the airway of patients with COVID-19.

Abstract
Background: Polypharmacy of sedatives (PP) is a potentially modifiable, iatrogenic risk factor for ICU delirium. The extent to which sedative polypharmacy influenced development of high rates of delirium among critically ill COVID-19 patients is unknown. We tested the hypothesis that PP, defined as the use of 4 or more classes of intravenous agents, is a mediator in the causal pathway of mechanical ventilation and delirium.

Methods: Retrospective cohort study of adults admitted with a primary diagnosis of RT-PCR+ for SARS-CoV2 to ICUs of a tertiary level academic medical center between February 2020-April 2021. Mediation analysis was conducted with bootstrap estimation to assess whether an association between mechanical ventilation and delirium was mediated by PP. Analyses were adjusted for potential confounders related to mechanical ventilation, mediator, and outcome, including age, gender, vasopressor use, median RASS scores, SOFA score within 24 hours of admission and maximum CRP levels.

Results: 212 patients were included in the analysis. 72.6%(154/212) of patients had delirium (CAM-ICU+) during ICU stay. 54.7%(116/212) patients received PP. Mechanical ventilation (OR 3.81 [1.16-12.52]) and PP (OR 7.38 [2.4-22.68]) were identified as risk factors for development of ICU delirium after adjusting for prespecified confounders. PP acts as a mediator in the causal pathway between mechanical ventilation and delirium. 39% (95% CI:17%-94%) of the effect of mechanical ventilation on delirium was mediated through PP.

Conclusion: PP mediates approximately 39% of the effect of mechanical ventilation on delirium, which is clinically and statistically significant. Studies should asses whether mitigating polypharmacy could lead to reduction in ICU delirium.

Abstract
Background: The efficacy and safety profiles of prone ventilation among intubated Coronavirus Disease 2019 (COVID-19) patients remain unclear. The primary objective was to examine the effect of prone ventilation on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) in intubated COVID-19 patients.

Methods: Databases of MEDLINE, EMBASE and CENTRAL were systematically searched from inception until March 2021. Case reports and case series were excluded.

Results: Eleven studies (n = 606 patients) were eligible. Prone ventilation significantly improved PaO2/FiO2 ratio (studies: 8, n = 579, mean difference 46.75, 95% CI 33.35‒60.15, p < 0.00001; evidence: very low) and peripheral oxygen saturation (SpO2) (studies: 3, n = 432, mean difference 1.67, 95% CI 1.08‒2.26, p < 0.00001; evidence: ow), but not the arterial partial pressure of carbon dioxide (PaCO2) (studies: 5, n = 396, mean difference 2.45, 95% CI 2.39‒7.30, p = 0.32; evidence: very low), mortality rate (studies: 1, n = 215, Odds Ratio 0.66, 95% CI 0.32‒1.33, p = 0.24; evidence: very low), or number of patients discharged alive (studies: 1, n = 43, Odds Ratio 1.49, 95% CI 0.72‒3.08, p = 0.28; evidence: very low).

Conclusion: Prone ventilation improved PaO2/FiO2 ratio and SpO2 in intubated COVID-19 patients. Given the substantial heterogeneity and low level of evidence, more randomized- controlled trials are warranted to improve the certainty of evidence, and to examine the adverse events of prone ventilation.

Abstract
Purpose: SARS-CoV-2 vaccines have been proven effective at preventing poor outcomes from COVID-19; however, voluntary vaccination rates have been suboptimal. We assessed the potential avoidable intensive care unit (ICU) resource use and associated costs had unvaccinated or partially vaccinated patients hospitalized with COVID-19 been fully vaccinated.

Methods: We conducted a retrospective, population-based cohort study of persons aged 12 yr or greater in Alberta (2021 population ~ 4.4 million) admitted to any ICU with COVID-19 from 6 September 2021 to 4 January 2022. We used publicly available aggregate data on COVID-19 infections, vaccination status, and health services use. Intensive care unit admissions, bed-days, lengths of stay, and costs were estimated for patients with COVID-19 and stratified by vaccination status.

Results: In total, 1,053 patients admitted to the ICU with COVID-19 were unvaccinated, 42 were partially vaccinated, and 173 were fully vaccinated (cumulative incidence 230.6, 30.8, and 5.5 patients/100,000 population, respectively). Cumulative incidence rate ratios of ICU admission were 42.2 (95% confidence interval [CI], 39.7 to 44.9) for unvaccinated patients and 5.6 (95% CI, 4.1 to 7.6) for partially vaccinated patients when compared with fully vaccinated patients. During the study period, 1,028 avoidable ICU admissions and 13,015 bed-days were recorded for unvaccinated patients and the total avoidable costs were CAD 61.3 million. The largest opportunity to avoid ICU bed-days and costs was in unvaccinated patients aged 50 to 69 yr.

Conclusions: Unvaccinated patients with COVID-19 had substantially greater rates of ICU admissions, ICU bed-days, and ICU-related costs than vaccinated patients did. This increased resource use would have been potentially avoidable had these unvaccinated patients been vaccinated against SARS-CoV-2.

Abstract
Objective: To investigate the association between demographic, clinical, psychological, cognitive, and health-related variables and the Central Sensitization Inventory (CSI) in previously hospitalized COVID-19 survivors exhibiting "de novo" post-COVID pain.

Methods: Seventy-seven (n = 77) COVID-19 survivors with "de novo" post-COVID pain completed demographic (age, height, and weight), clinical (duration and intensity of the pain), psychological (depressive/anxiety levels and sleep quality), cognitive (catastrophizing and kinesiophobia levels), and health-related quality of life variables as well as the CSI. A multivariable correlation analysis was conducted to determine the association between variables, and a stepwise multiple linear regression model was performed to identify CSI predictors.

Results: Patients were assessed a mean of 6.0 (SD 0.8) months after hospital discharge. Twenty-six (33.7%) individuals showed indications of sensitization-associated symptoms (CSI score ≥40 points). The CSI score was positively associated with pain intensity (r: 0.371), anxiety (r: 0.784), depressive (r: 0.709), catastrophizing (r: 0.620), and kinesiophobia (r: 0.359) levels (all, p < 0.001). The stepwise regression analysis revealed that 60.2% of CSI was explained by anxiety levels and pain intensity.

Conclusion: This study found that psychological and cognitive variables were associated with the CSI score in previously hospitalized COVID-19 survivors with "de novo" post-COVID pain. Anxiety levels and the intensity of pain symptoms were independently associated with CSI score suggesting a significant overlap with psychological construct. The "de novo" post-COVID pain association with CSI may indicate changes in the pain processing important for managing the pain.

Abstract
Background: Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants.

Methods: We used a case-control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1, 2021, and March 8, 2022, we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant (July 1, 2021, to December 18, 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022).

Results: A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 [12%] received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant's mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval [CI], 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy.

Conclusions: Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age. (Funded by the Centers for Disease Control and Prevention.).

Abstract
Coronavirus disease 19 infection clinical presentation varies from asymptomatic cases to acute respiratory distress syndromes. In some cases, pulmonary fibrosis is observed after or during the disease. Pirfenidone is an agent approved for the treatment of idiopathic pulmonary fibrosis. Here we report a patient treated with pirfenidone for pulmonary fibrosis related to coronavirus disease 19.

Abstract
While the coronavirus disease 2019 (COVID-19) pandemic placed a heavy burden on healthcare systems worldwide, it also induced urgent mobilisation of research teams to develop treatments preventing or curing the disease and its consequences. It has, therefore, challenged critical care research to rapidly focus on specific fields while forcing critical care physicians to make difficult ethical decisions. This narrative review aims to summarise critical care research -from organisation to research fields- in this pandemic setting and to highlight opportunities to improve research efficiency in the future, based on what is learned from COVID-19. This pressure on research revealed, i.e., i/ the need to harmonise regulatory processes between countries, allowing simplified organisation of international research networks to improve their efficiency in answering large-scale questions; ii/ the importance of developing translational research from which therapeutic innovations can emerge; iii/ the need for improved triage and predictive scores to rationalise admission to the intensive care unit. In this context, key areas for future critical care research and better pandemic preparedness are artificial intelligence applied to healthcare, characterisation of long-term symptoms, and ethical considerations. Such collaborative research efforts should involve groups from both high and low-to-middle income countries to propose worldwide solutions. As a conclusion, stress tests on healthcare organisations should be viewed as opportunities to design new research frameworks and strategies. Worldwide availability of research networks ready to operate is essential to be prepared for next pandemics. Importantly, researchers and physicians should prioritise realistic and ethical goals for both clinical care and research.

Abstract
Background: To investigate the use of internet resources by surgeons for continuing professional development (CPD).

Results: This cross-sectional study was carried out between July 1, 2021, to October 31, 2021, at the Department of Medicine, Health Sciences University Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey, with participants from nine surgical specialties: General surgery, neurosurgery, orthopedics, urology, plastic surgery, ear-nose-throat surgery, cardiovascular surgery, ophthalmology, and anesthesiology. All study participants were asked to complete a questionnaire comprising 23 questions regarding their age, duration of work experience, appointment status, venue, and time spent on internet resources and preferred online resources for CPD purposes. In addition, participants were divided into two groups according to their appointment status: academic faculty and staff surgeons. Data analysis was performed using IBM SPSS Statistics version 17.0. The target population consisted of 216 specialists. The survey was completed by 204 (94.4%) surgical specialists. The majority of the specialists (n = 137, 67.2%) reported using the internet for work-related purposes every day. Daily time spent on internet resources was reported to be 30-60 min by 39.2% (n = 80) participants, whereas 52 (25.5%) reported spending less than 30 min. The participants wished to spend more time on internet resources. The majority of surgeons found the hospital and home equally effective in using the internet and preferred to engage alone. The mean age, English language level, usage of online resources, and the attitude score toward the perceived credibility and usefulness of e-resources were significantly higher in the academic faculty group than staff surgeons (p < 0.005). On the other hand, the use of Google/Google scholar was similar between the two groups (p = 0.192). Technical difficulties such as slow internet, need for website registration, and article fees were considered drawbacks for internet resources among all the participants.

Conclusions: This study showed that most surgeons use internet resources daily for CPD and stated they would like to engage longer despite technical difficulties. Institutions should address these technical difficulties.

Abstract
Social distance regulations have been widely implemented to control the global COVID-19 pandemic. Individuals have thus been experiencing social pain through social distance regulations. Prior research has shown that social and physical pains share a common neural alarm system. Hence, COVID-19 social distancing should enhance sensitivity to physical pain. Two laboratory studies were conducted to test the spillover effect of COVID-19 social distancing on physical pain. The findings supported our hypothesis by showing that participants who were reminded of COVID-19 social distancing reported a higher level of pain perception in response to immersion in hot water (Experiment 1, N = 102) and expressed a lower pain threshold measured by a pressure algometer than did those of controls (Experiment 2, N = 140). This may be the first experimental evidence demonstrating that people primed with COVID-19 social distancing have increased sensitivity to physical pain. Our findings suggest that people might be more likely to experience physical pain under the impact of COVID-19 social distancing. The association between a heightened sense of social disconnection in a global pandemic and increased sensitivity to physical pain should receive more attention.

Abstract
Context: The COVID-19 pandemic has highlighted variability in intensity of care. We aimed to characterize intensity of care among hospitalized patients with COVID-19.

Objectives: Examine the prevalence and predictors of admission code status, palliative care consultation, comfort-measures-only orders, and cardiopulmonary resuscitation (CPR) among patients hospitalized with COVID-19.

Methods: This cross-sectional study examined data from an international registry of hospitalized patients with COVID-19. A proportional odds model evaluated predictors of more aggressive code status (i.e. Full Code) versus less (i.e. Do Not Resuscitate, DNR). Among decedents, logistic regression was used to identify predictors of palliative care consultation, comfort measures only, and CPR at time of death.

Results: We included 29,923 patients across 179 sites. Among those with admission code status documented, Full Code was selected by 90% (n=15,273). Adjusting for site, Full Code was more likely for patients who were of Black or Asian race (ORs 1.82, 95% CIs 1.5-2.19; 1.78, 1.15-3.09 respectively, relative to white race), Hispanic ethnicity (OR 1.89, CI 1.35 - 2.32), and male sex (OR 1.16, CI 1.0-1.33). Of the 4,951 decedents, 29% received palliative care consultation, 59% transitioned to comfort measures only, and 29% received CPR, with non-white racial and ethnic groups less likely to receive comfort measures only and more likely to receive CPR.

Conclusion: In this international cohort of patients with COVID-19, Full Code was the initial code status in the majority, and more likely among patients who were Black or Asian race, Hispanic ethnicity or male. These results provide direction for future studies to improve these disparities in care.

Abstract
Background: ICU admission due to COVID-19 may result in cognitive and physical impairment. We investigated the long-term cognitive and physical status of Danish ICU patients with COVID-19.

Methods: We included all patients with COVID-19 admitted to Danish ICUs between March 10th and May 19th , 2020. Patients were the contacted prospectively at 6 and 12 months for follow up. Our primary outcomes were cognitive function and frailty at 6 and 12 months after ICU admission, estimated by the Mini Montreal Cognitive Assessment, and the Clinical Frailty Scale. Secondary outcomes were 6- and 12-month mortality, health-related quality of life (HRQoL) assessed by EQ-5D-5L, functional status (Barthel Activities of Daily Living and Lawton-Brody Instrumental Activities of Daily Living), and fatigue (Fatigue Assessment Scale). The study had no information on pre-ICU admission status for the participants.

Results: A total of 326 patients were included. The 6- and 12-month mortality was 37% and 38%, respectively. Among the 204 6-month survivors, 105 (51%) participated in the 6-month follow-up; among the 202 12-month survivors, 95 (47%) participated in the 12-month follow-up. At 6 months, cognitive scores indicated impairment for 26% (95% CI, 11.4 - 12.4) and at 12 months for 17% (95% CI, 12.0 - 12.8) of participants. Frailty was indicated in 20% (95% CI, 3.4 - 3.9) at 6 months, and for 18% (95% CI, 3.3 - 3.8) at 12 months. Fatigue was reported by 52% at 6 months, and by 47% at 12 months. For HRQoL, moderate, severe, or extreme health problems were reported by 28% at 6 months, and by 25% at 12 months.

Conclusion: Long term cognitive, functional impairment was found in up to one-in-four of patients surviving intensive care for COVID-19. Fatigue was present in nearly half the survivors at both 6- and 12 months. However, pre-ICU admission status of the patients was unknown.

Abstract
Background.: The mechanisms underlying oxygenation improvement after prone positioning in COVID-19 ARDS have not been fully elucidated yet. We hypothesized that the oxygenation increase with prone positioning is secondary to the improvement of ventilation-perfusion matching.

Methods.: In a series of consecutive intubated COVID-19 ARDS patients receiving volume-controlled ventilation, we prospectively assessed the percent variation of ventilation-perfusion matching by electrical impedance tomography (EIT) before and 90 minutes after the first cycle of prone positioning (primary endpoint). We also assessed changes in the distribution and homogeneity of lung ventilation and perfusion, lung overdistention and collapse, respiratory system compliance, driving pressure, optimal positive end-expiratory pressure (PEEP), as assessed by EIT, and the ratio of partial pressure to fractional inspired oxygen (PaO2/FiO2) (secondary endpoints). Data are reported as medians [25th - 75th] or percentages.

Results.: We enrolled 30 consecutive patients, all analyzed without missing data. Compared to supine position, prone positioning overall improved ventilation-perfusion matching from 58 [43-69] % to 68 [56-75] % (p=0.042), with a median difference of 8.0% (95% Confidence Interval 0.1 to 16.0%) . Dorsal ventilation increased from 39 [31-43] % to 52 [44-62] % (p<0.001), while dorsal perfusion did not significantly vary. Prone positioning also reduced lung overdistension from 9 [4-11] % to 4 [2-6] % (p=0.025), while it did not significantly affect ventilation and perfusion homogeneity, lung collapse, static respiratory system compliance, driving pressure, and optimal PEEP. PaO2/FiO2 overall improved from 141 [104-182] mmHg to 235 [164-267] mmHg (p=0.019). However, 9 (30%) patients were non-responders, experiencing an increase in PaO2/FiO2 <20% with respect to baseline.

Conclusions.: In COVID-19 ARDS patients, prone positioning overall produced an early increase in ventilation-perfusion matching and dorsal ventilation. These effects were, however, heterogeneous among patients.

Abstract
Purpose: The study aims to compare anesthesia methods, clinical course, and maternal and fetal outcomes of symptomatic and asymptomatic pregnant women undergoing cesarean operation with confirmed COVID-19.

Methods: 254 pregnant women with COVID-19 who had a cesarean section in our hospital between March 2020 and March 2021 were included in the study. Demographic information, laboratory test results, radiological data, treatments, anesthesia methods, and prognoses of the patients were evaluated retrospectively.

Results: On admission, 160 (63%) patients were asymptomatic (Group A), and 94 (37%) patients were symptomatic (Group S). The ratio of patients who needed oxygen therapy in the obstetric ward (p < 0.001) and intraoperative period (p < 0.001) and ICU admission (p = 0.005) was higher in Group S. Neutrophil-to-lymphocyte ratio (NLR), ferritin, procalcitonin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were higher in Group S. In both groups, spinal anesthesia was performed predominantly. The rate of general anesthesia was significantly higher in Group S (16.0% vs. 4.4%, p = 0.003). No difference was found in the amount of sedatives during the spinal anesthesia.

Conclusion: Close follow-up of the laboratory values and comorbidities (especially asthma) of pregnant will provide information about the clinical course as in other patient groups. Spinal anesthesia is a safe and sufficient anesthesia method in both symptomatic and asymptomatic COVID-19 pregnant women when performed by experienced hands.

Abstract
Background: In the context of the coronavirus disease 2019 (COVID-19) pandemic, many retrospective single-centre or specialised centre reports have shown promising mortality rates with the use of extracorporeal membrane oxygenation (ECMO) therapy. However, the mortality rate of an entire country throughout the COVID-19 pandemic remains unknown.

Objectives: The primary objective is to determine the hospital mortality in COVID-19 patients receiving venovenous ECMO (VV-ECMO) and veno-arterial ECMO (VA-ECMO) therapy. Secondary objectives are the chronological development of mortality during the pandemic, the analysis of comorbidities, age and complications.

Design: Cohort study.

Setting: Inpatient data from January 2020 to September 2021 of all hospitals in Germany were analysed.

Participants: All COVID-19-positive patients who received ECMO therapy were analysed according to the appropriate international statistical classification of diseases and related health problem codes (ICDs) and process key codes (OPSs).

Main outcome measures: The primary outcome was the hospital mortality.

Results: In total, 4279 COVID-19-positive patients who received ECMO therapy were analysed. Among 404 patients treated with VA-ECMO and 3875 treated with VV-ECMO, the hospital mortality was high: 72% (n = 291) for VA-ECMO and 65.9% (n = 2552) for VV-ECMO. A total of 43.2% (n = 1848) of all patients were older than 60 years with a hospital mortality rate of 72.7% (n = 172) for VA-ECMO and 77.6% (n = 1301) for VV-ECMO. CPR was performed in 44.1% (n = 178) of patients with VA-ECMO and 16.4% (n = 637) of patients with VV-ECMO. The mortality rates widely varied from 48.1 to 84.4% in individual months and worsened from March 2020 (59.2%) to September 2021 (78.4%).

Conclusion: In Germany, a large proportion of elderly patients with COVID-19 were treated with ECMO, with an unacceptably high hospital mortality. Considering these data, the unconditional use of ECMO therapy in COVID-19 must be carefully considered and advanced age should be considered as a relative contraindication.

Abstract
Background: Neuraxial blocks is the recommended mode of analgesia and anesthesia in parturients with Coronavirus 19 (COVID-19). There is limited data on the hemodynamic responses to neuraxial blocks in COVID-19 patients. We aim to compare the hemodynamic responses to neuraxial blocks in COVID-19 positive and propensity-matched COVID-19 negative parturients.

Methods: We conducted retrospective, cross-sectional case-control study of hemodynamic changes associated with neuraxial blocks in COVID-19 positive parturients in a Tertiary care academic medical center. Fifty-one COVID-19 positive women confirmed by nasopharyngeal reverse transcription-polymerase chain reaction (RT-PCR), were compared with propensity-matched COVID negative controls (n = 51). Hemodynamic changes after neuraxial block were recorded by electronic medical recording system and analyzed using paired and unpaired T- test and Wilcoxon-Mann-Whitney Rank Sum tests. The primary outcome was ≥ 20% change in MAP and HR after neuraxial block placement.

Results: In the epidural group, 7% COVID-19 positive parturients had > 20% decrease in mean arterial pressure (MAP) from baseline compared to 15% COVID-19 negative parturients (P = 0.66). In the spinal group, 83% of COVID-19 positive parturients had a decrease in MAP more than 20% from baseline compared to 71% in control (P = 0.49). MAP drop of more than 40% occurred in 29% COVID positive parturients in the spinal group versus 17% in COVID-19 negative parturients (P = 0.5465). In COVID-19 positive spinal group, 54% required vasopressors whereas 38% in COVID-19 negative spinal group required vasopressors (P = 0.387). We found a significant correlation between body mass index (BMI) > 30 and hypotension in COVID ( +) parturient with odds ratio (8.63; 95% CI-1.93 - 37.21) (P = 0.007).

Conclusion: Incidence and severity of hypotension after neuraxial blocks were similar between COVID-19 positive and COVID-19 negative parturients. BMI > 30 was a significant risk factor for hypotension as described in preexisting literature, this correlation was seen in COVID-19 positive parturients. The likely reason for parturients with BMI > 30 in COVID negative patients not showing similar correlation, is that the sample size was small.

Abstract
Background: Tracheostomy is a commonly performed procedure in patients with coronavirus disease 2019 (COVID-19) receiving mechanical ventilation (MV). This review aims to investigate the occurrence of SARS-CoV-2 transmission from patients to healthcare workers (HCWs) when tracheostomies are performed.

Methods: This systematic review used the preferred reporting items for systematic reviews and meta-analysis framework. Studies reporting SARS-CoV-2 infection in HCWs involved in tracheostomy procedures were included.

Results: Sixty-nine studies (between 01/11/2019 and 16/01/2022) reporting 3117 tracheostomy events were included, 45.9% (1430/3117) were performed surgically. The mean time from MV initiation to tracheostomy was 16.7 ± 7.9 days. Location of tracheostomy, personal protective equipment used, and anaesthesia technique varied between studies. The mean procedure duration was 14.1 ± 7.5 minutes; was statistically longer for percutaneous tracheostomies compared with surgical tracheostomies (mean duration 17.5 ± 7.0 versus 15.5 ± 5.6 minutes, p = 0.02). Across 5 out of 69 studies that reported 311 tracheostomies, 34 HCWs tested positive for SARS-CoV-2 and 23/34 (67.6%) were associated with percutaneous tracheostomies.

Conclusions: In this systematic review we found that SARS-CoV-2 transmission to HCWs performing or assisting with a tracheostomy procedure appeared to be low, with all reported transmissions occurring in 2020, prior to vaccinations and more recent strains of SARS-CoV-2. Transmissions may be higher with percutaneous tracheostomies. However, an accurate estimation of infection risk was not possible in the absence of the actual number of HCWs exposed to the risk during the procedure and the inability to control for multiple confounders related to variable timing, technique, and infection control practices.

Abstract
Cardiovascular complications due to COVID-19, such as right ventricular dysfunction, are common. The combination of acute respiratory distress syndrome, invasive mechanical ventilation, thromboembolic disease and direct myocardial injury creates conditions where right ventricular dysfunction is likely to occur. We undertook a prospective, multicentre cohort study in 10 Scottish intensive care units of patients with COVID-19 pneumonitis whose lungs were mechanically ventilated. Right ventricular dysfunction was defined as the presence of severe right ventricular dilation and interventricular septal flattening. To explore the role of myocardial injury, high-sensitivity troponin and N-terminal pro B-type natriuretic peptide plasma levels were measured in all patients. We recruited 121 patients and 118 (98%) underwent imaging. It was possible to determine the primary outcome in 112 (91%). Severe right ventricular dilation was present in 31 (28%), with interventricular septal flattening present in nine (8%). Right ventricular dysfunction (the combination of these two parameters) was present in seven (6%, 95%CI 3-13%). Thirty-day mortality was 86% in those with right ventricular dysfunction as compared with 45% in those without (p = 0.051). Patients with right ventricular dysfunction were more likely to have: pulmonary thromboembolism (p < 0.001); higher plateau airway pressure (p = 0.048); lower dynamic compliance (p = 0.031); higher plasma N-terminal pro B-type natriuretic peptide levels (p = 0.006); and raised plasma troponin levels (p = 0.048). Our results demonstrate a prevalence of right ventricular dysfunction of 6%, which was associated with increased mortality (86%). Associations were also observed between right ventricular dysfunction and aetiological domains of: acute respiratory distress syndrome; ventilation; thromboembolic disease; and direct myocardial injury, implying a complex multifactorial pathophysiology.

Abstract
This review focuses on the literature published during the calendar year 2021 that is of interest to anesthesiologists taking care of children and adults with congenital heart disease. Four major themes are discussed, including cardiovascular disease in children with COVID-19, aortic valve repair and replacement, bleeding and coagulation, and enhanced recovery after surgery (ERAS).

Abstract
The intensive care units in North West London are part of one of the oldest critical care networks in the UK, forming a mature and established strategic alliance to share resources, experience and knowledge for the benefit of its patients. North West London saw an early surge in COVID-19 admissions, which urgently threatened the capacity of some of its intensive care units even before the UK government announced lockdown. The pre-existing relationships and culture within the network allowed its members to unite and work rapidly to develop agile and innovative solutions, protecting any individual unit from becoming overwhelmed, and ultimately protecting its patients. Within a short 50-day period 223 patients were transferred within the network to distribute pressures. This unprecedented number of critical care transfers, combined with the creation of extra capacity and new pathways, allowed the region to continue to offer timely and unrationed access to critical care for all patients who would benefit from admission. This extraordinary response is a testament to the power and benefits of a regionally networked approach to critical care, and the lessons learned may benefit other healthcare providers, managers and policy makers, especially in regions currently facing new outbreaks of COVID-19.

Abstract
Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides natural immunity against reinfection. Recent studies have shown waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown.

Methods: Using the Israeli Ministry of Health database, we extracted data for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. We used Poisson regression with adjustment for confounding factors to compare the rates of infection as a function of time since the last immunity-conferring event.

Results: The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously.

COMMENTARY. No abstract available.

Abstract
Background: The COVID-19 pandemic has disrupted clinician education. To address this challenge our divisional difficult airway program (AirEquip) designed and implemented small-group educational workshops for experienced clinicians. Our primary aim was to test the feasibility and acceptability of a small-group, flexible-curriculum skills workshop conducted during the clinical workday. Secondary objectives were to evaluate whether our workshop increased confidence in performing relevant skills and to assess the work-effort required for the new program.

Methods: We implemented a 1:1 and 1:2 airway skills workshop during the workday. A member of the AirEquip team temporarily relieved the attendee of clinical duties to facilitate participation. Attendance was encouraged but not required. Feasibility was assessed by clinician attendance, and acceptability was assessed using three Likert scale questions and derived from free-response feedback. Participants completed pre- and post-workshop surveys to assess familiarity and comfort with various aspects of airway management. A work-effort analysis was conducted and compared to the effort to run a previously-held larger-format difficult airway conference.

