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Introduction: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry., Methods: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality., Results: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis., Conclusions: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future., (© 2022 John Wiley & Sons Ltd.)

Purpose: To evaluate the association of estimated plasma volume (ePV) and plasma volume status (PVS) on admission with the outcomes in COVID-19-related acute respiratory distress syndrome (ARDS) patients., Materials and Methods: We performed a retrospective multi-center study on COVID-19-related ARDS patients who were admitted to the Mayo Clinic Enterprise health system. Plasma volume was calculated using the formulae for ePV and PVS, and these variables were analyzed for correlation with patient outcomes., Results: Our analysis included 1298 patients with sequential organ failure assessment (SOFA) respiratory score ≥ 2 (PaO 2 /FIO 2 ≤300 mmHg) and a mortality rate of 25.96%. A Cox proportional multivariate analysis showed PVS but not ePV as an independent correlation with 90-day mortality after adjusting for the covariates (HR: 1.015, 95% CI: 1.005-1.025, p = 0.002 and HR 1.054, 95% CI 0.958-1.159, p = 0.278 respectively)., Conclusion: A lower PVS on admission correlated with a greater chance of survival in COVID-19-related ARDS patients. The role of PVS in guiding fluid management should be investigated in future prospective studies., Competing Interests: Declaration of Competing Interest Rahul Kashyap: Grant and contracts - Gordan and Betty Moore Foundation, Jenssen and Jenssen LLC; all payments made to the institution. No conflict of interest related to this manuscript. Archer Kilbourne Martin: Consulting fees - Scientific Advisory Board, Attgeno AB; payments made to the institution. No conflict of interest related to this manuscript. Rest other authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To describe incidence and risk factors of loss of previous independent living through nonhome discharge or discharge home with health assistance in survivors of intensive care unit (ICU) admission for coronavirus disease 2019 (COVID-19)., Design: Multicenter observational study including patients admitted to the ICU from January 2020 till June 30, 2021., Hypothesis: We hypothesized that there is a high risk of nonhome discharge in patients surviving ICU admission due to COVID-19., Setting: Data were included from 306 hospitals in 28 countries participating in the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 registry., Patients: Previously independently living adult ICU survivors of COVID-19., Interventions: None., Measurements and Main Results: The primary outcome was nonhome discharge. Secondary outcome was the requirement of health assistance among patients who were discharged home. Out of 10 820 patients, 7101 (66%) were discharged alive; 3791 (53%) of these survivors lost their previous independent living status, out of those 2071 (29%) through nonhome discharge, and 1720 (24%) through discharge home requiring health assistance. In adjusted analyses, loss of independence on discharge among survivors was predicted by patient age ≥ 65 years (adjusted odds ratio [aOR] 2.78, 95% confidence interval [CI] 2.47-3.14, P  < .0001), former and current smoking status (aOR 1.25, 95% CI 1.08-1.46, P   =  .003 and 1.60 (95% CI 1.18-2.16), P   =  .003, respectively), substance use disorder (aOR 1.52, 95% CI 1.12-2.06, P   =  .007), requirement for mechanical ventilation (aOR 4.17, 95% CI 3.69-4.71, P  < .0001), prone positioning (aOR 1.19, 95% CI 1.03-1.38, P   =  .02), and requirement for extracorporeal membrane oxygenation (aOR 2.28, 95% CI 1.55-3.34, P  < .0001)., Conclusions: More than half of ICU survivors hospitalized for COVID-19 are unable to return to independent living status, thereby imposing a significant secondary strain on health care systems worldwide.

Objective: To provide insights into the nature, risk factors, impact and existing measures for reporting and preventing violence in the healthcare system. The under-reporting of violence against healthcare workers (HCWs) globally highlights the need for increased public awareness and education., Methods: The Violence Study of Healthcare Workers and Systems study used a survey questionnaire created using Research Electronic Data Capture (REDCap) forms and distributed from 6 June to 9 August 2022. Logistic regression analysis evaluated violence predictors, including gender, age, years of experience, institution type, respondent profession and night shift frequency. A χ 2 test was performed to determine the association between gender and different violence forms., Results: A total of 5405 responses from 79 countries were analysed. India, the USA and Venezuela were the top three contributors. Female respondents comprised 53%. The majority (45%) fell within the 26-35 age group. Medical students (21%), consultants (20%), residents/fellows (15%) and nurses (10%) constituted highest responders. Nearly 55% HCWs reported firsthand violence experience, and 16% reported violence against their colleagues. Perpetrators were identified as patients or family members in over 50% of cases, while supervisor-incited violence accounted for 16%. Around 80% stated that violence incidence either remained constant or increased during the COVID-19 pandemic. Among HCWs who experienced violence, 55% felt less motivated or more dissatisfied with their jobs afterward, and 25% expressed willingness to quit. Univariate analysis revealed that HCWs aged 26-65 years, nurses, physicians, ancillary staff, those working in public settings, with >1 year of experience, and frequent night shift workers were at significantly higher risk of experiencing violence. These results remained significant in multivariate analysis, except for the 55-65 age group, which lost statistical significance., Conclusion: This global cross-sectional study highlights that a majority of HCWs have experienced violence, and the incidence either increased or remained the same during the COVID-19 pandemic. This has resulted in decreased job satisfaction., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective : The association of non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) with intensive care unit (ICU) admissions and the need for mechanical ventilation and disease severity in COVID-19 patients. Material and Methods : A systematic literature review was conducted on the databases: Cochrane, Embase, PubMed, ScienceDirect, and the Web of Science from January 2019 to June 2022. Studies evaluating MAFLD using laboratory methods, non-invasive imaging, or liver biopsy were included. The study protocol was registered in PROSPERO (ID CRD42022313259), and PRISMA guidelines were followed. The NIH quality assessment tool was used for quality assessment. RevMan version 5.3 software was used for pooled analysis. A sensitivity analysis was performed to assess the result's stability. Results : A total of 37,974 patients from 17 studies were assessed for the association between MAFLD and ICU admission. A total of 3396 COVID-19 patients required ICU admission: 1236 (20.41%) in the MAFLD group and 2160 (6.77%) in the non-MAFLD group. The odds ratio was 1.86 for ICU admission, p = 0.007, and a (95% CI) of [1.18-2.91]. A total of 37,166 patients from 13 studies were included in the need for invasive mechanical ventilation analysis. A total of 1676 patients required mechanical ventilation: 805 in the MAFLD group (14.20% of all MAFLD patients) and 871 patients in the non-MAFLD group (2.76% of all non-MAFLD patients). The odds ratio was 2.05, p = 0.02, and a (95% CI) of [1.12-3.74]. A total of 5286 patients from 14 studies were included in the COVID-19 disease severity analysis. Severe COVID-19 was seen in 1623 patients, with 33.17% (901/2716) of MAFLD patients and 28.09% (722/2570) of non-MAFLD patients having severe disease. The odds ratio was 1.59 for disease severity, p = 0.010, and a (95% CI) of [1.12-2.26]. Conclusions : Our meta-analysis suggests that there are significantly increased odds of ICU admissions, a need for invasive mechanical ventilation, and disease severity in MAFLD patients who acquire COVID-19.

