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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II. We hypothesized that losartan compared to usual care decreases mortality and is safe in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of losartan versus usual care on 28-day mortality in patients hospitalized for acute COVID-19., Methods: Eligibility criteria included adults admitted for acute COVID-19. Exclusion criteria were hypotension, hyperkalemia, acute kidney injury, and use of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors within 7 days. Participants were randomized to losartan 25-100 mg/day orally for the hospital duration or 3 months or the control arm (usual care) in 29 hospitals in Canada and France. The primary outcome was 28-day mortality. Secondary outcomes were hospital mortality, organ support, and serious adverse events (SAEs)., Results: The trial was stopped early because of a serious safety concern with losartan. In 341 patients, any SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P = .01; hypotension: 30.4% vs 15.3%, respectively, P < .001) in both ward and intensive care patients. The 28-day mortality did not differ between losartan (6.5%) versus usual care (5.9%) (odds ratio, 1.11 [95% confidence interval, .47-2.64]; P = .81), nor did organ dysfunction or secondary outcomes., Conclusions: Caution is needed in deciding which patients to start or continue using ARBs in patients hospitalized with pneumonia to mitigate risk of hypotension, acute kidney injury, and other side effects. ARBs should not be added to care of patients hospitalized for acute COVID-19., Clinical Trials Registration: NCT04606563., Competing Interests: Potential conflicts of interest . J. A. R. reports patents owned by the University of British Columbia that are related to (i) the use of PCSK9 inhibitor(s) in sepsis, (ii) the use of vasopressin in septic shock, and (iii) a patent owned by Ferring for use of selepressin in septic shock; J. A. R. is an inventor on these patents. J. A. R. was a founder, director, and shareholder in Cyon Therapeutics Inc (now closed) and is a shareholder in Molecular You Corp; is the Senior Research Advisor of the British Columbia, Canada Post COVID–Interdisciplinary Clinical Care Network (PC-ICCN); reports receiving consulting fees in the last 3 years as a funded member of the data and safety monitoring board of a National Institutes of Health–sponsored trial of plasma in COVID-19 (PASS-IT-ON; 2020–2021); has received grants for COVID-19 and for pneumonia research from CIHR and the St Paul's Foundation; and was a nonfunded science advisor and member of the government of Canada COVID-19 Therapeutics Task Force (June 2020–2021). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: The thrombo-inflammatory response and outcomes of community-acquired pneumonia (CAP) due to various organisms (non-COVID-19 CAP) versus CAP due to a single virus, SARS-CoV-2 (i.e., COVID-19) may differ., Methods: Adults hospitalized with non-COVID-19 CAP (December 1, 2021-June 15, 2023) or COVID-19 (March 2, 2020-June 15, 2023) in Canada. We compared non-COVID-19 CAP and COVID-19 baseline, thrombo-inflammatory response, and mortality. We measured plasma cytokine and coagulation factor levels in a sample of patients, did hierarchical clustering, and compared cytokine and coagulation factor levels., Results: In 2,485 patients (non-COVID-19 CAP, n = 719; COVID-19 patients, n = 2,157), non-COVID-19 CAP patients had significantly lower 28-day mortality (CAP vs. COVID-19 waves 1 and 2; 10% vs. 18% and 16%, respectively), intensive care unit admission (CAP vs. all waves; 15% vs. 39%, 37%, 33%, and 24%, respectively), invasive ventilation (CAP vs. waves 1, 2, and 3 patients; 11% vs. 25%, 20%, and 16%), vasopressor use (CAP 12% vs. 23%, 21%, and 18%), and renal replacement therapy use (CAP 3% vs. Omicron 7%). Complexity of hierarchical clustering aligned directly with mortality: COVID-19 wave 1 and 2 patients had six clusters at admission and higher mortality than non-COVID-19 CAP and Omicron that had three clusters at admission. Pooling all COVID-19 waves increased complexity with seven clusters on admission., Conclusion: Complex thrombo-inflammatory responses aligned with mortality of CAP. At a fundamental level, the human thrombo-inflammatory response to a brand new virus was "confused" whereas humans had eons of time to develop a more concise efficient thrombo-inflammatory host response to CAP., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objectives: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components., Design: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup ( n = 46), recorded d -dimer ( n = 967), comparing males with females., Setting: ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces., Patients: One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included., Interventions: None., Measurements and Main Results: Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation ( p = 0.006) and vasopressors ( p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females., Conclusions: ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19., Competing Interests: Drs. Rocheleau’s, Cheng’s, Lee’s, Haljan’s, Vinh’s, Mann’s, Donohoe’s, and Russell’s institutions received funding from the Canadian Institutes for Health Research. Dr. Mohammed’s institution received funding from Genome Canada and Genome British Colombia. Dr. Goodlett disclosed that he is the founder of Pataigin LLC and Deurion LLC and that the University of Victoria Genome British Columbia Proteome Centre (for which he is a director) received funding from Genome Canada and Genome British Colombia. Dr. Burns disclosed that he is a consultant to JN Nova Pharma. Dr. Cheng’s institution received funding from McGill Interdisciplinary Initiative in Infection and Immunity; he received funding from GEn1E Lifesciences and NPlex Biosciences; he disclosed that he is the cofounder of Kanvas Biosciences and owns equity in the company; and he disclosed that he is a named coinventor on a pending patent entitled “Methods for assessing the severity and progression of SARS-CoV2 infections using cell-free DNA.” Dr. Slutsky received funding from Apeiron, GlaxoSmithKline, Baxter, Cellenkos, Diffusion, Edesa, Exvastat, Faron, and Novalung. Dr. Lee received funding from the Fonds de recherche du Quebec santé (FRQS). Dr. Haljan’s institution received funding from Michael Smith Foundation for Health Research and Surrey Hospital Foundation. Dr. Vinh’s institution received funding from the Jeffrey Modell Foundation and FRQS; he received funding from CSL Behring, Astra Zeneca, Moderna, Takeda, QU Biologics, Merck Canada, Novartis Canada, and the COVID Immunity Task Force (Public Health Agency of Canada); he disclosed he has patent applications pending (Encrypting File System Identification [EFS ID] 40101099; EFS ID 44321620). Dr. Russell reports patents owned by the University of British Columbia (UBC) that are related to the use of proprotein convertase subtilisin/kexin type 9 inhibitor(s) in sepsis and related to the use of vasopressin in septic shock and a patent owned by Ferring for use of selepressin in septic shock; he is an inventor on these patents; he was a founder, director, and shareholder in Cyon Therapeutics and is a shareholder in Molecular You Corp; he reports receiving consulting fees in the last 3 years from: Asahi Kesai Pharmaceuticals of America (was developing recombinant thrombomodulin in sepsis), SIB Therapeutics LLC (developing a sepsis drug), and Ferring Pharmaceuticals (manufactures vasopressin and developing selepressin); he is no longer actively consulting for the following: La Jolla Pharmaceuticals (developing angiotensin II; Dr. Russell chaired the Data Safety Monitoring Board of a trial of angiotensin II from 2015 to 2017), PAR Pharma (sells prepared bags of vasopressin); and he reports having received an investigator-initiated grant from Grifols (entitled “Is HBP a mechanism of albumin’s efficacy in human septic shock?”) that was provided to and administered by UBC. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: Healthcare workers have historically experienced symptoms of post-traumatic stress disorder, depression and anxiety with previous infectious outbreaks. It is unknown if critical care nurses have similar experiences., Objectives: The study aimed to examine the mental health of Critical Care Registered Nurses providing direct patient care during the initial phase of the COVID-19 pandemic in Canada., Design: This was a convergent parallel mixed method study utilizing validated questionnaires and semi-structured qualitative interviews., Setting: Critical care units in a single large 650 bed academic teaching hospital in western Canada. The critical care units serve a general mixed medical - surgical adult patient population., Participants: Critical Care Registered Nurses providing direct patient care in the intensive care and high acuity units at the designated site., Methods: 109 participants completed two self-reported validated surveys, the Impact of Events Scale - Revised and the Depression, Anxiety and Stress Scale. 15 participants completed one-on-one semi-structured interviews that were analyzed using inductive thematic analysis., Results: In the surveys, the participants reported clinical concern for (23%), probable (13%) and significant (38%) symptoms of post-traumatic stress disorder, as well as mild to severe depression (57%), anxiety (67%) and stress (54%). In the interviews, psychological distress was described as anxiety, worry, distress and fear related to: 1) rapidly changing policy and information, 2) overwhelming and unclear communication, 3) meeting patient care needs in new ways while staying safe, and 4) managing home and personal commitments to self and family., Conclusions: Critical care nurses experienced psychological distress associated with providing care to COVID-19 patients during the early phases of the pandemic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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