Results: Fifteen workshops were conducted over seven weeks; members of AirEquip were able to temporarily assume participants' clinical duties. Forty-seven attending anesthesiologists and 17 CRNAs attended the workshops, compared to six attending anesthesiologists and five CRNAs who attended the most recent large-format workshop. There was no change in confidence after workshop participation, but participants overwhelmingly expressed enthusiasm and satisfaction with the workshops. The number of facilitator person-hours required to operate the workshops (105 hours) was similar to that required to run a single all-day larger-format conference (104.5 hours).

Conclusion: It is feasible and acceptable to incorporate expert-led skills training into the clinical workday. Alongside conferences and large-format instruction, this modality enhances the way we are able to share knowledge with our colleagues. This concept can likely be applied to other skills in various clinical settings.

Abstract
Background: During the Coronavirus disease 2019 (COVID-19) pandemic, hospital visits were suspended and video calls were offered to connect patients with their family members, especially toward the end of life (EoL).

Aim: The primary aim was to describe EoL care for COVID-19 patients dying in an intensive care unit (ICU). The secondary aim was to explore whether making video calls and allowing visits was associated with lower death-related stress in family members.

Design: Single centre cross-sectional study. The setting was the ICU of a COVID-19 center in northern Italy, during the first year of the pandemic. Data on patients who died in the ICU were collected; death-related stress on their family members was measured using the Impact of Event Scale-Revised (IES-R). The statistical association was tested by means of logistic regression.

Results: The study sample included 70 patients and 56 family members. All patients died with mechanical ventilation, hydration, nutrition, analgesia and sedation ongoing. Resuscitation procedures were performed in 5/70 patients (7.1%). Only 6/56 (10.7%) of the family members interviewed had visited their loved ones in the ICU and 28/56 (50%) had made a video call. EoL video calls were judged useful by 53/56 family members (94.6%) but all (56/56, 100%) wished they could have visited the patient. High-stress levels were found in 38/56 family members (67.9%), regardless of whether they were allowed ICU access or made a video call. Compared with other degrees of kinship, patients' offspring were less likely to show a positive IES-R score (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.05 to 0.89).

Conclusions: During the first year of the COVID-19 pandemic, patients died without their family members at the bedside while on life-sustaining treatment. Stress levels were high in most family members, especially in patients' spouses. Video calls or ICU visits were judged favourably by family members but insufficient to alleviate death-related stress.

Relevance for clinical practice: During a pandemic, ICU access by patients' family members should be considered, particularly as the time of death approaches. Although generally appreciated by family members, EoL video calls should be arranged together with other measures to alleviate death-related stress, especially for the patient's spouse.

Learning Objectives
1. Explain how COVID-19 and other determinants of health uniquely impact marginalized communities, public health, and health equity
2. Distinguish both short-term and long-term implications on our health care and public health systems
3. Reimagine the vision and actions that ensure equity and justice
4. Describe the ways in which COVID-19 may have uniquely impacted minoritized and marginalized communities

Abstract
Background: Active immunization with the BNT162b2 vaccine (Pfizer-BioNTech) has been a critical mitigation tool against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the coronavirus disease 2019 (Covid-19) pandemic. In light of reports of waning protection occurring 6 months after the primary two-dose vaccine series, data are needed on the safety and efficacy of offering a third (booster) dose in persons 16 years of age or older.

Methods: In this ongoing, placebo-controlled, randomized, phase 3 trial, we assigned participants who had received two 30-μg doses of the BNT162b2 vaccine at least 6 months earlier to be injected with a third dose of the BNT162b2 vaccine or with placebo. We assessed vaccine safety and efficacy against Covid-19 starting 7 days after the third dose.

Results: A total of 5081 participants received a third BNT162b2 dose and 5044 received placebo. The median interval between dose 2 and dose 3 was 10.8 months in the vaccine group and 10.7 months in the placebo group; the median follow-up was 2.5 months. Local and systemic reactogenicity events from the third dose were generally of low grade. No new safety signals were identified, and no cases of myocarditis or pericarditis were reported. Among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated, Covid-19 with onset at least 7 days after dose 3 was observed in 6 participants in the vaccine group and in 123 participants in the placebo group, which corresponded to a relative vaccine efficacy of 95.3% (95% confidence interval, 89.5 to 98.3).

Conclusions: A third dose of the BNT162b2 vaccine administered a median of 10.8 months after the second dose provided 95.3% efficacy against Covid-19 as compared with two doses of the BNT162b2 vaccine during a median follow-up of 2.5 months. (Funded by BioNTech and Pfizer; C4591031 ClinicalTrials.gov number, NCT04955626.).

Abstract
Prolonged neurological symptoms such as "brain fog" and cognitive impairment have occurred after coronavirus disease 2019 (COVID-19) infection. In this report, we describe impaired consciousness caused by cefepime hydrochloride (CFPM) in a patient with cognitive sequalae of COVID-19. A 56-year-old male patient was diagnosed with penile abscess after COVID-19 infection, and a blood culture detected two drug-resistant Pseudomonas aeruginosa strains. Therefore, CFPM 2 g × twice/day was administered on day 71 after intensive care unit admission. Approximately 48 h after CFPM administration, the patient showed disturbances in consciousness. Contrast-enhanced computed tomography, magnetic resonance imaging, and spinal fluid examination revealed no obvious abnormalities. Therefore, CFPM-induced neurotoxicity was suspected. CFPM was discontinued and ceftazidime 2 g × three times/day was initiated. The patient's consciousness improved 30 h after the final administration of CFPM. Serum CFPM concentrations were 14.2, 21.7, 21.7, and 11.9 μg/mL on days 1, 2, and 3 after the initiation of CFPM and on the day after CFPM was discontinued, respectively. In conclusion, intensivists should pay attention to new neurological symptoms such as CFPM-induced encephalopathy in patients with prolonged neurological symptoms after COVID-19 infection.

bstract
Background: Whether prone position (PP) improves clinical outcomes in COVID-19 pneumonia treated with noninvasive ventilation (NIV) is unknown. We evaluated the effect of early PP on 28-day NIV failure, intubation and death in noninvasively ventilated patients with moderate-to-severe acute hypoxemic respiratory failure due to COVID-19 pneumonia and explored physiological mechanisms underlying treatment response.

Methods: In this controlled non-randomized trial, 81 consecutive prospectively enrolled patients with COVID-19 pneumonia and moderate-to-severe (paO2/FiO2 ratio < 200) acute hypoxemic respiratory failure treated with early PP + NIV during Dec 2020-May 2021were compared with 162 consecutive patients with COVID-19 pneumonia matched for age, mortality risk, severity of illness and paO2/FiO2 ratio at admission, treated with conventional (supine) NIV during Apr 2020-Dec 2020 at HUMANITAS Gradenigo Subintensive Care Unit, after propensity score adjustment for multiple baseline and treatment-related variables to limit confounding. Lung ultrasonography (LUS) was performed at baseline and at day 5. Ventilatory parameters, physiological dead space indices (DSIs) and circulating inflammatory and procoagulative biomarkers were monitored during the initial 7 days.

Results: In the intention-to-treat analysis. NIV failure occurred in 14 (17%) of PP patients versus 70 (43%) of controls [HR = 0.32, 95% CI 0.21-0.50; p < 0.0001]; intubation in 8 (11%) of PP patients versus 44 (30%) of controls [HR = 0.31, 95% CI 0.18-0.55; p = 0.0012], death in 10 (12%) of PP patients versus 59 (36%) of controls [HR = 0.27, 95% CI 0.17-0.44; p < 0.0001]. The effect remained significant within different categories of severity of hypoxemia (paO2/FiO2 < 100 or paO2/FiO2 100-199 at admission). Adverse events were rare and evenly distributed. Compared with controls, PP therapy was associated with improved oxygenation and DSIs, reduced global LUS severity indices largely through enhanced reaeration of dorso-lateral lung regions, and an earlier decline in inflammatory markers and D-dimer. In multivariate analysis, day 1 CO2 response outperformed O2 response as a predictor of LUS changes, NIV failure, intubation and death.

Conclusion: Early prolonged PP is safe and is associated with lower NIV failure, intubation and death rates in noninvasively ventilated patients with COVID-19-related moderate-to-severe hypoxemic respiratory failure. Early dead space reduction and reaeration of dorso-lateral lung regions predicted clinical outcomes in our study population.

Clinical trial registration: ISRCTN23016116 . Retrospectively registered on May 1, 2021.

Abstract
Introduction: Switzerland experienced two waves of COVID-19 in 2020, but with a different ICU admission and treatment management strategy. The timing of ICU admission and intubation remains a matter of debate in severe patients. The aim of our study was to describe the characteristics of ICU patients between two subsequent waves of COVID-19 who underwent a different management strategy and to assess whether the timing of intubation was associated with differences in mortality.

Patients and methods: We conducted a prospective observational study of all adult patients with acute respiratory failure due to COVID-19 who required intubation between the 9th of March 2020 and the 9th of January 2021 in the intensive care unit (ICU) at Geneva University Hospitals, Switzerland.

Results: Two hundred twenty-three patients were intubated during the study period; 124 during the first wave, and 99 during the second wave. Patients admitted to the ICU during the second wave had a higher SAPS II severity score (52.5 vs. 60; p = 0.01). The time from hospital admission to intubation was significantly longer during the second compared to the first wave (4 days [IQR, 1-7] vs. 2 days [IQR, 0-4]; p < 0.01). All-cause ICU mortality was significantly higher during the second wave (42% vs. 23%; p < 0.01). In a multivariate analysis, the delay between hospital admission and intubation was significantly associated with ICU mortality (OR 3.25 [95% CI, 1.38-7.67]; p < 0.05).

Conclusions: In this observational study, delayed intubation was associated with increased mortality in patients with severe COVID-19. Further randomised controlled trials are needed.

Abstract
To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Design: Prospective observational study.

Setting: One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry.

Patients: Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection.

Interventions: None.

Results: Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0-81.0 yr) versus 61 years (48.0-72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, -0.84, -1.34, and -0.84; p < 0.001).

Conclusions: Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

A discussion on how trauma-informed approaches impact advancing equity among minoritized and marginalized communities during COVID-19.

Abstract
Importance: Longitudinal mass testing using rapid antigen detection tests (RADT) for serial screening of asymptomatic persons has been proposed for preventing SARS-CoV-2 community transmission. The feasibility of this strategy relies on accurate self-testing.

Objective: To quantify the adequacy of serial self-performed SARS-CoV-2 RADT testing in the workplace, in terms of the frequency of correct execution of procedural steps and accurate interpretation of the range of possible RADT results.

Design, setting, and participants: This prospective repeated cross-sectional study was performed from July to October 2021 at businesses with at least 2 active cases of SARS-CoV-2 infection in Montreal, Canada. Participants included untrained persons in their workplace, not meeting Public Health quarantine criteria (ie, required quarantine for 10 days after a moderate-risk contact with someone infected with SARS-CoV-2). Interpretation and performance were compared between participants who received instructions provided by the manufacturer vs those who received modified instructions that were informed by the most frequent or most critical errors we observed. Data were analyzed from October to November 2021.

Exposures: RADT testing using a modified quick reference guide compared with the original manufacturer's instructions.

Main outcomes and measures: The main outcome was the difference in correctly interpreted RADT results. Secondary outcomes included difference in proportions of correctly performed procedural steps. Additional analyses, assessed among participants with 2 self-testing visits, compared the second self-test visit with the first self-test visit using the same measures.

Results: Overall, 1892 tests were performed among 647 participants, of whom 278 participants (median [IQR] age, 43 [31-55] years; 156 [56.1%] men) had at least 1 self-testing visit. For self-test visit 1, significantly better accuracy in test interpretation was observed among participants using the modified quick reference guide than those using the manufacturer's instructions for reading results that were weak positive (64 of 115 participants [55.6%] vs 20 of 163 participants [12.3%]; difference, 43.3 [95% CI, 33.0-53.8] percentage points), positive (103 of 115 participants [89.6%] vs 84 of 163 participants [51.5%]; difference, 38.1 [95% CI, 28.5-47.5] percentage points), strong positive (219 of 229 participants [95.6%] vs 274 of 326 participants [84.0%]; difference, 11.6 [95% CI, 6.8-16.3] percentage points), and invalid (200 of 229 participants [87.3%] vs 252 of 326 participants [77.3%]; difference, 10.0 [95% CI, 3.8-16.3] percentage points). Use of the modified guide was associated with improvements on self-test visit 2 for results that were weak positive (difference, 15.4 [95% CI, 0.7-30.1] percentage points), positive (difference, 19.0 [95% CI, 7.2-30.9] percentage points), and invalid (difference, 8.0 [95% CI, 0.8-15.4] percentage points). For procedural steps identified as critical for test validity, adherence to procedural testing steps did not differ meaningfully according to instructions provided or reader experience.

Conclusions and relevance: In this cross-sectional study of self-performed SARS-CoV-2 RADT in an intended-use setting, a modified quick reference guide was associated with significantly improved accuracy in RADT interpretations.

Abstract
Background: Patients with COVID-19 can require critical care for prolonged periods. Patients with persistent critical Illness can have complex recovery trajectories, but this has not been studied for patients with COVID-19. We examined the prevalence, risk factors, and long-term outcomes of critically ill patients with COVID-19 and persistent critical illness.

Methods: This was a national cohort study of all adults admitted to Scottish critical care units with COVID-19 from March 1, 2020 to September 4, 20. Persistent critical illness was defined as a critical care length of stay (LOS) of ≥10 days. Outcomes included 1-yr mortality and hospital readmission after critical care discharge. Fine and Gray competing risk analysis was used to identify factors associated with persistent critical Illness with death as a competing risk.

Results: A total of 2236 patients with COVID-19 were admitted to critical care; 1045 patients were identified as developing persistent critical Illness, comprising 46.7% of the cohort but using 80.6% of bed-days. Patients with persistent critical illness used more organ support, had longer post-critical care LOS, and longer total hospital LOS. Persistent critical illness was not significantly associated with long-term mortality or hospital readmission. Risk factors associated with increased hazard of persistent critical illness included age, illness severity, organ support on admission, and fewer comorbidities.

Conclusions: Almost half of all patients with COVID-19 admitted to critical care developed persistent critical illness, with high resource use in critical care and beyond. However, persistent critical illness was not associated with significantly worse long-term outcomes compared with patients who were critically ill for shorter periods.

Abstract
Objectives: Societal and health system pressures associated with the COVID-19 pandemic exacerbated the burden of chronic pain and limited access to pain management services for many. Online multidisciplinary pain programs offer an effective and scalable treatment option, but have not been evaluated within the context of COVID-19. This study aimed to investigate the uptake and effectiveness of the Reboot Online chronic pain program before and during the first year of the COVID-19 pandemic.

Methods: Retrospective cohort analyses were conducted on routine service users of the Reboot Online program, comparing those who commenced the program during the COVID-19 pandemic (March 2020-March 2021), to those prior to the pandemic (April 2017-March 2020). Outcomes included the number of course registrations; commencements; completion rates; and measures of pain severity, interference, self-efficacy, pain-related disability and distress.

Results: Data from 2585 course users were included (n = 1138 pre-COVID-19 and n = 1447 during-COVID-19). There was a 287% increase in monthly course registrations during COVID-19, relative to previously. Users were younger, and more likely to reside in a metropolitan area during COVID-19, but initial symptom severity was comparable. Course adherence and effectiveness were similar before and during COVID-19, with moderate effect size improvements in clinical outcomes post-treatment (g = 0.23-0.55).

Discussion: Uptake of an online chronic pain management program substantially increased during the COVID-19 pandemic. Program adherence and effectiveness were similar pre- and during-COVID. These findings support the effectiveness and scalability of online chronic pain management programs to meet increasing demand.

Abstract
Background: Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine.

Methods: In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases.

Results: A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%).

Conclusions: The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.).

Abstract
Aim: To determine whether the duration of respiratory distress symptoms in severe COVID-19 pneumonia affects the need for invasive mechanical ventilation and clinical outcomes.

Materials and methods: An observational multicentre cohort study of patients hospitalised in five COVID-19-designated ICUs of the University Hospitals of Emilia-Romagna Region. Patients included were adults with pneumonia due to SARS-CoV-2 with PaO₂/FiO₂ ratio <300 mmHg, respiratory distress symptoms, and need for mechanical ventilation (invasive or non-invasive). Exclusion criteria were an uncertain time of respiratory distress, end-of-life decision, and mechanical respiratory support before hospital admission.

Measurements and main results: We analysed 171 patients stratified into tertiles according to respiratory distress duration (distress time, DT) before application of mechanical ventilation support. The rate of patients requiring invasive mechanical ventilation was significantly different (p < 0.001) among the tertiles: 17/57 patients in the shortest duration, 29/57 in the intermediate duration, and 40/57 in the longest duration. The respiratory distress time significantly increased the risk of invasive ventilation in the univariate analysis (OR 5.5 [CI 2.48-12.35], p = 0.003). Multivariable regression analysis confirmed this association (OR 10.7 [CI 2.89-39.41], p < 0.001). Clinical outcomes (mortality and hospital stay) did not show significant differences between DT tertiles.

Discussion: Albeit preliminary and retrospective, our data raised the hypothesis that the duration of respiratory distress symptoms may play a role in COVID-19 patients' need for invasive mechanical ventilation. Furthermore, our observations suggested that specific strategies may be directed towards identifying and managing early symptoms of respiratory distress, regardless of the levels of hypoxemia and the severity of the dyspnoea itself.

Booster doses of COVID-19 vaccines were recommended for people aged 18 years or older in November 2021 following the recommendation of an additional primary dose of COVID-19 vaccine for select immunocompromised populations on August 13, 2021. As of February 26, 2022, more than 93 million booster doses of COVID-19 vaccines had been administered in the US; however, data on receipt of booster doses among pregnant individuals are lacking. We present findings on receipt of booster doses among pregnant individuals in the Vaccine Safety Datalink (VSD).

Abstract
Background and aims: During the coronavirus disease 2019 (COVID-19) pandemic, health care workers are at a high risk of infection from aerosols. In this study, we compared the ease of using the aerosol box (AB) with the traditional method during internal jugular vein cannulation attempts (IJVCA).

Methods: The study included 40 patients with COVID-19 who required central venous catheterisation during treatment in the ward. The patients were randomly allocated to one of the two protective equipment (PPE) groups and then randomly assigned to one of the five anaesthesiologists with at least 5 years of experience. Group P and A had both PPE and AB used, whereas Group P included patients where PPE was used alone. The physicians completed a survey after performing the procedure to evaluate the use of the AB.

Results: The preparation for the procedure and procedure durations were observed to be statistically longer in Group P and A (P = 0.002 and P = 0.001, respectively). The first attempt in Group P and A was unsuccessful in six patients, whereas the first attempt in Group P was unsuccessful in only two patients (P = 0.235). Anaesthesiologists described difficulty with manipulation during the procedure, discomfort using the box, and resulting cognitive load increase in Group P and A.

Conclusion: The IJVCA procedures were faster and easier and had greater satisfaction for physicians when the AB was not used. Also, the high complication rate, including carotid artery punctures and disruption of sterility and PPE, albeit not statistically significant, has clinical implications. Therefore, we do not recommend the use of ABs for IJVCA.

Abstract
Background: The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear.

Methods: We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2-positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 μg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization.

Results: A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events.

Conclusions: Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Abstract
Importance: Awake prone positioning may improve hypoxemia among patients with COVID-19, but whether it is associated with improved clinical outcomes remains unknown.

Objective: To determine whether the recommendation of awake prone positioning is associated with improved outcomes among patients with COVID-19-related hypoxemia who have not received mechanical ventilation.

Design, setting, and participants: This pragmatic nonrandomized controlled trial was conducted at 2 academic medical centers (Vanderbilt University Medical Center and NorthShore University HealthSystem) during the COVID-19 pandemic. A total of 501 adult patients with COVID-19-associated hypoxemia who had not received mechanical ventilation were enrolled from May 13 to December 11, 2020.

Interventions: Patients were assigned 1:1 to receive either the practitioner-recommended awake prone positioning intervention (intervention group) or usual care (usual care group).

Main outcomes and measures: Primary outcome analyses were performed using a bayesian proportional odds model with covariate adjustment for clinical severity ranking based on the World Health Organization ordinal outcome scale, which was modified to highlight the worst level of hypoxemia on study day 5.

Results: A total of 501 patients (mean [SD] age, 61.0 [15.3] years; 284 [56.7%] were male; and most [417 (83.2%)] were self-reported non-Hispanic or non-Latinx) were included. Baseline severity was comparable between the intervention vs usual care groups, with 170 patients (65.9%) vs 162 patients (66.7%) receiving oxygen via standard low-flow nasal cannula, 71 patients (27.5%) vs 62 patients (25.5%) receiving oxygen via high-flow nasal cannula, and 16 patients (6.2%) vs 19 patients (7.8%) receiving noninvasive positive-pressure ventilation. Nursing observations estimated that patients in the intervention group spent a median of 4.2 hours (IQR, 1.8-6.7 hours) in the prone position per day compared with 0 hours (IQR, 0-0.7 hours) per day in the usual care group. On study day 5, the bayesian posterior probability of the intervention group having worse outcomes than the usual care group on the modified World Health Organization ordinal outcome scale was 0.998 (posterior median adjusted odds ratio [aOR], 1.63; 95% credibility interval [CrI], 1.16-2.31). However, on study days 14 and 28, the posterior probabilities of harm were 0.874 (aOR, 1.29; 95% CrI, 0.84-1.99) and 0.673 (aOR, 1.12; 95% CrI, 0.67-1.86), respectively. Exploratory outcomes (progression to mechanical ventilation, length of stay, and 28-day mortality) did not differ between groups.

Conclusions and relevance: In this nonrandomized controlled trial, prone positioning offered no observed clinical benefit among patients with COVID-19-associated hypoxemia who had not received mechanical ventilation. Moreover, there was substantial evidence of worsened clinical outcomes at study day 5 among patients recommended to receive the awake prone positioning intervention, suggesting potential harm.

Abstract
Purpose: COVID-19 pandemic containment measures have led to changes in various areas of life, including restrictions on health care. Patients with chronic pain may have faced an increased burden during pandemic and the resources of this vulnerable population are unknown. Therefore, a qualitative study was conducted to understand how people with chronic pain have experienced the course of the pandemic.

Patients and methods: Twenty semi-structured telephone interviews were conducted six months after the initial lockdown in Germany. The participants were patients with chronic pain who exhibited varying changes in their pain during the first German lockdown, recruited from a German outpatient pain clinic at a Department of Anesthesiology and Intensive Care. The semi-structured interview guidelines were designed to explore how patients with chronic pain experienced their pain during the pandemic, how they coped, and how they experienced pain management during this time. The interview recordings were transcribed verbatim and coded using the qualitative content analysis method.

Results: Four themes emerged from the results: differential impact on pain experience, difficulty coping with pain, supportive pain management, and endurance.

Conclusion: During this uncertain time, it was particularly important to maintain pain treatment in order to establish a sense of safety and stability. This underscores the special role of maintaining therapeutic contact during a pandemic and the potentially special role of telemedicine.

Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic has caused significant changes. This study aimed to investigate the impact of COVID-19 on patients with chronic pain.

Methods: Patients with chronic pain from 23 university hospitals in South Korea participated in this study. The anonymous survey questionnaire consisted of 25 questions regarding the following: demographic data, diagnosis, hospital visit frequency, exercise duration, time outside, sleep duration, weight change, nervousness and anxiety, depression, interest or pleasure, fatigue, daily life difficulties, and self-harm thoughts. Depression severity was evaluated using the Patient Health Questionnaire-9 (PHQ-9). Logistic regression analysis was used to investigate the relationship between increased pain and patient factors.

Results: A total of 914 patients completed the survey, 35.9% of whom had decreased their number of visits to the hospital, mostly due to COVID-19. The pain level of 200 patients has worsened since the COVID-19 outbreak, which was more prominent in complex regional pain syndrome (CRPS). Noticeable post-COVID-19 changes such as exercise duration, time spent outside, sleep patterns, mood, and weight affected patients with chronic pain. Depression severity was more significant in patients with CRPS. The total PHQ-9 average score of patients with CRPS was 15.5, corresponding to major depressive orders. The patients' decreased exercise duration, decreased sleep duration, and increased depression were significantly associated with increased pain.

Conclusions: COVID-19 has caused several changes in patients with chronic pain. During the pandemic, decreased exercise and sleep duration and increased depression were associated with patients' increasing pain.

Abstract
Current or recent infection with SARS-CoV-2 increases the risk of perioperative morbidity and mortality. Consensus guidelines recommend delaying elective major surgery after acute SARS-CoV-2 infection for 7 or 8 weeks. However, because of the growing backlog of untreated surgical disease and the potential risks of delaying surgery, surgical services may be under pressure to reduce this period. Here, we discuss the risks and benefits of delaying surgery for patients with current or recent SARS-CoV-2 infection in the context of the evolving COVID-19 pandemic, the limited evidence supporting delays to surgery, and the need for more research in this area.

Abstract
Introduction: Barotrauma is rare in patients with acute respiratory distress syndrome undergoing mechanical ventilation. Its incidence seems increased among critically ill COVID-19 patients. We performed a systematic review and meta-analysis to investigate the incidence, risk factors and clinical outcomes of barotrauma among critically ill COVID-19 patients EVIDENCE ACQUISITION: PubMed was searched from March 1st, 2020 to August 31st, 2021; case series and retrospective cohort studies concerning barotrauma in adult critically ill COVID-19 patients, either hospitalized in the Intensive Care Unit (ICU) or invasively ventilated were included. Primary outcome was the incidence of barotrauma in COVID-19 versus non-COVID-19 patients. Secondary outcomes were clinical characteristics, ventilator parameters, mortality and length of stay between patients with and without barotrauma.

Evidence synthesis: We identified 21 studies (six case series, 15 retrospective cohorts). The overall incidence of barotrauma was 11 [95% CI: 8-14]% in critically ill COVID-19 patients, vs. 2 [1-3]% in non-COVID-19, P<0.001; the incidence in mechanically ventilated patients was 14 [11-17]% vs. 4 [2-5]% non-COVID-19 patients, P<0.001. There were no differences in demographic, clinical, ventilatory parameters between patients who did and did not develop barotrauma, while, on average, protective ventilation criteria were always respected. Among COVID-19 patients, those with barotrauma had a higher mortality (60 [55-66] vs. 48 [42-54]%, P<0.001) and a longer ICU length of stay (20 [14-26] vs. 13 [10,5-16] days, P=0.03).

Conclusions: Barotrauma is a frequent complication in critically ill COVID-19 patients and is associated with a poor prognosis. Since lung protective ventilation was delivered, the ventilatory management might not be the sole factor in the development of barotrauma.

Abstract
Objectives: To describe hospital variation in use of "guideline-based care" for acute respiratory distress syndrome (ARDS) due to COVID-19.

Design: Retrospective, observational study.

Setting: The Society of Critical Care Medicine's Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY.

Patients: Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021.

Interventions: Hospital-level use of "guideline-based care" for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100.

Measurements and main results: Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in "guideline-based care." A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1-3.4) for receipt of "guideline-based care" compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47-62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use "guideline-based care" quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3-1.9; p = 0.49).