Background: Limited data is available on the incidence and outcomes of pneumothorax (PTX), pneumomediastinum (PNM), and subcutaneous emphysema (SCE) in COVID-19 patients. This study aimed to investigate the characteristics of these complications in hospitalized COVID-19 patients., Research Design and Methods: A retrospective study was conducted, involving adult COVID-19 patients admitted to Mayo Clinic Florida from 03/2020-06/2022. Patients were divided into two groups based on the presence or absence of PTX/PNM/SCE., Results: 1926 hospitalized patients with COVID-19 were included, of which 518 were admitted to the ICU. The incidence of PTX/PNM/SCE was 6.3%. Patients with these complications were more likely to be male, Asian, and unvaccinated. Conversely, they were less likely to have chronic obstructive pulmonary disease. Patients who developed PTX/PNM/SCE after 72 hours of admission were more likely to receive high-dose corticosteroids and for an extended duration. The affected group had an adjusted odds ratio for in-hospital mortality of 13.32 (95%CI, 8.19-21.59) and ICU admission of 9.14 (95%CI, 5.3-12.78) compared to the unaffected group., Conclusion: Although the occurrence of PTX/PNM/SCE in hospitalized COVID-19 patients was rare, it was associated with worse outcomes. Corticosteroids may contribute to the pathogenesis of these complications; however, further studies are needed to investigate this relationship in more detail.

Background: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) are on the rise like any other liver disease, and tend to affect 25% of the United States population. The impact of NAFLD and MAFLD on patients with coronavirus disease 2019 (COVID-19) remains unclear., Aim: To identify the association of NAFLD and MAFLD with mortality, hospitalization, hospital length of stay, and supplemental oxygen utilization in COVID-19 patients., Methods: A systematic review of literature on Cochrane, Embase, PubMed, ScienceDirect, and Web of Science databases was conducted from January 2019 to July 2022. Studies that evaluated NAFLD/MAFLD using laboratory methods, noninvasive imaging, or liver biopsy were included. The study protocol was registered in PROSPERO (ID CRD42022313259) and PRISMA guidelines were followed. The National Institutes of Health quality assessment tool was used to assess the quality of the studies. Pooled analysis was conducted using software Rev Man version 5.3. The stability of the results was assessed using sensitivity analysis., Results: Thirty-two studies with 43388 patients were included in the meta-analysis of whom 8538 (20%) patients were observed to have NAFLD. There were 42254 patients from 28 studies included in the mortality analysis. A total of 2008 patients died from COVID-19; 837 (10.52%) in the NAFLD group and 1171 (3.41%) in the non-NAFLD group. The odds ratio (OR) was 1.38 for mortality with a 95% confidence interval (95%CI) = 0.97-1.95 and P = 0.07. A total of 5043 patients from eight studies were included in the hospital length of stay analysis. There were 1318 patients in the NAFLD group and 3725 patients in the non-NAFLD group. A qualitative synthesis showed that the mean difference in hospital length of stay was about 2 d between the NAFLD and non-NAFLD groups with a 95%CI = 0.71-3.27 and P = 0.002. For hospitalization rates, the OR was 3.25 with a 95%CI of 1.73-6.10 and P = 0.0002. For supplemental oxygen utilization, the OR was 2.04 with a 95%CI of 1.17-3.53 and P = 0.01., Conclusion: Our meta-analysis suggests that there are increased odds of hospitalization, longer hospital length of stay, and increased use of supplemental oxygen in NAFLD/MAFLD patients., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To develop and validate an updated lung injury prediction score for coronavirus disease 2019 (COVID-19) (c-LIPS) tailored for predicting acute respiratory distress syndrome (ARDS) in COVID-19., Patients and Methods: This was a registry-based cohort study using the Viral Infection and Respiratory Illness Universal Study. Hospitalized adult patients between January 2020 and January 2022 were screened. Patients who qualified for ARDS within the first day of admission were excluded. Development cohort consisted of patients enrolled from participating Mayo Clinic sites. The validation analyses were performed on remaining patients enrolled from more than 120 hospitals in 15 countries. The original lung injury prediction score (LIPS) was calculated and enhanced using reported COVID-19-specific laboratory risk factors, constituting c-LIPS. The main outcome was ARDS development and secondary outcomes included hospital mortality, invasive mechanical ventilation, and progression in WHO ordinal scale., Results: The derivation cohort consisted of 3710 patients, of whom 1041 (28.1%) developed ARDS. The c-LIPS discriminated COVID-19 patients who developed ARDS with an area under the curve (AUC) of 0.79 compared with original LIPS (AUC, 0.74; P<.001) with good calibration accuracy (Hosmer-Lemeshow P=.50). Despite different characteristics of the two cohorts, the c-LIPS's performance was comparable in the validation cohort of 5426 patients (15.9% ARDS), with an AUC of 0.74; and its discriminatory performance was significantly higher than the LIPS (AUC, 0.68; P<.001). The c-LIPS's performance in predicting the requirement for invasive mechanical ventilation in derivation and validation cohorts had an AUC of 0.74 and 0.72, respectively., Conclusion: In this large patient sample c-LIPS was successfully tailored to predict ARDS in COVID-19 patients., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Introduction: The goal of this investigation is to assess the association between prehospital use of aspirin (ASA) and patient-centered outcomes in a large global cohort of hospitalized COVID-19 patients., Methods: This study utilizes data from the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Registry. Adult patients hospitalized from February 15th, 2020, to September 30th, 2021, were included. Multivariable regression analyses were utilized to assess the association between pre-hospital use of ASA and the primary outcome of overall hospital mortality., Results: 21,579 patients were included from 185 hospitals (predominantly US-based, 71.3%), with 4691 (21.7%) receiving pre-hospital ASA. Patients receiving ASA, compared to those without pre-admission ASA use, were generally older (median 70 vs. 59 years), more likely to be male (58.7 vs. 56.0%), caucasian (57.4 vs. 51.6%), and more commonly had higher rates of medical comorbidities. In multivariable analyses, patients receiving pre-hospital ASA had lower mortality (HR: 0.89, 95% CI 0.82-0.97, p=0.01) and reduced hazard for progression to severe disease or death (HR: 0.91, 95% CI 0.84-0.99, p=0.02) and more hospital free days (1.00 days, 95% CI 0.66-1.35, p=0.01) compared to those without pre-hospital ASA use. The overall direction and significance of the results remained the same in sensitivity analysis, after adjusting the multivariable model for time since pandemic., Conclusions: In this large international cohort, pre-hospital use of ASA was associated with a lower hazard for death in hospitalized patients with COVID-19. Randomized controlled trials may be warranted to assess the utility of pre-hospital use of ASA., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: The COVID-19 pandemic severely restricted in-person learning. As a result, many educational institutions switched to online platforms to continue teaching. COVID-19 webinars have been useful for rapidly disseminating information to frontline healthcare workers. While conducting COVID-19 webinars through online platforms is a popular method to train medical professionals, their effectiveness has never been investigated. Our aim was to ascertain the usefulness of COVID-19 webinars during the pandemic., Methods: We conducted an online survey of about 400 frontline healthcare workers. 112 people responded to the survey (response rate = 28%). In it, we asked several questions to determine whether webinars had been a useful resource to help deal with COVID-19 patients., Results: We found that a majority of healthcare worker respondents had favorable opinions of online education during the pandemic as around 78% of respondents either agreed or highly agreed that webinars are a useful source of knowledge. A significant proportion (34%) did not participate in webinars and gave time constraints as their main reason for not participating., Conclusion: Our results indicated that while online education is a great way to disseminate information quickly to a large amount of people, it also comes with its disadvantages. As we transition into a post-pandemic world, we need to make sure that online teaching is designed with the best interests of the healthcare workers in mind to ensure that we get the most out of it.

