Coronavirus/COVID-19 resources: Other resources

Link: Gale Health and Wellness database
Password: hwrc

The IARS has convened a Scientific Advisory Board to curate the thousands of emerging peer-reviewed journal articles on COVID-19 and highlight those of greatest value to anesthesiologists, intensivists, related specialists, and investigators. The articles featured here are the result of extensive review and discussion among our panel of experts. Featured articles are openly available on their respective journal websites. Journal CME is available for selected articles.

ASM has also committed to making all of its COVID19 and coronavirus related publications, and the available data supporting them, immediately accessible in PubMed Central (PMC) and other public repositories.

EVERYTHING WE KNOW ABOUT THE COVID-19 CORONAVIRUS

The resources on these pages are designed to help you have conversations about what matters most to your patients and their whānau. They are easily accessed, clear and consistent, and are based on sound principles, evidence and experience.

This dataset is intended to mobilize researchers to apply recent advances in natural language processing to generate new insights in support of the fight against this infectious disease. The corpus will be updated weekly as new research is published in peer-reviewed publications and archival services like bioRxiv, medRxiv, and others.

SSRN, Elsevier’s world-leading platform devoted to the rapid worldwide dissemination of early-stage research, is committed to making coronavirus-related research available immediately. Research on SSRN is free to download and upload. It is important to note that these papers have not benefited from the pivotal role of peer-review, which validates and improves the quality of final published journal articles.

Abstract
Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection.

Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation.

Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28-2·40], p<0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65-3·22], p<0·0001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (2·35 [1·57-3·53], p<0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01-2·39], p=0·046), emergency versus elective surgery (1·67 [1·06-2·63], p=0·026), and major versus minor surgery (1·52 [1·01-2·31], p=0·047).

Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery.

Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.

Abstract
Introduction: The global pandemic of coronavirus disease 2019 (COVID-19) has caused significant worldwide disruption. Although Australia and New Zealand have not been affected as much as some other countries, resuscitation may still pose a risk to health care workers and necessitates a change to our traditional approach. This consensus statement for adult cardiac arrest in the setting of COVID-19 has been produced by the Australasian College for Emergency Medicine (ACEM) and aligns with national and international recommendations.

Main recommendations: In a setting of low community transmission, most cardiac arrests are not due to COVID-19. Early defibrillation saves lives and is not considered an aerosol generating procedure. Compression-only cardiopulmonary resuscitation is thought to be a low risk procedure and can be safely initiated with the patient's mouth and nose covered. All other resuscitative procedures are considered aerosol generating and require the use of airborne personal protective equipment (PPE). It is important to balance the appropriateness of resuscitation against the risk of infection. Methods to reduce nosocomial transmission of COVID-19 include a physical barrier such as a towel or mask over the patient's mouth and nose, appropriate use of PPE, minimising the staff involved in resuscitation, and use of mechanical chest compression devices when available. If COVID-19 significantly affects hospital resource availability, the ethics of resource allocation must be considered.

Changes in management: The changes outlined in this document require a significant adaptation for many doctors, nurses and paramedics. It is critically important that all health care workers have regular PPE and advanced life support training, are able to access in situ simulation sessions, and receive extensive debriefing after actual resuscitations. This will ensure safe, timely and effective management of the patients with cardiac arrest in the COVID-19 era.

Summary
The Covid-19 pandemic is a source of anxiety for many clinicians. We studied the factors most related to front-line providers’ anxiety, and thereby developed effective responses, by surveying the clinical members of our department to better understand the effect of providing care during the pandemic on their self-reported levels of anxiety. While the strongest predictor of anxiety during the pandemic is a clinician's general tendency to feel anxious, another strong predictor is the culture of anxiety they observed in their colleagues around them related to the pandemic. Feeling like one’s work during the pandemic is valued by one’s immediate supervisor was associated with lower anxiety. Also, feeling like one has the necessary PPE to maintain safety and that one is in a psychologically safe environment were both related to a lower culture of anxiety, and as such indirectly related to lower state anxiety. In this paper, we provide a number of suggestions for reducing the anxiety felt during this anxiety-inducing crisis, as well as promoting the emotional well-being and effectiveness of our front-line providers in addressing the Covid-19 pandemic. While the study was conducted among anesthesia providers, we believe its results are applicable to any front-line providers working in the high-stress Covid-19 environment.

This document provides guidance on the use of personal protective equipment (PPE) for health care workers during the COVID-19 pandemic. The recommendations in this document were developed with advice from the National COVID-19 Clinical Evidence Taskforce Infection Prevention and Control Panel (IPC).

COVID-19 symptoms can sometimes persist for months. The virus can damage the lungs, heart and brain, which increases the risk of long-term health problems.

Case definition and testing guidance for health practitioners based on expert advice from the Ministry of Health's Technical Advisory Group.

Guidance on the use of personal protective equipment (PPE) in health and disability care settings.

The Therapeutic Goods Administration (TGA) is undertaking a post-market review of face masks included in the Australian Register of Therapeutic Goods (ARTG). This page introduces the review and provides guidance for suppliers and users of face masks. For outcomes of the review, including a list of cancelled ARTG entries and non-compliance notices, see Post-market review of face masks: Cancelled ARTG entries and Non-compliance notices .

Rapid evidence checks are based on a simplified review method and may not be entirely exhaustive, but aim to provide a balanced assessment of what is already known about a specific problem or issue.
This brief has not been peer-reviewed and should not be a substitute for individual clinical judgement, nor is it an endorsed position of NSW Health.

Healthcare associated infection is one of the most common adverse events in health care worldwide. Up to 10 percent of patients admitted to modern hospitals in the developed world acquire one or more infections.

Excerpt
The emergence of a novel human coronavirus in late 2002 alarmed populations across the globe, elicited a massive public health response, gave rise to a multinational research network, gripped the news media, wreaked political havoc in China, and struck a blow to the tourism and travel industries of several countries. By the time this coronavirus, labeled SCoV, apparently receded from human hosts in July 2003, nearly 10 percent of more than 8,000 individuals who fit the probable case definition had died of the disease now known as severe acute respiratory syndrome (SARS) (World Health Organization [WHO], 2003a). Analyses of this epidemic could lead to improvements in the global community’s preparedness for and response to future global outbreaks of infectious disease. For these reasons, the Institute of Medicine’s (IOM’s) Forum on Microbial Threats convened the workshop Learning from SARS: Preparing for the Next Disease Outbreak on September 30 and October 1, 2003. Participants discussed the emergence, detection, spread, and containment of SARS; political responses to the epidemic; its economic consequences; basic research on coronaviruses; preparations for a possible reemergence of SCoV; and lessons learned from the SARS epidemic that could shape responses to future microbial threats.

where there is sustained transmission of COVID-19, taking into account individual risk assessment for this new and emerging pathogen, NHS and independent sector

This is the first edition of guidance on infection prevention and control (IPC) strategies for use when infection with a novel coronavirus (2019-nCoV) is suspected. It has been adapted from WHO’s Infection prevention and control during health care for probable or confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection,1 based on current knowledge of the situation in China and other countries where cases were identified and experiences with severe acute respiratory syndrome (SARS)-CoV and MERS-CoV. 2

WHO will update these recommendations as new information becomes available.

This guidance is intended for healthcare workers (HCWs), healthcare managers and IPC teams at the facility level but it is also relevant for the national and district/provincial level. Full guidelines are available from WHO.2

------

1 Infection prevention and control during health care for probable or confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: interim guidance, updated October 2019. Geneva: World Health Organization; 2019 (WHO/MERS/IPC/15.1 Rev. 1; https://apps.who.int/iris/handle/10665/174652, accessed 17 January 2020).

2 Infection prevention and control of epidemic- and pandemic-prone acute respiratory infections in health care: WHO guidelines. Geneva: World Health Organization; 2014 (hhttp://apps.who.int/iris/10665/112656, accessed 17 January 2020).

Overview
This publication is an update to the World Health Organization (WHO) interim guidelines Infection prevention and control of epidemic- and pandemic-prone acute respiratory diseases in health care (2007). These updated guidelines incorporate the emergency guidance given in the WHO publication Infection prevention and control during health care for confirmed, probable, or suspected cases of pandemic (H1N1) 2009 virus infection and influenza-like illness (2009). The revision was informed by both evidence that has emerged since the first edition was published and the practical lessons learnt during the influenza pandemic in 2009.

The WHO guidelines Infection prevention and control of epidemic- and pandemic-prone acute respiratory infections in health care provide recommendations, best practices and principles for non-pharmacological aspects of infection prevention and control (IPC) for acute respiratory infections (ARI) in health care, with special emphasis on ARI that can present as epidemics or pandemics. The guidelines are intended to help policy-makers, administrators and health-care workers to prioritize effective IPC measures.

The document also provides guidance on the application of basic IPC precautions, such as Standard Precautions, and on the importance of maintaining appropriate IPC measures in routine circumstances to strengthen a healthcare facility’s capacity to put them into practice during outbreaks. These measures should therefore be part of the hospital’s permanent IPC strategy.

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 and 13 (7-22) days, respectively. Thromboembolic events were reported in 146 patients (17.1%), of those 78 (9.2%) were PE. ICU mortality occurred in 335/852 (39.3%) patients. ET was used in 274 (32.1%) patients, and it was independently associated with significant reduction in ICU mortality (log odds = 0.64 [95% CIs 0.18-1.1; p = 0.0069]) but not an increased risk of critical haemorrhage (log odds = 0.187 [95%CI - 0.591 to - 0.964; p = 0.64]).

Conclusions: In a cohort of critically ill patients with a high prevalence of thromboembolic events, ET was associated with reduced ICU mortality without an increased burden of haemorrhagic complications. This study suggests ET strategies are safe and associated with favourable outcomes. Whilst full anticoagulation has been questioned for prophylaxis in these patients, our results suggest that there may nevertheless be a role for enhanced / intermediate levels of prophylaxis. Clinical trials investigating causal relationship between intermediate thromboprophylaxis and clinical outcomes are urgently needed.

Abstract
Background: Tracheal intubation for patients with COVID-19 is required for invasive mechanical ventilation. The authors sought to describe practice for emergency intubation, estimate success rates and complications, and determine variation in practice and outcomes between high-income and low- and middle-income countries. The authors hypothesized that successful emergency airway management in patients with COVID-19 is associated with geographical and procedural factors.