Conclusions: During the first year of the COVID-19 pandemic, only half of patients received "guideline-based care" for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

Abstract
During the recent COVID-19 pandemic, the rapidly progressive shortage of intravenous sedative drugs led numerous intensive care units to look for potential alternatives in patients requiring mechanical ventilation for severe acute respiratory distress syndrome (ARDS). Inhalational sedation using the AnaConDa® device for sevoflurane administration is a possible option. In a 54-year-old COVID-19 patient with severe ARDS requiring extracorporeal membranous oxygenation (ECMO), sevoflurane on AnaConDa® device was administered for 8 days but was complicated by the development of nephrogenic diabetes insipidus (NDI). Other causes of NDI or central diabetes insipidus were reasonably excluded, as in other previously published cases of NDI in ICU patients receiving prolonged sevoflurane-based sedation. In addition, the postmortem examination suggested a lower expression of aquaporin-2 in renal tubules. This observation should prompt further investigations to elucidate the role of aquaporin-2 in sevoflurane-related NDI. Inhaled isoflurane sedation is a possible alternative.

Abstract
Background: Effective analgosedation for control of dyspnoea and for toleration of prone positioning (PP) in severe coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS) is difficult to adjust. This study was designed to evaluate the feasibility and safety of sedation with inhaled sevoflurane in combination with intravenous esketamine during PP in patients with COVID-19-ARDS (CARDS).

Methods: All mechanically ventilated COVID-19 patients admitted to the departmental intensive care unit from March to June 2020 were included in this epidemiological cohort study. Patients were sedated with inhaled sevoflurane in combination with eske-tamine during PP and not or only lightly sedated during the supine position. Assisted spontaneous breathing was applied in both prone and supine position.

Results: Adverse events were documented prospectively, and routine ventilation parameters, hemodynamic parameters, Richmond Agitation and Sedation Scale (RASS) and sevoflurane consumption were monitored. Altogether, 146 episodes of PP in 15 patients were observed. No severe sedation-related event was observed during 2610 hours of PP. In 2498 hours (96%) patients were successfully converted to a pressure-supported spontaneous breathing mode.

Conclusions: Inhaled sedation with the AnaConDa-S-System (Sedana Medical AB, Danderyd, Sweden) alone is insufficient as soon as minute volume exceeds 7-8 L min-1, most likely due to technical reasons. Inhaled sedation with sevoflurane in combination with esketamine, however, safely enables prolonged prone positioning in patients with CARDS. Moreover, sedation depth was light enough to enable assisted spontaneous breathing during prone positioning.

Abstract
Background: The COVID-19 pandemic dramatically altered perioperative medical practice due to safety concerns, postponing elective or non-emergent procedures, supply chain shortages, and reallocating perioperative staff to care for patients with COVID-19. However, the impact of the pandemic on the conduct on Anesthesiology clinical research is unknown.

Objective: The primary objective was to quantify the magnitude of the COVID-19 pandemic's impact on anesthesiology clinical research.

Methods: We performed a systematic search using ClinicalTrials.gov to identify clinical trials related to the practice of anesthesiology. We searched through trials with status updates between January 1, 2020 through October 1, 2021 to capture trials potentially affected by the COVID-19 pandemic by the time of our search. Investigators screened for relevant studies and extracted trial characteristics along with the reason for discontinuation reported on the clinical trial registry.

Results: A total of 823 clinical trials met inclusion criteria, and 146 clinical trials were discontinued within the designated date range. Twenty-four (16.4%) of the 146 clinical trials were halted explicitly due to the COVID-19 pandemic. A significant association existed between trial enrollment numbers and the likelihood of discontinuation due to COVID-19, as larger trials were more likely to be disrupted (z= -2.914, P=.0036).

Conclusions: The COVID-19 pandemic has been reportedly associated with the discontinuation of anesthesiology-related clinical trials. With the uncertain course of the COVID-19 pandemic, developing anesthesia trial protocols to help minimize social interaction and prevent premature trial disruption are imperative.

Abstract
Background: The Sequential Organ Failure Assessment (SOFA) score has been developed to score the severity of organ dysfunction in critically ill sepsis patients and has been proven to have a high predictive value for intensive care unit (ICU) mortality in severely ill patients. Our goal was to evaluate the prognostic value of the SOFA score as well as trends in SOFA score for ICU mortality in COVID-19 patients.

Methods: All consecutive patients with confirmed COVID-19 pneumonia admitted to the ICU between March 13th, 2020, and October 17th, 2020 were included in this retrospective cohort study. The worst SOFA score was evaluated daily. Multiple logistic regression models were used to evaluate the predictive value of SOFA in ICU mortality.

Results: 103 patients were included in this study. 30 patients (29%) died during their ICU stay and 73 (71%) patients were discharged alive. The ICU admission SOFA score was 5.2 ± 3.3 in ICU non-survivors vs. 4.3 ± 2.9 in ICU survivors (P = 0.15). The maximum SOFA score in ICU non-survivors was 11.7 ± 4.7 vs. 7.4 ± 4.3 in ICU survivors. SOFA scores increased the first week in both survivors and non-survivors, but the increase was less pronounced in survivors. In the multiple logistic regression models, neither admission SOFA score nor combination with delta SOFA in the first 48 hours was statistically significantly related to ICU mortality. Only the maximum SOFA score remained significant (OR = 1.23, 95% CI: 1.11-1.37, P < 0.001) in the multiple logistic models with an AUC of 0.91.

Conclusions: Evaluation of SOFA scores in the first 48 hours after ICU admission is not a good prognostic indicator in COVID-19 patients. Only the maximum SOFA score was predictive for ICU mortality.

Abstract
Background: The coronavirus disease 2019 (COVID-19) has a high prevalence and mortality worldwide. Thousands of patients with acute respiratory failure caused by COVID-19 are daily hospitalized in intensive care units (ICUs) around the world. Many of these patients require full mechanical respiratory support and long-term ventilator use. Using different ventilators and calculating important variables can be helpful in meeting therapeutic needs of patients.

Objectives: The aim of present study was to investigate the effect of expiratory time constant (RCEXP) on the course of treatment and duration of mechanical ventilation in patients with acute respiratory failure hospitalized in ICU.

Methods: The present cross-sectional study was conducted on 60 patients with acute respiratory failure who were hospitalized in the ICU and underwent mechanical ventilation due to COVID-19 in the first six months of 2020. The variables of RCEXP, lung compliance and lung resistance in all patients were recorded daily and analyzed. Then, based on clinical outcome, the patients were divided into two groups: the patients with wean outcome (N = 40) and those with death outcome (N = 20).

Results: The mean ± SD of lung compliance in patients who were separated from ventilator and patients with death outcome were 74.73 (18.58) mL/cm H2O and 36.92 (10.56) mL/cm H2O, respectively, which was statistically significant (P = 0.001). The mean ± SD of lung resistance in patients who were separated from ventilator and patients with death outcome were calculated at 9.25 (4.62) and 14 (6.5), respectively, which was statistically significant (P = 0.015). Also, there was a statistically significant difference between the two groups in terms of mean ± SD of RCEXP (0.67 (0.23) vs. 0.49 (0.19), P = 0.010).

Conclusions: According to the results of this study, there was a significant difference between high resistance, low compliance, RCEXP, and weaning success of intubation in patients hospitalized in the ICU.

Abstract
Background: Awake prone positioning has been broadly utilised for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure, but the results from published randomised controlled trials (RCTs) in the past year are contradictory. We aimed to systematically synthesise the outcomes associated with awake prone positioning, and evaluate these outcomes in relevant subpopulations.

Methods: In this systematic review and meta-analysis, two independent groups of researchers searched MEDLINE, Embase, PubMed, Web of Science, Scopus, MedRxiv, BioRxiv, and ClinicalTrials.gov for RCTs and observational studies (with a control group) of awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure published in English from Jan 1, 2020, to Nov 8, 2021. We excluded trials that included patients intubated before or at enrolment, paediatric patients (ie, younger than 18 years), or trials that did not include the supine position in the control group. The same two independent groups screened studies, extracted the summary data from published reports, and assessed the risk of bias. We used a random-effects meta-analysis to pool individual studies. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty and quality of the evidence. The primary outcome was the reported cumulative intubation risk across RCTs, and effect estimates were calculated as risk ratios (RR;95% CI). The analysis was primarily conducted on RCTs, and observational studies were used for sensitivity analyses. No serious adverse events associated with awake prone positioning were reported. The study protocol was prospectively registered with PROSPERO, CRD42021271285.

Findings: A total of 1243 studies were identified, we assessed 138 full-text articles and received the aggregated results of three unpublished RCTs; therefore, after exclusions, 29 studies were included in the study. Ten were RCTs (1985 patients) and 19 were observational studies (2669 patients). In ten RCTs, awake prone positioning compared with the supine position significantly reduced the need for intubation in the overall population (RR 0·84 [95% CI 0·72-0·97]). A reduced need for intubation was shown among patients who received advanced respiratory support (ie, high-flow nasal cannula or non-invasive ventilation) at enrolment (RR 0·83 [0·71-0·97]) and in intensive care unit (ICU) settings (RR 0·83 [0·71-0·97]) but not in patients receiving conventional oxygen therapy (RR 0·87 [0·45-1·69]) or in non-ICU settings (RR 0·88 [0·44-1·76]). No obvious risk of bias and publication bias was found among the included RCTs for the primary outcome.

Interpretation: In patients with COVID-19-related acute hypoxaemic respiratory failure, awake prone positioning reduced the need for intubation, particularly among those requiring advanced respiratory support and those in ICU settings. Awake prone positioning should be used in patients who have acute hypoxaemic respiratory failure due to COVID-19 and require advanced respiratory support or are treated in the ICU.

Funding: OpenAI, Rice Foundation, National Institute for Health Research, and Oxford Biomedical Research Centre.

Abstract
Objective: Coronavirus disease-19 (COVID-19) primarily affects the respiratory system. In some cases, the heart, kidney, liver, circulatory system, and nervous system are also affected. COVID-19-related acute kidney injury (AKI) occurs in more than 20% of hospitalized patients and more than 50% of patients in the intensive care unit (ICU). In this study, we aimed to review the prevalence of COVID-19-related acute kidney injury, risk factors, hospital and ICU length of stay, the need for renal replacement therapy. We also examined the effect of AKI on mortality in patients in the ICU that we treated during a 1-year period.

Patients and methods: The files of patients with COVID-19 (n=220) who were treated in our ICU between March 21st, 2020, and June 1st, 2021, were analyzed retrospectively. Demographic data of the patients, laboratory data, and treatments were examined. Patients were divided into two groups, group I patients without AKI and, group II patients with AKI. The patients with AKI were evaluated according to the theKidney Disease Improving Global Outcomes (KDIGO) classification and were graded.

Results: Of the 220 patients included in the study, 89 were female and 131 were male. The mean age of patients with AKI (70.92±11.28 years) was statistically significantly higher than among those without AKI (58.87±13.63 years) (p<0.001). In patients with AKI, ICU length of stay, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, initial lactate levels, need for mechanical ventilation, duration of mechanical ventilation, and secondary infection rates were found to be statistically significantly higher. Discharge rates from the ICU in patients without AKI were statistically higher (75.3% vs. 26.6%), and mortality rates were significantly higher in patients with AKI (67.8% vs. 14.3%).

Conclusions: Various studies conducted have shown that patients with COVID-19 are at risk for AKI, and this is closely related to age, sex, and disease severity. The presence of AKI in patients with COVID-19 increases mortality, and this is more evident in patients hospitalized in the ICU. In our study, the prevalence of AKI was higher in older patients with high APACHE II scores and initial lactate levels. Comorbidities such as hypertension, chronic kidney disease, and coronary artery disease in patients with AKI were higher than in those without AKI.

Abstract
Objective: Few data are available on the ICU management and on the possible respiratory complications of invasively ventilated pregnant patients affected by COVID-19 pneumonia, especially in the early phase of pregnancy. Tension pneumothorax has been previously described as a rare cause of respiratory failure after delivery, but its occurrence in the postpartum of COVID-19 patient has not been reported yet. We hereby describe the ICU management of a 23rd gestational week pregnant woman who underwent invasive mechanical ventilation, prone positioning, and cesarean delivery during her ICU stay for COVID-19 related pneumonia. Moreover, we focused on the occurrence and management of recurrent tension pneumothorax after the cesarean delivery.

Case report: A 23rd gestational week pregnant woman was admitted to the ICU for a COVID-19 bilateral pneumonia and underwent invasive mechanical ventilation and prone positioning. Cesarean delivery was planned during the ICU stay, while the patient was receiving invasive mechanical ventilation. After delivery, the patient experienced a recurrent pneumothorax that required the positioning of multiple chest drains.

Conclusions: In pregnant critically ill COVID-19 patients, mechanical ventilation management is particularly challenging, especially in the postpartum period. Prone positioning is feasible and can improve oxygenation and respiratory system compliance, while tension pneumothorax must be suspected if the respiratory function suddenly deteriorates after delivery.

Abstract
This diagnostic/prognostic study compares the results of antigen vs real-time reverse transcription–polymerase chain reaction tests among quarantined students 5 days after exposure to SARS-CoV-2 during the surge of Delta variant cases in the COVID-19 pandemic.

Abstract
As a complement to vaccines, small-molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, which cause COVID-19. Affinity selection-mass spectrometry was used for the discovery of botanical ligands to the SARS-CoV-2 spike protein. Cannabinoid acids from hemp (Cannabis sativa) were found to be allosteric as well as orthosteric ligands with micromolar affinity for the spike protein. In follow-up virus neutralization assays, cannabigerolic acid and cannabidiolic acid prevented infection of human epithelial cells by a pseudovirus expressing the SARS-CoV-2 spike protein and prevented entry of live SARS-CoV-2 into cells. Importantly, cannabigerolic acid and cannabidiolic acid were equally effective against the SARS-CoV-2 alpha variant B.1.1.7 and the beta variant B.1.351. Orally bioavailable and with a long history of safe human use, these cannabinoids, isolated or in hemp extracts, have the potential to prevent as well as treat infection by SARS-CoV-2.

Abstract
Background: A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines.

Methods: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease caused by the omicron and delta (B.1.617.2) variants in England. Vaccine effectiveness was calculated after primary immunization with two doses of BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine and after a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273.

Results: Between November 27, 2021, and January 12, 2022, a total of 886,774 eligible persons infected with the omicron variant, 204,154 eligible persons infected with the delta variant, and 1,572,621 eligible test-negative controls were identified. At all time points investigated and for all combinations of primary course and booster vaccines, vaccine effectiveness against symptomatic disease was higher for the delta variant than for the omicron variant. No effect against the omicron variant was noted from 20 weeks after two ChAdOx1 nCoV-19 doses, whereas vaccine effectiveness after two BNT162b2 doses was 65.5% (95% confidence interval [CI], 63.9 to 67.0) at 2 to 4 weeks, dropping to 8.8% (95% CI, 7.0 to 10.5) at 25 or more weeks. Among ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased to 62.4% (95% CI, 61.8 to 63.0) at 2 to 4 weeks after a BNT162b2 booster before decreasing to 39.6% (95% CI, 38.0 to 41.1) at 10 or more weeks. Among BNT162b2 primary course recipients, vaccine effectiveness increased to 67.2% (95% CI, 66.5 to 67.8) at 2 to 4 weeks after a BNT162b2 booster before declining to 45.7% (95% CI, 44.7 to 46.7) at 10 or more weeks. Vaccine effectiveness after a ChAdOx1 nCoV-19 primary course increased to 70.1% (95% CI, 69.5 to 70.7) at 2 to 4 weeks after an mRNA-1273 booster and decreased to 60.9% (95% CI, 59.7 to 62.1) at 5 to 9 weeks. After a BNT162b2 primary course, the mRNA-1273 booster increased vaccine effectiveness to 73.9% (95% CI, 73.1 to 74.6) at 2 to 4 weeks; vaccine effectiveness fell to 64.4% (95% CI, 62.6 to 66.1) at 5 to 9 weeks.

Conclusions: Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time. (Funded by the U.K. Health Security Agency.).

Abstract
Background: The awake prone positioning strategy for patients with acute respiratory distress syndrome is a safe, simple and cost-effective technique used to improve hypoxaemia. We aimed to evaluate intubation and mortality risk in patients with coronavirus disease 2019 (COVID-19) who underwent awake prone positioning during hospitalisation.

Methods: In this retrospective, multicentre observational study conducted between 1 May 2020 and 12 June 2020 in 27 hospitals in Mexico and Ecuador, nonintubated patients with COVID-19 managed with awake prone or awake supine positioning were included to evaluate intubation and mortality risk through logistic regression models; multivariable and centre adjustment, propensity score analyses, and E-values were calculated to limit confounding.

Results: 827 nonintubated patients with COVID-19 in the awake prone (n=505) and awake supine (n=322) groups were included for analysis. Fewer patients in the awake prone group required endotracheal intubation (23.6% versus 40.4%) or died (19.8% versus 37.3%). Awake prone positioning was a protective factor for intubation even after multivariable adjustment (OR 0.35, 95% CI 0.24-0.52; p<0.0001, E=2.12), which prevailed after propensity score analysis (OR 0.41, 95% CI 0.27-0.62; p<0.0001, E=1.86) and mortality (adjusted OR 0.38, 95% CI 0.26-0.55; p<0.0001, E=2.03). The main variables associated with intubation among awake prone patients were increasing age, lower baseline peripheral arterial oxygen saturation/inspiratory oxygen fraction ratio (P aO2 /F IO2 ) and management with a nonrebreather mask.

Conclusions: Awake prone positioning in hospitalised nonintubated patients with COVID-19 is associated with a lower risk of intubation and mortality.

Trial registration: ClinicalTrials.gov NCT04407468.

Abstract
Objective: The SARS-CoV-2 (COVID-19) pandemic has profoundly impacted healthcare delivery and strained medical training. This study explores resident and faculty perceptions regarding the impact of the COVID-19 crisis on technical skill decay of surgical and anesthesia residents. We hypothesized that many residents perceived that their technical abilities diminished due to a short period of interruption in their training.

Design: An IRB-exempt, web-based cross-sectional survey distributed to residents and faculty SETTING: Two large academic tertiary medical centers, North Shore University Hospital and Long Island Jewish Medical Center, of the Northwell Health System in New York.

Participants: General surgery, anesthesiology, plastic surgery, cardiothoracic surgery, orthopedic surgery, oral maxillofacial surgery, urology, podiatry residents and faculty.

Results: All residents reported a significant impact on their training. Residents (82%) and faculty (94%) reported a significant reduction in case volumes due to the COVID-19 pandemic (p < 0.05). 64% of residents reported a reduction in technical skills, and 75% of faculty perceived a decrease in resident technical skills. Residents were concerned about fulfilling ACGME case requirements, however faculty were more optimistic that residents would achieve level-appropriate proficiency by the conclusion of their training. Both residents and faculty felt that resident critical care skills improved as a result of redeployment to COVID-19 intensive care units (66% and 94%). Additionally, residents reported increased confidence in their ability to care for critically ill patients and positive impact on professional competencies.

Conclusions: Effects of the COVID-19 pandemic on residency training are multi-dimensional. The majority of surgical and anesthesia residents perceived that their technical ability diminished as a result of skill decay, whereas other skillsets improved. Longitudinal surveillance of trainees is warranted to evaluate the effect of reduced operative volume and redeployment on professional competency.

Abstract
Background: The awake prone positioning strategy for patients with acute respiratory distress syndrome is a safe, simple and cost-effective technique used to improve hypoxaemia. We aimed to evaluate intubation and mortality risk in patients with coronavirus disease 2019 (COVID-19) who underwent awake prone positioning during hospitalisation.

Methods: In this retrospective, multicentre observational study conducted between 1 May 2020 and 12 June 2020 in 27 hospitals in Mexico and Ecuador, nonintubated patients with COVID-19 managed with awake prone or awake supine positioning were included to evaluate intubation and mortality risk through logistic regression models; multivariable and centre adjustment, propensity score analyses, and E-values were calculated to limit confounding.

Results: 827 nonintubated patients with COVID-19 in the awake prone (n=505) and awake supine (n=322) groups were included for analysis. Fewer patients in the awake prone group required endotracheal intubation (23.6% versus 40.4%) or died (19.8% versus 37.3%). Awake prone positioning was a protective factor for intubation even after multivariable adjustment (OR 0.35, 95% CI 0.24-0.52; p<0.0001, E=2.12), which prevailed after propensity score analysis (OR 0.41, 95% CI 0.27-0.62; p<0.0001, E=1.86) and mortality (adjusted OR 0.38, 95% CI 0.26-0.55; p<0.0001, E=2.03). The main variables associated with intubation among awake prone patients were increasing age, lower baseline peripheral arterial oxygen saturation/inspiratory oxygen fraction ratio (P aO2 /F IO2 ) and management with a nonrebreather mask.

Conclusions: Awake prone positioning in hospitalised nonintubated patients with COVID-19 is associated with a lower risk of intubation and mortality.

Trial registration: ClinicalTrials.gov NCT04407468.

Abstract
Coronavirus disease 2019 (COVID-19) pneumonia is an evolving disease. We will focus on the development of its pathophysiologic characteristics over time, and how these time-related changes determine modifications in treatment. In the emergency department: the peculiar characteristic is the coexistence, in a significant fraction of patients, of severe hypoxaemia, near-normal lung computed tomography imaging, lung gas volume and respiratory mechanics. Despite high respiratory drive, dyspnoea and respiratory rate are often normal. The underlying mechanism is primarily altered lung perfusion. The anatomical prerequisites for PEEP (positive end-expiratory pressure) to work (lung oedema, atelectasis, and therefore recruitability) are lacking. In the high-dependency unit: the disease starts to worsen either because of its natural evolution or additional patient self-inflicted lung injury (P-SILI). Oedema and atelectasis may develop, increasing recruitability. Noninvasive supports are indicated if they result in a reversal of hypoxaemia and a decreased inspiratory effort. Otherwise, mechanical ventilation should be considered to avert P-SILI. In the intensive care unit: the primary characteristic of the advance of unresolved COVID-19 disease is a progressive shift from oedema or atelectasis to less reversible structural lung alterations to lung fibrosis. These later characteristics are associated with notable impairment of respiratory mechanics, increased arterial carbon dioxide tension (P aCO2 ), decreased recruitability and lack of response to PEEP and prone positioning.

Abstract
Background: The B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified on November 25, 2021, in Gauteng province, South Africa. Data regarding the seroprevalence of SARS-CoV-2 IgG in Gauteng before the fourth wave of coronavirus disease 2019 (Covid-19), in which the omicron variant was dominant, are needed.

Methods: We conducted a seroepidemiologic survey from October 22 to December 9, 2021, in Gauteng to determine the seroprevalence of SARS-CoV-2 IgG. Households included in a previous seroepidemiologic survey (conducted from November 2020 to January 2021) were contacted; to account for changes in the survey population, there was a 10% increase in the households contacted, with the use of the same sampling framework. Dried-blood-spot samples were tested for IgG against SARS-CoV-2 spike protein and nucleocapsid protein with the use of quantitative assays. We also evaluated Covid-19 epidemiologic trends in Gauteng, including cases, hospitalizations, recorded deaths, and excess deaths from the start of the pandemic through January 12, 2022.

Results: Samples were obtained from 7010 participants, of whom 1319 (18.8%) had received a Covid-19 vaccine. The seroprevalence of SARS-CoV-2 IgG ranged from 56.2% (95% confidence interval [CI], 52.6 to 59.7) among children younger than 12 years of age to 79.7% (95% CI, 77.6 to 81.5) among adults older than 50 years of age. Vaccinated participants were more likely to be seropositive for SARS-CoV-2 than unvaccinated participants (93.1% vs. 68.4%). Epidemiologic data showed that the incidence of SARS-CoV-2 infection increased and subsequently declined more rapidly during the fourth wave than it had during the three previous waves. The incidence of infection was decoupled from the incidences of hospitalization, recorded death, and excess death during the fourth wave, as compared with the proportions seen during previous waves.

Conclusions: Widespread underlying SARS-CoV-2 seropositivity was observed in Gauteng before the omicron-dominant wave of Covid-19. Epidemiologic data showed a decoupling of hospitalizations and deaths from infections while omicron was circulating. (Funded by the Bill and Melinda Gates Foundation.).

Abstract
Background: The increasing incidence of pediatric hospitalizations associated with coronavirus disease 2019 (Covid-19) caused by the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States has offered an opportunity to assess the real-world effectiveness of the BNT162b2 messenger RNA vaccine in adolescents between 12 and 18 years of age.

Methods: We used a case-control, test-negative design to assess vaccine effectiveness against Covid-19 resulting in hospitalization, admission to an intensive care unit (ICU), the use of life-supporting interventions (mechanical ventilation, vasopressors, and extracorporeal membrane oxygenation), or death. Between July 1 and October 25, 2021, we screened admission logs for eligible case patients with laboratory-confirmed Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2) in case patients as compared with two hospital-based control groups: patients who had Covid-19-like symptoms but negative results on testing for SARS-CoV-2 (test-negative) and patients who did not have Covid-19-like symptoms (syndrome-negative).

Results: A total of 445 case patients and 777 controls were enrolled. Overall, 17 case patients (4%) and 282 controls (36%) had been fully vaccinated. Of the case patients, 180 (40%) were admitted to the ICU, and 127 (29%) required life support; only 2 patients in the ICU had been fully vaccinated. The overall effectiveness of the BNT162b2 vaccine against hospitalization for Covid-19 was 94% (95% confidence interval [CI], 90 to 96); the effectiveness was 95% (95% CI, 91 to 97) among test-negative controls and 94% (95% CI, 89 to 96) among syndrome-negative controls. The effectiveness was 98% against ICU admission and 98% against Covid-19 resulting in the receipt of life support. All 7 deaths occurred in patients who were unvaccinated.

Conclusions: Among hospitalized adolescent patients, two doses of the BNT162b2 vaccine were highly effective against Covid-19-related hospitalization and ICU admission or the receipt of life support. (Funded by the Centers for Disease Control and Prevention.).

Abstract
This study examines breakthrough SARS-CoV-2 infections, hospitalizations, and mortality in March-August 2021, when the Delta variant predominated, among a general US cohort vaccinated with mRNA-1273 or BNT162b2.

Abstract
Background: The risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decreases substantially among patients who have recovered from coronavirus disease 2019 (Covid-19). However, it is unknown how long protective immunity lasts. Current guidelines recommend vaccination of recovered patients even though data regarding vaccine effectiveness in such cases are still limited.

Methods: In this retrospective cohort study, we reviewed electronic medical records from a large health care organization in Israel to assess reinfection rates in patients who had recovered from SARS-CoV-2 infection before any vaccination against Covid-19. We compared reinfection rates among patients who had subsequently received the BNT162b2 vaccine (Pfizer-BioNTech) and those who had not been vaccinated between March 1 and November 26, 2021. We used a Cox proportional-hazards regression model with time-dependent covariates to estimate the association between vaccination and reinfection after adjustment for demographic factors and coexisting illnesses. Vaccine effectiveness was estimated as 1 minus the hazard ratio. In a secondary analysis, we evaluated the vaccine effectiveness of one dose as compared with two doses.

Results: A total of 149,032 patients who had recovered from SARS-CoV-2 infection met the eligibility criteria. Of these patients, 83,356 (56%) received subsequent vaccination during the 270-day study period. Reinfection occurred in 354 of the vaccinated patients (2.46 cases per 100,000 persons per day) and in 2168 of 65,676 unvaccinated patients (10.21 cases per 100,000 persons per day). Vaccine effectiveness was estimated at 82% (95% confidence interval [CI], 80 to 84) among patients who were 16 to 64 years of age and 60% (95% CI, 36 to 76) among those 65 years of age or older. No significant difference in vaccine effectiveness was found for one dose as compared with two doses.