Objective: As of early 2021, there have been over 3.5 million pediatric cases of SARS-CoV-2, including 292 pediatric deaths in the United States. Although most pediatric patients present with mild disease, they are still at risk for developing significant morbidity requiring hospitalization and intensive care unit (ICU) level of care. This study was performed to evaluate if the presence of concurrent respiratory viral infections in pediatric patients admitted to the hospital with SARS-CoV-2 was associated with an increased rate of ICU level of care., Design: A multicenter, international, noninterventional, cross-sectional study using data provided through The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study database., Setting: The medical ward and ICU of 67 participating hospitals., Patients: Pediatric patients younger than 18 years hospitalized with SARS-CoV-2., Interventions: None., Measurements and Main Results: A total of 922 patients were included. Among these patients, 391 required ICU level care and 31 had concurrent non-SARS-CoV-2 viral coinfection. In a multivariate analysis, after accounting for age, positive blood culture, positive sputum culture, preexisting chronic medical conditions, the presence of a viral respiratory coinfection was associated with need for ICU care (odds ratio, 3.6; 95% confidence interval, 1.6-9.4; P < 0.01)., Conclusions: This study demonstrates an association between concurrent SARS-CoV-2 infection with viral respiratory coinfection and the need for ICU care. Further research is needed to identify other risk factors that can be used to derive and validate a risk-stratification tool for disease severity in pediatric patients with SARS-CoV-2., Competing Interests: Disclosure: Includes departmental funds. A.J.W. receives funding from the National Institutes of Health/National Heart, Lung and Blood Institute grants R01HL151607, R01HL139751, R01HL136660, Agency of Healthcare Research and Quality, R01HS026485, Boston Biomedical Innovation Center/NIH/NHLBI 5U54HL119145-07 and royalties from UptoDate. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Describe the incidence and associated outcomes of gastrointestinal (GI) manifestations of acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in hospitalized children (MIS-C)., Methods: Retrospective review of the Viral Infection and Respiratory Illness Universal Study registry, a prospective observational, multicenter international cohort study of hospitalized children with acute COVID-19 or MIS-C from March 2020 to November 2020. The primary outcome measure was critical COVID-19 illness. Multivariable models were performed to assess for associations of GI involvement with the primary composite outcome in the entire cohort and a subpopulation of patients with MIS-C. Secondary outcomes included prolonged hospital length of stay defined as being >75th percentile and mortality., Results: Of the 789 patients, GI involvement was present in 500 (63.3%). Critical illness occurred in 392 (49.6%), and 18 (2.3%) died. Those with GI involvement were older (median age of 8 yr), and 18.2% had an underlying GI comorbidity. GI symptoms and liver derangements were more common among patients with MIS-C. In the adjusted multivariable models, acute COVID-19 was no associated with the primary or secondary outcomes. Similarly, despite the preponderance of GI involvement in patients with MIS-C, it was also not associated with the primary or secondary outcomes., Conclusions: GI involvement is common in hospitalized children with acute COVID-19 and MIS-C. GI involvement is not associated with critical illness, hospital length of stay or mortality in acute COVID-19 or MIS-C., Competing Interests: U.B. is currently funded by National Institute of Health (Site Principal Investigator for Stress Hydrocortisone in Pediatric Septic Shock—R01HD096901), The Children’s Hospital of Philadelphia (Site Principal Investigator for Pediatric Resuscitation Quality Collaborative-PediResQ), Voelcker Pilot Grant (PI for project on prearrest electrocardiographic changes), The Children’s Hospital of San Antonio Endowed Chair Funds for ancillary projects related to Society of Critical Care Medicine VIRUS (COVID-19) Registry and Society of Critical Care Medicine VIRUS electronic medical record automation pilot. The other authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The use of high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) for hypoxemic respiratory failure secondary to COVID-19 are recommended by critical-care guidelines; however, apprehension about viral particle aerosolization and patient self-inflicted lung injury may have limited use. We aimed to describe hospital variation in the use and clinical outcomes of HFNC and NIV for the management of COVID-19., Methods: This was a retrospective observational study of adults hospitalized with COVID-19 who received supplemental oxygen between February 15, 2020, and April 12, 2021, across 102 international and United States hospitals by using the COVID-19 Registry. Associations of HFNC and NIV use with clinical outcomes were evaluated by using multivariable adjusted hierarchical random-effects logistic regression models. Hospital variation was characterized by using intraclass correlation and the median odds ratio., Results: Among 13,454 adults with COVID-19 who received supplemental oxygen, 8,143 (60%) received nasal cannula/face mask only, 2,859 (21%) received HFNC, 878 (7%) received NIV, 1,574 (12%) received both HFNC and NIV, with 3,640 subjects (27%) progressing to invasive ventilation. The hospital of admission contributed to 24% of the risk-adjusted variation in HFNC and 30% of the risk-adjusted variation in NIV. The median odds ratio for hospital variation of HFNC was 2.6 (95% CI 1.4-4.9) and of NIV was 3.1 (95% CI 1.2-8.1). Among 5,311 subjects who received HFNC and/or NIV, 2,772 (52%) did not receive invasive ventilation and survived to hospital discharge. Hospital-level use of HFNC or NIV were not associated with the rates of invasive ventilation or mortality., Conclusions: Hospital variation in the use of HFNC and NIV for acute respiratory failure secondary to COVID-19 was great but was not associated with intubation or mortality. The wide variation and relatively low use of HFNC/NIV observed within our study signaled that implementation of increased HFNC/NIV use in patients with COVID-19 will require changes to current care delivery practices. (ClinicalTrials.gov registration NCT04323787.)., (Copyright © 2022 by Daedalus Enterprises.)