Methods: The authors performed a prospective observational cohort study between March 23, 2020, and October 24, 2020, which included 4,476 episodes of emergency tracheal intubation performed by 1,722 clinicians from 607 institutions across 32 countries in patients with suspected or confirmed COVID-19 requiring mechanical ventilation. The authors investigated associations between intubation and operator characteristics, and the primary outcome of first-attempt success.

Results: Successful first-attempt tracheal intubation was achieved in 4,017/4,476 (89.7%) episodes, while 23 of 4,476 (0.5%) episodes required four or more attempts. Ten emergency surgical airways were reported-an approximate incidence of 1 in 450 (10 of 4,476). Failed intubation (defined as emergency surgical airway, four or more attempts, or a supraglottic airway as the final device) occurred in approximately 1 of 120 episodes (36 of 4,476). Successful first attempt was more likely during rapid sequence induction versus non-rapid sequence induction (adjusted odds ratio, 1.89 [95% CI, 1.49 to 2.39]; P < 0.001), when operators used powered air-purifying respirators versus nonpowered respirators (odds ratio, 1.60 [95% CI, 1.16 to 2.20]; P = 0.006), and when performed by operators with more COVID-19 intubations recorded (odds ratio, 1.03 for each additional previous intubation [95% CI, 1.01 to 1.06]; P = 0.015). Intubations performed in low- or middle-income countries were less likely to be successful at first attempt than in high-income countries (odds ratio, 0.57 [95% CI, 0.41 to 0.79]; P = 0.001).

Conclusions: The authors report rates of failed tracheal intubation and emergency surgical airway in patients with COVID-19 requiring emergency airway management, and identified factors associated with increased success. Risks of tracheal intubation failure and success should be considered when managing COVID-19.

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

Abstract
Introduction: Hospitalised patients with coronavirus disease 19 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require non-invasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes.

Methods: A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations.

Results: Based on the available evidence at the time of guideline development (February 20th, 2021) the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for IL-6 receptor antagonist monoclonal antibody treatment and high flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine and azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made.

Conclusion: The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.

Abstract
To date, COVID-19 has spread to more than 108 million people globally, with a death toll surpassing 2 1/2 million. With the United States Food and Drug Administration (FDA) approval of two highly effective COVID-19 vaccines from Pfizer-BioNtech and Moderna, we now have a novel approach to contain COVID-19 related morbidity and mortality. Chronic pain care has faced unprecedented challenges for patients and providers in this ever-changing climate. With the approval of COVID-19 vaccines, we now face questions relating to the potential effects of pain treatments utilizing steroids on vaccine efficacy. In this analysis, we address these issues and provide guidance for steroid therapies based on available data and expert recommendations.

Abstract
Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19.

Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone.

Design, setting, and participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200).

Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55).

Main outcomes and measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay.

Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99).

Conclusions and relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation.

Abstract
The COVID-19 disease, caused by Coronavirus SARS-CoV-2, often results in severe hypoxemia requiring airway management. Because SARS CoV-2 virus is spread via respiratory droplets, bag-mask ventilation, intubation, and extubation may place health care workers (HCW) at risk. While existing recommendations address airway management in patients with COVID-19, no guidance exists specifically for difficult airway management. Some strategies normally recommended for difficult airway management may not be ideal in the setting of COVID-19 infection. To address this issue the Society for Airway Management (SAM) created a task force to review existing literature and current Practice Guidelines for management of the difficult airway by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. SAM task force created recommendations for management of known or suspected difficult airway in the setting of known or suspected COVID-19 infection. The goal of the task force was to optimize successful airway management while minimizing exposure risk. Each member conducted a literature review on specific clinical practice section utilizing standard search engines (PubMed, Ovid, Google Scholar). Existing recommendations and evidence for difficult airway management in COVID-19 context were developed. Each specific recommendation was discussed among task force members and modified until unanimously approved by all task force members. Elements of AGREE Reporting Checklist for dissemination of clinical practice guidelines were utilized to develop this statement. Airway management in the COVID-19 patient increases HCW exposure risk. and difficult airway management often takes longer, may involve multiple procedures with aerosolization potential, strict adherence to personal protective equipment (PPE) protocols is mandatory to reduce risk to providers. When patient's airway risk assessment suggests awake tracheal intubation is an appropriate choice of technique, procedures that may cause increased aerosolization of secretions should be avoided. Optimal preoxygenation before induction with tight seal facemask may be performed to reduce risk of hypoxemia. Unless the patient is experiencing oxygen desaturation, positive pressure bag-mask ventilation after induction may be avoided to reduce aerosolization. For optimal intubating conditions, patients should be anesthetized with full muscle relaxation. Videolaryngoscopy is recommended as first-line strategy for airway management. If emergent invasive airway access is indicated, we recommend a surgical technique such as scalpel-bougie-tube, rather than an aerosolizing generating procedure, such as transtracheal jet ventilation. This statement represents recommendations by SAM task force for the difficult airway management of adults with COVID-19 with the goal to optimize successful airway management while minimizing the risk of clinician exposure.

Abstract
Objectives: This study retrospectively compares the effectiveness of methylprednisolone to dexamethasone in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) requiring intensive care.

Design: This is an institutional review board approved cohort study in patients with COVID-19 requiring intensive care unit (ICU) admission. Patients admitted and requiring oxygen supplementation were treated with no steroids, methylprednisolone, or dexamethasone.

Setting: This study takes place in the ICU's at a large, tertiary, public teaching hospital serving a primarily low-income community in urban Los Angeles.

Patients: All eligible patients admitted to the ICU for COVID-19 respiratory failure from March 1 to July 31, 2020 were included in this study.

Interventions: A total of 262 patients were grouped as receiving usual care (n = 75), methylprednisolone dosed at least at 1mg/kg/day for ≥ 3 days (n = 104), or dexamethasone dosed at least at 6 mg for ≥7 days (n = 83).

Measurements and main results: All-cause mortality within 50 days of initial corticosteroid treatment as compared to usual care was calculated. The mortality effect was then stratified based on levels of respiratory support received by the patient. In this cohort of 262 patients with severe COVID-19, all-cause mortalities in the usual care, methylprednisolone, and dexamethasone groups were 41.3%, 16.4% and 26.5% at 50 days (P < 0.01) respectively. In patients requiring mechanical ventilation, mortality was 42% lower in the methylprednisolone group than in the dexamethasone group (hazard ratio 0.48, 95% CI: 0.235-0.956, P = 0.0385).

Conclusions: In COVID-19 patients requiring mechanical ventilation, sufficiently dosed methylprednisolone can lead to a further decreased mortality as compared to dexamethasone.

Abstract
SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the largest pandemic facing humanity since the Spanish flu pandemic in the early twentieth century. Since there is no specific antiviral treatment, optimized support is the most relevant factor in the patient's prognosis. In the hospital setting, the identification of high-risk patients for clinical deterioration is essential to ensure access to intensive treatment of severe conditions in a timely manner. The initial management of hypoxemia includes conventional oxygen therapy, high-flow nasal canula oxygen, and non-invasive ventilation. For patients requiring invasive mechanical ventilation, lung-protective ventilation with low tidal volumes and plateau pressure is recommended. Cardiovascular complications are frequent and include myocardial injury, thrombotic events, myocarditis, and cardiogenic shock. Acute renal failure is a common complication and is a marker of poor prognosis, with significant impact in costs and resources allocation. Regarding promising therapies for COVID-19, the most promising drugs until now are remdesivir and corticosteroids although further studies may be needed to confirm their effectiveness. Other therapies such as, tocilizumab, anakinra, other anti-cytokine drugs, and heparin are being tested in clinical trials. Thousands of physicians are living a scenario that none of us have ever seen: demand for hospital exceed capacity in most countries. Until now, the certainty we have is that we should try to decrease the number of infected patients and that an optimized critical care support is the best strategy to improve patient's survival.

Abstract
Importance: Several jurisdictions in the United States have secured hotels to temporarily house people experiencing homelessness who require isolation or quarantine for confirmed or suspected coronavirus disease 2019 (COVID-19). To our knowledge, little is known about how these programs serve this vulnerable population outside the hospital setting.

Objective: To assess the safety of a hotel-based isolation and quarantine (I/Q) care system and its association with inpatient hospital capacity.

Design, setting, and participants: This retrospective cohort study of a hotel-based I/Q care system for homeless and unstably housed individuals in San Francisco, California, was conducted from March 19 to May 31, 2020. Individuals unable to safely isolate or quarantine at home with mild to moderate COVID-19, persons under investigation, or close contacts were referred from hospitals, outpatient settings, and public health surveillance to 5 I/Q hotels. Of 1009 I/Q hotel guests, 346 were transferred from a large county public hospital serving patients experiencing homelessness.

Exposure: A physician-supervised team of nurses and health workers provided around-the-clock support, including symptom monitoring, wellness checks, meals, harm-reduction services, and medications for opioid use disorder.

Main outcomes and measures: Characteristics of I/Q hotel guests, program retention, county hospital readmissions, and mean length of stay.

Results: Overall, the 1009 I/Q hotel guests had a median age of 44 years (interquartile range, 33-55 years), 756 (75%) were men, 454 (45%) were Latinx, and 501 (50%) were persons experiencing sheltered (n = 295) or unsheltered (n = 206) homelessness. Overall, 463 (46%) received a diagnosis of COVID-19; 303 of 907 (33%) had comorbid medical disorders, 225 of 907 (25%) had comorbid mental health disorders, and 236 of 907 (26%) had comorbid substance use disorders. A total of 776 of 955 guests (81%) completed their I/Q hotel stay; factors most strongly associated with premature discontinuation were unsheltered homelessness (adjusted odds ratio, 4.5; 95% CI, 2.3-8.6; P < .001) and quarantine status (adjusted odds ratio, 2.6; 95% CI, 1.5-4.6; P = .001). In total, 346 of 549 patients (63%) were transferred from the county hospital; of 113 ineligible referrals, 48 patients (42%) had behavioral health needs exceeding I/Q hotel capabilities. Thirteen of the 346 patients transferred from the county hospital (4%) were readmitted for worsening COVID-19. Overall, direct transfers to I/Q hotels from emergency and outpatient departments were associated with averting many hospital admissions. There was a nonsignificant decrease in the mean hospital length of stay for inpatients with confirmed or suspected COVID-19 from 5.5 to 2.7 days from March to May 2020 (P = .11).