Conclusions: Among patients who had recovered from Covid-19, the receipt of at least one dose of the BNT162b2 vaccine was associated with a significantly lower risk of recurrent infection.

Abstract
Background: The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters.

Methods: We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2.

Results: Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 97% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer-BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously.

Conclusions: Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050.).

Abstract in English, French
Purpose: Numerous guideline recommendations for airway and perioperative management during the COVID-19 pandemic have been published. We identified, synthesized, and compared guidelines intended for anesthesiologists.

Source: Member society websites of the World Federation of Societies of Anesthesiologists and the European Society of Anesthesiologists were searched. Recommendations that focused on perioperative airway management of patients with proven or potential COVID-19 were included. Accelerated screening was used; data were extracted by one reviewer and verified by a second. Data were organized into themes based on perioperative phase of care.

Principal findings: Thirty unique sets of recommendations were identified. None reported methods for systematically searching or selecting evidence to be included. Four were updated following initial publication. For induction and airway management, most recommended minimizing personnel and having the most experienced anesthesiologist perform tracheal intubation. Significant congruence was observed among recommendations that discussed personal protective equipment. Of those that discussed tracheal intubation methods, most (96%) recommended videolaryngoscopy, while discordance existed regarding use of flexible bronchoscopy. Intraoperatively, 23% suggested specific anesthesia techniques and most (63%) recommended a specific operating room for patients with COVID-19. Postoperatively, a minority discussed extubation procedures (33%), or care in the recovery room (40%). Non-technical considerations were discussed in 27% and psychological support for healthcare providers in 10%.

Conclusion: Recommendations for perioperative airway management of patients with COVID-19 overlap to a large extent but also show significant differences. Given the paucity of data early in the pandemic, it is not surprising that identified publications largely reflected expert opinion rather than empirical evidence. We suggest future efforts should promote coordinated responses and provide suggestions for studying and establishing best practices in perioperative patients.

Study registration: Open Science Framework ( https://osf.io/a2k4u/ ); date created, 26 March 2020.

Abstract
Purpose of review: COVID-19 pandemic has created profound ethical challenges, not only for clinical decision-making but also for defining physician professional conduct.

Recent findings: Multiple ethical questions arose as the COVID-19 pandemic ravaged globally, including physician obligations in a pandemic, allotment of personal protective equipment, care of unvaccinated patients, discern between evidence-based and unreliable information, addressing end-of-life wishes, implications of involving medical students in a public health crisis, and finally physician burnout aggravated by a pandemic.

Summary: There is a need to redefine existing medical professionalism standards so that future healthcare professionals are well prepared to deal with similar public health crisis.

Abstract
Importance: One-year outcomes in patients who have had COVID-19 and who received treatment in the intensive care unit (ICU) are unknown.

Objective: To assess the occurrence of physical, mental, and cognitive symptoms among patients with COVID-19 at 1 year after ICU treatment.

Design, setting, and participants: An exploratory prospective multicenter cohort study conducted in ICUs of 11 Dutch hospitals. Patients (N = 452) with COVID-19, aged 16 years and older, and alive after hospital discharge following admission to 1 of the 11 ICUs during the first COVID-19 surge (March 1, 2020, until July 1, 2020) were eligible for inclusion. Patients were followed up for 1 year, and the date of final follow-up was June 16, 2021.

Exposures: Patients with COVID-19 who received ICU treatment and survived 1 year after ICU admission.

Main outcomes and measures: The main outcomes were self-reported occurrence of physical symptoms (frailty [Clinical Frailty Scale score ≥5], fatigue [Checklist Individual Strength-fatigue subscale score ≥27], physical problems), mental symptoms (anxiety [Hospital Anxiety and Depression {HADS} subscale score ≥8], depression [HADS subscale score ≥8], posttraumatic stress disorder [mean Impact of Event Scale score ≥1.75]), and cognitive symptoms (Cognitive Failure Questionnaire-14 score ≥43) 1 year after ICU treatment and measured with validated questionnaires.

Results: Of the 452 eligible patients, 301 (66.8%) patients could be included, and 246 (81.5%) patients (mean [SD] age, 61.2 [9.3] years; 176 men [71.5%]; median ICU stay, 18 days [IQR, 11 to 32]) completed the 1-year follow-up questionnaires. At 1 year after ICU treatment for COVID-19, physical symptoms were reported by 182 of 245 patients (74.3% [95% CI, 68.3% to 79.6%]), mental symptoms were reported by 64 of 244 patients (26.2% [95% CI, 20.8% to 32.2%]), and cognitive symptoms were reported by 39 of 241 patients (16.2% [95% CI, 11.8% to 21.5%]). The most frequently reported new physical problems were weakened condition (95/244 patients [38.9%]), joint stiffness (64/243 patients [26.3%]) joint pain (62/243 patients [25.5%]), muscle weakness (60/242 patients [24.8%]) and myalgia (52/244 patients [21.3%]).

Conclusions and relevance: In this exploratory study of patients in 11 Dutch hospitals who survived 1 year following ICU treatment for COVID-19, physical, mental, or cognitive symptoms were frequently reported.

Abstract
Introduction: During the COVID-19 pandemic, anesthesiology residents faced increased risk of exposure to SARS-CoV-2 while performing aerosolizing procedures. We developed an airway simulation on the out-of-operating-room management of COVID-19 patients. Methods: A 90-minute simulation focused on caring for a 45-year-old COVID-19 patient provided training in donning and doffing personal protective equipment, intubation, management of postinduction hypotension, management of ICU ventilators, treatment strategies for acute respiratory distress syndrome (ARDS), interpersonal communication, and resource management. Presimulation, postsimulation, and 3-months postsimulation questionnaires measured changes in confidence, knowledge, and clinical practice. Statistical analysis was completed using related-samples Wilcoxon signed rank tests. Results: Twenty-four residents participated in the simulation. Questionnaire response rates were 100% presimulation and postsimulation and 88% 3-months postsimulation. Confidence scores (1 = not at all, 5 = extremely) improved with donning and doffing personal protective equipment (from 3.0 to 4.1, p < .001), ARDS management (from 3.1 to 4.0, p < .001), and COVID-19 airway management (from 2.8 to 4.0, p < .001). Correct answers on 10 knowledge questions increased significantly between presimulation and postsimulation (from 5.1 to 9.0, p < .001) but not between presimulation and 3-months postsimulation (from 5.1 to 5.8, p = .27). All participants who cared for COVID-19 patients at 3 months agreed or strongly agreed that their current management of COVID-19 patients was directly influenced by the simulation session (M = 4.4). Discussion: This simulation is a safe, effective method of providing the experiential training necessary to care for actual COVID-19 patients during an active pandemic.

Abstract
The emergence of epidemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in December 2019 in Wuhan, China causing Coronavirus Disease 2019 (COVID-19) and its rapid expansion around the world, leading to a global pandemic of dimensions not observed at least since the "Spanish influenza" pandemic in 1917-18, has had great consequences at all levels, including social, health and economic spheres. This pandemic situation forces us, as health care workers, to redefine our medical and surgical actions to adapt them to this new reality. It is important, when the rules of the game change, to rethink and to reevaluate if the balance between risk and benefit have moved to a different point of equilibrium, and if our indications of certain surgical interventions need to be redefined. In this article we try to answer the doubts that arise about the suitability of the NI-VATS technique and assess whether its use in these new pandemic circumstances might add advantages, especially in relation to minimize the risks of virus contagion between patients and all healthcare personnel during the surgical procedure, as well as the known advantages described in many articles the last ten years.

Abstract
Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies.

Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure.

Design, setting, and participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021.

Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475).

Main outcomes and measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days.

Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group.

Conclusions and relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings.

Abstract
This study examines the risk of multisystem inflammatory syndrome in children among those aged 12 years or older by COVID-19 vaccination status during September 2021 and October 2021 in France.

Abstract
Purpose of review: Critically ill Coronavirus disease 2019 (COVID-19) patients needing endotracheal intubation are on the verge of rapid decompensation. The aims of this review were to assess the risks, the preoxygenation, the device and the hemodynamic management of a patient with COVID-19.

Recent findings: The proceduralist performing endotracheal intubation with the entire team are at an increased risk for exposure to COVID-19. Appropriate personal protective equipment and other measures remain essential. For preoxygenation, noninvasive ventilation allows higher oxygen saturation during intubation in severely hypoxemic patients and can be associated with apneic oxygenation and mask ventilation during apnea in selected cases. The COVID-19 pandemic has further highlighted the place of videolaryngoscopy during intubation in intensive care unit (ICU). Hemodynamic optimization is mandatory to limit hypotension and cardiac arrest associated with airway management.

Summary: Future trials will better define the role of videolaryngoscopy, apneic oxygenation and mask ventilation during apnea for intubation of COVID-19 patients in ICU. The use of fluid loading and vasopressors remains to be investigated in large randomized controlled studies. Choosing the right time for intubation remains uncertain in clinical practice, and future works will probably help to identify earlier the patients who will need intubation.

Abstract
Background: The Ad26.COV2.S vaccine, which was approved as a single-shot immunization regimen, has been shown to be effective against severe coronavirus disease 2019. However, this vaccine induces lower severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S)-specific antibody levels than those induced by messenger RNA (mRNA)-based vaccines. The immunogenicity and reactogenicity of a homologous or heterologous booster in persons who have received an Ad26.COV2.S priming dose are unclear.

Methods: In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, we assessed immunogenicity and reactogenicity 28 days after a homologous or heterologous booster vaccination. The participants were assigned to receive no booster, an Ad26.COV2.S booster, an mRNA-1273 booster, or a BNT162b2 booster. The primary end point was the level of S-specific binding antibodies, and the secondary end points were the levels of neutralizing antibodies, S-specific T-cell responses, and reactogenicity. A post hoc analysis was performed to compare mRNA-1273 boosting with BNT162b2 boosting.

Results: Homologous or heterologous booster vaccination in 434 participants resulted in higher levels of S-specific binding antibodies, neutralizing antibodies, and T-cell responses than a single Ad26.COV2.S vaccination. The increase in binding antibodies was significantly larger with heterologous regimens that included mRNA-based vaccines than with the homologous booster. The mRNA-1273 booster was most immunogenic and was associated with higher reactogenicity than the BNT162b2 and Ad26.COV2.S boosters. Local and systemic reactions were generally mild to moderate in the first 2 days after booster administration.

Conclusions: The Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting. (Funded by the Netherlands Organization for Health Research and Development ZonMw; SWITCH ClinicalTrials.gov number, NCT04927936.).

Abstract
Importance: Assessing COVID-19 vaccine performance against the rapidly spreading SARS-CoV-2 Omicron variant is critical to inform public health guidance.

Objective: To estimate the association between receipt of 3 doses of Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccine and symptomatic SARS-CoV-2 infection, stratified by variant (Omicron and Delta).

Design, setting, and participants: A test-negative case-control analysis among adults 18 years or older with COVID-like illness tested December 10, 2021, through January 1, 2022, by a national pharmacy-based testing program (4666 COVID-19 testing sites across 49 US states).

Exposures: Three doses of mRNA COVID-19 vaccine (third dose ≥14 days before test and ≥6 months after second dose) vs unvaccinated and vs 2 doses 6 months or more before test (ie, eligible for a booster dose).

Main outcomes and measures: Association between symptomatic SARS-CoV-2 infection (stratified by Omicron or Delta variants defined using S-gene target failure) and vaccination (3 doses vs unvaccinated and 3 doses vs 2 doses). Associations were measured with multivariable multinomial regression. Among cases, a secondary outcome was median cycle threshold values (inversely proportional to the amount of target nucleic acid present) for 3 viral genes, stratified by variant and vaccination status.

Results: Overall, 23 391 cases (13 098 Omicron; 10 293 Delta) and 46 764 controls were included (mean age, 40.3 [SD, 15.6] years; 42 050 [60.1%] women). Prior receipt of 3 mRNA vaccine doses was reported for 18.6% (n = 2441) of Omicron cases, 6.6% (n = 679) of Delta cases, and 39.7% (n = 18 587) of controls; prior receipt of 2 mRNA vaccine doses was reported for 55.3% (n = 7245), 44.4% (n = 4570), and 41.6% (n = 19 456), respectively; and being unvaccinated was reported for 26.0% (n = 3412), 49.0% (n = 5044), and 18.6% (n = 8721), respectively. The adjusted odds ratio for 3 doses vs unvaccinated was 0.33 (95% CI, 0.31-0.35) for Omicron and 0.065 (95% CI, 0.059-0.071) for Delta; for 3 vaccine doses vs 2 doses the adjusted odds ratio was 0.34 (95% CI, 0.32-0.36) for Omicron and 0.16 (95% CI, 0.14-0.17) for Delta. Median cycle threshold values were significantly higher in cases with 3 doses vs 2 doses for both Omicron and Delta (Omicron N gene: 19.35 vs 18.52; Omicron ORF1ab gene: 19.25 vs 18.40; Delta N gene: 19.07 vs 17.52; Delta ORF1ab gene: 18.70 vs 17.28; Delta S gene: 23.62 vs 20.24).

Conclusions and relevance: Among individuals seeking testing for COVID-like illness in the US in December 2021, receipt of 3 doses of mRNA COVID-19 vaccine (compared with unvaccinated and with receipt of 2 doses) was less likely among cases with symptomatic SARS-CoV-2 infection compared with test-negative controls. These findings suggest that receipt of 3 doses of mRNA vaccine, relative to being unvaccinated and to receipt of 2 doses, was associated with protection against both the Omicron and Delta variants, although the higher odds ratios for Omicron suggest less protection for Omicron than for Delta.

Abstract
Backgrounds: COVID-19 related reduction of surgical procedures jeopardizes learning on the job of surgical residents. Many educators resorted to digital resources in the search for alternatives. However, these resources are often limited to the extent they offer resident-surgeon interaction like a joint surgical performance does. Here we present a roadmap of livestreaming surgical procedures, and evaluate how surgical livestreams on human cadavers address the unmet educational needs of surgical residents in our Dutch nationwide initiative.

Methods: Technical and organizational feasibility, and definition of outcome deliverables for the livestream series and per livestream were essential in livestream development. Faculty selected interventions, lecture contents, and participant preparations. Appropriate location, technical setup, and support were imperative for a stable, high-quality stream with integrated interaction, while maintaining digital privacy. A survey was sent to livestream participants to evaluate each livestream, and allow for constant improvement during the broadcasting of the series. Only surveys which were completed by surgical residents were included in the analysis of this study.

Results: Each livestream attracted 139-347 unique viewers and a total of 307 surveys were completed by participants (response rate of 23-38% per livestream). Sixty percent of surveys (n = 185) were completed by surgical residents. Livestreams were highly valued (appreciation 7.7 ± 1.1 and recommendation 8.6 ± 1.1), especially the live procedures combined with interaction and theoretical backgrounds. Criticized were technical difficulties and timing of the livestreams between 5 and 7 pm, which interfered with clinical duties.

Conclusion: Livestreaming surgical procedures on human cadavers is a valid and valued solution to augment resident education. Digital privacy and a stable, high-quality interactive stream are essential, as are appropriate moderation and relevant lectures. While livestreaming cannot replace hands-on training in the operating room, it enables surgeon-resident interaction which is key in education-and missed in pre-recorded surgical procedures which are currently available online.

Abstract
Background: Intubation, laryngoscopy and extubation are considered highly aerosol-generating procedures, and additional safety protocols are used during COVID-19 pandemic in these procedures. However, previous studies are mainly experimental and have neither analyzed staff exposure to aerosol generation in the real-life operating room environment nor compared the exposure to aerosol concentrations generated during normal patient care. To assess operational staff exposure to potentially infectious particle generation during general anesthesia, we measured particle concentration and size distribution with patients undergoing surgery with Optical Particle Sizer.

Methods: A single-center observative multidisciplinary clinical study in Helsinki University Hospital with 39 adult patients who underwent general anesthesia with tracheal intubation. Mean particle concentrations during different anesthesia procedures were statistically compared with cough control data collected from 37 volunteers to assess the differences in particle generation.

Results: This study measured 25 preoxygenations, 30 mask ventilations, 28 intubations and 24 extubations. The highest total aerosol concentration of 1153 particles (p)/cm³ was observed during mask ventilation. Preoxygenations, mask ventilations and extubations as well as uncomplicated intubations generated mean aerosol concentrations statistically comparable to coughing. It is noteworthy that difficult intubation generated significantly fewer aerosols than either uncomplicated intubation (p=0.007) or coughing (p=0.006).

Conclusions: Anesthesia induction generates mainly small (<1 µm) aerosol particles. Based on our results, general anesthesia procedures are not highly aerosol-generating compared with coughing. Thus, their definition as high-risk aerosol-generating procedures should be re-evaluated due to comparable exposures during normal patient care.

Abstract
Background: Respiratory failure is the main cause of mortality and morbidity among ICU patients with coronavirus disease 2019 (COVID-19). In these patients, supplemental oxygen therapy is essential, but there is limited evidence the optimal target. To address this, the ongoing handling oxygenation targets in COVID-19 (HOT-COVID) trial was initiated to investigate the effect of a lower oxygenation target (partial pressure of arterial oxygen (PaO2 ) of 8 kPa) versus a higher oxygenation target (PaO2 of 12 kPa) in the ICU on clinical outcome in patients with COVID-19 and hypoxaemia.

Methods: The HOT-COVID is planned to enrol 780 patients. This paper presents the protocol and statistical analysis plan for the conduct of a secondary Bayesian analysis of the primary outcome of HOT-COVID being days alive without life-support at 90 days and the secondary outcome 90-day all-cause mortality. Furthermore, both outcomes will be investigated for the presence heterogeneity of treatment effects based on four baseline parameters being sequential organ failure assessment score, PaO2 /fraction of inspired oxygen ratio, highest dose of norepinephrine during the 24 h before randomisation, and plasma concentration of lactate at randomisation.

Conclusion: The results of this pre-planned secondary Bayesian analysis will complement the primary frequentist analysis of the HOT-COVID trial and may facilitate a more nuanced interpretation of the trial results.

The unprecedented morbidity and mortality of the COVID-19 pandemic have been at the forefront of our consciousness. However, the ravages of COVID-19 extend beyond death and disease.

Abstract
Background: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines.

Methods: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants.

Results: Vaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults.

Conclusions: We observed limited waning in vaccine effectiveness against Covid-19-related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.

Abstract
Background: The increasing incidence of pediatric hospitalizations associated with coronavirus disease 2019 (Covid-19) caused by the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States has offered an opportunity to assess the real-world effectiveness of the BNT162b2 messenger RNA vaccine in adolescents between 12 and 18 years of age.

Methods: We used a case-control, test-negative design to assess vaccine effectiveness against Covid-19 resulting in hospitalization, admission to an intensive care unit (ICU), the use of life-supporting interventions (mechanical ventilation, vasopressors, and extracorporeal membrane oxygenation), or death. Between July 1 and October 25, 2021, we screened admission logs for eligible case patients with laboratory-confirmed Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2) in case patients as compared with two hospital-based control groups: patients who had Covid-19-like symptoms but negative results on testing for SARS-CoV-2 (test-negative) and patients who did not have Covid-19-like symptoms (syndrome-negative).

Results: A total of 445 case patients and 777 controls were enrolled. Overall, 17 case patients (4%) and 282 controls (36%) had been fully vaccinated. Of the case patients, 180 (40%) were admitted to the ICU, and 127 (29%) required life support; only 2 patients in the ICU had been fully vaccinated. The overall effectiveness of the BNT162b2 vaccine against hospitalization for Covid-19 was 94% (95% confidence interval [CI], 90 to 96); the effectiveness was 95% (95% CI, 91 to 97) among test-negative controls and 94% (95% CI, 89 to 96) among syndrome-negative controls. The effectiveness was 98% against ICU admission and 98% against Covid-19 resulting in the receipt of life support. All 7 deaths occurred in patients who were unvaccinated.

Conclusions: Among hospitalized adolescent patients, two doses of the BNT162b2 vaccine were highly effective against Covid-19-related hospitalization and ICU admission or the receipt of life support. (Funded by the Centers for Disease Control and Prevention.).

Abstract
Background and aims: The coronavirus disease 2019 (COVID-19) pandemic has initiated modified protocols for aerosol-generating procedures. A simulation study using dye was conducted to highlight contamination at intubation and extubation and to encourage adherence to the new COVID-19 protocol among anaesthesia personnel in our institution.

Methods: A video demonstrating the new COVID-19 protocols was circulated in the Department of Anaesthesiology a week prior to the study. Thirty teams, each comprising an anaesthesia resident and a staff technician, were enroled. Each team was asked to demonstrate the steps of preparation, intubation and extubation on a mannequin in a COVID-19 scenario. Checklists were used to assess points of contamination and adherence to the protocols. Following debriefing, a repeat simulation was conducted. The use of a dye highlighted the points of contamination. The study subjects provided feedback on the usefulness of the session and practical difficulties encountered in adapting to the new protocols.

Results: The average contamination scores decreased by 3.4 (95% confidence interval (CI): 2.4-4.4, P < 0.001) in the post-debrief session. Adherence to the steps of the modified protocol improved by a score of 2.7 (CI: 3.6-1.83) among anaesthesiologists and by 4.3 (CI: 5.3-3.3) among technicians. Further, 93% felt that the use of the colour indicator reinforced awareness of the possible points of contamination.

Conclusion: Simulation with a low-fidelity mannequin by using colour indicator for secretions is an effective teaching tool to reduce health hazards during airway management in COVID-19 times.

Abstract
Background: After promising initial results from the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) to persons 60 years of age or older, the booster campaign in Israel was gradually expanded to persons in younger age groups who had received a second dose at least 5 months earlier.

Methods: We extracted data for the period from July 30 to October 10, 2021, from the Israel Ministry of Health database regarding 4,696,865 persons 16 years of age or older who had received two doses of BNT162b2 at least 5 months earlier. In the primary analysis, we compared the rates of confirmed coronavirus disease 2019 (Covid-19), severe illness, and death among those who had received a booster dose at least 12 days earlier (booster group) with the rates among those who had not received a booster (nonbooster group). In a secondary analysis, we compared the rates in the booster group with the rates among those who had received a booster 3 to 7 days earlier (early postbooster group). We used Poisson regression models to estimate rate ratios after adjusting for possible confounding factors.

Results: The rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of approximately 10 (range across five age groups, 9.0 to 17.2) and was lower in the booster group than in the early postbooster group by a factor of 4.9 to 10.8. The adjusted rate difference ranged from 57.0 to 89.5 infections per 100,000 person-days in the primary analysis and from 34.4 to 38.3 in the secondary analysis. The rates of severe illness in the primary and secondary analyses were lower in the booster group by a factor of 17.9 (95% confidence interval [CI], 15.1 to 21.2) and 6.5 (95% CI, 5.1 to 8.2), respectively, among those 60 years of age or older and by a factor of 21.7 (95% CI, 10.6 to 44.2) and 3.7 (95% CI, 1.3 to 10.2) among those 40 to 59 years of age. The adjusted rate difference in the primary and secondary analyses was 5.4 and 1.9 cases of severe illness per 100,000 person-days among those 60 years of age or older and 0.6 and 0.1 among those 40 to 59 years of age. Among those 60 years of age or older, mortality was lower by a factor of 14.7 (95% CI, 10.0 to 21.4) in the primary analysis and 4.9 (95% CI, 3.1 to 7.9) in the secondary analysis. The adjusted rate difference in the primary and secondary analyses was 2.1 and 0.8 deaths per 100,000 person-days.

Conclusions: Across the age groups studied, rates of confirmed Covid-19 and severe illness were substantially lower among participants who received a booster dose of the BNT162b2 vaccine than among those who did not.

Abstract
Due to a lack of published evidence on the topic, a modified Delphi approach was used to develop recommendations useful for chronic pain management during and after the COVID-19 pandemic. Focusing on the available literature and personal clinical expertise, an Italian board of nine professionals from different disciplines identified four main topics: prevention of chronic pain, treatment of chronic pain, consequences of inadequate treatment, and perspectives. They elaborated a semi-structured questionnaire. A multidisciplinary panel of experts in the field of pain management was requested to comment on the statements. Based on the answers provided, a structured questionnaire was prepared (Round 1). It included 21 statements divided into three categories (organizational issues; diagnosis and therapies; telemedicine and future perspectives). A five-point Likert scale was adopted. The threshold for consensus was set at a minimum of 70% of the number of respondents (level of agreement ≥ 4, Agree or Strongly Agree). A final questionnaire with rephrasing of the statements that did not reach the consensus threshold was elaborated (Round 2). A total of 29 clinicians were included in the panel. Twenty clinicians (69%) responded in both the first and second round. After two rounds, consensus (≥70%) was achieved in 20 out of 21 statements. The lack of consensus was recorded for the statement regarding the management of post-COVID pain (55%; Median 4; IQR 2.3). Another statement on telemedicine reached the threshold in the first round (70%), but the value was not confirmed in Round 2 (65%; Median 4; IQR 2). Most of the proposed items reached consensus, suggesting the need to make organizational changes, the structuring of careful diagnostic and therapeutic pathways, and the application of new technologies in pain medicine. Long-COVID-19 care is an issue that needs further research. Remote assistance for chronic pain must be regulated.

Abstract
The coronavirus disease 2019 (COVID-19) pandemic has revealed that even the best-resourced hospitals may lack sufficient ventilators to support patients under surge conditions. During a pandemic or mass trauma, an affordable, low-maintenance, off-the-shelf device that would allow health care teams to rapidly expand their ventilator capacity could prove lifesaving, but only if it can be safely integrated into a complex and rapidly changing clinical environment. Here, we define an approach to safe ventilator sharing that prioritizes predictable and independent care of patients sharing a ventilator. Subsequently, we detail the design and testing of a ventilator-splitting circuit that follows this approach and describe our clinical experience with this circuit during the COVID-19 pandemic. This circuit was able to provide individualized and titratable ventilatory support with individualized positive end-expiratory pressure (PEEP) to 2 critically ill patients at the same time, while insulating each patient from changes in the other's condition. We share insights from our experience using this technology in the intensive care unit and outline recommendations for future clinical applications.

bstract
Background: Tracheostomy is performed in patients expected to require prolonged mechanical ventilation, but to date optimal timing of tracheostomy has not been established. The evidence concerning tracheostomy in COVID-19 patients is particularly scarce. We aimed to describe the relationship between early tracheostomy (≤10 days since intubation) and outcomes for patients with COVID-19.

Methods: This was a prospective cohort study performed in 152 centres across 16 European countries from February to December 2020. We included patients aged ≥70 yr with confirmed COVID-19 infection admitted to an intensive care unit, requiring invasive mechanical ventilation. Multivariable analyses were performed to evaluate the association between early tracheostomy and clinical outcomes including 3-month mortality, intensive care length of stay, and duration of mechanical ventilation.

Results: The final analysis included 1740 patients with a mean age of 74 yr. Tracheostomy was performed in 461 (26.5%) patients. The tracheostomy rate varied across countries, from 8.3% to 52.9%. Early tracheostomy was performed in 135 (29.3%) patients. There was no difference in 3-month mortality between early and late tracheostomy in either our primary analysis (hazard ratio [HR]=0.96; 95% confidence interval [CI], 0.70-1.33) or a secondary landmark analysis (HR=0.78; 95% CI, 0.57-1.06).

Conclusions: There is a wide variation across Europe in the timing of tracheostomy for critically ill patients with COVID-19. However, we found no evidence that early tracheostomy is associated with any effect on survival amongst older critically ill patients with COVID-19.