Introduction: There are concerns regarding the effectiveness and safety of SARS-CoV-2 vaccine in inflammatory Bowel Disease (IBD) patients. This systematic review and meta-analysis comprehensively summarises the available literature regarding the safety and effectiveness of SARS-CoV-2 vaccine in IBD., Methods: Three independent reviewers performed a comprehensive review of all original articles describing the response of SARS-CoV-2 vaccines in patients with IBD. Primary outcomes were (1) pooled seroconversion rate SARS-CoV-2 vaccination in IBD patients (2) comparison of breakthrough COVID-19 infection rate SARS-CoV-2 vaccination in IBD patients with control cohort and (3) pooled adverse event rate of SARS-CoV-2 vaccine. All outcomes were evaluated for one and two doses of SARS-CoV-2 vaccine. Meta-regression was performed. Probability of publication bias was assessed using funnel plots and with Egger's test., Results: Twenty-one studies yielded a pooled seroconversion rate of 73.7% and 96.8% in IBD patients after one and two doses of SARS-CoV-2 vaccine respectively. Sub-group analysis revealed non-statistically significant differences between different immunosuppressive regimens for seroconversion. Meta-regression revealed that the vaccine type and study location independently influenced seroconversion rates. There was no statistically significant difference in breakthrough infection in IBD patients as compared to control after vaccination., Conclusion: In summary, the systematic review and meta-analysis suggest that SARS-CoV-2 vaccine is safe and effective in IBD patients., (© 2022 John Wiley & Sons Ltd.)

Background: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern., Methods: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators., Results: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds., Conclusions: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk., (© 2022. The Author(s).)