Conclusions and relevance: To support persons experiencing homelessness during the COVID-19 pandemic, San Francisco rapidly and safely scaled a hotel-based model of I/Q that was associated with reduced strain on inpatient capacity. Strategies to improve guest retention and address behavioral health needs not met in hotel settings are intervention priorities.

Abstract
Background: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU.

Methods: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility.

Results: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning.

Conclusion: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.

Abstract
The current COVID-19 pandemic has had a global impact on vaccination rates. Delays in routine healthcare and immunization have led to a rise in concerns about resurgence of vaccine-preventable diseases around the world. With the release and distribution of COVID-19 vaccines, plans to improve immunization rates need to be explored and implemented across disciplines. One approach would be the consideration of perioperative vaccinations; however, the effects of anesthesia and surgery on the immune response and complications associated with vaccination during the perioperative period are still poorly understood, and opinions are divided. To ascertain the value of a perioperative vaccination program, it is important to understand the basics of immunization and common vaccinations; the potential vaccine complications in the pediatric cohort; the implications of anesthesia and surgery on the immune response; and current recommendations. In addition, we believe it is important to discuss the logistics and feasibility of coordinating perioperative immunization should this become a regular opportunity.

Abstract
On Mar 11, 2020, the World Health Organization declared coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a pandemic. Because COVID-19 has a pre-symptomatic period of up to 2 weeks, SARS-CoV-2 infection has continued to spread. Some individuals with SARS-CoV-2 infection have a severe clinical course, while most individuals have mild or moderate symptoms. Because SARS-CoV-2 is transmitted via droplets and secretions, anesthesiologists have higher risks of infection, especially during airway management. Therefore, general anesthesia requiring airway management can be a challenging procedure for anesthesiologists. During the pandemic, many elective surgeries have been postponed or cancelled in most affected countries. Recently, the number of elective surgeries is gradually recovering from the effect of the COVID-19 pandemic, and hence, safe clinical practice and protocols to prevent SARS-CoV-2 transmission to medical staff should be established. This mini-review focuses on the preoperative assessment and decision with regard to scheduling surgery in elective and emergency cases during the COVID-19 pandemic. A standardized questionnaire and algorithm regarding COVID-19 should be used to assess surgical patients preoperatively as it increases the reproducibility and accuracy of the decision whether to proceed with surgery.

Abstract
Purpose: Coronavirus disease 2019 (COVID-19) has placed a great burden on critical care services worldwide. Data regarding critically ill COVID-19 patients and their demand of critical care services outside of initial COVID-19 epicenters are lacking. This study described clinical characteristics and outcomes of critically ill COVID-19 patients and the capacity of a COVID-19-dedicated intensive care unit (ICU) in Kobe, Japan.

Methods: This retrospective observational study included critically ill COVID-19 patients admitted to a 14-bed COVID-19-dedicated ICU in Kobe between March 3, 2020 and June 21, 2020. Clinical and daily ICU occupancy data were obtained from electrical medical records. The last follow-up day was June 28, 2020.

Results: Of 32 patients included, the median hospital follow-up period was 27 (interquartile range 19-50) days. The median age was 68 (57-76) years; 23 (72%) were men and 25 (78%) had at least one comorbidity. Nineteen (59%) patients received invasive mechanical ventilation for a median duration of 14 (8-27) days. Until all patients were discharged from the ICU on June 5, 2020, the median daily ICU occupancy was 50% (36-71%). As of June 28, 2020, six (19%) died during hospitalization. Of 26 (81%) survivors, 23 (72%) were discharged from the hospital and three (9%) remained in the hospital.

Conclusion: During the first months of the outbreak in Kobe, most critically ill patients were men aged ≥ 60 years with at least one comorbidity and on mechanical ventilation; the ICU capacity was not strained, and the case-fatality rate was 19%.

Abstract
Bacterial and fungal co-infection has been reported in patients with COVID-19, but there is limited experience on these infections in critically ill patients. The objective of this study was to assess the characteristics and ouctome of ICU-acquired infections in COVID-19 patients. We conducted a retrospective single-centre, case-control study including 140 patients with severe COVID-19 admitted to the ICU between March and May 2020. We evaluated the epidemiological, clinical, and microbiological features, and outcome of ICU-acquired infections. Fifty-seven patients (40.7%) developed a bacterial or fungal nosocomial infection during ICU stay. Infection occurred after a median of 9 days (IQR 5-11) of admission and was significantly associated with the APACHE II score (p = 0.02). There were 91 episodes of infection: primary (31%) and catheter-related (25%) bloodstream infections were the most frequent, followed by pneumonia (23%), tracheobronchitis (10%), and urinary tract infection (8%) that were produced by a wide spectrum of Gram-positive (55%) and Gram-negative bacteria (30%) as well as fungi (15%). In 60% of cases, infection was associated with septic shock and a significant increase in SOFA score. Overall ICU mortality was 36% (51/140). Infection was significantly associated with death (OR 2.7, 95% CI 1.2-5.9, p = 0.015) and a longer ICU stay (p < 0.001). Bacterial and fungal nosocomial infection is a common complication of ICU admission in patients with COVID-19. It usually presents as a severe form of infection, and it is associated with a high mortality and longer course of ICU stay.

Abstract
Rationale: Treatment with non-invasive ventilation (NIV) in COVID-19 is frequent. Shortage of Intensive care unit (ICU) beds led clinicians to deliver NIV also outside intensive care units (ICUs). Data about the use of NIV in COVID-19 is limited.

Objective: To describe the prevalence and clinical characteristics of patients with COVID-19 treated with NIV outside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death).

Methods: In this prospective single day observational study, we enrolled adult COVID-19 patients, treated with NIV outside the ICU from thirty-one hospitals in Lombardy, Italy.

Results: We collected data on demographic, clinical characteristics, ventilatory management and patients' outcome. Of 8753 COVID-19 patients present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. 778/909 (85%) patients were treated with Continuous Positive Airway Pressure (CPAP), delivered by helmet in 617 (68%). NIV failed in 300 patients (37.6%), while 498 (62.4%) were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with a PaO2/FiO2 ratio < 150 mmHg. Higher C-reactive protein, lower PaO2/FiO2, and platelet counts were independently associated with increased risk of NIV failure.

Conclusions: The use of NIV outside the ICUs, in COVID-19 was common, with a predominant use of helmet CPAP, with a rate of success greater than 60% and close to 75% in full treatment patients. C-reactive protein, PaO2/FiO2, platelet counts were independently associated with increased risk of NIV failure. Clinical trial registered with ClinicalTrials.gov (NCT04382235).

Abstract
Background: Critically ill coronavirus disease 2019 (COVID-19) patients present with a hypercoagulable state with high rates of macrovascular and microvascular thrombosis, for which hypofibrinolysis might be an important contributing factor.

Methods: We retrospectively analysed 20 critically ill COVID-19 patients at Innsbruck Medical University Hospital whose coagulation function was tested with ClotPro® and compared with that of 60 healthy individuals at Augsburg University Clinic. ClotPro is a viscoelastic whole blood coagulation testing device. It includes the TPA test, which uses tissue factor (TF)-activated whole blood with added recombinant tissue-derived plasminogen activator (r-tPA) to induce fibrinolysis. For this purpose, the lysis time (LT) is measured as the time from when maximum clot firmness (MCF) is reached until MCF falls by 50%. We compared COVID-19 patients with prolonged LT in the TPA test and those with normal LT.

Results: Critically ill COVID-19 patients showed hypercoagulability in ClotPro assays. MCF was higher in the EX test (TF-activated assay), IN test (ellagic acid-activated assay), and FIB test (functional fibrinogen assay) with decreased maximum lysis (ML) in the EX test (hypofibrinolysis) and highly prolonged TPA test LT (decreased fibrinolytic response), as compared with healthy persons. COVID-19 patients with decreased fibrinolytic response showed higher fibrinogen levels, higher thrombocyte count, higher C-reactive protein levels, and decreased ML in the EX test and IN test.

Conclusion: Critically ill COVID-19 patients have impaired fibrinolysis. This hypofibrinolytic state could be at least partially dependent on a decreased fibrinolytic response.

Abstract
Infection with SARS-CoV-2 has become pandemic and the duration of protective immunity to the virus is unknown. Cases of persons reinfected with the virus are being reported with increasing frequency. At present it is unclear how common reinfection with SARS-CoV-2 is and how long serum antibodies and virus-specific T cells persist after infection. For many other respiratory virus infections, including influenza and the seasonal coronaviruses that cause colds, serum antibodies persist for only months to a few years and reinfections are very common. Here we review what is known about the duration of immunity and reinfection with coronaviruses, including SARS-CoV-2, and well as the duration of immunity to other viruses and virus vaccines. These findings have implications for the need of continued protective measures and for vaccines for persons previously infected with SARS-CoV-2.

Abstract
Background: The hemostatic balance in patients with coronavirus disease 2019 (COVID-19) seems to be shifted toward a hypercoagulable state. The aim of the current study was to assess the associated coagulation alterations by point-of-care-diagnostics, focusing on details of clot formation and lysis in these severely affected patients.

Methods: The authors' prospective monocentric observational study included critically ill patients diagnosed with COVID-19. Demographics and biochemical data were recorded. To assess the comprehensive hemostatic profile of this patient population, aggregometric (Multiplate) and viscoelastometric (CloPro) measures were performed in the intensive care unit of a university hospital at a single occasion. Coagulation analysis and assessment of coagulation factors were performed. Data were compared to healthy controls.