Clinical trial registration: ClinicalTrials.gov NCT04321265.

Abstract
The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.

Abstract
Background: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain.

Methods: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28.

Results: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group.

Conclusions: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).

Abstract
Introduction: Veterans with chronic pain may be vulnerable during the COVID-19 pandemic. We qualitatively explored the impact of the COVID-19 pandemic on a sample of Veterans receiving brief counseling focused on pain management in an ongoing clinical trial and discuss how the pandemic affected the process of motivating Veterans with chronic pain to engage in interdisciplinary multimodal pain treatment at the Department of Veteran Affairs.

Methods: Segments of audio-recorded counseling sessions containing content about the pandemic were transcribed and coded to identify key concepts emerging from individual counselor-participant transactions. Themes that emerged were examined using constant comparison analysis.

Results: Three major themes emerged (1) The pandemic caused a disruption in pain management service delivery, resulting in changes to the way Veterans receive services or manage their pain symptoms. (2) The pandemic offered opportunities for resilience and personal growth as Veterans with chronic pain reflected on their life and personal goals. (3) The pandemic brought Veterans' mental health issues to the forefront, which should be addressed as part of a comprehensive pain management approach.

Discussion: Discussion of the COVID-19 pandemic during pain treatment counseling sessions highlighted negative and positive ways participants were affected by the pandemic. These discussions provided counselors with a unique opportunity to facilitate behavior change by focusing on characteristics of resilience to motivate individuals with chronic pain to adapt and adopt positive behaviors and outlooks to improve their pain experience and quality of life.

Conclusions: Counselors can leverage feelings of resilience and personal growth to motivate Veterans' use of adaptive coping skills and a wider array of pain management services.

Keywords: COVID-19; buprenorphine; chronic pain management; interdisciplinary pain care; virtual care.

Abstract
Background: Before the emergence of the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination reduced transmission of SARS-CoV-2 from vaccinated persons who became infected, potentially by reducing viral loads. Although vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated persons who are infected with the delta variant call into question the degree to which vaccination prevents transmission.

Methods: We used contact-testing data from England to perform a retrospective observational cohort study involving adult contacts of SARS-CoV-2-infected adult index patients. We used multivariable Poisson regression to investigate associations between transmission and the vaccination status of index patients and contacts and to determine how these associations varied with the B.1.1.7 (alpha) and delta variants and time since the second vaccination.

Results: Among 146,243 tested contacts of 108,498 index patients, 54,667 (37%) had positive SARS-CoV-2 polymerase-chain-reaction (PCR) tests. In vaccinated index patients who became infected with the alpha variant, two vaccinations with either BNT162b2 or ChAdOx1 nCoV-19 (also known as AZD1222), as compared with no vaccination, were independently associated with reduced PCR positivity in contacts (adjusted rate ratio with BNT162b2, 0.32; 95% confidence interval [CI], 0.21 to 0.48; and with ChAdOx1 nCoV-19, 0.48; 95% CI, 0.30 to 0.78). Vaccine-associated reductions in transmission of the delta variant were smaller than those with the alpha variant, and reductions in transmission of the delta variant after two BNT162b2 vaccinations were greater (adjusted rate ratio for the comparison with no vaccination, 0.50; 95% CI, 0.39 to 0.65) than after two ChAdOx1 vaccinations (adjusted rate ratio, 0.76; 95% CI, 0.70 to 0.82). Variation in cycle-threshold (Ct) values (indicative of viral load) in index patients explained 7 to 23% of vaccine-associated reductions in transmission of the two variants. The reductions in transmission of the delta variant declined over time after the second vaccination, reaching levels that were similar to those in unvaccinated persons by 12 weeks in index patients who had received ChAdOx1 nCoV-19 and attenuating substantially in those who had received BNT162b2. Protection in contacts also declined in the 3-month period after the second vaccination.

Conclusions: Vaccination was associated with a smaller reduction in transmission of the delta variant than of the alpha variant, and the effects of vaccination decreased over time. PCR Ct values at diagnosis of the index patient only partially explained decreased transmission. (Funded by the U.K. Government Department of Health and Social Care and others.).

Abstract
Background: Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age.

Methods: A phase 1, dose-finding study and an ongoing phase 2-3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-μg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed.

Results: During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3).

Conclusions: A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

Abstract
Background: COVID-19 has stressed healthcare systems and workers worldwide. GPs, as first points of contact between suspected cases and the healthcare system, have assumed frontline roles in this crisis. While the prevalence of mental health problems and illnesses arising in healthcare workers (HCWs) from tertiary care settings during the COVID-19 pandemic is well-examined,1 the impact on GPs remains understudied.

Aim: To describe the prevalence and predictors of anxiety, burnout, depression, and post-traumatic stress disorder (PTSD) among GPs during the COVID-19 pandemic.

Design & setting: Survey of GPs operating in Singapore primary care clinics.

Method: GPs completed a survey that comprised of four validated psychometric instruments. Open-ended questions asked about responders' challenges and their envisaged support. Data were analysed with multiple logistic regression with demographic data as covariates; concepts of grounded theory were used to analyse the qualitative responses.

Results: A total of 257 GPs participated. Fifty-five (21.4%) met the scales' criteria for anxiety, 211 (82.1%) for burnout, 68 (26.6%) for depression, and 23 (8.9%) for PTSD. Multivariate regression analysis showed working in a public primary care setting was associated with anxiety and depression. Qualitative analyses uncovered possible stressors: changes to clinical and operational practices; increased workloads; and financial difficulties.

Conclusion: Mental health issues were found to be present in Singaporean GPs during the pandemic. Prevalence of anxiety, burnout, and depression were found to be higher than those reported pre-COVID-19. The findings also provide determinants of the issues that serve as possible foci for targeted interventions.Abstract
Background: COVID-19 has stressed healthcare systems and workers worldwide. GPs, as first points of contact between suspected cases and the healthcare system, have assumed frontline roles in this crisis. While the prevalence of mental health problems and illnesses arising in healthcare workers (HCWs) from tertiary care settings during the COVID-19 pandemic is well-examined,1 the impact on GPs remains understudied.

Aim: To describe the prevalence and predictors of anxiety, burnout, depression, and post-traumatic stress disorder (PTSD) among GPs during the COVID-19 pandemic.

Design & setting: Survey of GPs operating in Singapore primary care clinics.

Method: GPs completed a survey that comprised of four validated psychometric instruments. Open-ended questions asked about responders' challenges and their envisaged support. Data were analysed with multiple logistic regression with demographic data as covariates; concepts of grounded theory were used to analyse the qualitative responses.

Results: A total of 257 GPs participated. Fifty-five (21.4%) met the scales' criteria for anxiety, 211 (82.1%) for burnout, 68 (26.6%) for depression, and 23 (8.9%) for PTSD. Multivariate regression analysis showed working in a public primary care setting was associated with anxiety and depression. Qualitative analyses uncovered possible stressors: changes to clinical and operational practices; increased workloads; and financial difficulties.

Conclusion: Mental health issues were found to be present in Singaporean GPs during the pandemic. Prevalence of anxiety, burnout, and depression were found to be higher than those reported pre-COVID-19. The findings also provide determinants of the issues that serve as possible foci for targeted interventions.

Abstract
Background: The use of awake prone position concomitant to non-invasive mechanical ventilation in acute respiratory distress syndrome (ARDS) secondary to COVID-19 has shown to improve gas exchange, whereas its effect on the work of breathing remain unclear. The objective of this study was to evaluate the effects of awake prone position during helmet continuous positive airway pressure (CPAP) ventilation on inspiratory effort, gas exchange and comfort of breathing.

Methods: Forty consecutive patients presenting with ARDS due to COVID-19 were prospectively enrolled. Gas exchange, esophageal pressure swing (ΔPes), dynamic transpulmonary pressure (dTPP), modified pressure time product (mPTP), work of breathing (WOB) and comfort of breathing, were recorded on supine position and after 3 h on prone position.

Results: The median applied PEEP with helmet CPAP was 10 [8-10] cmH2O. The PaO2/FiO2 was higher in prone compared to supine position (Supine: 166 [136-224] mmHg, Prone: 314 [232-398] mmHg, p < 0.001). Respiratory rate and minute ventilation decreased from supine to prone position from 20 [17-24] to 17 [15-19] b/min (p < 0.001) and from 8.6 [7.3-10.6] to 7.7 [6.6-8.6] L/min (p < 0.001), respectively. Prone position did not reduce ΔPes (Supine: - 7 [- 9 to - 5] cmH2O, Prone: - 6 [- 9 to - 5] cmH2O, p = 0.31) and dTPP (Supine: 17 [14-19] cmH2O, Prone: 16 [14-18] cmH2O, p = 0.34). Conversely, mPTP and WOB decreased from 152 [104-197] to 118 [90-150] cmH2O/min (p < 0.001) and from 146 [120-185] to 114 [95-151] cmH2O L/min (p < 0.001), respectively. Twenty-six (65%) patients experienced a reduction in WOB of more than 10%. The overall sensation of dyspnea was lower in prone position (p = 0.005).

Conclusions: Awake prone position with helmet CPAP enables a reduction in the work of breathing and an improvement in oxygenation in COVID-19-associated ARDS.

Abstract
Background: Simulation-based education has become the most important part of resident training in anesthesiology, especially during the pandemic. It allows learning the skills and the management of different situations without putting residents in risk of contamination, considering COVID-19 is highly contagious. The hypothesis was that simulation is still associated with improvement of knowledge acquisitions despite the context of the COVID-19 pandemic.

Methods: Residents of anesthesiology and intensive care subjected to an anaphylaxis simulation scenario. Their knowledge levels were assessed by true/false questions before and one month after the simulation session. The STAI test was used to measure anxiety levels before and after the scenario. Data were analyzed statistically using Wilcoxon and Mc Nemar tests.

Results: Junior residents (< 2 years) received significantly higher scores in post-training theoretical tests compared to their pre-training scores (79.2 ± 9.6, 84.5 ± 8.2, p = 0.002, n = 21). There was no difference between pre and post-test scores of seniors (80.2 ± 9, 81.8 ± 10.4, p = 0.3). Pre- and post-anxiety inventory scores were nearly the same and both were in the moderate group (39.8 ± 10.1, 39.3 ± 12.1, p = 0.8).

Conclusion: Simulation-based education improved the knowledge levels of the residents without raising anxiety levels. Thus, simulation-based training showed its value as an important tool of education during the pandemic, which needs to be further popularized for training at all institutions. Enlightening medical educators about this accomplished teaching method may lead to improved quality of medical education in developing countries and reshape how tomorrow's doctors are trained during pandemics.

Abstract
COVID-19 infection immediately after liver transplantation presents a unique and challenging situation. In this report, we present the case of an 11-year-old girl who underwent emergency living donor liver transplantation for acute liver failure. After an uneventful intra-operative course, the patient was transferred to the intensive care unit. On the second postoperative day, the patient developed unexplained severe hypoxia. A polymerase chain reaction test was positive for SARS-CoV-2 virus and a hypercoagulable state was indicated by laboratory investigations. Despite therapies such as mechanical ventilation and therapeutic anticoagulation, further clinical deterioration occurred. On the seventh postoperative day, the patient's pupils were fully dilated bilaterally and unreactive to light, and brain death was later confirmed. This report highlights unique challenges pertaining to oxygenation, coagulation and immunosuppression after liver transplantation in a child with COVID-19. Hypoxia of unknown origin in the postoperative period should prompt consideration of COVID-19 as a possible cause.

Abstract
COVID-19 is mainly considered an "adult pandemic," but it also has strong implications for children and consequently for pediatric anesthesia. Despite the lethality of SARS-CoV-2 infection being directly correlated with age, children have equally experienced the negative impacts of this pandemic. In fact, the spectrum of COVID-19 symptoms among children ranges from very mild to those resembling adults, but may also present as a multisystemic inflammatory syndrome. Moreover, the vast majority of children might be affected by asymptomatic or pauci-symptomatic infection making them the "perfect" carriers for spreading the disease in the community. Beyond the clinical manifestations of SARS-CoV-2 infection, the COVID-19 pandemic may ultimately have catastrophic health and socioeconomic consequences for children and adolescents, which are yet to be defined. The aim of this narrative review is to highlight how COVID-19 pandemic has affected and changed the pediatric anesthesia practice and which lessons are to be learned in case of a future "pandemic." In particular, the rapid evolution and dissemination of research and clinical findings have forced the scientific community to adapt and alter clinical practice on an unseen and pragmatic manner. Equally, implementation of new platforms, techniques, and devices together with artificial intelligence and large-scale collaborative efforts may present a giant step for mankind. The valuable lessons of this pandemic will ultimately translate into new treatments modalities for various diseases but will also have the potential for safety improvement and better quality of care. However, this pandemic has revealed the vulnerability and deficiencies of our health-care system. If not addressed properly, we may end up with a tsunami of burnout and compassionate fatigue among health-care professionals. Pediatric anesthesia and critical care staff are no exceptions.

Abstract
Background: Critically ill COVID-19 patients have a high reported incidence of thromboembolic complications and the optimal dose of thromboprophylaxis is not yet determined. The aim of this study was to investigate if 90-day mortality differed between patients treated with intermediate- or high-dose thromboprophylaxis.

Method: In this retrospective study, all critically ill COVID-19 patients admitted to intensive care from March 6th until July 15th, 2020, were eligible. Patients were categorized into groups according to daily dose of thromboprophylaxis. Dosing was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios of death within 90 days from ICU admission. Multivariable models were adjusted for sex, age, body-mass index, Simplified Acute Physiology Score III, invasive respiratory support, glucocorticoids, and dosing strategy of thromboprophylaxis.

Results: A total of 165 patients were included; 92 intermediate- and 73 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. The 90-day mortality was 19.6% in patients with intermediate-dose and 19.2% in patients with high-dose thromboprophylaxis. Multivariable hazard ratio of death within 90 days was 0.74 (95% CI, 0.36-1.53) for the high-dose group compared to intermediate-dose group. Multivariable hazard ratio for thromboembolic events and bleedings within 28 days was 0.93 (95% CI 0.37-2.29) and 0.84 (95% CI 0.28-2.54) for high versus intermediate dose, respectively.

Conclusions: A difference in 90-day mortality between intermediate- and high-dose thromboprophylaxis could neither be confirmed nor rejected due to a small sample size.

Abstract
Background: NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America.

Methods: We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed.

Results: Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose.

Conclusions: NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).

Early lab results suggest that existing vaccines could be less effective against the fast-spreading coronavirus variant, but boosters should improve immunity.

Abstract
The latest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron (B.1.1.529) has ushered panic responses around the world due to its contagious and vaccine escape mutations. The essential infectivity and antibody resistance of the SARS-CoV-2 variant are determined by its mutations on the spike (S) protein receptor-binding domain (RBD). However, a complete experimental evaluation of Omicron might take weeks or even months. Here, we present a comprehensive quantitative analysis of Omicron's infectivity, vaccine-breakthrough, and antibody resistance. An artificial intelligence (AI) model, which has been trained with tens of thousands of experimental data points and extensively validated by experimental data on SARS-CoV-2, reveals that Omicron may be over ten times more contagious than the original virus or about twice as infectious as the Delta variant. Based on 132 three-dimensional (3D) structures of antibody-RBD complexes, we unveil that Omicron may be twice more likely to escape current vaccines than the Delta variant. The Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) from Eli Lilly may be seriously compromised. Omicron may also diminish the efficacy of mAbs from Celltrion and Rockefeller University. However, its impact on Regeneron mAb cocktail appears to be mild.

The continuing spread of SARS-CoV-2 remains a Public Health Emergency of International Concern. What physicians need to know about transmission, diagnosis, and treatment of Covid-19 is the subject of ongoing updates from infectious disease experts at the Journal.
In this audio interview conducted on November 29, 2021, the editors are joined by South African researcher Salim Abdool Karim to discuss the omicron variant recently identified in southern Africa.

Abstract
Background: The emergence of the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 and the reduced effectiveness over time of the BNT162b2 vaccine (Pfizer-BioNTech) led to a resurgence of coronavirus disease 2019 (Covid-19) cases in populations that had been vaccinated early. On July 30, 2021, the Israeli Ministry of Health approved the use of a third dose of BNT162b2 (booster) to cope with this resurgence. Evidence regarding the effectiveness of the booster in lowering mortality due to Covid-19 is still needed.

Methods: We obtained data for all members of Clalit Health Services who were 50 years of age or older at the start of the study and had received two doses of BNT162b2 at least 5 months earlier. The mortality due to Covid-19 among participants who received the booster during the study period (booster group) was compared with that among participants who did not receive the booster (nonbooster group). A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association of booster status with death due to Covid-19, with adjustment for sociodemographic factors and coexisting conditions.

Results: A total of 843,208 participants met the eligibility criteria, of whom 758,118 (90%) received the booster during the 54-day study period. Death due to Covid-19 occurred in 65 participants in the booster group (0.16 per 100,000 persons per day) and in 137 participants in the nonbooster group (2.98 per 100,000 persons per day). The adjusted hazard ratio for death due to Covid-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% confidence interval, 0.07 to 0.14; P<0.001).

Conclusions: Participants who received a booster at least 5 months after a second dose of BNT162b2 had 90% lower mortality due to Covid-19 than participants who did not receive a booster.

Abstract
Background: After promising initial results from the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) to persons 60 years of age or older, the booster campaign in Israel was gradually expanded to persons in younger age groups who had received a second dose at least 5 months earlier.

Methods: We extracted data for the period from July 30 to October 10, 2021, from the Israel Ministry of Health database regarding 4,696,865 persons 16 years of age or older who had received two doses of BNT162b2 at least 5 months earlier. In the primary analysis, we compared the rates of confirmed coronavirus disease 2019 (Covid-19), severe illness, and death among those who had received a booster dose at least 12 days earlier (booster group) with the rates among those who had not received a booster (nonbooster group). In a secondary analysis, we compared the rates in the booster group with the rates among those who had received a booster 3 to 7 days earlier (early postbooster group). We used Poisson regression models to estimate rate ratios after adjusting for possible confounding factors.

Results: The rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of approximately 10 (range across five age groups, 9.0 to 17.2) and was lower in the booster group than in the early postbooster group by a factor of 4.9 to 10.8. The adjusted rate difference ranged from 57.0 to 89.5 infections per 100,000 person-days in the primary analysis and from 34.4 to 38.3 in the secondary analysis. The rates of severe illness in the primary and secondary analyses were lower in the booster group by a factor of 17.9 (95% confidence interval [CI], 15.1 to 21.2) and 6.5 (95% CI, 5.1 to 8.2), respectively, among those 60 years of age or older and by a factor of 21.7 (95% CI, 10.6 to 44.2) and 3.7 (95% CI, 1.3 to 10.2) among those 40 to 59 years of age. The adjusted rate difference in the primary and secondary analyses was 5.4 and 1.9 cases of severe illness per 100,000 person-days among those 60 years of age or older and 0.6 and 0.1 among those 40 to 59 years of age. Among those 60 years of age or older, mortality was lower by a factor of 14.7 (95% CI, 10.0 to 21.4) in the primary analysis and 4.9 (95% CI, 3.1 to 7.9) in the secondary analysis. The adjusted rate difference in the primary and secondary analyses was 2.1 and 0.8 deaths per 100,000 person-days.

Conclusions: Across the age groups studied, rates of confirmed Covid-19 and severe illness were substantially lower among participants who received a booster dose of the BNT162b2 vaccine than among those who did not.

Abstract
Background: The incidence of coronavirus disease 2019 (Covid-19) among adolescents between 12 and 17 years of age was approximately 900 per 100,000 population from April 1 through June 11, 2021. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in adolescents are unknown.

Methods: In this ongoing phase 2-3, placebo-controlled trial, we randomly assigned healthy adolescents (12 to 17 years of age) in a 2:1 ratio to receive two injections of the mRNA-1273 vaccine (100 μg in each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of mRNA-1273 in adolescents and the noninferiority of the immune response in adolescents as compared with that in young adults (18 to 25 years of age) in a phase 3 trial. Secondary objectives included the efficacy of mRNA-1273 in preventing Covid-19 or asymptomatic severe acute respiratory syndrome coronavirus 2 infection.

Results: A total of 3732 participants were randomly assigned to receive mRNA-1273 (2489 participants) or placebo (1243 participants). In the mRNA-1273 group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 93.1% and 92.4%, respectively), headache (in 44.6% and 70.2%, respectively), and fatigue (in 47.9% and 67.8%, respectively); in the placebo group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 34.8% or 30.3%, respectively), headache (in 38.5% and 30.2%, respectively), and fatigue (in 36.6% and 28.9%, respectively). No serious adverse events related to mRNA-1273 or placebo were noted. The geometric mean titer ratio of pseudovirus neutralizing antibody titers in adolescents relative to young adults was 1.08 (95% confidence interval [CI], 0.94 to 1.24), and the absolute difference in serologic response was 0.2 percentage points (95% CI, -1.8 to 2.4), which met the noninferiority criterion. No cases of Covid-19 with an onset of 14 days after the second injection were reported in the mRNA-1273 group, and four cases occurred in the placebo group.

Conclusions: The mRNA-1273 vaccine had an acceptable safety profile in adolescents. The immune response was similar to that in young adults, and the vaccine was efficacious in preventing Covid-19. (Funded by Moderna and the Biomedical Advanced Research and Development Authority; Teen COVE ClinicalTrials.gov number, NCT04649151.).

Abstract
Background: Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear.

Methods: We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months.

Results: The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman's rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46).

Conclusions: Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

Abstract
Background: We present the care of 17 consecutive pregnant patients who required mechanical ventilation for Coronavirus disease 2019 (COVID-19) pneumonia at a quaternary referral center in the United States. We retrospectively describe the management of these patients, maternal and fetal outcomes, as well as the feasibility of prone positioning and delivery.

Methods: Between March 2020 and June 2021, all pregnant and postpartum patients who were mechanically ventilated for COVID-19 pneumonia were identified. Details of their management including prone positioning, maternal and neonatal outcomes, and complications were noted.

Results: Seventeen pregnant patients required mechanical ventilation for COVID-19. Thirteen patients received prone positioning, with a total of 49 prone sessions. One patient required extracorporeal membrane oxygenation. All patients in this series survived until at least discharge. Nine patients delivered while mechanically ventilated, and all neonates survived, subsequently testing negative for SARS-CoV-2. There was one spontaneous abortion. Four emergent cesarean deliveries were prompted by refractory maternal hypoxemia or non-reassuring fetal heart rate after maternal intubation.

Conclusions: Overall, maternal and neonatal survival were favorable even in the setting of severe COVID-19 pneumonia requiring mechanical ventilation. Prone positioning was well tolerated although the impact of prone positioning or fetal delivery on maternal oxygenation and ventilation are unclear.

Abstract
Background: Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored.

Methods: We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech). The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention. We abstracted the presentation, clinical course, and outcome from the patient's electronic health record. We performed a Kaplan-Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose.

Results: Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock. After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge. Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge. Of these patients, 5 underwent subsequent testing that revealed normal heart function.

Conclusions: Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years. Most cases of myocarditis were mild or moderate in severity. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

Abstract
Purpose of review: Cardiovascular involvement in coronavirus disease 2019 (CoVID-19) is relatively common and portends an increased risk of morbidity and mortality. Manifestations of myocardial injury may exhibit significant overlap and result in diagnostic uncertainty. This review will summarize recent literature around cardiovascular complications of CoVID-19.

Recent findings: Venous thromboembolism, atrial fibrillation, and type II myocardial infarction are observed commonly in CoVID-19, while severe acute respiratory syndrome coronavirus 2 viral myocarditis remains quite rare. Although infrequent, CoVID-19 vaccination has been associated with myocarditis and pericarditis in young individuals.

Summary: Various forms of CoVID-19-related myocardial injury have been associated with increased utilization of mechanical ventilation, hemodynamic deterioration, and mortality. Manifestations of myocardial injury in CoVID-19 are varied, but share common drivers of illness including sequelae of sepsis, immune-mediated factors, and a prothrombotic state. Understanding the forms of myocardial injury in CoVID-19 may aid in rapid diagnosis and treatment.

Abstract
Background: During the COVID-19 crisis it was necessary to generate a specific care network and reconvert operating rooms to attend emergency and high-acuity patients undergoing complex surgery. The aim of this study is to classify postoperative complications and mortality and to assess the impact that the COVID-19 pandemic may have had on the results.

Methods: this is a non-inferiority retrospective observational study. Two different groups of surgical patients were created: Pre-pandemic COVID and Pandemic COVID. Severity of illness was rated according to the Diagnosis-related Groups (DRG) score. Comparisons were made between groups and between DRG severity score-matched samples. Non-inferiority was set at up to 10 % difference for grade III to V complications according to the Clavien-Dindo classification, and up to 2 % difference in mortality.

Results: A total of 1649 patients in the PreCOVID group and 763 patients in the COVID group were analysed; 371 patients were matched for DRG severity score 3-4 (236 preCOVID and 135 COVID). No differences were found in relation to re-operation (22.5 % vs. 21.5 %) or late admission to critical care unit (5.1 % vs. 4.5 %). Clavien grade III to V complications occurred in 107 patients (45.3 %) in the PreCOVID group and in 56 patients (41.5 %) in the COVID group, and mortality was 12.7 % and 12.6 %, respectively. During the pandemic, 3 % of patients tested positive for Covid-19 on PCR: 12 patients undergoing elective surgery and 11 emergency surgery; there were 5 deaths, 3 of which were due to respiratory failure following Covid-19-induced pneumonia.

Conclusions: Although this study has some limitations, it has shown the non-inferiority of surgical outcomes during the COVID pandemic, and indicates that resuming elective surgery is safe.

Trial registration: Clinicaltrials.gov identifier: NCT04780594 .

Abstract
We present the acute worsening of clinical presentation in complex regional pain syndrome (CRPS), following mRNA-based COVID-19 vaccination. We report the case series of three patients diagnosed with CRPS type I who presented with acute worsening of symptoms after mRNA-based COVID-19 vaccination and their medical management. The acute clinical worsening after mRNA-based COVID-19 vaccination was transient and effectively managed with adjustment of individualized therapy in all three patients. The mortality and morbidity of COVID-19 infection are serious, and vaccination is recommended in the general population, including patients with a diagnosis of CRPS. However, clinicians should be aware of the possibility that there may be a clinical worsening CRPS after mRNA-based COVID-19 vaccination.

Researchers are racing to determine whether a fast-spreading coronavirus variant poses a threat to COVID vaccines’ effectiveness.

Abstract
Objective: To develop a practical thromboelastograph guided (TEG) anticoagulation protocol to guide the management of COVID-19 critically ill patients.

Design: An inter disciplinary team reviewed the current literature on hypercoagulability in critically ill COVID-19 patients, clinical management practices and challenges with high rates of thrombotic events despite anticoagulant therapies.

Setting: The largest tertiary care hospital within the Northwell Health System in New York.

Patients: COVID-19 invasively mechanically ventilated patients in Medical Intensive Care Unit Settings.

Methods: TEG was monitored in critically ill COVID-19 patients. Patterns were reviewed to guide the development of a treatment protocol leveraging TEG parameters to select anticoagulant therapy. Three patients are reported to highlight TEG profiles that led to the development of the algorithm. Clinical trajectory and treatment decisions were extracted retrospectively from the Electronic Health Record, with input from the intensivists. Anticoagulant use, laboratory and TEG values, and venous/arterial lower extremity (LE) ultrasound results were recorded.