Rationale: The impact of palliative care consultation on end-of-life care has not previously been evaluated in a multi-center study., Objectives: To evaluate the impact of palliative care consultation on the incidence of cardiopulmonary resuscitation (CPR) performed and comfort care received at the end-of-life in hospitalized patients with COVID-19., Methods: We used the Society of Critical Care Medicine's COVID-19 registry to extract clinical data on patients hospitalized with COVID-19 between March 31st, 2020 to March 17th, 2021 and died during their hospitalization. The proportion of patients who received palliative care consultation was assessed in patients who did and did not receive CPR (primary outcome) and comfort care (secondary outcome). Propensity matching was used to account for potential confounding variables., Measurements and Main Results: 3,227 patients were included in the analysis. There was no significant difference in the incidence of palliative care consultation between the CPR and no-CPR groups (19.9% vs. 19.4%, p = 0.8334). Patients who received comfort care at the end-of-life were significantly more likely to have received palliative care consultation (43.3% vs. 7.7%, p < 0.0001). After propensity matching for comfort care on demographic characteristics and comorbidities, this relationship was still significant (43.2% vs. 8.5%; p < 0.0001)., Conclusion: Palliative care consultation was not associated with CPR performed at the end-of-life but was associated with increased incidence of comfort care being utilized. These results suggest that utilizing palliative care consultation at the end-of-life may better align the needs and values of patients with the care they receive., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Kumar is currently funded by funding the Gordon and Betty Moore Foundation, Centers for Disease Control and Prevention Foundation through the University of Washington, and Janssen Research & Development, LLC. Dr. Kashyap receives funding from the NIH/National Heart, Lung and Blood Institute: R01HL 130881, UG3/UH3HL 141722; Gordon and Betty Moore Foundation and Janssen Research & Development, LLC; and royalties from Ambient Clinical Analytics. Inc. Dr. Gajic receives funding from the Agency of Healthcare Research and Quality R18HS 26609-2, NIH/National Heart, Lung and Blood Institute: R01HL 130881, UG3/UH3HL 141722; Department of Defense DOD W81XWH; American Heart Association Rapid Response Grant—COVID-19; and royalties from Ambient Clinical Analytics. Inc. Dr. Walkey currently receives funding from the NIH/National Heart, Lung and Blood Institute grants R01HL151607, R01HL139751, R01HL136660, Agency of Healthcare Research and Quality, R01HS026485, Boston Biomedical Innovation Center/NIH/NHLBI 5U54HL119145-07, and royalties from UpToDate., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry., Design: Retrospective study., Setting: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry., Patients: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021., Interventions: None., Measurements and Main Results: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16-25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased., Conclusions: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults., Competing Interests: Dr. Bhalala is currently funded by the National Institutes of Health (NIH) (Site Principal Investigator [PI] for Stress Hydrocortisone in Pediatric Septic Shock—R01HD096901), The Children’s Hospital of Philadelphia (Site-PI for Pediatric Resuscitation Quality Collaborative – PediResQ), Voelcker Pilot Grant (PI for project on prearrest electrocardiographic changes), The Children’s Hospital of San Antonio Endowed Chair Funds for ancillary projects related to Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) (coronavirus disease 2019 [COVID-19]) Registry and SCCM VIRUS electronic medical records, automation pilot. Ms. Boman’s institution received funding from The Gordon and Betty Moore Foundation. Ms. Boman and Drs. Kumar and Kashyap's institutions received funding from Janssen Research and Development, LLC. Dr. Kumar is currently funded by Gordon and Betty Moore Foundation, Centers for Disease Control and Prevention (CDC) Foundation through University of Washington and Janssen Research & Development, LLC. Dr. Chiotos funded by Agency for Healthcare Research and Quality(K12-HS026393). Dr. Bjornstad’s institution received funding from the International Society of Nephrology, The NIH-National Institute of Diabetes and Digestive and Kidney Diseases/T32, and Bioporto. Dr. Dapul disclosed that the deidentified data of some patients submitted to the VIRUS registry were also used in the Overcoming COVID-19 Virus Registry. Dr. Blatz funded by NIH grant T32GM-075766. Dr. Levy’s institution received funding from the CDC (No. 75D30120C07725) and the National Institute of Allergy and Infectious Diseases (AI 144301); she received funding from SinoUnited Health Shanghai Children’s Hospital. Drs. Kaufman’s, Abdelaty’s, and Briton’s institutions received funding from SCCM. Dr. Kaufman received funding from EngleWood Health for consulting work as medical director. Dr. Khanna’s institution received funding for COVID-19 trials Blood Volume Analyzer-Daxor and Chair Steering Committee for the Siltuximab in Selected Hospitalized Patients With Viral Acute Respiratory Distress Syndrome trial. Dr. Khanna is currently funded by a Clinical Translational Science Institute NIH/National Center for Advanced Translational Science KL2 TR001421 award for a trial on continuous postoperative hemodynamic and saturation monitoring and is a site PI (institutional funding) for a randomized trial of cytokine filtration in severe COVID-19 and a prospective observational trial of blood volume assessment in COVID-19. His institution also received funding for the SCCM VIRUS EMR automation pilot. Dr. Stulce received funding from the American Physician Institute. Dr. Anderson III disclosed that he is on the Advisory Board for the Gift of Life Michigan. Dr. Bello disclosed government work. Dr. Walkey currently funded the NIH/National Heart, Lung and Blood Institute (NHLBI) grants R01HL151607, R01HL139751, R01HL136660, Agency of Healthcare Research and Quality, R01HS026485, Boston Biomedical Innovation Center/NIH/NHLBI 5U54HL119145-07, and royalties from UptoDate. Dr. Bihorac received support for article research from the NIH. His institution received funding from the NIH (R01 GM110240 R21 EB 027344), Atox Bio, Astute Medical Research, Mallinckrodt Pharmaceuticals, and La Jolla Pharmaceuticals; she disclosed three institutional patents (20200161000, WO2020172607A12020, and 20190326013). Dr. Zimmerman’s institution received funding from the NIH-National Institute of Child Health and Human Development and Immunexpress; he received funding from Elsevier Publishing. Dr. Kashyap receives funding from the NIH/NHLBI: R01HL 130881, UG3/UH3HL 141722; Gordon and Betty Moore Foundation, and Janssen Research & Development, LLC; and royalties from Ambient Clinical Analytics. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome., Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19., Design, Setting, and Participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021., Exposures: Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia., Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS)., Results: Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P < .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P < .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P < .001; 3 criteria: 817 patients with ARDS [19.3%]; P < .001; 4 criteria: 203 patients with ARDS [24.3%]; P < .001)., Conclusions and Relevance: These findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present.