Results: In total, 27 patients (21 male; mean age, 60 yr) were included. Impedance aggregometry displayed no greater platelet aggregability in COVID-19 in comparison with healthy controls (area under the receiver operating characteristics curve [AUC] in adenosine diphosphate test, 68 ± 37 U vs. 91 ± 29 U [Hodges-Lehmann 95% CI, -27 (-48 to -1); P = 0.043]; AUC in arachidonic acid test, 102 ± 54 U vs. 115 ± 26 U [Hodges-Lehmann 95% CI, -21 (-51 to 21); P = 0.374]; AUC in thrombin receptor activating peptide 6 test, 114 ± 61 U vs. 144 ± 31 U [Hodges-Lehmann 95% CI, -31 (-69 to -7); P = 0.113]). Comparing the thromboelastometric results of COVID-19 patients to healthy controls, the authors observed significant differences in maximum clot firmness in fibrin contribution to maximum clot firmness assay (37 ± 11 mm vs. 15 ± 4 mm [Hodges-Lehmann 95% CI, 21 (17 to 26); P < 0.001]) and lysis time in extrinsic activation and activation of fibrinolysis by tissue plasminogen activator assay (530 ± 327 s vs. 211 ± 80 s [Hodges-Lehmann 95% CI, 238 (160 to 326); P < 0.001]).

Conclusions: Thromboelastometry in COVID-19 patients revealed greater fibrinolysis resistance. The authors did not find a greater platelet aggregability based on impedance aggregometric tests. These findings may contribute to our understanding of the hypercoagulable state of critically ill patients with COVID-19.

Many patients with coronavirus disease (COVID-19) will develop acute respiratory distress syndrome (ARDS). Prone positioning is an important non-pharmacologic strategy that should be considered for all invasively ventilated patients with moderate to severe ARDS (including those with COVID-19). Prone positioning offers several physiologic and clinical benefits, including improving hypoxemia, matching ventilation with perfusion, reducing regional hyperinflation, and improving survival. To safely offer prone positioning, appropriate training, simulation, and health system planning should be undertaken. In this review, we offer ten tips, based on the Alberta provincial prone positioning strategy during COVID-19, to safely implement and improve the appropriate use of prone positioning. We provide special considerations for its use during the COVID-19 pandemic or future respiratory pandemics.

Abstract
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is highly contagious. To protect healthcare workers from infection during airway management, some expert recommendations and guidelines recommended wearing P2/N95 masks, goggles or glasses, glove, face-shields, and gowns as standard personal protective equipment (PPE). Nevertheless, several simulation studies have suggested that the standard PPE may not fully protect healthcare workers. Dr. Hsien Yung Lai introduced an acrylic box ("aerosol box") as a part of PPE during airway management. Since then, several companies and healthcare workers have made their own modified devices ("aerosol containment device"), and the use of such a device has spread worldwide, without being formally assessed for its effectiveness, efficacy and safety. Several simulation studies have indicated that "aerosol containment device" would make tracheal intubation more difficult. In addition, the device would prevent the spread of droplets from a patient, but may increase the risk of healthcare workers being exposed to a higher concentration of viral aerosols. Therefore, the current state of knowledge indicates that an "aerosol containment device" without vacuum mechanism has only limited efficacy in protecting healthcare workers from viral transmission.

Abstract
The last two decades have seen an increasing frequency of zoonotic origin viral diseases including Severe Acute Respiratory Syndrome Coronaviruses, SARS-CoV-2. Respiratory component of the infectious disease program against SARS-CoV-2 incorporates use of protective airborne respiratory equipment. In this narrative review, we explore the features of Powered Air Purifying Respirators (PAPR) as well as logistical and evidence based advantages and disadvantages. Simulation study findings support increased heat tolerance and wearer comfort with a PAPR. Although PAPRs have been recommended for high risk procedures on suspected or confirmed COVID-19 patients, this recommendation remains controversial due to lack of evidence. International regulatory bodies do not mandate the use of PAPR for high risk aerosol generating procedures in patients with SARS-CoV-2. Current reports of the choice of protective respiratory technology during the SARS-CoV-2 pandemic are disparate. Patterns of use appear to be related to geographical locations. Field observational studies do not indicate a difference in healthcare worker infection utilizing PAPR devices versus other compliant respiratory equipment in healthcare workers performing AGPs. Whether a higher PAPR filtration factor translates to decreased infection rates of HCWs remains to be elucidated. Utilization of PAPR with high filtration efficiency may represent an example of "precautionary principle". Action taken to reduce risk may be guided by logistical advantages of the PAPR system, rather than high level evidence.

Abstract
The COVID-19 pandemic has altered approaches to anesthesiology education by shifting educational paradigms. This vision paper discusses pre-COVID-19 educational methodologies and best evidence, adaptations required under COVID-19 and evidence for these modifications and suggests future directions for anesthesiology education.Learning management systems provide structure to online learning. They have been increasingly utilized to improve access to didactic materials asynchronously. Despite some historic reservations, the pandemic has necessitated a rapid uptake across programs. Commercially available systems offer a wide range of peer-reviewed curricular options.The flipped classroom promotes learning foundational knowledge prior to teaching sessions with a focus on application during structured didactics. There is growing evidence that this approach is preferred by learners and may increase knowledge gain. The flipped classroom works well with learning management systems to disseminate focused pre-class work. Care must be taken to keep virtual sessions interactive.Simulation, already used in anesthesiology, has been critical in preparation for the care of COVID-19 patients. Multidisciplinary, in-situ simulations allow for rapid dissemination of new team workflows. Physical distancing and reduced availability of providers have required more sessions. Early pandemic decreases in operating volumes have allowed for this; future planning will have to incorporate smaller groups, sanitizing of equipment, and attention to use of personal protective equipment.Effective technical skills training requires instruction to mastery levels, use of deliberate practice, and high-quality feedback. Reduced sizes of skills training workshops and approaches for feedback that are not in-person will be required.Mock oral and OSCE examinations allow for training and assessment of competencies often not addressed otherwise. They provide formative and summative data and objective measurements of ACGME Milestones. They also allow for preparation for the ABA APPLIED examination. Adaptations to teleconferencing or videoconferencing can allow for continued use.Benefits of teaching in this new era include enhanced availability of asynchronous learning and opportunities to apply universal, expert-driven curricula. Burdens include decreased social interactions and potential need for an increased amount of smaller, live sessions.Acquiring learning management systems and holding more frequent simulation and skills sessions with fewer learners may increase cost. With the increasing dependency on multimedia and technology support for teaching and learning, one important focus of educational research is on the development and evaluation of strategies that reduce extraneous processing and manage essential and generative processing in virtual learning environments. Collaboration to identify and implement best practices has the potential to improve education for all learners.

Abstract
Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over four million people worldwide. There are multiple reports of prolonged viral shedding in people infected with SARS-CoV-2 but the presence of viral RNA on a test does not necessarily correlate with infectivity. The duration of quarantine required after clinical recovery to definitively prevent transmission is therefore uncertain. In addition, asymptomatic and presymptomatic transmission may occur, and infectivity may be highest early after onset of symptoms, meaning that contact tracing, isolation of exposed individuals and social distancing are essential public health measures to prevent further spread. This review aimed to summarise the evidence around viral shedding vs infectivity of SARS-CoV-2.

Abstract
Background: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major global public health issue. SARS-CoV-2 infection is confirmed by the detection of viral RNA using reverse transcription polymerase chain reaction (RT-PCR). Prolonged viral shedding has been reported in patients with SARS-CoV-2 infection, but the presence of viral RNA does not always correlate with infectivity. Therefore, the present study aimed to confirm the presence of viable virus in asymptomatic or mildly symptomatic patients in the later phase of the disease, more than two weeks after diagnosis.

Method: Asymptomatic or mildly symptomatic COVID-19 patients who had been diagnosed with the disease at least two weeks previously and admitted to a community treatment center (CTC) from 15 March to 10 April 2020 were enrolled in this study. Nasopharyngeal and salivary swab specimens were collected from each patient. Using these specimens, RT-PCR assay and viral culture were performed.

Result: In total, 48 patients were enrolled in this study. There were no significant differences in baseline characteristics between the asymptomatic and mildly symptomatic patient groups. RT-PCR assay and viral culture of SARS-CoV-2 were performed using nasopharyngeal and salivary swabs. The results of RT-PCR performed using salivary swab specimens, in terms of cycle threshold (Ct) values, were similar to those of RT-PCR using nasopharyngeal swab specimens. In addition, no viable virus could be cultured from swab specimens collected from the late-phase COVID-19 patients with prolonged viral RNA shedding.

Conclusions: In conclusion, our study suggests that even if viral shedding is sustained in asymptomatic or mildly symptomatic patients with later phase of COVID-19, it can be expected that the transmission risk of the virus is low. In addition, saliva can be used as a reliable specimen for the diagnosis of SARS-CoV-2 infection.

Abstract
With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medical providers should take care to prevent the transmission of SARS-CoV-2 in hospitals including super-spreading. Understanding super-spreading would be useful to reduce future transmission. Some publications have shown clusters of SARS-CoV-2 such as at choir practice and in hospitals. Aerosol can be considered as a primary transmission route. As SARS-CoV-2 stability in aerosol is similar to SARS-CoV-1 with the higher reproductive number of SARS-CoV-2 than SARS-CoV-1, another factor causes rapidly spread-out, e.g. a higher discharge ratio from infected people or a higher viral intake ratio to human body. A basic research suggests higher infectivity of SARS-CoV-2 in the nose than the peripheral lung. Universal masking would be important to prevent the exposure of SARS-CoV-2 droplet to uninfected people. To detect SARS-CoV-2 infection, laboratory tests such as reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays are applied. Although sensitivity and specificity are provided for the ability of the test, positive or negative prediction values are useful to indicate the possiblity of infection or non-infection in clinical practice. We have to realize that the positive and negative prediction values depend on the sensitivity, specificity, and infection probability of the patient.

Abstract
Background: The role of repeated prone positioning in intubated subjects with acute respiratory distress syndrome caused by COVID-19 remains unclear.

Methods: We conducted a retrospective observational cohort study of critically ill intubated patients with COVID-19 who were placed in the prone position between March 18, 2020 and March 31, 2020. Exclusion criteria were pregnancy, reintubation, and previous prone positioning at a referring hospital. Patients were followed up until hospital discharge. The primary outcome was oxygenation assessed by partial pressure of oxygen/fraction of inspired oxygen ratio (Pao2/Fio2) ratio. A positive response to proning was defined as an increase in Pao2/Fio2 ratio ≥20%. Treatment failure of prone positioning was defined as death or requirement for extracorporeal membrane oxygenation (ECMO).