Main results: These patients demonstrated hypercoagulable TEG results despite prophylactic or therapeutic dosages of unfractionated heparin or low-molecular-weight heparin (LMHW). TEG surveillance identified functional fibrinogen and maximum amplitude in high-risk patients with hyper inflammatory markers. Anticoagulation assessment, TEG parameters, and LE ultrasound monitoring for venous and arterial thrombus were used to construct an algorithm to guide and escalate anticoagulant therapy.

Conclusions: TEG provides patient-specific evidence for a hypercoagulable state in patients receiving all types of anticoagulant therapy. The proposed TEG algorithm guides anticoagulation management decisions to maintain or escalate anticoagulant dose and/or change choice of anticoagulant. A TEG algorithm may help negotiate the potential harm/benefit balance of full-dose anticoagulation in critically ill COVID-19 patients, by allowing for a more individualized approach that goes beyond the review of activated partial thromboplastin time (aPTT) levels.

bstract
The emergence of epidemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in December 2019 in Wuhan, China causing Coronavirus Disease 2019 (COVID-19) and its rapid expansion around the world, leading to a global pandemic of dimensions not observed at least since the "Spanish influenza" pandemic in 1917-18, has had great consequences at all levels, including social, health and economic spheres. This pandemic situation forces us, as health care workers, to redefine our medical and surgical actions to adapt them to this new reality. It is important, when the rules of the game change, to rethink and to reevaluate if the balance between risk and benefit have moved to a different point of equilibrium, and if our indications of certain surgical interventions need to be redefined. In this article we try to answer the doubts that arise about the suitability of the NI-VATS technique and assess whether its use in these new pandemic circumstances might add advantages, especially in relation to minimize the risks of virus contagion between patients and all healthcare personnel during the surgical procedure, as well as the known advantages described in many articles the last ten years.

Abstract
Purpose of review: To summarize the current knowledge about the application of advanced monitoring techniques in coronavirus disease 2019 (COVID-19).

Recent findings: Due to the heterogeneity between patients, management of COVID-19 requires daily monitoring of and/or aeration and inspiratory effort. Electrical impedance tomography can be used to optimize positive end-expiratory pressure, monitor the response to changes in treatment or body position and assess pulmonary perfusion and ventilation/perfusion matching. Lung ultrasound is more readily available and can be used to measure and monitor recruitment, provide an indication of diaphragm function and pulmonary perfusion disturbances. Esophageal pressure measurements enable the calculation of the transpulmonary pressure and inspiratory effort in order to prevent excessive stress on the lung. While esophageal pressure measurements are the golden standard in determining inspiratory effort, alternatives like P0.1, negative pressure swing during a single airway occlusion and change in central venous pressure are more readily available and capable of diagnosing extreme inspiratory efforts.

Summary: Although there is little data on the effectiveness of advanced monitoring techniques in COVID-19, regular monitoring should be a central part of the management of COVID-19-related acute respiratory distress syndrome (C-ARDS).

Abstract
Background: The COVID-19 pandemic has resulted in a range of unprecedented disruptions to maternity care with documented impacts on perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne has endured one of the longest and most stringent lockdowns in globally. This paper presents the protocol for a multicentre study to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic.

Methods: Multicentre observational study analysing monthly deidentified maternal and newborn outcomes from births >20 weeks at all 12 public maternity services in Melbourne. Data will be merged centrally to analyse outcomes and create run charts according to established methods for detecting non-random 'signals' in healthcare. Perinatal outcomes will include weekly rates of total births, stillbirths, preterm births, neonatal intensive care admissions, low Apgar scores and fetal growth restriction. Maternal outcomes will include weekly rates of: induced labour, caesarean section, births before arrival to hospital, postpartum haemorrhage, length of stay, general anaesthesia for caesarean birth, influenza and COVID-19 vaccination status, and gestation at first antenatal visit. A prepandemic median for all outcomes will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≥6 consecutive weeks, all above or below the prepandemic median. Additional statistical analyses such as regression, time series and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests.

Ethics and dissemination: Ethics approval for the collaborative maternity and newborn dashboard project has been obtained from the Austin Health (HREC/64722/Austin-2020) and Mercy Health (ref. 2020-031).

Trial registration number: ACTRN12620000878976; Pre-results.

Abstract
Background: The COVID-19 pandemic has forced sweeping social and behavioral changes that have adversely affected the general population. Many changes, such as business closures, working from home, increased psychological distress, and delayed access to health care, could have unique adverse effects on patients diagnosed with chronic pain (CP). The present study sought to examine perceived changes in the CP experience brought about by the COVID-19 pandemic.

Design: Participants included 487 self-reported patients with musculoskeletal, neuropathic, or postsurgical pain recruited using CloudResearch. A 53-item survey was created to assess changes in perceived pain, mood, control over pain, physical activity, employment, and medical access since the onset of the pandemic.

Results: Results suggested a worsening of the pain experience, particularly for women, with greater pain, negative affect, sedentary functioning, perceived decline in treatment quality, and increased treatment delays. Of note, pandemic-related declines in control over pain, which represents an important clinical target, are associated with other pandemic-related declines and also mediates relevant associations.

Conclusions: For frontline treatment providers, particularly primary care nurses and physicians, these findings may be relevant in order to reduce the likelihood of a worsening of symptoms, loss of self-efficacy regarding management of pain and/or potential maladaptive increase in the use of pain medications.

Abstract
Background: Millions of people globally have been affected by the Covid-19 pandemic. It's impact on pain management nurses roles' remains unknown.

Aims: To explore role changes among pain management nurses performing patient care during the Covid-19 pandemic.

Design: Qualitative descriptive research study.

Settings: The American Society for Pain Management Nursing's listserv, E-News Brief postings, and snowball sampling.

Participants/subjects: English-speaking registered nurses or advanced practice registered nurses who provided direct patient care since 2020 were eligible.

Method: Data were collected through individual, semi-structured telephone interviews. An interview guide was used and included questions about participants' characteristics and the effect of the Covid-19 pandemic on their roles in clinical work. Data were analyzed using qualitative content analysis.

Results: A homogenous sample of eighteen nurses from the United States was interviewed. Their normal roles, roles during the pandemic, and surges in patients with Covid-19 as the condition for role changes emerged from their descriptions. Most participants did not experience significant changes in their normal roles, but all described how their normal functions were impacted by the pandemic.

Conclusions: As the infectious variants of this disease evolve or other disastrous conditions occur, further changes to roles may occur. The skill sets of pain management nurses, including understanding assessment of pain across the lifespan, administration of opioids and multimodal analgesia, monitoring of patients, and communicating by educating and consultations, reinforce the significant contribution pain management nurses have as valued team members in times of crisis.

Abstract
Introduction: There are many possible sources of medical information; however, the quality of the information varies. Poor quality or inaccurate resources may be harmful if they are trusted by providers. This study aimed to analyze the quality of coronavirus disease 2019 (COVID-19)-related intubation videos on YouTube.

Methods: The term "COVID-19 intubation" was searched on YouTube. The top 100 videos retrieved were sorted by relevance and the 37 videos were included. The video demographics were recorded. The quality of the videos was analyzed using an 18-point checklist, which was designed for evaluating COVID-19 intubation. Videos were also evaluated using general video quality scores and the modified Journal of the American Medical Association score.

Results: The educational quality was graded as good for eight (21.6%) videos, moderate for 13 (35.1%) videos, and poor for 16 (43.2%) videos. The median safe COVID-19 intubation score (SCIS) was 11 (IQR = 5-13). The SCISs indicated that videos prepared in an intensive care unit were higher in quality than videos from other sources (p < 0.05). The length of the video was predictive of quality (area under the curve = 0.802, 95% CI = 0.658-0.945, p = 0.10).

Conclusions: The quality of YouTube videos for COVID-19 intubation is substandard. Poor quality videos may provide inaccurate knowledge to viewers and potentially cause harm.

Abstract
Background: Coronavirus disease 2019 (Covid-19) disproportionately results in hospitalization or death in older patients and those with underlying conditions. Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease.

Methods: In this ongoing, multicenter, double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, nonhospitalized patients with symptomatic Covid-19 (≤5 days after the onset of symptoms) and at least one risk factor for disease progression to receive a single infusion of sotrovimab at a dose of 500 mg or placebo. The primary efficacy outcome was hospitalization (for >24 hours) for any cause or death within 29 days after randomization.

Results: In this prespecified interim analysis, which included an intention-to-treat population of 583 patients (291 in the sotrovimab group and 292 in the placebo group), 3 patients (1%) in the sotrovimab group, as compared with 21 patients (7%) in the placebo group, had disease progression leading to hospitalization or death (relative risk reduction, 85%; 97.24% confidence interval, 44 to 96; P = 0.002). In the placebo group, 5 patients were admitted to the intensive care unit, including 1 who died by day 29. Safety was assessed in 868 patients (430 in the sotrovimab group and 438 in the placebo group). Adverse events were reported by 17% of the patients in the sotrovimab group and 19% of those in the placebo group; serious adverse events were less common with sotrovimab than with placebo (in 2% and 6% of the patients, respectively).

Conclusions: Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression. No safety signals were identified. (Funded by Vir Biotechnology and GlaxoSmithKline; COMET-ICE ClinicalTrials.gov number, NCT04545060.).

Abstract
Background: The COVID-19 pandemic created a situation with an urgent need to produce a virtual system for the 2019-2020 pediatric anesthesiology fellowship cycle. With fellowship interviews beginning in April 2020, there was minimal time for programs to adapt. Each program rapidly developed its own platform, expectations, materials, and process for interviews - all while under the stress of managing the unfolding patient care, financial, and leadership crises of the unfolding pandemic.

Aims: The aim of this survey-based study was to help identify changes compared to previous traditional cycles, obstacles encountered, and program director attitudes towards this, and possible future, virtual application cycles. We separately report the results of an applicant-based survey about the 2020 virtual interview cycle1 .

Methods: A 50-question survey was developed utilizing Qualtrics. An anonymous survey link was sent to all pediatric anesthesiology program directors with an invitation for one program leader (either the program director or assistant/associate program director but not both) from each program to complete the voluntary survey.

Result: 30 respondents completed the survey, for a response rate of 50% based on the 60 ACGME-approved pediatric anesthesiology fellowships. Compared to previous traditional cycles, almost half of respondents (14/29, 48.3%) reported no increase in the number of applications received, and a majority of respondents (16/29, 55.2%) reported that they offered the same number of interview spots for the year. The virtual interview process appears to have gone smoothly, as a majority of programs reported they never or rarely had technical problems across a number of different domains. Importantly, the majority of respondents were either somewhat satisfied or extremely satisfied (21/28, 75%) with the overall virtual interview process. Given the choice of preferred interview format going forward, half of the respondents (14/28) would offer a combination of traditional and virtual interviews.

Conclusions: These results demonstrate that virtual interviews are a viable alternative to traditional interviews and can be completed without many technological complications. PDs were overall satisfied with virtual interviews, despite not having appropriate time to plan and coordinate, and would be interested in continuing this option into the future. There are areas where improvements can be made and with appropriate planning could look to mitigate some of the areas where virtual interviews fall short of traditional interviews. In combination with our previously published survey of applicants1 , these data form a more complete picture of virtual interview best practices going forward.

Abstract
Coronavirus disease 2019 (COVID-19) pneumonia is an evolving disease. We will focus on the development of its pathophysiologic characteristics over time, and how these time-related changes determine modifications in treatment. In the emergency department: the peculiar characteristic is the coexistence, in a significant fraction of patients, of severe hypoxaemia, near-normal lung computed tomography imaging, lung gas volume and respiratory mechanics. Despite high respiratory drive, dyspnoea and respiratory rate are often normal. The underlying mechanism is primarily altered lung perfusion. The anatomical prerequisites for PEEP (positive end-expiratory pressure) to work (lung oedema, atelectasis, and therefore recruitability) are lacking. In the high-dependency unit: the disease starts to worsen either because of its natural evolution or additional patient self-inflicted lung injury (P-SILI). Oedema and atelectasis may develop, increasing recruitability. Noninvasive supports are indicated if they result in a reversal of hypoxaemia and a decreased inspiratory effort. Otherwise, mechanical ventilation should be considered to avert P-SILI. In the intensive care unit: the primary characteristic of the advance of unresolved COVID-19 disease is a progressive shift from oedema or atelectasis to less reversible structural lung alterations to lung fibrosis. These later characteristics are associated with notable impairment of respiratory mechanics, increased arterial carbon dioxide tension (P aCO2 ), decreased recruitability and lack of response to PEEP and prone positioning.

Abstract
Background: Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age.

Methods: A phase 1, dose-finding study and an ongoing phase 2-3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2-3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-μg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed.

Results: During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study. In the phase 2-3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3).

Conclusions: A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

Abstract
Post-acute coronavirus disease 2019 (COVID-19) syndrome is a novel, poorly understood clinical entity with life-impacting ramifications. Patients with this syndrome, also known as "COVID-19 long-haulers," often present with nonspecific ailments involving more than one body system. The most common complaints include dyspnea, fatigue, brain fog, and chest pain. There currently is no single agreed-upon definition for post-acute COVID-19 syndrome, but most agree that criterion for this syndrome is the persistence of mental and physical health consequences after initial infection. Given the millions of acute infections in the United States over the course of the pandemic, perioperative providers will encounter these patients in clinical practice in growing numbers. Symptoms of the COVID-19 long-haulers should not be minimized, as these patients are at higher risk for postoperative respiratory complications and perioperative mortality for up to seven weeks after initial illness. Instead, a cautious multidisciplinary preoperative evaluation should be performed. Perioperative care should be viewed through the prism of best practices already in use, such as avoidance of benzodiazepines in patients with cognitive impairment and use of lung-protective ventilation. Recommendations especially relevant to the COVID-19 long-haulers include assessment of critical care myopathies and neuropathies to determine suitable neuromuscular blocking agents and reversal, preoperative workup of insidious cardiac or pulmonary pathologies in previously healthy patients, and, thorough medication review, particularly of anticoagulation regimens and chronic steroid use. In this article, the authors define the syndrome, synthesize the available scientific evidence, and make pragmatic suggestions regarding the perioperative clinical care of COVID-19 long-haulers.

Abstract
Background: BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, conditionally approved, or authorized for emergency use worldwide. At the time of initial authorization, data beyond 2 months after vaccination were unavailable.

Methods: In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy trial, we randomly assigned 44,165 participants 16 years of age or older and 2264 participants 12 to 15 years of age to receive two 30-μg doses, at 21 days apart, of BNT162b2 or placebo. The trial end points were vaccine efficacy against laboratory-confirmed Covid-19 and safety, which were both evaluated through 6 months after vaccination.

Results: BNT162b2 continued to be safe and have an acceptable adverse-event profile. Few participants had adverse events leading to withdrawal from the trial. Vaccine efficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2) through 6 months of follow-up among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in populations with diverse ages, sexes, race or ethnic groups, and risk factors for Covid-19 among participants without evidence of previous infection with SARS-CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was predominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed.

Conclusions: Through 6 months of follow-up and despite a gradual decline in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing Covid-19. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).

Abstract
Background: Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear.

Methods: We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months.

Results: The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman's rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46).

Conclusions: Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

Abstract
Background: Coronavirus disease 2019 (Covid-19) disproportionately results in hospitalization or death in older patients and those with underlying conditions. Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease.

Methods: In this ongoing, multicenter, double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, nonhospitalized patients with symptomatic Covid-19 (≤5 days after the onset of symptoms) and at least one risk factor for disease progression to receive a single infusion of sotrovimab at a dose of 500 mg or placebo. The primary efficacy outcome was hospitalization (for >24 hours) for any cause or death within 29 days after randomization.

Results: In this prespecified interim analysis, which included an intention-to-treat population of 583 patients (291 in the sotrovimab group and 292 in the placebo group), 3 patients (1%) in the sotrovimab group, as compared with 21 patients (7%) in the placebo group, had disease progression leading to hospitalization or death (relative risk reduction, 85%; 97.24% confidence interval, 44 to 96; P = 0.002). In the placebo group, 5 patients were admitted to the intensive care unit, including 1 who died by day 29. Safety was assessed in 868 patients (430 in the sotrovimab group and 438 in the placebo group). Adverse events were reported by 17% of the patients in the sotrovimab group and 19% of those in the placebo group; serious adverse events were less common with sotrovimab than with placebo (in 2% and 6% of the patients, respectively).

Conclusions: Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression. No safety signals were identified. (Funded by Vir Biotechnology and GlaxoSmithKline; COMET-ICE ClinicalTrials.gov number, NCT04545060.).

Abstract
Importance: Safety surveillance of vaccines against COVID-19 is critical to ensure safety, maintain trust, and inform policy.

Objectives: To monitor 23 serious outcomes weekly, using comprehensive health records on a diverse population.

Design, setting, and participants: This study represents an interim analysis of safety surveillance data from Vaccine Safety Datalink. The 10 162 227 vaccine-eligible members of 8 participating US health plans were monitored with administrative data updated weekly and supplemented with medical record review for selected outcomes from December 14, 2020, through June 26, 2021.

Exposures: Receipt of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccination, with a risk interval of 21 days for individuals after vaccine dose 1 or 2 compared with an interval of 22 to 42 days for similar individuals after vaccine dose 1 or 2.

Main outcomes and measures: Incidence of serious outcomes, including acute myocardial infarction, Bell palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome. Incidence of events that occurred among vaccine recipients 1 to 21 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. For a signal, a 1-sided P < .0048 was required to keep type I error below .05 during 2 years of weekly analyses. For 4 additional outcomes, including anaphylaxis, only descriptive analyses were conducted.

Results: A total of 11 845 128 doses of mRNA vaccines (57% BNT162b2; 6 175 813 first doses and 5 669 315 second doses) were administered to 6.2 million individuals (mean age, 49 years; 54% female individuals). The incidence of events per 1 000 000 person-years during the risk vs comparison intervals for ischemic stroke was 1612 vs 1781 (RR, 0.97; 95% CI, 0.87-1.08); for appendicitis, 1179 vs 1345 (RR, 0.82; 95% CI, 0.73-0.93); and for acute myocardial infarction, 935 vs 1030 (RR, 1.02; 95% CI, 0.89-1.18). No vaccine-outcome association met the prespecified requirement for a signal. Incidence of confirmed anaphylaxis was 4.8 (95% CI, 3.2-6.9) per million doses of BNT162b2 and 5.1 (95% CI, 3.3-7.6) per million doses of mRNA-1273.

Conclusions and relevance: In interim analyses of surveillance of mRNA COVID-19 vaccines, incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination. While CIs were wide for many outcomes, surveillance is ongoing.

Abstract
Objective: Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID-19 patients. Given that platelets are key regulators of thrombosis, inflammation, and immunity they represent prime candidates as mediators of COVID-19-associated pathogenesis. The objective of this study was to understand the contribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the platelet phenotype via phenotypic (activation, aggregation) and transcriptomic characterization.

Approach and results: In a cohort of 3915 hospitalized COVID-19 patients, we analyzed blood platelet indices collected at hospital admission. Following adjustment for demographics, clinical risk factors, medication, and biomarkers of inflammation and thrombosis, we find platelet count, size, and immaturity are associated with increased critical illness and all-cause mortality. Bone marrow, lung tissue, and blood from COVID-19 patients revealed the presence of SARS-CoV-2 virions in megakaryocytes and platelets. Characterization of COVID-19 platelets found them to be hyperreactive (increased aggregation, and expression of P-selectin and CD40) and to have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets. In vitro mechanistic studies highlight that the interaction of SARS-CoV-2 with megakaryocytes alters the platelet transcriptome, and its effects are distinct from the coronavirus responsible for the common cold (CoV-OC43).

Conclusions: Platelet count, size, and maturity associate with increased critical illness and all-cause mortality among hospitalized COVID-19 patients. Profiling tissues and blood from COVID-19 patients revealed that SARS-CoV-2 virions enter megakaryocytes and platelets and associate with alterations to the platelet transcriptome and activation profile.

Abstract
Purpose: The Coronavirus disease 2019 (COVID-19) has led to an unparalleled influx of patients. Prognostic scores could help optimizing healthcare delivery, but most of them have not been comprehensively validated. We aim to externally validate existing prognostic scores for COVID-19.

Methods: We used "COVID-19 Evidence Alerts" (McMaster University) to retrieve high-quality prognostic scores predicting death or intensive care unit (ICU) transfer from routinely collected data. We studied their accuracy in a retrospective multicenter cohort of adult patients hospitalized for COVID-19 from January 2020 to April 2021 in the Greater Paris University Hospitals. Areas under the receiver operating characteristic curves (AUC) were computed for the prediction of the original outcome, 30-day in-hospital mortality and the composite of 30-day in-hospital mortality or ICU transfer.

Results: We included 14,343 consecutive patients, 2583 (18%) died and 5067 (35%) died or were transferred to the ICU. We examined 274 studies and found 32 scores meeting the inclusion criteria: 19 had a significantly lower AUC in our cohort than in previously published validation studies for the original outcome; 25 performed better to predict in-hospital mortality than the composite of in-hospital mortality or ICU transfer; 7 had an AUC > 0.75 to predict in-hospital mortality; 2 had an AUC > 0.70 to predict the composite outcome.

Conclusion: Seven prognostic scores were fairly accurate to predict death in hospitalized COVID-19 patients. The 4C Mortality Score and the ABCS stand out because they performed as well in our cohort and their initial validation cohort, during the first epidemic wave and subsequent waves, and in younger and older patients.

bstract
Background: Waning of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (Covid-19) is a concern. The persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the B.1.351 (or beta) and B.1.617.2 (or delta) variants have dominated incidence and polymerase-chain-reaction testing is done on a mass scale, is unclear.

Methods: We used a matched test-negative, case-control study design to estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of Covid-19, from January 1 to September 5, 2021.

Results: Estimated BNT162b2 effectiveness against any SARS-CoV-2 infection was negligible in the first 2 weeks after the first dose. It increased to 36.8% (95% confidence interval [CI], 33.2 to 40.2) in the third week after the first dose and reached its peak at 77.5% (95% CI, 76.4 to 78.6) in the first month after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose. Effectiveness against symptomatic infection was higher than effectiveness against asymptomatic infection but waned similarly. Variant-specific effectiveness waned in the same pattern. Effectiveness against any severe, critical, or fatal case of Covid-19 increased rapidly to 66.1% (95% CI, 56.8 to 73.5) by the third week after the first dose and reached 96% or higher in the first 2 months after the second dose; effectiveness persisted at approximately this level for 6 months.

Conclusions: BNT162b2-induced protection against SARS-COV-2 infection appeared to wane rapidly following its peak after the second dose, but protection against hospitalization and death persisted at a robust level for 6 months after the second dose. (Funded by Weill Cornell Medicine-Qatar and others.).

Abstract
Background: Vaccine effectiveness studies have not differentiated the effect of the delta (B.1.617.2) variant and potential waning immunity in observed reductions in effectiveness against SARS-CoV-2 infections. We aimed to evaluate overall and variant-specific effectiveness of BNT162b2 (tozinameran, Pfizer-BioNTech) against SARS-CoV-2 infections and COVID-19-related hospital admissions by time since vaccination among members of a large US health-care system.

Methods: In this retrospective cohort study, we analysed electronic health records of individuals (≥12 years) who were members of the health-care organisation Kaiser Permanente Southern California (CA, USA), to assess BNT162b2 vaccine effectiveness against SARS-CoV-2 infections and COVID-19-related hospital admissions for up to 6 months. Participants were required to have 1 year or more previous membership of the organisation. Outcomes comprised SARS-CoV-2 PCR-positive tests and COVID-19-related hospital admissions. Effectiveness calculations were based on hazard ratios from adjusted Cox models. This study was registered with ClinicalTrials.gov, NCT04848584.

Findings: Between Dec 14, 2020, and Aug 8, 2021, of 4 920 549 individuals assessed for eligibility, we included 3 436 957 (median age 45 years [IQR 29-61]; 1 799 395 [52·4%] female and 1 637 394 [47·6%] male). For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95% CI 72-74) and against COVID-19-related hospital admissions was 90% (89-92). Effectiveness against infections declined from 88% (95% CI 86-89) during the first month after full vaccination to 47% (43-51) after 5 months. Among sequenced infections, vaccine effectiveness against infections of the delta variant was high during the first month after full vaccination (93% [95% CI 85-97]) but declined to 53% [39-65] after 4 months. Effectiveness against other (non-delta) variants the first month after full vaccination was also high at 97% (95% CI 95-99), but waned to 67% (45-80) at 4-5 months. Vaccine effectiveness against hospital admissions for infections with the delta variant for all ages was high overall (93% [95% CI 84-96]) up to 6 months.

Interpretation: Our results provide support for high effectiveness of BNT162b2 against hospital admissions up until around 6 months after being fully vaccinated, even in the face of widespread dissemination of the delta variant. Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably primarily due to waning immunity with time rather than the delta variant escaping vaccine protection.

Funding: Pfizer.

Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression.

Methods: We performed a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of RCTs to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30 day mortality. Secondary outcomes included need for mechanical ventilation and ICU admission. Data sources were PubMed, Embase, MedRxiv, and the Cochrane library on July 2, 2021.

Results: We identified 17 RCTs that recruited 15 587 patients with 8027 (51.5%) allocated to receive convalescent plasma. Convalescent plasma use was not associated with a mortality benefit (24.7% vs 25.5%; odds ratio [OR]=0.94 [0.85-1.04]; P=0.23; I2=4%; TSA adjusted confidence interval [CI], 0.84-1.05), or reduction in need for mechanical ventilation (15.7% vs 15.4%; OR=1.01 [0.92-1.11]; P=0.82; I2=0%; TSA adjusted CI, 0.91-1.13), or ICU admission (22.4% vs 16.7%; OR=0.80 [0.21-3.09]; P=0.75; I2=63%; TSA adjusted CI, 0.0-196.05). Meta-regression did not reveal association with titre of convalescent plasma, timing of administration, or risk of death and treatment effect (P>0.05). Risk of bias was high in most studies.

Conclusions: In patients with COVID-19, there was no clear mortality benefit associated with convalescent plasma treatment. In patients with mild disease, convalescent plasma did not prevent either the need for mechanical ventilation or ICU admission.

Clinical trial registration: CRD42021234201 (PROSPERO).

Abstract
Background: On July 30, 2021, the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) was approved in Israel for persons who were 60 years of age or older and who had received a second dose of vaccine at least 5 months earlier. Data are needed regarding the effect of the booster dose on the rate of confirmed coronavirus 2019 disease (Covid-19) and the rate of severe illness.

Methods: We extracted data for the period from July 30 through August 31, 2021, from the Israeli Ministry of Health database regarding 1,137,804 persons who were 60 years of age or older and had been fully vaccinated (i.e., had received two doses of BNT162b2) at least 5 months earlier. In the primary analysis, we compared the rate of confirmed Covid-19 and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (nonbooster group). In a secondary analysis, we evaluated the rate of infection 4 to 6 days after the booster dose as compared with the rate at least 12 days after the booster. In all the analyses, we used Poisson regression after adjusting for possible confounding factors.

Results: At least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% confidence interval [CI], 10.4 to 12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9 to 29.5). In a secondary analysis, the rate of confirmed infection at least 12 days after vaccination was lower than the rate after 4 to 6 days by a factor of 5.4 (95% CI, 4.8 to 6.1).

Conclusions: In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.

Abstract
This cohort study analyzes milk samples from lactating mothers to determine if COVID-19 vaccine–related messenger RNA was detectable in human milk after vaccination.