Objective: To describe the impact of obesity on disease severity and outcomes of coronavirus disease 2019 (COVID-19) among hospitalized children., Methods: This retrospective cohort study from the Society of Critical Care Medicine Viral Respiratory Illness Universal Study registry included all children hospitalized with COVID-19 from March 2020 to January 2021. Obesity was defined by Centers for Disease Control and Prevention BMI or World Health Organization weight for length criteria. Critical illness definition was adapted from National Institutes of Health criteria of critical COVID. Multivariate mixed logistic and linear regression was performed to calculate the adjusted odds ratio of critical illness and the adjusted impact of obesity on hospital length of stay., Results: Data from 795 patients (96.4% United States) from 45 sites were analyzed, including 251 (31.5%) with obesity and 544 (68.5%) without. A higher proportion of patients with obesity were adolescents, of Hispanic ethnicity, and had other comorbidities. Those with obesity were also more likely to be diagnosed with multisystem inflammatory syndrome in children (35.7% vs 28.1%, P = .04) and had higher ICU admission rates (57% vs 44%, P < .01) with more critical illness (30.3% vs 18.3%, P < .01). Obesity had more impact on acute COVID-19 severity than on multisystem inflammatory syndrome in children presentation. The adjusted odds ratio for critical illness with obesity was 3.11 (95% confidence interval: 1.8-5.3). Patients with obesity had longer adjusted length of stay (exponentiated parameter estimate 1.3; 95% confidence interval: 1.1-1.5) compared with patients without obesity but did not have increased mortality risk due to COVID-19 (2.4% vs 1.5%, P = .38)., Conclusion: In a large, multicenter cohort, a high proportion of hospitalized children from COVID-19 had obesity as comorbidity. Furthermore, obesity had a significant independent association with critical illness., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: Interleukin-6 receptor antagonists (IL-6RAs) and steroids are emerging immunomodulatory therapies for severe and critical coronavirus disease (COVID-19). In this preliminary report, we aim to describe the epidemiology, clinical characteristics, and outcomes of adult critically ill COVID-19 patients, requiring invasive mechanical ventilation (iMV), and receiving IL-6RA and steroids therapy over the last 11 months., Materials and Methods: International, multicenter, cohort study derived from Viral Infection and Respiratory Illness University Study registry and conducted through Discovery Network, Society of Critical Care Medicine. Data were collected between March 01, 2020, and January 10, 2021., Results: Of 860 patients who met eligibility criteria, 589 received steroids, 170 IL-6RAs, and 101 combinations. Patients who received IL-6RAs were younger (median age of 57.5 years vs. 61.1 and 61.8 years in the steroids and combination groups, respectively). The median C-reactive protein level was > 75 mg/L, indicating a hyperinflammatory phenotype. The median daily steroid dose was 7.5 mg dexamethasone or equivalent (interquartile range: 6-14 mg); 80.8% and 19.2% received low-dose and high-dose steroids, respectively. Of the patients who received IL-6RAs, the majority received one dose of tocilizumab and sarilumab (dose range of 600-800 mg for tocilizumab and 200-400 mg for sarilumab). Regarding the timing of administration, we observed that steroid and IL-6RA administration on day 0 of ICU admission was only 55.6% and 39.5%, respectively. By day 28, when compared with steroid use alone, IL-6RA use was associated with an adjusted incidence rate ratio (aIRR) of 1.12 (95% confidence interval [CI] 0.88, 1.4) for ventilator-free days, while combination therapy was associated with an aIRR of 0.83 (95% CI 0.6, 1.14). IL-6RA use was associated with an adjusted odds ratio (aOR) of 0.68 (95% CI 0.44, 1.07) for the 28-day mortality rate, while combination therapy was associated with an aOR of 1.07 (95% CI 0.67, 1.70). Liver dysfunction was higher in IL-6RA group (p = 0.04), while the bacteremia rate did not differ among groups., Conclusions: Discordance was observed between the registry utilization patterns (i.e., timing of steroids and IL-6RA administration) and new evidence from the recent randomized controlled trials and guideline recommendations. These data will help us to identify areas of improvement in prescribing patterns and enhance our understanding of IL-6RA safety with different steroid regimens. Further studies are needed to evaluate the drivers of hospital-level variation and their impact on clinical outcomes. Trial registration ClinicalTrials.gov: NCT04486521. Registered on July 2020., (© 2021. The Author(s).)

Here we analyze hospitalized andintensive care unit coronavirus disease 2019 (COVID-19) patient outcomes from the international VIRUS registry (https://clinicaltrials.gov/ct2/show/NCT04323787). We find that COVID-19 patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (390 of 1012 = 39%) compared to patients administered enoxaparin but not unfractionated heparin (270 of 1939 = 14%), presenting a risk ratio of 2.79 (95% confidence interval [CI]: [2.42, 3.16]; p = 4.45e-52). This difference persists even after balancing on a number of covariates including demographics, comorbidities, admission diagnoses, and method of oxygenation, with an increased mortality rate on discharge from the hospital of 37% (268 of 733) for unfractionated heparin versus 22% (154 of 711) for enoxaparin, presenting a risk ratio of 1.69 (95% CI: [1.42, 2.00]; p = 1.5e-8). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to patients administered enoxaparin, including acute kidney injury, acute cardiac injury, septic shock, and anemia. Furthermore, a higher percentage of Black/African American COVID patients (414 of 1294 [32%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (671 of 2644 [25%]), risk ratio 1.26 (95% CI: [1.14, 1.40]; p = 7.5e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (311 of 1047 [30%] for Black/African American vs. 263 of 1047 [25%] for White/Caucasian, p = .02, risk ratio 1.18; 95% CI: [1.03, 1.36]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research into the observed racial disparity in anticoagulant use and outcomes for severe COVID-19 patients., (© 2021 The Authors. Journal of Medical Virology Published by Wiley Periodicals LLC.)