Results: Forty-two subjects (29 males; age: 59 [52-69] yr) were eligible for analysis. Nine subjects were placed in the prone position only once, with 25 requiring prone positioning on three or more occasions. A total of 31/42 (74%) subjects survived to discharge, with five requiring ECMO; 11/42 (26%) subjects died. After the first prone positioning session, Pao2/Fio2 (mean (standard deviation)) ratio increased from 17.9 kPa (7.2) to 28.2 kPa (12.2) (P<0.01). After the initial prone positioning session, subjects who were discharged from hospital were more likely to have an improvement in Pao2/Fio2 ratio ≥20%, compared with those requiring ECMO or who died.

Conclusion: Patients with COVID-19 acute respiratory distress syndrome frequently responded to initial prone positioning with improved oxygenation. Subsequent prone positioning in subjects discharged from hospital was associated with greater improvements in oxygenation.

Abstract
Background: In face of the Coronavirus Disease (COVID)-19 pandemic, best practice for mechanical ventilation in COVID-19 associated Acute Respiratory Distress Syndrome (ARDS) is intensely debated. Specifically, the rationale for high positive end-expiratory pressure (PEEP) and prone positioning in early COVID-19 ARDS has been questioned.

Methods: The first 23 consecutive patients with COVID-19 associated respiratory failure transferred to a single ICU were assessed. Eight were excluded: five were not invasively ventilated and three received veno-venous ECMO support. The remaining 15 were assessed over the first 15 days of mechanical ventilation. Best PEEP was defined by maximal oxygenation and was determined by structured decremental PEEP trials comprising the monitoring of oxygenation, airway pressures and trans-pulmonary pressures. In nine patients the impact of prone positioning on oxygenation was investigated. Additionally, the effects of high PEEP and prone positioning on pulmonary opacities in serial chest x-rays were determined by applying a semiquantitative scoring-system. This investigation is part of the prospective observational PA-COVID-19 study.

Findings: Patients responded to initiation of invasive high PEEP ventilation with markedly improved oxygenation, which was accompanied by reduced pulmonary opacities within 6 h of mechanical ventilation. Decremental PEEP trials confirmed the need for high PEEP (17.9 (SD ± 3.9) mbar) for optimal oxygenation, while driving pressures remained low. Prone positioning substantially increased oxygenation (p<0.01).

Interpretation: In early COVID-19 ARDS, substantial PEEP values were required for optimizing oxygenation. Pulmonary opacities resolved during mechanical ventilation with high PEEP suggesting recruitment of lung volume.

Funding: German Research Foundation, German Federal Ministry of Education and Research.

Abstract
Background: Mortality rates in COVID-19 patients in need of mechanical ventilation are high, with wide variations between countries. Most studies were retrospective, and results may not be generalizable due to differences in demographics, healthcare organization and surge capacity. We present a cohort of mechanically ventilated COVID-19 patients from a resource-rich, publicly financed healthcare system.

Methods: Prospective study from a tertiary hospital. Consecutive SARS-CoV-2 positive adult patients admitted to the ICU for mechanical ventilation 10.03.20-04.05.20 were included. Triage and treatment were protocolized. High-dose dalteparin was adjusted by D-dimer. Demographics, treatments, and high-resolution physiological variables were collected. Outcomes were 30-day and hospital mortality. Data are medians(quartiles).

Results: Of the 1484 persons in the hospital catchment area testing positive for SARS-CoV-2, 201 (13.5%) were hospitalized. Thirty-eight (19%) patients were mechanically ventilated, of whom five (13%) died. Of 163 patients treated with supplemental oxygen, eight (5%) died. In ventilated patients (75% males, age 61 (53-70) years), severe, moderate, and mild ARDS was present in 25%, 70%, and 5%. Tidal volume ≤8 mL/kg ideal bodyweight was achieved in 34 (94%) of patients. Proning and neuromuscular blockers were used in 19 (54%) and 20 (61%). Duration of ventilation was 12 days (8-23). D-dimer peaked 3.8 mg/L (2.1-5.3), maximum dalteparin dose was 15,000 IU/24h (10,000-15,000). Despite organizational changes a high degree of adherence to treatment protocols was achieved.

Conclusion: In a prospective cohort study of mechanically ventilated COVID-19 patients treated in a resource-rich, publicly financed healthcare system, mortality was considerably lower than previously reported in retrospective studies.

Abstract
Background:
Covid-19 emerged as a public health crisis that disrupted normal patterns of health care in the New York City metropolitan area. In preparation for a large influx of critically ill patients, operating rooms (ORs) at NewYork-Presbyterian Hospital/Columbia University Irving Medical Center (NYP-Columbia) were converted into a novel intensive care unit area, the ORICU.

Methods:
23 ORs were converted into an 82-bed ORICU. Adaptations to the OR environment permitted the delivery of standard critical care therapies. Non-intensive-care-trained staff were educated on the basics of critical care and deployed in a hybrid staffing model. Anesthesia machines were repurposed as critical care ventilators, with accommodations to ensure reliable function and patient safety. To compare ORICU survivorship to outcomes in more traditional environments, we performed Kaplan-Meier survival analysis of all patients cared for in the ORICU, censoring data at the time of ORICU closure. We hypothesized that age, gender, and obesity may have influenced the risk of death. Thus, we estimated hazard ratios for death using Cox proportional hazard regression models with age, gender, and body mass index (BMI) as covariables and, separately, using older age (65 years and older) adjusted for gender and BMI.

Results:
The ORICU cared for 133 patients from March 24 – May 14, 2020. Patients were transferred to the ORICU from other ICUs, inpatient wards, the Emergency Department, and other institutions. Patients remained in the ORICU until either transfer to another unit or death. As the hospital patient load decreased, patients were transferred out of the ORICU. This process was completed on May 14, 2020. At time of data censoring, 55 (41.4%) of patients had died. The estimated probability of survival 30 days after admission was 0.61 (95% CI 0.52 – 0.69). Age was significantly associated with increased risk of mortality (HR = 1.05, 95% CI 1.03 – 1.08, p < 0.001 for a 1 year increase in age). Patients who were 65 years or older were an estimated 3.17 times more likely to die than younger patients (95% CI 1.78 – 5.63, p < 0.001) when adjusting for gender and BMI.

Conclusions:
A large number of critically ill Covid-19 patients were cared for in the ORICU, which substantially increased ICU capacity at NYP-Columbia. The estimated ORICU survival rate at 30 days was comparable to other reported rates, suggesting this was an effective approach to manage the influx of critically ill Covid-19 patients during a time of crisis.

Abstract
Defining the duration of infectivity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has major implications for public health and infection control practice in healthcare facilities. Early in the pandemic, most hospitals required 2 negative RT-PCR tests before discontinuing isolation in patients with Covid-19. Many patients, however, have persistently positive RT-PCR tests for weeks to months following clinical recovery, and multiple studies now indicate that these generally do not reflect replication-competent virus. SARS-CoV-2 appears to be most contagious around the time of symptom onset, and infectivity rapidly decreases thereafter to near-zero after about 10 days in mild-moderately ill patients and 15 days in severely-critically ill and immunocompromised patients. The longest interval associated with replication-competent virus thus far is 20 days from symptom onset. This review summarizes evidence-to-date on the duration of infectivity of SARS-CoV-2, and how this has informed evolving public health recommendations on when it is safe to discontinue isolation precautions.

Abstract
Background: Current guidelines for perioperative management of coronavirus disease 19 (COVID-19) are mainly based on extrapolated evidence or expert opinion. We aimed to systematically investigate how COVID-19 affects perioperative management and clinical outcomes, to develop evidence-based guidelines.

Methods: First, we conducted a rapid literature review in EMBASE, MEDLINE, PubMed, Scopus, and Web of Science (January 1 to July 1, 2020), using a predefined protocol. Second, we performed a retrospective cohort analysis of 166 women undergoing Caesarean section at Tongji Hospital, Wuhan during the COVID-19 pandemic. Demographic, imaging, laboratory, and clinical data were obtained from electronic medical records.

Results: The review identified 26 studies, mainly case reports/series. One large cohort reported greater mortality in elective surgery patients diagnosed after, rather than before surgery. Higher 30 day mortality was associated with emergency surgery, major surgery, poorer preoperative condition and surgery for malignancy. Regional anaesthesia was favoured in most studies and personal protective equipment (PPE) was generally used by healthcare workers (HCWs), but its use was poorly described for patients. In the retrospective cohort study, duration of surgery, oxygen therapy and hospital stay were longer in suspected or confirmed patients than negative patients, but there were no differences in neonatal outcomes. None of the 262 participating HCWs was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when using level 3 PPE perioperatively.

Conclusions: When COVID-19 is suspected, testing should be considered before non-urgent surgery. Until further evidence is available, HCWs should use level 3 PPE perioperatively for suspected or confirmed patients, but research is needed on its timing and specifications. Further research must examine longer-term outcomes.

Clinical trial registration: CRD42020182891 (PROSPERO).

Abstract
Background: Disease severity in coronavirus disease 2019 (COVID-19) may be associated with inoculation dose. This has triggered interest in intubation barrier devices to block droplet exposure; however, aerosol protection with these devices is not known. This study hypothesized that barrier devices reduce aerosol outside of the barrier.

Methods: Aerosol containment in closed, semiclosed, semiopen, and open barrier devices was investigated: (1) "glove box" sealed with gloves and caudal drape, (2) "drape tent" with a drape placed over a frame, (3) "slit box" with armholes and caudal end covered by vinyl slit diaphragms, (4) original "aerosol box," (5) collapsible "interlocking box," (6) "simple drape" over the patient, and (7) "no barrier." Containment was investigated by (1) vapor instillation at manikin's right arm with video-assisted visual evaluation and (2) submicrometer ammonium sulfate aerosol particles ejected through the manikin's mouth with ventilation and coughs. Samples were taken from standardized locations inside and around the barriers using a particle counter and a mass spectrometer. Aerosol evacuation from the devices was measured using standard hospital suction, a surgical smoke evacuator, and a Shop-Vac.

Results: Vapor experiments demonstrated leakage via arm holes and edges. Only closed and semiclosed devices and the aerosol box reduced aerosol particle counts (median [25th, 75th percentile]) at the operator's mouth compared to no barrier (combined median 29 [-11, 56], n = 5 vs. 157 [151, 166], n = 5). The other barrier devices provided less reduction in particle counts (133 [128, 137], n = 5). Aerosol evacuation to baseline required 15 min with standard suction and the Shop-Vac and 5 min with a smoke evacuator.