Abstract
Importance: Much remains unknown about the transmission dynamics of COVID-19. How the severity of the index case and timing of exposure is associated with disease in close contacts of index patients with COVID-19 and clinical presentation in those developing disease is not well elucidated.

Objectives: To investigate the association between the timing of exposure and development of disease among close contacts of index patients with COVID-19 and to evaluate whether the severity of the index case is associated with clinical presentation in close contacts who develop COVID-19.

Design, setting, and participants: This study used a large, population-based cohort of 730 individuals (index patients) who received a diagnosis of COVID-19 in Zhejiang Province, China, from January 8 to July 30, 2020, along with a contact tracing surveillance program. Field workers visited 8852 close contacts of the index patients and evaluated them for COVID-19 through August 2020. A timeline was constructed to characterize different exposure periods between index patients and their contacts.

Main outcomes and measures: The primary outcome was the attack rate of COVID-19, defined as the total number of new COVID-19 cases diagnosed among contacts of index patients divided by the total number of exposed contacts. A secondary outcome was asymptomatic clinical presentation among infected contacts. Relative risks were calculated to investigate risk factors for COVID-19 among contacts and asymptomatic clinical presentation among infected contacts.

Results: Among 8852 close contacts (4679 male contacts [52.9%]; median age, 41 years [interquartile range, 28-54 years]) of 730 index patients (374 male patients [51.2%]; median age, 46 years [interquartile range, 36-56 years]), contacts were at highest risk of COVID-19 if they were exposed between 2 days before and 3 days after the index patient's symptom onset, peaking at day 0 (adjusted relative risk [ARR], 1.3; 95% CI, 1.2-1.5). Compared with being exposed to an asymptomatic index patient, the risk of COVID-19 among contacts was higher when they were exposed to index patients with mild (ARR, 4.0; 95% CI, 1.8-9.1) and moderate (ARR, 4.3; 95% CI, 1.9-9.7) cases of COVID-19. As index case severity increased, infected contacts were less likely to be asymptomatic (exposed to patient with mild COVID-19: ARR, 0.3; 95% CI, 0.1-0.9; exposed to patient with moderate COVID-19: ARR, 0.3; 95% CI, 0.1-0.8).

Conclusions and relevance: This cohort study found that individuals with COVID-19 were most infectious a few days before and after symptom onset. Infected contacts of asymptomatic index patients were less likely to present with COVID-19 symptoms, suggesting that quantity of exposure may be associated with clinical presentation in close contacts.

Abstract
Importance: Two mRNA-based vaccines against coronavirus disease 2019 (COVID-19) were found to be highly efficacious in phase 3 clinical trials in the US. However, patients with chronic illnesses, including cirrhosis, were excluded from clinical trials. Patients with cirrhosis have immune dysregulation that is associated with vaccine hyporesponsiveness.

Objective: To study the association of receipt of the Pfizer BNT162b2 mRNA or the Moderna mRNA-1273 vaccines in patients with cirrhosis compared with a propensity-matched control group of patients at similar risk of infection and severe disease from COVID-19.

Design, setting, and participants: We performed a retrospective cohort study of patients with cirrhosis who received at least 1 dose of a COVID-19 mRNA vaccine at the Veterans Health Administration. Patients who received at least 1 dose of the vaccine (n = 20 037) were propensity matched with 20 037 controls to assess the associations of vaccination with new COVID-19 infection and COVID-19 hospitalization and death.

Exposures: Receipt of at least 1 dose of the BNT162b2 mRNA or the mRNA-1273 vaccines between December 18, 2020, and March 17, 2021.

Main outcomes and measures: COVID-19 infection as documented by a positive result for COVID-19 by polymerase chain reaction, hospitalization, and death due to COVID-19 infection.

Results: The median (interquartile range) age of the vaccinated individuals in the study cohort was 69.1 (8.4) years and 19 465 (97.2%) of the participants in each of the vaccinated and unvaccinated groups were male, consistent with a US veteran population. The mRNA-1273 vaccine was administered in 10 236 (51%) and the BNT162b2 mRNA in 9801 (49%) patients. Approximately 99.7% of patients who received the first dose of either vaccine with a follow-up of 42 days or more received a second dose. The number of COVID-19 infections in the vaccine recipients was similar to the control group in days 0 to 7, 7 to 14, 14 to 21, and 21 to 28 after the first dose. After 28 days, receipt of 1 dose of an mRNA vaccine was associated with a 64.8% reduction in COVID-19 infections and 100% protection against hospitalization or death due to COVID-19 infection. The association of reduced COVID-19 infections after the first dose was lower among patients with decompensated (50.3%) compared with compensated cirrhosis (66.8%). Receipt of a second dose was associated with a 78.6% reduction in COVID-19 infections and 100% reduction in COVID-19-related hospitalization or death after 7 days.

Conclusions and relevance: This cohort study of US veterans found that mRNA vaccine administration was associated with a delayed but modest reduction in COVID-19 infection but an excellent reduction in COVID-19-related hospitalization or death in patients with cirrhosis.

Abstract
This cohort study examines the rate of SARS-CoV-2 reinfection among people in Lombardy, Italy, who previously recovered from COVID-19.

Problem: The most effective way to train clinicians to safely don and doff personal protective equipment (PPE) and perform aerosol-generating procedures (AGPs), such as intubations, is unknown when clinician educators are unavailable, as they have been during the COVID-19 pandemic. Proper PPE and airway management techniques are critical to prevent the transmission of respiratory illnesses such as COVID-19.

Approach: In March 2020, the authors implemented a structured train-the-trainers curriculum to teach PPE techniques and a modified airway management algorithm for suspected COVID-19 patients. A single emergency medicine physician trainer taught 17 subsequent emergency medicine and critical care physician trainers the proper PPE and airway management techniques. The initial trainer and 7 of the subsequent trainers then instructed 99 other emergency medicine resident and attending physicians using in situ simulation. Trainers and learners completed retrospective pre-post surveys to assess their comfort teaching the material and performing the techniques, respectively.

Outcomes: The surveys demonstrated a significant increase in the trainers' comfort in teaching simulation-based education, from 4.00 to 4.53 on a 5-point Likert scale (P < .005), and in teaching the airway management techniques through simulation, from 2.47 to 4.47 (P < .001). There was no difference in the change in comfort level between those learners who were taught by the initial trainer and those who were taught by the subsequent trainers. These results suggest that the subsequent trainers were as effective in teaching the simulation material as the initial trainer.

Next steps: Work is ongoing to investigate clinician- and patient-specific outcomes, including PPE adherence, appropriate AGP performance, complication rate, and learners' skill retention. Future work will focus on implementing similar train-the-trainers strategies for other health professions, specialties, and high-risk or rare procedures.

Background: The global reputation of coronavirus disease (COVID-19) has led universities in China to conduct online teaching. However, the actual feedback from medical teachers and students regarding online education remains unclear.

Methods: A prospective questionnaire survey examined the current opinions of online education from teachers and students at the Medical School of Tongji University.

Results: A total of 488 valid questionnaires were collected (223 males, 45.7%; 265 females, 54.3%), including 394 students (80.7%) and 94 teachers (19.3%). Most teachers and students were "in favor of online teaching," had "positive views for online education," were "satisfied with online teaching," and "expected for regular online education," although students thought that "too much learning tasks had been assigned" (90.4% teachers vs. 43.1% students, P < 0.001) and "less teaching effect than in offline classes" (68.1% teachers vs. 43.4% students). Compared to female counterpart, male students had higher "learning interest" (27.6% vs. 14.9%), "learning attention" (29.2% vs. 14.4%), "learning efficiency" (30.2% vs. 16.7%), and "better learning effect" (27.6% vs. 15.3%). Furthermore, male students had a significantly rise in attendance rate. Compared with male teachers, female teachers had less "experience in online educational course recording" (25.9% vs. 50%) and "past training for online teaching" (53.7% vs. 77.5%). Furthermore, they tended to be more "resistant to online teaching" (44.4% vs. 22.5%) and less "ready for online teaching" (70.4% vs. 87.5%). There was no significant difference in the acceptance of online teaching among teachers in different age groups.

Conclusions: Most teachers and students supported and were satisfied with the implementation of online education during the pandemic. Although teachers were less adaptable to online education, they still had positive opinions. Sex influenced the acceptance of online teaching. Male teachers and students showed better adaptability than their female counterparts. Although online teaching has advantages, it still cannot completely replace traditional offline teaching. As online education is a trend for future learning, universities should make more efforts to improve it, especially to provide more attention to female teachers and students.

Background: The COVID-19 pandemic significantly impacted residency recruitment in 2020, posing unique challenges for programs and applicants alike. Anesthesiology programs have adopted alternate methods of recruitment, including virtual open houses and social media, due to limiting personal contact rules implemented by AAMC. This study was undertaken to determine the frequency of virtual events hosted and social media accounts created by programs.

Methods: Anesthesiology residency programs and departments were examined for social media presence on Twitter, Instagram, and Facebook. Programs' websites and social media posts were reviewed for virtual open house opportunities. Available sub-internships were collected from the Visiting Student Application Service database. Data was collected after 2020-2021 pre-interview recruitment in October 2020.

Results: Of 153 total anesthesiology residency programs, 96 (63%) had some form of social media presence. The platforms of choice for programs with social media accounts included Twitter (71, or 46%), Instagram (67, or 44%), and Facebook (47, or 31%). Forty of seventy-six residency-affiliated accounts were created after March 1, 2020; Instagram accounts (26 of 40) represented most of these. Most Anesthesiology programs (59%) offered virtual open houses for prospective applicants. Twitter (25%), Instagram (22%), and Facebook (8%) were used by programs to advertise these events.

Conclusions: Social media presence of anesthesiology residency programs has grown steadily over the past decade, with exponential growth experienced in 2020. This data suggests that anesthesiology residency programs are employing new, mostly virtual, methods to reach prospective applicants during an unprecedented application cycle amidst the COVID-19 pandemic.

Abstract
Objective: To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19).

Design: Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data.

Data sources: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021).

Study selection: Trials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate.

Methods: After duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm.

Results: As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) -4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD -4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD -3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD -4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative.

Conclusion: In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit.

Systematic review registration: This review was not registered. The protocol established a priori is included as a data supplement.

Funding: This study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321).

Readers' note: This article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website (www.covid19lnma.com).

Abstract
Background: Immunosuppression may worsen SARS-CoV-2 infection. We conducted a nationwide cohort study of the effect of exposure to immunosuppressants on the prognosis of SARS-CoV-2 infection in Denmark.

Methods: We identified all SARS-CoV-2 test-positive patients from February to October 2020 and linked health care data from nationwide registers, including prescriptions for the exposure, immunosuppressant drugs. We estimated relative risks of hospital admission, intensive care unit (ICU) admission, and death (each studied independently up to 30 days from testing) with a log linear binomial regression adjusted for confounders using a propensity score-based matching weights model.

Results: A composite immunosuppressant exposure was associated with a significantly increased risk of death (adjusted relative risk 1·56 [95% confidence interval 1.10-2.22]). The increased risk of death was mainly driven by exposure to systemic glucocorticoids (aRR 2.38 [95% CI 1.72-3.30]), which were also associated with an increased risk of hospital admission (aRR 1.34 [95% CI 1.10-1.62]), but not ICU admission (aRR 1.76 [95% CI [0.93-3.35]); these risks were greater for high cumulative doses of glucocorticoids than for moderate doses. Exposure to selective immunosuppressants, tumour necrosis factor inhibitors, or interleukin inhibitors, was not associated with an increased risk of hospitalisation, ICU admission, or death, nor was exposure to calcineurin inhibitors, other immunosuppressants, hydroxychloroquine, or chloroquine.

Conclusions: Exposure to glucocorticoids was associated with increased risks of hospital admission and death. Further investigation is needed to determine the optimal management of COVID-19 in patients with pre-morbid glucocorticoid usage, specifically whether these patients require altered doses of glucocorticoids.

Abstract
The current pandemic has highlighted the need to protect both patients and medical staff. The increased use of regional anaesthesia as a primary anaesthetic modality for operations and other invasive procedures has limited the number of aerosol-generating procedures performed during general anaesthesia. Its use is further characterized by decreases in postoperative pain and length of hospitalization. This article provides an overview of regional anaesthetic techniques (peripheral nerve locks, epidural and spinal anaesthesia) and their uses during the COVID pandemic.

Since the time the World Health Organization (WHO) has declared the coronavirus disease (COVID) as a pandemic on March 11, 2020, over 175 million people have been infected globally, with over 3 million deaths. The state where the present study was conducted recorded a total of 8,09,014 from March to December 2020. The state, like the rest of the country, was in a complete lockdown from March 24 to May 31, 2020. During this time, our centre, a 3,000-bedded tertiary care facility, halted non-COVID work and postponed elective surgeries. The elective surgeries in our centre resumed in June 2020 and were restricted to malignancy and trauma surgeries.

Studies have been conducted on the stress and anxiety induced by the COVID-19 pandemic in both the general population as well as specific groups, such as health care workers, pregnant women and adolescents.[1234] Given that anxiety has a strong bearing on the physical, mental and emotional well-being of the patients and their subsequent recovery from surgery and other procedures, we were interested in assessing anxiety among the patients presenting for elective procedures in the post-lockdown phase of the pandemic. The primary objective of the present study was to assess the anxiety levels among the preoperative patients scheduled for elective surgeries in the post-lockdown phase of the COVID-19 pandemic, and the secondary objective was to assess the factors accentuating the same.

Abstract
Background: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

Methods: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

Results: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose.

Conclusions: AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.).

Abstract
Background: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern.

Methods: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated.

Results: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups.

Conclusions: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).

Abstract
Background: There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic.

Methods: We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients' vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation.

Results: The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 85 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit.

Conclusions: Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).

Abstract
Background: Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.

Methods: We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.

Results: In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.

Conclusions: In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

This briefing, prepared by researchers at Battelle, is intended to provide timely information about SARS-CoV-2 vaccines and variants to libraries, archives, and museums (LAMs), and their stakeholders. This is a review of scientific literature published through 16 August 2021, and should be used in conjunction with other timely resources to ensure decision-making in LAMs reflects the latest scientific understanding. Continual re-evaluation of SARS-CoV-2 policies is highly recommended as new scientific discoveries are published.

Abstract
Importance: Data on BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) effectiveness and safety in pregnancy are currently lacking because pregnant women were excluded from the phase 3 trial.

Objective: To assess the association between receipt of BNT162b2 mRNA vaccine and risk of SARS-CoV-2 infection among pregnant women.

Design, setting, and participants: This was a retrospective cohort study within the pregnancy registry of a large state-mandated health care organization in Israel. Pregnant women vaccinated with a first dose from December 19, 2020, through February 28, 2021, were 1:1 matched to unvaccinated women by age, gestational age, residential area, population subgroup, parity, and influenza immunization status. Follow-up ended on April 11, 2021.

Exposures: Exposure was defined by receipt of the BNT162b2 mRNA vaccine. To maintain comparability, nonexposed women who were subsequently vaccinated were censored 10 days after their exposure, along with their matched pair.

Main outcomes and measures: The primary outcome was polymerase chain reaction-validated SARS-CoV-2 infection at 28 days or more after the first vaccine dose.

Results: The cohort included 7530 vaccinated and 7530 matched unvaccinated women, 46% and 33% in the second and third trimester, respectively, with a mean age of 31.1 years (SD, 4.9 years). The median follow-up for the primary outcome was 37 days (interquartile range, 21-54 days; range, 0-70). There were 118 SARS-CoV-2 infections in the vaccinated group and 202 in the unvaccinated group. Among infected women, 88 of 105 (83.8%) were symptomatic in the vaccinated group vs 149 of 179 (83.2%) in the unvaccinated group (P ≥ .99). During 28 to 70 days of follow-up, there were 10 infections in the vaccinated group and 46 in the unvaccinated group. The hazards of infection were 0.33% vs 1.64% in the vaccinated and unvaccinated groups, respectively, representing an absolute difference of 1.31% (95% CI, 0.89%-1.74%), with an adjusted hazard ratio of 0.22 (95% CI, 0.11-0.43). Vaccine-related adverse events were reported by 68 patients; none was severe. The most commonly reported symptoms were headache (n = 10, 0.1%), general weakness (n = 8, 0.1%), nonspecified pain (n = 6, <0.1%), and stomachache (n = 5, <0.1%).

Conclusions and relevance: In this retrospective cohort study of pregnant women, BNT162b2 mRNA vaccination compared with no vaccination was associated with a significantly lower risk of SARS-CoV-2 infection. Interpretation of study findings is limited by the observational design.

Abstract
Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients.

Abstract
Introduction: Coronavirus disease 2019 (COVID‐19) is a contagious disease that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Health care workers are at risk of infection from aerosolisation of respiratory secretions, droplet and contact spread. There are a number of procedures that represent a high risk of aerosol generation during cardiothoracic surgery. It is important that adequate training, equipment and procedures are in place to reduce that risk.

Recommendations: We provide a number of key recommendations, which reduce the risk of aerosol generation during cardiothoracic surgery and help protect patients and staff. These include general measures such as patient risk stratification, appropriate use of personal protective equipment, consideration to delay surgery in positive patients, and careful attention to theatre planning and preparation. There are also recommended procedural interventions during airway management, transoesophageal echocardiography, cardiopulmonary bypass, chest drain management and specific cardiothoracic surgical procedures. Controversies exist regarding the management of low risk patients undergoing procedures at high risk of aerosol generation, and recommendations for these patients will change depending on the regional prevalence, risk of community transmission and the potential for asymptomatic patients attending for these procedures.

Changes in management as a result of this statement: This statement reflects changes in management based on expert opinion, national guidelines and available evidence. Our knowledge with regard to COVID‐19 continues to evolve and with this, guidance may change and develop. Our colleagues are urged to follow national guidelines and institutional recommendations regarding best practices to protect their patients and themselves.

Endorsed by: Australian and New Zealand Society of Cardiac and Thoracic Surgeons and the Anaesthetic Continuing Education Cardiac Thoracic Vascular and Perfusion Special Interest Group.

Abstract
Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern pose a challenge to the effectiveness of current vaccines. A vaccine that could prevent infection caused by known and future variants of concern as well as infection with pre-emergent sarbecoviruses (i.e., those with potential to cause disease in humans in the future) would be ideal. Here we provide data showing that potent cross-clade pan-sarbecovirus neutralizing antibodies are induced in survivors of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) infection who have been immunized with the BNT162b2 messenger RNA (mRNA) vaccine. The antibodies are high-level and broad-spectrum, capable of neutralizing not only known variants of concern but also sarbecoviruses that have been identified in bats and pangolins and that have the potential to cause human infection. These findings show the feasibility of a pan-sarbecovirus vaccine strategy. (Funded by the Singapore National Research Foundation and National Medical Research Council.).

Abstract
Background: A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT and to assess whether VITT is associated with poorer outcomes.

Methods: For this multicentre cohort study, clinicians were asked to submit all cases in which COVID-19 vaccination preceded the onset of cerebral venous thrombosis, regardless of the type of vaccine, interval between vaccine and onset of cerebral venous thrombosis symptoms, or blood test results. We collected clinical characteristics, laboratory results (including the results of tests for anti-platelet factor 4 antibodies where available), and radiological features at hospital admission of patients with cerebral venous thrombosis after vaccination against COVID-19, with no exclusion criteria. We defined cerebral venous thrombosis cases as VITT-associated if the lowest platelet count recorded during admission was below 150 × 109 per L and, if the D-dimer was measured, the highest value recorded was greater than 2000 μg/L. We compared the VITT and non-VITT groups for the proportion of patients who had died or were dependent on others to help them with their activities of daily living (modified Rankin score 3-6) at the end of hospital admission (the primary outcome of the study). The VITT group were also compared with a large cohort of patients with cerebral venous thrombosis described in the International Study on Cerebral Vein and Dural Sinus Thrombosis.

Findings: Between April 1 and May 20, 2021, we received data on 99 patients from collaborators in 43 hospitals across the UK. Four patients were excluded because they did not have definitive evidence of cerebral venous thrombosis on imaging. Of the remaining 95 patients, 70 had VITT and 25 did not. The median age of the VITT group (47 years, IQR 32-55) was lower than in the non-VITT group (57 years; 41-62; p=0·0045). Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed (median three, IQR 2-4) than non-VITT patients (two, 2-3; p=0·041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compared with non-VITT patients (one [4%] of 25 patients; p=0·0003). The primary outcome of death or dependency occurred more frequently in patients with VITT-associated cerebral venous thrombosis (33 [47%] of 70 patients) compared with the non-VITT control group (four [16%] of 25 patients; p=0·0061). This adverse outcome was less frequent in patients with VITT who received non-heparin anticoagulants (18 [36%] of 50 patients) compared with those who did not (15 [75%] of 20 patients; p=0·0031), and in those who received intravenous immunoglobulin (22 [40%] of 55 patients) compared with those who did not (11 [73%] of 15 patients; p=0·022).

Interpretation: Cerebral venous thrombosis is more severe in the context of VITT. Non-heparin anticoagulants and immunoglobulin treatment might improve outcomes of VITT-associated cerebral venous thrombosis. Since existing criteria excluded some patients with otherwise typical VITT-associated cerebral venous thrombosis, we propose new diagnostic criteria that are more appropriate.

Funding: None.

bstract
Background: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a new syndrome associated with the ChAdOx1 nCoV-19 adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2. Data are lacking on the clinical features of and the prognostic criteria for this disorder.

Methods: We conducted a prospective cohort study involving patients with suspected VITT who presented to hospitals in the United Kingdom between March 22 and June 6, 2021. Data were collected with the use of an anonymized electronic form, and cases were identified as definite or probable VITT according to prespecified criteria. Baseline characteristics and clinicopathological features of the patients, risk factors, treatment, and markers of poor prognosis were determined.

Results: Among 294 patients who were evaluated, we identified 170 definite and 50 probable cases of VITT. All the patients had received the first dose of ChAdOx1 nCoV-19 vaccine and presented 5 to 48 days (median, 14) after vaccination. The age range was 18 to 79 years (median, 48), with no sex preponderance and no identifiable medical risk factors. Overall mortality was 22%. The odds of death increased by a factor of 2.7 (95% confidence interval [CI], 1.4 to 5.2) among patients with cerebral venous sinus thrombosis, by a factor of 1.7 (95% CI, 1.3 to 2.3) for every 50% decrease in the baseline platelet count, by a factor of 1.2 (95% CI, 1.0 to 1.3) for every increase of 10,000 fibrinogen-equivalent units in the baseline d-dimer level, and by a factor of 1.7 (95% CI, 1.1 to 2.5) for every 50% decrease in the baseline fibrinogen level. Multivariate analysis identified the baseline platelet count and the presence of intracranial hemorrhage as being independently associated with death; the observed mortality was 73% among patients with platelet counts below 30,000 per cubic millimeter and intracranial hemorrhage.

Conclusions: The high mortality associated with VITT was highest among patients with a low platelet count and intracranial hemorrhage. Treatment remains uncertain, but identification of prognostic markers may help guide effective management. (Funded by the Oxford University Hospitals NHS Foundation Trust.).

Abstract
Background: The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear.

Methods: We used a test-negative case-control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike (S) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients' vaccination status.

Results: Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant.

Conclusions: Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.).

Abstract
Introduction: One-third of the general public will not accept Coronavirus disease 2019 (COVID-19) vaccination but factors influencing vaccine acceptance among health care personnel (HCP) are not known. We investigated barriers and facilitators to vaccine acceptance within 3 months of regulatory approval (primary outcome) among adult employees and students at a tertiary-care, academic medical center.

Methods: We used a cross-sectional survey design with multivariable logistic regression. Covariates included age, gender, educational attainment, self-reported health status, concern about COVID-19, direct patient interaction, and prior influenza immunization.

Results: Of 18,250 eligible persons, 3,347 participated. Two in 5 (40.5%) HCP intend to delay (n = 1020; 30.6%) or forgo (n = 331; 9.9%) vaccination. Male sex (adjusted OR [aOR], 2.43; 95% confidence interval [CI], 2.00-2.95; P < .001), prior influenza vaccination (aOR, 2.35; 95% CI, 1.75-3.18; P < .001), increased concern about COVID-19 (aOR, 2.40; 95% CI, 2.07-2.79; P < .001), and postgraduate education (aOR, 1.41; 95% CI, 1.21-1.65; P < .001) - but not age, direct patient interaction, or self-reported overall health - were associated with vaccine acceptance in multivariable analysis. Barriers to vaccination included concerns about long-term side effects (n = 1197, 57.1%), safety (n = 1152, 55.0%), efficacy (n = 777, 37.1%), risk-to-benefit ratio (n = 650, 31.0%), and cost (n = 255, 12.2%).Subgroup analysis of Black respondents indicates greater hesitancy to accept vaccination (only 24.8% within 3 months; aOR 0.13; 95% CI, 0.08-0.21; P < .001).

Conclusions: Many HCP intend to delay or refuse COVID-19 vaccination. Policymakers should impartially address concerns about safety, efficacy, side effects, risk-to-benefit ratio, and cost. Further research with minority subgroups is urgently needed.

Abstract
Background: Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity.

Methods: At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case-control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity.

Results: Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented.

Conclusions: Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

The emergence of worrisome variants of the SARS-CoV-2 virus has exposed the limited scale of surveillance efforts in the United States.

Abstract
Objectives: This study aimed to determine whether patients on extracorporeal membrane oxygenation (ECMO) with coronavirus disease 2019 (COVID-19) achieved lower rates of physical therapy participation and required more sedation than those on ECMO without COVID-19.

Design: Retrospective, observational, matched-cohort study.

Setting: Bicenter academic quaternary medical centers.

Participants: All adults on ECMO for severe COVID-19-associated acute respiratory distress syndrome (ARDS) during 2020 and matched (matched 1:1 based on age ± 15 years and medical center) adults on ECMO for ARDS not associated with COVID-19.

Interventions: Observational only.

Measurements and main results: Measurements were collected retrospectively during the first 20 days of ECMO support and included daily levels of physical therapy activity, number of daily sedation infusions and doses, and level of sedation and agitation (Richmond Agitation and Sedation Score). During the first 20 days of ECMO support, the 22 patients who were on ECMO for COVID-19-associated ARDS achieved a similar proportion of days with active physical therapy participation while on ECMO compared to matched patients on ECMO for non-COVID-19 ARDS (22.5% v 7.5%, respectively; p value 0.43), a similar proportion of days with Richmond Agitation and Sedation Score ≥-2 while on ECMO (47.5% v 27.5%, respectively; p value 0.065), and a similar proportion of days with chemical paralysis while on ECMO (8.4% v 18.0%, respectively; p value 0.35).

Conclusions: The results of this matched cohort study supported that sedation requirements were not dramatically greater and did not significantly limit early physical therapy for patients who had COVID-19-associated ARDS and were on venovenous extracorporeal membrane oxygenation (VV-ECMO) versus those without COVID-19-associated ARDS who were on VV-ECMO.

Abstract
We sought to validate prognostic scores in coronavirus disease 2019 including National Early Warning Score, Modified Early Warning Score, and age-based modifications, and define their performance characteristics.

Design: We analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected daily during the trial, Modified Early Warning Score was calculated, and age applied to both scores. We assessed prognostic value for the end points of recovery, mechanical ventilation, and death for score at enrollment, average, and slope of score over the first 48 hours.

Setting: A multisite international inpatient trial.