Objectives: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry., Design: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies., Setting: About 168 hospitals in 16 countries within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry., Patients: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation)., Interventions: None., Measurements and Main Results: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69)., Conclusions: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation., Competing Interests: Drs. Kumar’s, Denson’s, Walkey’s, and Kashyap’s institutions received funding from the Gordon and Betty Moore Foundation. Drs. Kumar’s and Kashyap’s institutions received funding from Janssen Research & Development, LLC. Drs. Kaufman’s and Denson’s institutions received funding from the Society of Critical Care Medicine. Dr. Banner-Goodspeed received partial salary support through her home institution from multiple federal research grants (including from the National Institutes of Health [NIH] and Department of Defense) as key personnel, not the principal investigator. Dr. Anderson III disclosed he is an Advisory Board member for Gift of Life Michigan. Dr. Denson received other support from American Diabetes Association Grant #7-20-COVID-53. Dr. Gajic received support for article research from Gordon and Betty Moore Foundation. Dr. Walkey receives funding from the NIH/National Heart, Lung and Blood Institute grants R01HL151607, R01HL139751, and R01HL136660, Agency of Healthcare Research and Quality, R01HS026485, Boston Biomedical Innovation Center/NIH/NHLBI 5U54HL119145-07, and royalties from UptoDate. They had no influence on acquisition, analysis, interpretation, and reporting of pooled data for this article. Dr. Harhay’s institution receives funding from the NIH/National Heart, Lung and Blood Institute grant R00 HL141678, and he received support for article research from the NIH. They had no influence on acquisition, analysis, interpretation, and reporting of pooled data for this article. Dr. Gajic receives funding from the Agency of Healthcare Research and Quality R18HS 26609-2, NIH/National Heart, Lung and Blood Institute: R01HL 130881 and UG3/UH3HL 141722; Department of Defense W81XWH; American Heart Association Rapid Response Grant—coronavirus disease 2019 (COVID-19); and royalties from Ambient Clinical Analytics. They had no influence on acquisition, analysis, interpretation, and reporting of pooled data for this article. Dr. Kashyap receives funding from the NIH/National Heart, Lung and Blood Institute: R01HL 130881 and UG3/UH3HL 141722; Gordon and Betty Moore Foundation, and Janssen Research & Development, LLC; and royalties from Ambient Clinical Analytics. They had no influence on acquisition, analysis, interpretation, and reporting of pooled data for this article. Dr. St. Hill receives funding from the Minnesota Department of Health. They had no influence on acquisition, analysis, interpretation, and reporting of pooled data for this article. Dr. Denson receives funding for COVID-19 research from the American Diabetes Association grant #7-20-COVID-053, Centers for Disease Control and Prevention BroadAgency Announcement 75D301-20-R-67897, and National Institute of General Medical Sciences/NIH award U54 GM104940, which funds the Louisiana Clinical and Translational Science Center. They had no influence on acquisition, analysis, interpretation, and reporting of pooled data for this article. Dr. Martin receives funding from the Biomedical Advanced Research and Development Authority and NIH through the National Institute of Biomedical Imaging and Bioengineering U54 EB-027690, the National Heart, Lung and Blood Institute: U54 HL-143541-02S2, the National Institute for General Medical Sciences R01 GM-104323, and the Office of the Director OT2 OD-026551; as well as funding from Genentech for clinical trial monitoring. They had no influence on acquisition, analysis, interpretation, and reporting of pooled data for this article. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

ObjectivesTo describe hospital variation in use of "guideline-based care" for acute respiratory distress syndrome (ARDS) due to COVID-19.DesignRetrospective, observational study.SettingThe Society of Critical Care Medicine's Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY.PatientsAdult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021.InterventionsHospital-level use of "guideline-based care" for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100.Measurements and main resultsAmong 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in "guideline-based care." A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1-3.4) for receipt of "guideline-based care" compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47-62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use "guideline-based care" quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3-1.9; p = 0.49).ConclusionsDuring the first year of the COVID-19 pandemic, only half of patients received "guideline-based care" for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).

Background: The rapid emergence of the COVID-19 pandemic globally collapsed health care organizations worldwide. Incomplete knowledge of best practices, progression of disease, and its impact could result in fallible care. Data on symptoms and advancement of the SARS-CoV-2 virus leading to critical care admission have not been captured or communicated well between international organizations experiencing the same impact from the virus. This led to the expedited need for establishing international communication and data collection on the critical care patients admitted with COVID-19. Objective: Developing a global registry to collect patient data in the critical care setting was imperative with the goal of analyzing and ameliorating outcomes. Methods: A prospective, observational global registry database was put together to record extensive deidentified clinical information for patients hospitalized with COVID-19. Results: Project management was crucial for prompt implementation of the registry for synchronization, improving efficiency, increasing innovation, and fostering global collaboration for valuable data collection. The Society of Critical Care Medicine Discovery VIRUS (Viral Infection and Respiratory Illness Universal Study): COVID-19 Registry would compile data for crucial longitudinal outcomes for disease, treatment, and research. The agile project management approach expedited establishing the registry in 15 days and submission of institutional review board agreement for 250 participating sites. There has been enrollment of sites every month with a total of 306 sites from 28 countries and 64,114 patients enrolled (as of June 7, 2021). Conclusions: This protocol addresses project management lessons in a time of crises which can be a precept for rapid project management for a large-scale health care data registry. We aim to discuss the approach and methodology for establishing the registry, the challenges faced, and the factors contributing to successful outcomes. [ABSTRACT FROM AUTHOR]

The number of ED visits/Hospitalization rate, and adverse events were not statistically significant between the groups (OR 0.73, 95% CI 0.32-1.70, p= 0.47 I SP 2 sp =75% and OR 1.10 95% CI 0.67-1.82, p=0.70, I SP 2 sp =28%). The primary outcome was overall mortality and secondary outcomes included symptom-based clinical improvement rates at day 14, ER visits or hospitalization, and adverse events. B Conclusions: b This meta-analysis shows that the therapeutic use of ICS in COVID-19 is associated with higher symptom-based clinical improvement rates. [Extracted from the article]

B Introduction: b Studies of hospitalized patients with COVID-19 have found varying clinical outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. A total of 1,122,329 patients were included, of which 10,466 patients died (2,289 out of 824,005 in ICS arm patients and 8,177 out of 298,324 in the non-ICS arm), resulting in the unadjusted odds of death (OR 1.36, 95% CI 1.09-1.70, I SP 2 sp =82%). [Extracted from the article]

We performed a meta-analysis of Randomized Controlled Trials (RCT) and observational studies assessing the effect of Baricitinib on mortality outcomes in hospitalized patients with COVID-19. Using the random-effects model, the odds of mortality in the therapeutic Baricitinib use showed a statistically significant reduction in all-cause mortality in hospitalized COVID-19 patients (OR 0.67, 95% CI 0.50-0.90; p=0.008, I SP 2 sp =79%). B Introduction: b The reduction of mortality in COVID-19 has been clinically established only for Dexamethasone and Tocilizumab to date, but the overall mortality in COVID-19 remains high. [Extracted from the article]