Conclusions: Barrier devices may reduce exposure to droplets and aerosol. With meticulous tucking, the glove box and drape tent can retain aerosol during airway management. Devices that are not fully enclosed may direct aerosol toward the laryngoscopist. Aerosol evacuation reduces aerosol content inside fully enclosed devices. Barrier devices must be used in conjunction with body-worn personal protective equipment.

Abstract
The Coronavirus Disease 2019 (COVID-19) pandemic has infected millions of individuals and posed unprecedented challenges to health care systems. Acute care hospitals have been forced to expand hospital and intensive care capacity and deal with shortages in personal protective equipment. This guide will review two areas where the anesthesiologists will be caring for COVID-19 patients: the operating room and on airway teams. General principles for COVID-19 preparation and hospital procedures will be reviewed to serve as a resource for anesthesia departments to manage COVID-19 or future pandemics.

Abstract
In March 2020, the New York City metropolitan area became the epicenter of the United States' SARS-CoV-2 pandemic and the surge of new cases threatened to overwhelm the area's hospital systems. This article describes how an anesthesiology department at a large urban academic hospital rapidly adapted and deployed to meet the threat head-on. Topics included are preparatory efforts, development of a team-based staffing model, and a new strategy for resource management. While still maintaining a fully functioning operating theater, discrete teams were deployed to both COVID-19 and non-COVID-19 intensive care units, rapid response/airway management team, the difficult airway response team, and labor and delivery. Additional topics include the creation of a temporary 'pop-up' anesthesiology-run COVID-19 intensive care unit utilizing anesthesia machines for monitoring and ventilatory support as well as the development of a simulation and innovation team that was instrumental in the rapid prototyping of a controlled split-ventilation system and conversion of readily available BIPAP units into emergency ventilators. As the course of the disease is uncertain, the goal of this article is to assist others in preparation for what may come next with COVID-19 as well as potential future pandemics.

Abstract
Background: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2.

Methods: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18-55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606.

Findings: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001).

Interpretation: ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme.

Funding: UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen.

Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Abstract
The coronavirus disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence, and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume severe respiratory failure centre in London.

Abstract
Background: The role of tracheostomy in coronavirus disease 2019 (COVID-19) is unclear, with several consensus guidelines advising against this practice. We developed both a dedicated airway team and coordinated education programme to facilitate ward management of tracheostomised COVID-19 patients. Here, we report outcomes in the first 100 COVID-19 patients who underwent tracheostomy at our institution.

Methods: This was a prospective observational cohort study of patients confirmed to have COVID-19 who required mechanical ventilation at Queen Elizabeth Hospital, Birmingham, UK. The primary outcome measure was 30-day survival, accounting for severe organ dysfunction (Acute Physiology and Chronic Health [APACHE]-II score>17). Secondary outcomes included duration of ventilation, ICU stay, and healthcare workers directly involved in tracheostomy care acquiring COVID-19.

Results: A total of 164 patients with COVID-19 were admitted to the ICU between March 9, 2020 and April 21, 2020. A total of 100 patients (mean [standard deviation] age: 55 [12] yr; 29% female) underwent tracheostomy; 64 (age: 57 [14] yr; 25% female) did not undergo tracheostomy. Despite similar APACHE-II scores, 30-day survival was higher in 85/100 (85%) patients after tracheostomy, compared with 27/64 (42%) non-tracheostomised patients {relative risk: 3.9 (95% confidence intervals [CI]: 2.3-6.4); P<0.0001}. In patients with APACHE-II scores ≥17, 68/100 (68%) tracheotomised patients survived, compared with 12/64 (19%) non-tracheotomised patients (P<0.001). Tracheostomy within 14 days of intubation was associated with shorter duration of ventilation (mean difference: 6.0 days [95% CI: 3.1-9.0]; P<0.0001) and ICU stay (mean difference: 6.7 days [95% CI: 3.7-9.6]; P<0.0001). No healthcare workers developed COVID-19.

Conclusion: Independent of the severity of critical illness from COVID-19, 30-day survival was higher and ICU stay shorter in patients receiving tracheostomy. Early tracheostomy appears to be safe in COVID-19.

Abstract
Background: Numerous barrier devices have recently been developed and rapidly deployed worldwide in an effort to protect healthcare workers (HCWs) from exposure to COVID-19 during high-risk procedures. However, only a few studies have examined their impact on the dispersion of droplets and aerosols, which are both thought to be significant contributors to the spread of COVID-19.

Methods: Two commonly used barrier devices, an intubation box and a clear plastic intubation sheet, were evaluated using a physiologically accurate cough simulator. Aerosols were modeled using a commercially available fog machine and droplets were modeled with fluorescein dye. Both particles were propelled by the cough simulator in a simulated intubation environment. Data was captured by high-speed flash photography and aerosol and droplet dispersion were assessed qualitatively with and without a barrier in place.

Results: Droplet contamination after a simulated cough was seemingly contained by both barrier devices. Simulated aerosol escaped the barriers and flowed towards the head of the bed. During barrier removal, simulated aerosol trapped underneath was released and propelled towards the HCW at the head of the bed. Usage of the intubation sheet concentrated droplets onto a smaller area. If no barrier was used, positioning the patient in slight reverse Trendelenburg directed aerosols away from the healthcare worker located at the head of the bed.

Conclusion: Our observations imply that intubation boxes and sheets may reduce HCW exposure to droplets, but they both may merely redirect aerosolized particles, potentially resulting in increased exposure to aerosols in certain circumstances. Aerosols may remain within the barrier device after a cough and manipulation of the box may release them. Patients should be positioned to facilitate intubation, but slight reverse Trendelenburg may direct infectious aerosols away from the HCW. Novel barrier devices should be used with caution and further validation studies are necessary.

Abstract
The rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a global pandemic. The 2019 coronavirus disease (COVID-19) presents with a spectrum of symptoms ranging from mild to critical illness requiring intensive care unit (ICU) admission. Acute respiratory distress syndrome is a major complication in patients with severe COVID-19 disease. Currently, there are no recognized pharmacological therapies for COVID-19. However, a large number of COVID-19 patients require respiratory support, with a high percentage requiring invasive ventilation. The rapid spread of the infection has led to a surge in the rate of hospitalizations and ICU admissions, which created a challenge to public health, research, and medical communities. The high demand for several therapies, including sedatives, analgesics, and paralytics, that are often utilized in the care of COVID-19 patients requiring mechanical ventilation, has created pressure on the supply chain resulting in shortages in these critical medications. This has led clinicians to develop conservation strategies and explore alternative therapies for sedation, analgesia, and paralysis in COVID-19 patients. Several of these alternative approaches have demonstrated acceptable levels of sedation, analgesia, and paralysis in different settings but they are not commonly used in the ICU. Additionally, they have unique pharmaceutical properties, limitations, and adverse effects. This narrative review summarizes the literature on alternative drug therapies for the management of sedation, analgesia, and paralysis in COVID-19 patients. Also, this document serves as a resource for clinicians in current and future respiratory illness pandemics in the setting of drug shortages.

Abstract
The coronavirus disease (COVID-19) pandemic has brought critical challenges to anesthesiologists and perioperative practice. Whereas anesthesiologists may be primarily concerned with airway and respiratory management, the COVID-19 data accumulated to date indicate that primary and/or secondary cardiovascular complications are common. Previous studies have demonstrated that the mortality rate is significantly higher in patients with cardiovascular disease (CVD) than in patients without CVD. Dysregulation of immune function in patients with CVD may be involved in the prognosis of COVID-19 patients. Anesthesia and surgical procedures can modulate the immune system, and some patients undergoing surgery, particularly those undergoing cardiovascular procedures, have CVD. In perioperative management for patients with suspected or diagnosed COVID-19 and those who have recovered from COVID-19, it is important for anesthesiologists to be concerned not only with airway and respiratory management, but also with cardiovascular complications and perioperative circulatory management to control the progression of the disease in patients with COVID-19.

Abstract
A substantial proportion of patients with coronavirus disease 19 (COVID-19) develop severe respiratory failure. Although the exact pathophysiology of severe COVID-19 pneumonia remains unknown and the characteristics of these patients are heterogeneous, the acute respiratory failure often fulfills criteria for acute respiratory distress syndrome (ARDS) and the clinical characteristics are also consistent with what is previously known about ARDS. Cohort studies also report distinctively high association between perioperative COVID-19 and postoperative mortality. In this special article, we review several publications on the pathophysiology of COVID-19, and discuss intraoperative ventilatory management for patients with COVID-19 based on the respiratory characteristics of COVID-19 pneumonia in light of the ongoing controversy of clinical phenotypes.

Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease [coronavirus disease 2019 (COVID-19) infection] first appeared in December 2019 in China and is now spreading worldwide. Because SARS-CoV-2 can be transmitted via aerosols and surface contaminations of the environment, appropriate use of anesthesia machines and appropriate behavior in the operation room (OR) are required specifically in relation to this disease. The use of high-performance hydrophobic filters with a high rate of virus rejection is recommended as the type of viral filter, and surgical team behaviors that result in aerosol splashes should be avoided. Appropriate hand hygiene by the anesthesiologist is crucial to prevent unexpected environmental contamination. When the anesthesia machine is used instead of an intensive care unit ventilator, it is important to keep the fresh gas flow at least equal to the minute ventilation to prevent excessive humidity in the circuit and to monitor condensation in the circuit and inspiratory carbon dioxide pressure. In addition, both the surgical smoke inherent in thermal tissue destruction and the surgical team's shoe soles may be factors for the presence of SARS-CoV-2 in the operating room. Ensuring social distancing-even with a mask in the OR-may be beneficial because healthcare providers may be asymptomatic carriers. After the acute crisis period of COVID-19, the number of cases of essential but nonurgent surgeries for waiting patients is likely to increase; therefore, optimization of OR scheduling will be an important topic. Anesthesiologists will benefit from new standard practices focusing on the prevention of COVID-19 infection.