Patients: A total of 1,062 adult nonpregnant inpatients with severe coronavirus disease 2019 pneumonia.

Interventions: Adaptive COVID-19 Treatment Trial 1 randomized participants to receive remdesivir or placebo. The prognostic value of predictive scores was evaluated in both groups separately to assess for differential performance in the setting of remdesivir treatment.

Measurements and main results: For mortality, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.60-0.68), and improved with addition of age (c-index, 0.66-0.74). For recovery, baseline National Early Warning Score and Modified Early Warning Score demonstrated somewhat better prognostic ability (c-index, 0.65-0.69); however, National Early Warning Score+age and Modified Early Warning Score+age further improved performance (c-index, 0.68-0.71). For deterioration, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.59-0.69) and improved with addition of age (c-index, 0.63-0.70). All prognostic performance improvements due to addition of age were significant (p < 0.05).

Conclusions: In the Adaptive COVID-19 Treatment Trial 1 cohort, National Early Warning Score and Modified Early Warning Score demonstrated moderate prognostic performance in patients with severe coronavirus disease 2019, with improvement in predictive ability for National Early Warning Score+age and Modified Early Warning Score+age. Area under receiver operating curve for National Early Warning Score and Modified Early Warning Score improved in patients receiving remdesivir versus placebo early in the pandemic for recovery and mortality. Although these scores are simple and readily obtainable in myriad settings, in our data set, they were insufficiently predictive to completely replace clinical judgment in coronavirus disease 2019 and may serve best as an adjunct to triage, disposition, and resourcing decisions.

Abstract
The COVID-19 pandemic has impacted on every human activity and, because of the urgency of finding the proper responses to such an unprecedented emergency, it generated a diffused societal debate. The online version of this discussion was not exempted by the presence of misinformation campaigns, but, differently from what already witnessed in other debates, the COVID-19 -intentional or not- flow of false information put at severe risk the public health, possibly reducing the efficacy of government countermeasures. In this manuscript, we study the effective impact of misinformation in the Italian societal debate on Twitter during the pandemic, focusing on the various discursive communities. In order to extract such communities, we start by focusing on verified users, i.e., accounts whose identity is officially certified by Twitter. We start by considering each couple of verified users and count how many unverified ones interacted with both of them via tweets or retweets: if this number is statically significant, i.e. so great that it cannot be explained only by their activity on the online social network, we can consider the two verified accounts as similar and put a link connecting them in a monopartite network of verified users. The discursive communities can then be found by running a community detection algorithm on this network. We observe that, despite being a mostly scientific subject, the COVID-19 discussion shows a clear division in what results to be different political groups. We filter the network of retweets from random noise and check the presence of messages displaying URLs. By using the well known browser extension NewsGuard, we assess the trustworthiness of the most recurrent news sites, among those tweeted by the political groups. The impact of low reputable posts reaches the 22.1% in the right and center-right wing community and its contribution is even stronger in absolute numbers, due to the activity of this group: 96% of all non reputable URLs shared by political groups come from this community.

Supplementary information: The online version contains supplementary material available at 10.1140/epjds/s13688-021-00289-4.

Abstract
Spain was, together with Italy, the first European country severely affected by the COVID-19 pandemic. After one month of strict lockdown and eight weeks of partial restrictions, Spanish residents are expected to have revised some of their beliefs. We conducted a survey one year before the pandemic, at its outbreak and during de-escalation (N = 1706). Despite the lockdown, most respondents tolerated being controlled by authorities, and acknowledged the importance of group necessities over individual rights. However, de-escalation resulted in a belief change towards the intrusiveness of authorities and the preeminence of individual rights. Besides, transcendental beliefs-God answering prayers and the existence of an afterlife-declined after the outbreak, but were strengthened in the de-escalation. Results were strongly influenced by political ideology: the proportion of left-sided voters who saw authorities as intrusive greatly decreased, and transcendental beliefs prevailed among right-sided voters. Our results point to a polarization of beliefs based on political ideology as a consequence of the pandemic.

Telehealth has emerged as an unexpected silver lining of the COVID-19 pandemic, improving access to care and facilitating a transition toward digital medicine. Cementing these gains now could help make healthcare more equitable once the pandemic has ended.

Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic is a public health crisis of unprecedented proportions that has altered the practice of medicine. The pandemic has required pain clinics to transition from in-person visits to telemedicine, postpone procedures, and cancel face-to-face educational sessions. There are no data on how fellowship programs have adapted.

Methods: A 17-question survey was developed covering topics including changes in education, clinical care, and psychological stress due to the COVID pandemic. The initial survey was hosted by Qualtrics Inc and disseminated by the Association of Pain Program Directors on April 10, 2020, to program directors at Accreditation Council for Graduate Medical Education (ACGME)-accredited fellowships. Results are reported descriptively and stratified by COVID infection rate, which was calculated from Centers for Disease Control and Prevention data on state infections, and census data.

Results: Among 107 surveys distributed, 70 (65%) programs responded. Twenty-nine programs were located in states in the upper tertile for per capita infection rates, 17 in the middle third, and 23 in the lowest tertile. Nearly all programs (93%) reported a decreased workload, with 11 (16%) reporting a dramatic decrease (only urgent or emergent cases). Just more than half of programs had either already deployed (14%) or credentialed (39%) fellows to provide nonpain care. Higher state infection rates were significantly associated with reduced clinical demand (Rs = 0.31, 95% confidence interval [CI], 0.08-0.51; P = .011) and redeployment of fellows to nonpain areas (Rs = 0.30, 95% CI, 0.07-0.50; P = .013). Larger program size but not infection rate was associated with increased perceived anxiety level of trainees.

Conclusions: We found a shift to online alternatives for clinical care and education, with correlations between per capita infection rates, and clinical care demands and redeployment, but not with overall trainee anxiety levels. It is likely that medicine in general, and pain medicine in particular, will change after COVID-19, with greater emphasis on telemedicine, virtual education, and greater national and international cooperation. Physicians should be prepared for these changes.

Although pandemics and natural disasters have had economic repercussions, none have arguably had as much effect on the physician job market as COVID-19

Abstract
Tocilizumab (TCZ) is a recombinant anti-interleukin-6 monoclonal antibody which showed uprising evidence as an anti-inflammatory agent which modulates the cytokine storm in patients with COVID-19. However, proper use of the drug requires selection of the appropriate patient and timing. The two main factors which might improve patient selection are the degree of respiratory failure and systemic inflammation. TCZ can decrease the mortality and progression to invasive mechanical ventilation in patients with severe COVID-19 who are not yet invasively ventilated. However, its use in invasively ventilated patients did not yet gain the same level of evidence especially when administered after > 1 day from mechanical ventilation. Being an anti-inflammatory and immunomodulatory drug, TCZ was mostly used in patients with COVID-19 who have clear signs of cytokine storm. However, the drug still showed positive response in some studies which did not strictly select patients with elevated markers of systemic inflammation. Thus, it is warranted to investigate and/or re-analyze the role of the drug in patients with severe COVID-19 and with no signs of systemic inflammation. TCZ is used in a dose of 8 mg/kg which can be repeated if there was no clinical improvement. However, there are no clear criteria for judgment of the success of the first dose. Being a drug with a major effect on gross outcomes in a serious pandemic with millions of mortalities, TCZ should be meticulously investigated to reach definitive indications and number of doses to avoid drug overuse, shortage, and side effects.

Developing a pathway to prioritise clinical research and prepare for future pandemics remains an urgent need.

The research response in Australia has been rapid, but better coordination is imperative.

The Olympic Games raise many infection control, health security and ethical challenges.

Abstract
This qualitative improvement study investigates COVID-19 vaccine approvals at 3 medicine regulatory agencies in the US, EU, and Canada, characterizing and contrasting regulatory review times, and analyzing the clinical evidence supporting authorization.

Determining the duration of protective immunity to infection by SARS-CoV-2 is crucial for understanding and predicting the course of the COVID-19 pandemic. Clinical studies now indicate that immunity will be long-lasting.

Abstract
Purpose: In this retrospective study, we compared inhaled sedation with isoflurane to intravenous propofol in invasively ventilated COVID-19 patients with ARDS (Acute Respiratory Distress Syndrome).

Methods: Charts of all 20 patients with COVID-19 ARDS admitted to the ICU of a German University Hospital during the first wave of the pandemic between 22/03/2020 and 21/04/2020 were reviewed. Among screened 333 days, isoflurane was used in 97 days, while in 187 days, propofol was used for 12 h or more. The effect and dose of these two sedatives were compared. Mixed sedation days were excluded.

Results: Patients' age (median [interquartile range]) was 64 (60-68) years. They were invasively ventilated for 36 [21-50] days. End-tidal isoflurane concentrations were high (0.96 ± 0.41 Vol %); multiple linear regression yielded the ratio (isoflurane infusion rate)/(minute ventilation) as the single best predictor. Infusion rates were decreased under ECMO (3.5 ± 1.4 versus 7.1 ± 3.2 ml∙h-1; p < 0.001). In five patients, the maximum recommended dose of propofol of 4 mg∙hour-1∙kg-1ABW was exceeded on several days. On isoflurane compared to propofol days, neuro-muscular blocking agents (NMBAs) were used less frequently (11% versus 21%; p < 0.05), as were co-sedatives (7% versus 31%, p < 0.001); daily opioid doses were lower (720 [720-960] versus 1080 [720-1620] mg morphine equivalents, p < 0.001); and RASS scores indicated deeper levels of sedation (- 4.0 [- 4.0 to - 3.0] versus - 3.0 [- 3.6 to - 2.5]; p < 0.01).

Conclusion: Isoflurane provided sufficient sedation with less NMBAs, less polypharmacy and lower opioid doses compared to propofol. High doses of both drugs were needed in severely ill COVID-19 patients.

Abstract
The usefulness and safety of continuous glucose monitoring (CGM) systems in adult patients with severe coronavirus disease (COVID-19) have been reported. Using CGM might reduce the exposure patients and healthcare workers to COVID-19 and limit the use of personal protective equipment during the pandemic. CGM devices measure glucose in the subcutaneous interstitial fluid, but the accuracy of this technique has not been established in critically ill patients. The artificial pancreas, STG-55 (Nikkiso, Tokyo), is a closed-loop device that conducts continuous blood glucose monitoring using a peripheral vein. We used the STG-55 for glucose control in a 60-year-old woman with severe COVID-19 admitted to the intensive care unit. Due to severe respiratory failure, the patient was intubated, and extracorporeal membrane oxygenation was introduced. Because she had hyperglycemia despite high-dose intravenous insulin therapy, we decided to use STG-55 for glucose control. The STG-55 safely titrated the insulin infusion and monitored glucose levels. Fifty-six hours after adopting the STG-55, it was removed because the blood sampling failed. No episodes of hypoglycemia were observed despite deep sedation during this period. In conclusion, this case demonstrates the potential utility of an artificial pancreas in patients with severe COVID-19.

Abstract
Background: The COVID-19 pandemic has heavily impacted elective and emergency surgery around the world. We aimed to confirm the incidence of perioperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated mortality after surgery.

Methods: Analysis of routine electronic health record data from NHS hospitals in England. We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between January 1, 2020 and February 28, 2021. The exposure was SARS-CoV-2 infection defined by International Classification of Diseases (ICD)-10 codes. The primary outcome measure was 90 day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson Comorbidity Index, Index of Multiple Deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals (CI).

Results: We identified 2 666 978 patients undergoing surgery of whom 28 777 (1.1%) had SARS-CoV-2 infection. In total, 26 364 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 6153/28 777 [21.4%] vs no SARS-CoV-2: 20 211/2 638 201 [0.8%]; OR=5.7 [95% CI, 5.5-5.9]; P<0.001). Amongst patients undergoing elective surgery, 2412/1 857 586 (0.1%) had SARS-CoV-2, of whom 172/2412 (7.1%) died, compared with 1414/1 857 586 (0.1%) patients without SARS-CoV-2 (OR=25.8 [95% CI, 21.7-30.9]; P<0.001). Amongst patients undergoing emergency surgery, 22 918/582 292 (3.9%) patients had SARS-CoV-2, of whom 5752/22 918 (25.1%) died, compared with 18 060/559 374 (3.4%) patients without SARS-CoV-2 (OR=5.5 [95% CI, 5.3-5.7]; P<0.001).

Conclusions: The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.

Abstract
Background: A significant proportion of healthcare resource has been diverted to the care of those with COVID-19. This study reports the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Methods: We used hospital episode statistics for all adult patients undergoing surgery between January 1, 2020 and December 31, 2020 in England and Wales. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from 2016 to 2019 with the actual number of procedures in 2020. Using a linear regression model, we calculated the expected cumulative number of cancelled procedures by December 31, 2021.

Results: The total number of surgical procedures carried out in England and Wales in 2020 was 3 102 674 compared with the predicted number of 4 671 338 (95% confidence interval [CI]: 4 218 740-5 123 932). This represents a 33.6% reduction in the national volume of surgical activity. There were 763 730 emergency surgical procedures (13.4% reduction) compared with 2 338 944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1 568 664 (95% CI: 1 116 066-2 021 258). We estimate that this will increase to 2 358 420 (95% CI: 1 667 587-3 100 808) up to December 31, 2021.

Conclusions: The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in more than 1.5 million cancelled operations. This deficit will continue to grow in 2021.

Abstract
Background: The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19.

Methods: We did a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19-EAVE II-database comprising linked vaccination, primary care, real-time reverse transcription-PCR testing, and hospital admission patient records for 5·4 million people in Scotland (about 99% of the population) registered at 940 general practices. Individuals who had previously tested positive were excluded from the analysis. A time-dependent Cox model and Poisson regression models with inverse propensity weights were fitted to estimate effectiveness against COVID-19 hospital admission (defined as 1-adjusted rate ratio) following the first dose of vaccine.

Findings: Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated over the study period. The mean age of those vaccinated was 65·0 years (SD 16·2). The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85-94) for reduced COVID-19 hospital admission at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 88% (95% CI 75-94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72-89 at 28-34 days post-vaccination).

Interpretation: Mass roll-out of the first doses of the BNT162b2 mRNA and ChAdOx1 vaccines was associated with substantial reductions in the risk of hospital admission due to COVID-19 in Scotland. There remains the possibility that some of the observed effects might have been due to residual confounding.

Funding: UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK.

Abstract
COVID-19 poses an infectious risk to healthcare workers especially during airway management. We compared the impact of early versus late intubation on infection control and performance in a randomised in situ simulation, using fluorescent powder as a surrogate for contamination. Twenty anaesthetists and intensivists intubated a simulated patient with COVID-19. The primary outcome was the degree of contamination. The secondary outcomes included the use of bag-valve-mask ventilation, the incidence of manikin cough, intubation time, first attempt success and heart rate variability as a measure of stress. The contamination score was significantly increased in the late intubation group, mean (standard deviation, SD) 17.20 (6.17), 95% confidence intervals (CI) 12.80 to 21.62 versus the early intubation group, mean (SD) 9.90 (5.13), 95% CI 6.23 to 13.57, P = 0.005. The contamination score was increased after simulated cough occurrence (mean (SD) 18.0 (5.09) versus 5.50 (2.10) in those without cough; P<0.001), and when first attempt laryngoscopy failed (mean (SD) of 17.1 (6.41) versus 11.6 (6.20) P = 0.038). The incidence of bag-mask ventilation was higher in the late intubation group (80% versus 30%; P=0.035). There was no significant difference in intubation time, incidence of failed first attempt laryngoscopy or heart rate variability between the two groups. Late intubation in patients with COVID-19 may be associated with greater laryngoscopist contamination and potential aerosol-generating events compared with early intubation. There was no difference in performance measured by intubation time and incidence of first attempt success. Late intubation, especially when resources are limited, may be a valid approach. However, strict infection control and appropriate personal protective equipment usage is recommended in such cases.

Abstract
This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19-related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19-related ARDS, myocarditis, or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.

bstract
The current coronavirus disease of 2019 (COVID-19) pandemic has presented unique health challenges in the pediatric population. Compared to adults, the most significant change in viral disease manifestation is encompassed by the multisystem inflammatory syndrome in children (MIS-C). MIS-C is a new inflammatory syndrome which develops 2-4 weeks after COVID-19 exposure, with evidence suggesting it is a post-infectious immune reaction. We describe its epidemiology, pathophysiology, diagnosis (which varies based on definition used) and treatment options based on published recommendations. A systematic literature search we conducted through MEDLINE yielded 518 abstracts and identified five studies that reported more than 100 cases of MIS-C and their mortality. Most cases developed multiorgan dysfunction, including cardiovascular, dermatologic, neurological, renal, and respiratory issues, and required intensive care unit (ICU) admission. Many patients admitted to the ICU needed inotrope support and invasive mechanical ventilation, and the most severe cases required extracorporeal membrane oxygenation support. Most clinicians treated MIS-C with intravenous immunoglobulin, systemic steroids, and biological therapies. Overall mortality was low (2-3%) in all studies. Further research is needed to: understand if early intervention can prevent its progression; optimize its treatment; and improve outcomes of this new syndrome for the patients who develop MIS-C.

This prospective study investigated whether antibodies from SARS-CoV-2 immunization of nursing mothers transferred to infants as a potentially protective effect.

Abstract
Background: The Covid-19 pandemic is pushing health care systems to their limits. Dramatic reductions in the adult elective surgery are ubiquitous but corresponding changes in pediatric services are not well described. The Swedish Perioperative Registry (SPOR) contains data on all anesthetic procedures in Sweden, and therefore provides a unique opportunity to analyze the effect of the pandemic on the pediatric anesthesia capacity on a national level. We hypothesized that there would be a significant reduction in pediatric elective procedures. The aim was to determine the effects on pediatric surgical and anesthetic services during the first wave of the Covid-19 pandemic in Sweden.

Methods: For this retrospective registry cohort study, we extracted all procedures performed on patients < 18 years of age in 2020 and 2019. Week 12 to 26 of 2020 was defined as the first wave and data was analyzed according to level of care, type of surgery, procedure code and emergency or elective surgery.

Results: We found 7015 fewer procedures during the first wave epoch. Elective cases were reduced by 53.7% (p<0.001); emergency surgery was not significantly affected. During the peak of the first wave in April, there was a 72.8% reduction in elective cases; ENT/maxillofacial surgery showed the greatest reduction (86.7%). The surgical and anesthesia capacity recovered to near normal levels by the end of June 2020.

Conclusion: We conclude that the impact of Covid-19 on pediatric surgical procedures in Sweden during the first wave of the pandemic was dramatic but elective services were restored a few months after the peak.

Background Thrombo-inflammation may contribute to morbidity and mortality in Covid-19. We hypothesized that therapeutic-dose anticoagulation may improve outcomes in non-critically ill patients hospitalized for Covid-19. Methods In an open-label adaptive multiplatform randomized controlled trial, non-critically ill patients hospitalized for Covid-19, defined by the absence of critical care-level organ support at enrollment, were randomized to a pragmatic strategy of therapeutic-dose anticoagulation with heparin or usual care pharmacological thromboprophylaxis. The primary outcome combined survival to hospital discharge and days free of organ support through 21 days, which was evaluated with Bayesian statistical models according to baseline D-dimer. Results The trial was stopped when prespecified criteria for superiority were met for therapeutic-dose anticoagulation in groups defined by high (≥2-fold elevated) and low (<2-fold elevated) D-dimer. Among 2219 participants in the final analysis, the probability that therapeutic anticoagulation increased organ support-free days compared to thromboprophylaxis was 99.0% (adjusted odds ratio 1.29, 95% credible interval 1.04 to 1.61). The adjusted absolute increase in survival to hospital discharge without organ support with therapeutic-dose anticoagulation was 4.6% (95% credible interval 0.7 to 8.1). In the primary adaptive stopping groups, the final probabilities of superiority for therapeutic anticoagulation were 97.3% in the high D-dimer group and 92.9% in the low D-dimer group. Major bleeding occurred in 1.9% and 0.9% of participants randomized to therapeutic anticoagulation and thromboprophylaxis, respectively. Conclusions In non-critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increases the probability of survival to hospital discharge with reduced use of organ support.

Abstract
Importance: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021.

Objective: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt.

Design, setting, and participants: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021).

Exposures: Receipt of Ad26.COV2.S vaccine.

Main outcomes and measures: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians.

Results: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4).

Conclusions and relevance: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

Abstract
Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1-2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission.

Methods: In this phase 2a-b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)-negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 μg of recombinant spike protein with 50 μg of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection.

Results: Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV-positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, -0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups.

Conclusions: The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT04533399.).

Abstract
Background: Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy.

Methods: From December 14, 2020, to February 28, 2021, we used data from the "v-safe after vaccination health checker" surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons.

Results: A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases).

Conclusions: Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.

Abstract
Background: Coronavirus disease 19 (COVID-19) is associated with high perioperative morbidity and mortality among adults. The incidence and severity of anesthetic complications in children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We hypothesized that there would be an increased incidence of intra- and postoperative complications in children with SARS-CoV-2 infection as compared to those with negative testing.

Methods: We conducted a retrospective cohort study analyzing complications for children under 18 years of age who underwent anesthesia between April 28 and September 30, 2020 at a large, academic pediatric hospital. Each child with a positive SARS-CoV-2 test within the prior 10 days was matched to a patient with a negative SARS-CoV-2 test based on American Society of Anesthesiologists (ASA) classification, age, gender, and procedure. Children who were intubated prior to the procedure, underwent organ transplant surgery, or had severe COVID-19 were excluded. The primary outcome was the risk difference of a composite of intra- or postoperative respiratory complications in children positive for SARS-CoV-2 compared to those with negative testing. Secondarily, we used logistic regression to determine the odds ratio for respiratory complications before and after adjustment using propensity scores weighting to adjust for possible confounders. Other secondary outcomes included neurologic, cardiovascular, hematologic, and renal complications, unanticipated postoperative admission to the intensive care unit, length of hospital stay, and mortality.

Results: During the study period, 9,812 general anesthetics that had a preoperative SARS-CoV-2 test were identified. Sixty encounters occurred in patients who had positive SARS-CoV-2 testing preoperatively and 51 were included for analysis. The matched controls cohort included 99 encounters. A positive SARS-CoV-2 test was associated with a higher incidence of respiratory complications (11.8% vs 1.0%; risk difference 10.8%, 95% CI 1.6-19.8%; P = 0.003). After adjustment, the odds ratio for respiratory complications was 14.37 (95% CI 1.59-130.39; P = 0.02) for SARS-CoV-2 positive children as compared to controls. There was no occurrence of acute respiratory distress syndrome, postoperative pneumonia, or perioperative mortality in either group.

Conclusions: Pediatric patients with non-severe SARS-CoV-2 infection had higher rates of perianesthetic respiratory complications than matched controls with negative testing. However, severe morbidity was rare and there were no mortalities. The incidence of complications was similar to previously published rates of perianesthetic complications in the setting of an upper respiratory tract infection. This risk persisted after adjustment for preoperative upper respiratory symptoms, suggesting an increased risk in symptomatic or asymptomatic SARS-CoV-2 infection.

Pandemics like coronavirus disease (COVID-19) cause a significant strain on the trauma healthcare services which are already overworked especially in a resource limited country with a large population. Developing countries lack dedicated infectious disease hospitals and so a rapid transformation in the services and infrastructure of existing trauma centres is of paramount importance to curb the spread of the infectious disease and maintain the safety of the health care provider especially during aerosol generating procedures like airway management. This review article illustrates the principles adopted in transforming the trauma emergency in a level 1 trauma centre in lines with a functional infectious disease isolation unit. Installation of cubicles, limitation of aerosol generating procedures in the red area , routine use of videolaryngoscope, use of disposable airway intubation kits, regular hand hygiene, establishment of a two member airway management response team, formulation of separate treatment pathways and identification of physically distant areas for management of patients reported as negative or positive for COVID-19 and patients awaiting results of testing can be replicated to other centres of the developing world to protect the medical personnel and ensure timeliness of effective interventions during the outbreak of COVID-19. Preparedness of our center and effectiveness of the measures adopted is highlighted by the 270 successful intubations performed out of the 9000 admissions during the pandemic as per revised protocols with no shortage of airway equipment or personal protective equipment over a 6 month period. Occupational health and safety was maintained with only 5 anesthesiologists reporting a breach in personal protective equipment and only 3 developing COVID -19 with mild symptoms; 7.96% of work days were lost in a 6 month time span in view of sick leaves availed by all health care workers.

Abstract
Background: To allow better allocation of staff and resources, rapid response teams attending to acutely deteriorating or aggressive patients with suspected or confirmed COVID-19 infection were pre-warned with the announcement of 'Code-95' with calls.

Aim: To assess healthcare worker (HCW) perspectives on pre-warning rapid response calls (RRC) with 'Code-95' in announcements when attending to deteriorating or aggressive patients with suspected/confirmed COVID-19 infection.

Methods: Design: prospective cross-sectional single-centre survey of HCW over a 3-week period.

Setting: tertiary public hospital.

Participants: HCW caring for deteriorating or aggressive patients.

Main outcome measures: the primary outcome was to assess HCW perspectives in attending Code-95 calls. Secondary outcomes were to identify any differences related to craft group, age, experience or presence of comorbidities.

Results: A total of 297 responses was analysed; 86.7% of HCW (n = 257) attending Code-95 calls reported anxiety. Medical staff reported greater anxiety in comparison to nursing staff (93.8% vs 78.5%; P = 0.002). Efferent team reported higher anxiety in contrast to afferent team (92.6% vs 58.8%; P = 0.021). There was no significant difference in perceived anxiety based on age (≤40 vs >40 years of age), years of experience (≤5 vs >5 years), comorbidities or mental illness; 54% reported concerns about adequacy of infection-control policies and personal protective equipment; 45% were worried about inadequate training for responding to Code-95 calls.

Conclusions: Most surveyed HCW supported Code-95 announcements pre-warning them of potential COVID-19 exposure when attending a RRC. However, the majority of HCW reported anxiety when attending these calls. Medical and efferent team HCW perceived greater anxiety compared to nursing and afferent team HCW. The Code-95 system to pre-warn rapid response teams may be a useful addition to protecting HCW from infectious diseases, although broader implementation will require greater resourcing, training and support.

Abstract
Introduction: Critical illness from SARS-CoV-2 infection (COVID-19) is associated with a high burden of pulmonary embolism (PE) and thromboembolic events despite standard thromboprophylaxis. Available guidance is discordant, ranging from standard care to the use of therapeutic anticoagulation for enhanced thromboprophylaxis (ET). Local ET protocols have been empirically determined and are generally intermediate between standard prophylaxis and full anticoagulation. Concerns have been raised in regard to the potential risk of haemorrhage associated with therapeutic anticoagulation. This report describes the prevalence and safety of ET strategies in European Intensive Care Unit (ICUs) and their association with outcomes during the first wave of the COVID pandemic, with particular focus on haemorrhagic complications and ICU mortality.

Methods: Retrospective, observational, multi-centre study including adult critically ill COVID-19 patients. Anonymised data included demographics, clinical characteristics, thromboprophylaxis and/or anticoagulation treatment. Critical haemorrhage was defined as intracranial haemorrhage or bleeding requiring red blood cells transfusion. Survival was collected at ICU discharge. A multivariable mixed effects generalised linear model analysis matched for the propensity for receiving ET was constructed for both ICU mortality and critical haemorrhage.

Results: A total of 852 (79% male, age 66 [37-85] years) patients were included from 28 ICUs. Median body mass index and ICU length of stay were 27.7 (25.1-30.7) Kg/m2