B Introduction: b During the COVID-19 pandemic, the burden on the healthcare system makes it critical to examine readmission patterns. In this study, we evaluated the readmission rates and risk factors associated with COVID-19 from the large SCCM Discovery VIRUS: COVID-19 Registry. [Extracted from the article]

To predict the tropism of human coronaviruses, we profile 28 SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) using single-cell transcriptomics across various healthy human tissues. SCARFs include cellular factors both facilitating and restricting viral entry. Intestinal goblet cells, enterocytes, and kidney proximal tubule cells appear highly permissive to SARS-CoV-2, consistent with clinical data. Our analysis also predicts non-canonical entry paths for lung and brain infections. Spermatogonial cells and prostate endocrine cells also appear to be permissive to SARS-CoV-2 infection, suggesting male-specific vulnerabilities. Both pro- and anti-viral factors are highly expressed within the nasal epithelium, with potential age-dependent variation, predicting an important battleground for coronavirus infection. Our analysis also suggests that early embryonic and placental development are at moderate risk of infection. Lastly, SCARF expression appears broadly conserved across a subset of primate organs examined. Our study establishes a resource for investigations of coronavirus biology and pathology. • Single-cell transcriptome profiling of SCARFs in various somatic and reproductive tissues • Intestine, kidneys, placenta, and spermatogonia appear most permissive for coronavirus • Nasal epithelium exhibits high expression of both promoting and restricting factors • SCARF expression is conserved across the major organs of human, chimpanzee, and macaque Singh et al. provide a resource to predict the tropism and identify the plausible entry points for SARS-CoV-2 and other pathogenic coronaviruses throughout the human body. The RNA levels of 28 genes dubbed "SCARFs," for SARS-CoV-2 and coronavirus-associated receptors and factors, are profiled in human tissues at the single-cell level. [ABSTRACT FROM AUTHOR]

Objectives: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19.Design: Retrospective observational study.Setting: Multicenter, international COVID-19 registry.Subjects: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021.Interventions: None.Measurements and Main Results: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001).Conclusions: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients. [ABSTRACT FROM AUTHOR]

B Introduction: b Better delineation of COVID-19 presentations in different climatological conditions might assist with prompt diagnosis and isolation of patients. When adjusted for baseline differences, at lower latitudes (< 30°) patients presented less commonly with gastrointestinal symptoms (p< 0.001, odds ratios for latitudes 15°, 25°, and 30°: 0.32, 0.81, and 0.98, respectively). [Extracted from the article]

B Introduction: b Gastrointestinal symptoms are common is patients with COVID-19. There were significant differences in baseline demographics, and signs and symptoms and comorbidities at hospital admission between patients with and without gastrointestinal symptoms. Upon hospitalization, patients presenting with gastrointestinal symptoms (isolated or along with other non-gastrointestinal symptoms), may have a better prognosis than patients with non-gastrointestinal symptoms. [Extracted from the article]

OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation. [ABSTRACT FROM AUTHOR]

Objectives: Use of observational data to inform the response and care of patients during a pandemic faces unique challenges.Design: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID 2019 Registry Core data and research methodology team convened over virtual meetings throughout March to June 2020 to determine best practice goals for development of a pandemic disease registry to support rapid data collection and analysis.Setting: International, multi-center registry of hospitalized patients.Patients: None.Interventions: None.Measurements and Main Results: Large-scale observational data collection requires: 1) quality assurance and harmonization across many sites; 2) a transparent process for selecting from among many potential research questions; 3) the use of best practices in design of descriptive, predictive, and inferential studies; (4) innovative approaches to characterize random error in the setting of constantly updated data; (5) rapid peer-review and reporting; and (6) transitions from a focus on discovery to implementation. Herein, we describe the guiding principles to best practices and suggestions for innovations to study design and reporting within the coronavirus disease 2019 Viral Infection and Respiratory Illness Universal Study pandemic registry.Conclusions: Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry sought to develop and implement prespecified best practices combined with grassroots efforts from clinical sites worldwide in order to develop clinically useful knowledge in response to a pandemic. [ABSTRACT FROM AUTHOR]

COVID-19 patients with NAFLD had worse COVID-19 infection outcomes compared to those without NAFLD (OR 1.59, 95%CI 1.12-2.26, p-value=0.01, I2=81%) (Figure 4). B Introduction: b Non-alcoholic fatty liver disease (NAFLD) and its hepatic manifestation, metabolic-associated fatty liver disease (MAFLD) have a rising prevalence worldwide in the background of the ongoing global pandemic. This meta-analysis aims to investigate the association between NAFLD and MAFLD with the severity of COVID-19 infection and the need for mechanical ventilation. [Extracted from the article]

B Introduction: b There is published literature about COVID-19 disease associated coagulopathy in hospitalized patients. B Conclusions: b Early administration of heparin in patients with moderate to severe COVID-19 sepsis was associated with reduced utilization of IMV and NIMV and reduced hospital LOS. We aim to study association of early heparin use among adult patients with COVID-19 and sepsis and hospital outcomes. [Extracted from the article]

B Conclusions: b Prehospital use of anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower severity of disease in COVID-19 patients. The risk of thromboembolic events in COVID-19 infected patients on chronic anticoagulation is the primary outcome and severity of COVID-19 disease in terms of ICU admission or invasive mechanical ventilation/intubation requirements, and all-cause mortality were the secondary outcomes. B Introduction: b Coagulopathy and thromboembolic events are poor prognostic indicators of COVID-19 disease. [Extracted from the article]

B Conclusions: b Most respondents agree that webinars are an important medium for the dissemination of information on COVID-19 and that these webinars have informed their clinical practice. Around 75% of respondents either agreed or highly agreed that webinars are a useful source of knowledge despite only 68% of them reporting to have active participation in webinars relating to COVID-19 treatment/management. Overall, our survey showed a strong interest from front liners for COVID-19 webinars. [Extracted from the article]