Abstract
Coronavirus disease 2019 (COVID-19) has affected anesthetic care worldwide, including the provision of anesthesia for pediatric patients. Hospitals have balanced the risks associated with the potential surges of resource-intensive COVID-19 patients against the probable morbidity of delaying elective surgical procedures. These decisions are complicated by the unclear influence that COVID-19 has on the perioperative risk for disease-positive pediatric patients. We conducted a comprehensive literature search on MEDLINE for publications involving pediatric patients with COVID-19 who underwent general anesthesia. A total of eight publications met inclusion criteria, and together described 20 patients. Nine patients had documented preoperative COVID-19 symptoms and one perioperative death was reported. Overall, further studies are needed to increase patient numbers and properly assess the perioperative risk. As we continue to provide care without clear guiding data, we present a discussion of modified anesthetic techniques for pediatric patients with suspected or confirmed COVID-19.

Abstract
The collapse of global cooperation and a failure of international solidarity have led to many low-income and middle-income countries being denied access to molecular diagnostics in the COVID-19 pandemic response. Yet the scarcity of knowledge on the dynamics of the immune response to infection has led to hesitation on recommending the use of rapid immunodiagnostic tests, even though rapid serology tests are commercially available and scalable. On the basis of our knowledge and understanding of viral infectivity and host response, we urge countries without the capacity to do molecular testing at scale to research the use of serology tests to triage symptomatic patients in community settings, to test contacts of confirmed cases, and in situational analysis and surveillance. The WHO R&D Blue Print expert group identified eight priorities for research and development, of which the highest is to mobilise research on rapid point-of-care diagnostics for use at the community level. This research should inform control programmes of the required performance and utility of rapid serology tests, which, when applied specifically for appropriate public health measures to then be put in place, can make a huge difference.

Abstract
The Covid 19 pandemic will be remembered for the rapidity with which it spread, the morbidity and mortality associated with it and the paucity of evidence-based management guidelines. One of the major concerns of hospitals was to limit spread of infection to health care workers. Since the virus is spread mainly by respiratory droplets and aerosolized particles, procedures which may potentially disperse viral particles, the so called "aerosol-generating procedures" or AGPs were avoided whenever possible. Included in this category were non-invasive ventilation (NIV), high flow nasal cannula (HFNC) and awake (non-intubated) proning. Accordingly, at many health care facilities, patients who had increasing oxygen requirements were emergently intubated and mechanically ventilated to avoid exposure to AGPs. With experience, clinicians realized that mortality of invasively ventilated patients was high and it was not easy to extubate many of these patients. This raised the concern that HFNC and NIV were being underutilized to avoid intubation and to facilitate extubation. In this article, we attempt to separate fact from fiction and perception from reality pertaining to the aerosol dispersion with NIV, HFNC and AP. We describe precautions that hospitals and health care providers must take to mitigate risks with these devices. Finally, we take a practical approach in describing how we use the three techniques, including the common indications, contraindications and practical aspects of application.

Abstract:
Purpose: Under times of supply chain stress, the availability of some medical equipment and supplies may become limited. The current pandemic involving severe acute respiratory syndrome coronavirus 2 has highlighted limitations to the ordinary provision of personal protective equipment (PPE). For perioperative healthcare workers, N95 masks provide a stark example of PPE in short supply necessitating the creation of scientifically valid protocols for their decontamination and reuse.

Methods: We performed a systematic literature search of MEDLINE, Embase, Cochrane CENTRAL databases, and ClinicalTrials.gov to identify peer-reviewed articles related to N95 mask decontamination and subsequent testing for the integrity of mask filtration and facial seal. To expand this search, we additionally surveyed the official statements from key health agencies, organizations, and societies for relevant citations.

Results: Our initial database search resulted in five articles that met inclusion criteria, with 26 articles added from the expanded search. Our search did not reveal any relevant randomized clinical trials or cohort studies. We found that moist mask heating (65-80°C at 50-85% relative humidity for 20-30 min) and vaporous hydrogen peroxide treatment were supported by the literature to provide consistent viral decontamination without compromising mask seal and filtration efficiency. Other investigated decontamination methods lacked comprehensive scientific evidence for all three of these key criteria.

Conclusions: N95 mask reprocessing using either moist heat or vaporous hydrogen peroxide is recommended to ensure healthcare worker safety.

Background: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.

Methods: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.

Results: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.

Conclusions: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).

dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase_ 0.58 (0.36, 0.94)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%

Abstract
The treatment of surgical patients who are confirmed or suspected of coronavirus disease 2019 (COVID-19) is a challenge for all anesthesiologists. The safety of both patients and healthcare workers should be taken into consideration when performing anesthesia management for patients with COVID-19. General anesthesia requiring airway intervention may exacerbate COVID-19 pneumonia, and aerosol generation during airway intervention risks COVID-19 transmission to medical staff. However, regional anesthesia is not an aerosol-generating procedure. The neuraxial anesthesia may have little adverse influence on clinical outcomes in patients with COVID-19 after reviewing previous case reports. Regional anesthesia may have some advantages over general anesthesia for this group of patients, but unplanned conversion to general anesthesia during surgery is not preferred. Thus, careful consideration should be given to ensure that the surgery is performed entirely under regional anesthesia. The use of ultrasound guidance and the performance by an experienced physician may reduce the incidence of failed block and complications. The use of long-acting local anesthetic prolongs the anesthetic effect of regional anesthesia. Besides, a safe and sufficient dose of local anesthetic should be used.

Abstract
Background: Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.

Methods: In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison.

Results: A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55).

Conclusions: In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.).

Abstract
COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called "cytokine storm" induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.

Abstract
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.

Methods: We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group.

Results: After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.

Conclusions: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).

Copyright © 2020 Massachusetts Medical Society.

Abstract
During the SARS-CoV-2 pandemic in 2020, departments of anesthesiology worldwide have encountered new and unique challenges. In this short communication, we present and assess our recommendations for orotracheal intubation, a frequent high-risk procedure. We will point out that interdisciplinary cooperation with "non-patient care" departments like the Institute for Medical Microbiology and Hygiene tremendously helped us in creating this and other new, clear standards for anesthesiological procedures. Moreover, to reliably implement our newly created measures, we distributed incisive posters and organized comprehensive training sessions. Eventually, we summarize and analyze the occurring problems of our suggestions for intubation during their realization.

Abstract
Importance: The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19.

Observations: SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies.

Conclusions and relevance: As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

Abstract
Recently published case reports relating to anesthesia in patients with coronavirus disease (COVID-19) were reviewed. The diagnosis of COVID-19 was confirmed by positive results of reverse transcriptase polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Numerous reports handled emergency cesarean delivery. Primary symptoms and laboratory data of pregnant women with COVID-19 were similar to those of non-pregnant patients. Although the mortality rate is reported to be high after surgery in patients with COVID-19, cesarean delivery was successfully performed under regional anesthesia in most cases and postoperative course was favorable both in the parents and newborns. There is no direct evidence of vertical mother-to-child transmission of SARS-CoV-2; however, a diagnosis of COVID-19 was made in a newborn two hours after delivery from a pregnant woman with COVID-19, based on the increased immunoglobulin levels and deranged liver function, suggesting that its possibility cannot be completely eliminated. Emergency cerebral shunt reconstruction was performed repeatedly in an eight-month-old boy with COVID-19. The tracheal tube was removed in the operating room after surgery and postoperative course was uneventful. All the procedures should be performed in isolated operating rooms with medical staff with level-3 personal protection to ensure the safety of patients and health care providers.

Methods: A single ventilator in pressure control mode was used with flow control valves to simultaneously ventilate two patients with different lung compliances. The system was first evaluated using high-fidelity human patient simulator mannequins and then tested for 1 h in two pairs of COVID-19 patients with acute respiratory failure. Patients were matched on positive end-expiratory pressure, fractional inspired oxygen tension, and respiratory rate. Tidal volume and peak airway pressure (PMAX) were recorded from each patient using separate independent spirometers and arterial blood gas samples drawn at 0, 30, and 60 min. The authors assessed acid-base status, oxygenation, tidal volume, and PMAX for each patient. Stability was assessed by calculating the coefficient of variation.

Results: The valves performed as expected in simulation, providing a stable tidal volume of 400 ml each to two mannequins with compliance ratios varying from 20:20 to 20:90 ml/cm H2O. The system was then tested in two pairs of patients. Pair 1 was a 49-yr-old woman, ideal body weight 46 kg, and a 55-yr-old man, ideal body weight 64 kg, with lung compliance 27 ml/cm H2O versus 35 ml/cm H2O. The coefficient of variation for tidal volume was 0.2 to 0.6%, and for PMAX 0 to 1.1%. Pair 2 was a 32-yr-old man, ideal body weight 62 kg, and a 56-yr-old woman, ideal body weight 46 kg, with lung compliance 12 ml/cm H2O versus 21 ml/cm H2O. The coefficient of variation for tidal volume was 1.4 to 7.7%, and for PMAX 0 to 2.1%.

Conclusions: Differential ventilation using a single ventilator is feasible. Flow control valves enable delivery of stable tidal volume and PMAX similar to those provided by individual ventilators. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: In previous mass casualty situations where intensive care unit or emergency room surge conditions have resulted, the use of ventilator splitting to ventilate two or more patients has been proposed.The concept has received renewed attention with the global COVID-19 pandemic.The impaired respiratory mechanics similar to the acute respiratory distress syndrome seen in COVID-19 patients pose significant engineering challenges to optimally ventilate one patient while preventing damage to a paired patient.

What this article tells us that is new: Custom designed three-dimensional printed inspiratory flow control valves designed to allow individualized setting of tidal volume and airway pressure were evaluated using high-fidelity simulator mannequins with similar or different lung compliance and were found to perform as expected with stable tidal volumes delivered to each mannequin.Testing for 60 min in two pairs of volunteer COVID-19 patients with acute respiratory failure, matched on positive end-expiratory pressure level, fractional inspired oxygen tension level, and respiratory rate, demonstrated stable system performance. Continuous assessment of tidal volume and peak airway pressure in each patient during the study allowed for dynamic alteration of tidal volume in response to respiratory acidosis.This study suggests that custom designed flow control valves may facilitate the use of split ventilation techniques in a surge setting.

Abstract
The coronavirus disease 2019 (COVID-19) pandemic is caused by a coronavirus that is transmitted primarily via aerosol, droplets or direct contact. This may place anesthetists at higher risk of infection due to their frequent involvement in aerosol-generating airway interventions. Many anesthethetic COVID-19 guidelines have emerged, whose underlying management principles include minimizing aerosol contamination and protecting healthcare workers. These guidelines originate from Australia and New Zealand, Canada, China, India, Italy, Korea, Singapore, the United States and the United Kingdom. Hospitalized COVID-19 patients may require airway interventions, and difficult tracheal intubation secondary to laryngeal edema has been reported. Pre-pandemic difficult airway guidelines include those from Canada, France, Germany, India, Japan, Scandinavia, the United States and the United Kingdom. These difficult airway guidelines require modifications in order to align with the principles of the anesthetic COVID-19 guidelines. In turn, most of the anesthetic COVID-19 guidelines do not, or only briefly, discuss an airway strategy after failed tracheal intubation. Our article identifies and compares pre-pandemic difficult airway guidelines with the recent anesthetic COVID-19 guidelines. We combine the principles from both sets of guidelines and explain the necessary modifications to the airway guidelines, to form a failed tracheal intubation airway strategy in the COVID-19 patient. Valuing, and a greater understanding of, these differences and modifications may lead to greater adherence to the new COVID-19 guidelines.

Abstract
Current evidence suggests that Coronavirus Disease 2019 (COVID-19) spread occurs via respiratory droplets (particles >5 µm), and possibly through aerosol. The rate of transmission remains high during airway management. This was evident during the 2003 severe acute respiratory syndrome epidemic where those who were involved in tracheal intubation had a higher risk of infection than those who were not involved (odds ratio 6.6). We describe specific airway management principles for patients with known or suspected COVID-19 disease for an array of critical care and procedural settings. We conducted a thorough search of the available literature of airway management of COVID-19 across a variety of international settings. In addition, we have analyzed various medical professional body recommendations for common procedural practices such as interventional cardiology, gastroenterology and pulmonology. A systematic process that aims to protect the operators involved via appropriate personal protective equipment, avoidance of unnecessary patient contact and minimalization of periprocedural aerosol generation are key components to successful airway management. For operating room cases requiring general anesthesia or complex interventional procedures, tracheal intubation should be the preferred option. For interventional procedures when tracheal intubation is not indicated, cautious conscious sedation appears to be a reasonable approach. Awake intubation should be avoided unless it is absolutely necessary. Extubation is a high-risk procedure for aerosol and droplet spread and needs thorough planning and preparation. As updates and modifications in the management of COVID-19 are still evolving, local guidelines, appraised at regular intervals, are vital in optimizing clinical management.

Abstract
Background: It is nearly impossible to overestimate the burden of chronic pain, which is associated with enormous personal and socioeconomic costs. Chronic pain is the leading cause of disability in the world, is associated with multiple psychiatric comorbidities, and has been causally linked to the opioid crisis. Access to pain treatment has been called a fundamental human right by numerous organizations. The current COVID-19 pandemic has strained medical resources, creating a dilemma for physicians charged with the responsibility to limit spread of the contagion and to treat the patients they are entrusted to care for.

Methods: To address these issues, an expert panel was convened that included pain management experts from the military, Veterans Health Administration, and academia. Endorsement from stakeholder societies was sought upon completion of the document within a one-week period.

Results: In these guidelines, we provide a framework for pain practitioners and institutions to balance the often-conflicting goals of risk mitigation for health care providers, risk mitigation for patients, conservation of resources, and access to pain management services. Specific issues discussed include general and intervention-specific risk mitigation, patient flow issues and staffing plans, telemedicine options, triaging recommendations, strategies to reduce psychological sequelae in health care providers, and resource utilization.

Conclusions: The COVID-19 public health crisis has strained health care systems, creating a conundrum for patients, pain medicine practitioners, hospital leaders, and regulatory officials. Although this document provides a framework for pain management services, systems-wide and individual decisions must take into account clinical considerations, regional health conditions, government and hospital directives, resource availability, and the welfare of health care providers.

Abstract
Chronic pain causes significant suffering, limitation of daily activities and reduced quality of life. Infection from COVID-19 is responsible for an ongoing pandemic that causes severe acute respiratory syndrome, leading to systemic complications and death. Led by the World Health Organization, healthcare systems across the world are engaged in limiting the spread of infection. As a result, all elective surgical procedures, outpatient procedures and patient visits, including pain management services, have been postponed or cancelled. This has affected the care of chronic pain patients. Most are elderly with multiple comorbidities, which puts them at risk of COVID-19 infection. Important considerations that need to be recognised during this pandemic for chronic pain patients include: ensuring continuity of care and pain medications, especially opioids; use of telemedicine; maintaining biopsychosocial management; use of anti-inflammatory drugs; use of steroids; and prioritising necessary procedural visits. There are no guidelines to inform physicians and healthcare providers engaged in caring for patients with pain during this period of crisis. We assembled an expert panel of pain physicians, psychologists and researchers from North America and Europe to formulate recommendations to guide practice. As the COVID-19 situation continues to evolve rapidly, these recommendations are based on the best available evidence and expert opinion at this present time and may need adapting to local workplace policies.

Abstract.
Purpose: To assess the management and safety of epidural or general anesthesia for Cesarean delivery in parturients with coronavirus disease (COVID-19) and their newborns, and to evaluate the standardized procedures for protecting medical staff.

Methods: We retrospectively reviewed the cases of parturients diagnosed with severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection disease (COVID-19). Their epidemiologic history, chest computed tomography scans, laboratory measurements, and SARS-CoV-2 nucleic acid positivity were evaluated. We also recorded the patients' demographic and clinical characteristics, anesthesia and surgery-related data, maternal and neonatal complications, as well as the health status of the involved medical staff.

Results: The clinical characteristics of 17 pregnant women infected with SARS-CoV-2 were similar to those previously reported in non-pregnant adult patients. All of the 17 patients underwent Cesarean delivery with anesthesia performed according to standardized anesthesia/surgery procedures. Fourteen of the patients underwent continuous epidural anesthesia with 12 experiencing significant intraoperative hypotension. Three patients received general anesthesia with tracheal intubation because emergency surgery was needed. Three of the parturients are still recovering from their Cesarean delivery and are receiving in-hospital treatment for COVID-19. Three neonates were born prematurely. There were no deaths or serious neonatal asphyxia events. All neonatal SARS-CoV-2 nucleic acid tests were negative. No medical staff were infected throughout the patient care period.

Conclusions: Both epidural and general anesthesia were safely used for Cesarean delivery in the parturients with COVID-19. Nevertheless, the incidence of hypotension during epidural anesthesia appeared excessive. Proper patient transfer, medical staff access procedures, and effective biosafety precautions are important to protect medical staff from COVID-19.

Across the world, pain treatment centres have closed their doors. Because of the COVID-19 pandemic, healthcare providers are abruptly changing their care delivery to protect patients and staff from infection and to reallocate resource towards the greatest acute needs.
Elective, routine, and nonemergency casework has stopped in secondary and tertiary centres, while in primary care, patients are requested to stay away or “socially distance,” and in residential care facilities and hospices, strict isolation and separation protocols have been introduced.

By January 7, 2020, Chinese scientists confirmed that the outbreak was caused by a novel coronavirus, initially referred to as the 2019-nCoV,2 and recently renamed as severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), and the disease is now termed coronavirus disease 2019 (COVID-19) by the WHO. As of February 20, 2020, more than 75,748 confirmed cases of COVID-19 have been reported in 28 countries (including China) and international conveyance (cruise ship in the Japanese territorial waters), with approximately 99% of cases occurring in mainland China.

Abstract.
A global health emergency has been declared by the World Health Organization as the 2019-nCoV outbreak spreads across the world, with confirmed patients in Canada. Patients infected with 2019-nCoV are at risk for developing respiratory failure and requiring admission to critical care units. While providing optimal treatment for these patients, careful execution of infection control measures is necessary to prevent nosocomial transmission to other patients and to healthcare workers providing care. Although the exact mechanisms of transmission are currently unclear, human-to-human transmission can occur, and the risk of airborne spread during aerosol-generating medical procedures remains a concern in specific circumstances. This paper summarizes important considerations regarding patient screening, environmental controls, personal protective equipment, resuscitation measures (including intubation), and critical care unit operations planning as we prepare for the possibility of new imported cases or local outbreaks of 2019-nCoV. Although understanding of the 2019-nCoV virus is evolving, lessons learned from prior infectious disease challenges such as Severe Acute Respiratory Syndrome will hopefully improve our state of readiness regardless of the number of cases we eventually manage in Canada.

Abstract.
The coronavirus disease 2019 (COVID-19) outbreak has been designated a public health emergency of international concern. To prepare for a pandemic, hospitals need a strategy to manage their space, staff, and supplies so that optimum care is provided to patients. In addition, infection prevention measures need to be implemented to reduce in-hospital transmission. In the operating room, these preparations involve multiple stakeholders and can present a significant challenge. Here, we describe the outbreak response measures of the anesthetic department staffing the largest (1,700-bed) academic tertiary level acute care hospital in Singapore (Singapore General Hospital) and a smaller regional hospital (Sengkang General Hospital). These include engineering controls such as identification and preparation of an isolation operating room, administrative measures such as modification of workflow and processes, introduction of personal protective equipment for staff, and formulation of clinical guidelines for anesthetic management. Simulation was valuable in evaluating the feasibility of new operating room set-ups or workflow. We also discuss how the hierarchy of controls can be used as a framework to plan the necessary measures during each phase of a pandemic, and review the evidence for the measures taken. These containment measures are necessary to optimize the quality of care provided to COVID-19 patients and to reduce the risk of viral transmission to other patients or healthcare workers.

Editor—Wuhan, the core city of central China, has reported an outbreak of atypical pneumonia caused by a 2019 novel coronavirus in late 2019. This coronavirus is officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1,2 There are many pregnant women presenting with coronavirus disease 2019 (COVID-19), which undoubtedly threatens the lives of both mother and baby. Currently, there are no statistics regarding pregnant women infected with COVID-19. A retrospective review has indicated the clinical characteristics of nine pregnant women with COVID-19.3 However, how anaesthesia was undertaken during delivery is unknown. Here, we report a case of successful spinal anaesthesia in a woman with confirmed COVID-19 who required emergency Caesarean section. Of note, there were 35 cases with confirmed COVID-19 undergoing emergency Caesarean delivery in Wuhan Union Hospital from 23 January, 2020 to 20 February, 2020, with further clinical investigation in progress.