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Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19

  1. Author:
    Aggarwal, Neil R [ORCID]
    Nordwall, Jacquie
    Braun, Dominique L
    Chung, Lucy
    Coslet, Jordan
    Der, Tatyana
    Eriobu, Nnakelu
    Ginde, Adit A
    Hayanga, Awori J
    Highbarger, Helene
    Holodniy, Mark
    Horcajada, Juan P
    Jain, Mamta K
    Kim, Kami
    Laverdure, Sylvain
    Lundgren, Jens
    Natarajan, Ven
    Nguyen, Hien H
    Pett, Sarah L
    Phillips, Andrew
    Poulakou, Garyphallia
    Price, David A
    Robinson, Philip
    Rogers, Angela J
    Sandkovsky, Uriel
    Shaw-Saliba, Katy
    Sturek, Jeffrey M
    Trautner, Barbara W
    Waters, Michael
    Reilly, Cavan

  2. Author Address

    Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA., Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA., Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., CAMRIS International (under contract no. 75N93019D00025 with National Institute of Allergy and Infectious Diseases, Department of Health and Human Services), National Institute of Health, Bethesda, Maryland, USA., Velocity Clinical Research, Chula Vista, California, USA., Department of General Internal Medicine, Duke University School of Medicine, Durham, North Carolina, USA., Institute of Human Virology Nigeria, Abuja, Nigeria., Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA., Department of Cardiovascular Thoracic Surgery, West Virginia University School of Medicine, Morgantown, West Virginia, USA., Virus Isolation and Serology Laboratory, Frederick National Laboratory, National Cancer Institute, Frederick, Maryland, USA., Veterans Affairs Palo Alto Health Care System, Division of Infectious Diseases and Geographic Medicine, Stanford University, Palo Alto, California, USA., Department of Infectious Diseases, Hospital del Mar Research Insititute, UPF, Barcelona, Spain., CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain., Division of Infectious Diseases and Geotropical Medicine, UT Southwestern Medical Center and Parkland Health and Hospital System, Dallas, Texas, USA., Division of Infectious Disease and International Medicine, Morsani College of Medicine, University of South Florida and Global Emerging Diseases Institute, Tampa General Hospital, Tampa, Florida, USA., Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory, National Cancer Institute, Frederick, Maryland, USA., CHIP Center of Excellence for Health, Immunity, and Infections and Department of Infectious Diseases, Righospitalet, University of Copenhagen, Copenhagen, Denmark., Laboratory of Molecular Cell Biology, Frederick National Laboratory, National Cancer Institute, Frederick, Maryland, USA., Division of Infectious Diseases, Veterans Affairs Northern California, University of California, Davis, Sacramento, California, USA., The Medical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, United Kingdom., Institute for Global Health, University College London, London, United Kingdom., Third Department of Medicine and Laboratory National and Kapodistrian University of Athens Medical School, Athens, Greece., Newcastle Upon Tyne NHUS Hospitals Foundation Trust, Newcastle Upon Tyne, United Kingdom., Infection Prevention and Hospital Epidemiology, Hoag Memorial Hospital Presbyterian, Newport Beach, California, USA., Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Palo Alto, California, USA., Division of Infectious Diseases, Baylor University Medical Center, Dallas, Texas, USA., National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, Maryland, USA., Division of Pulmonary and Critical Care Medicine, Department of Medicine, UVA Health, Charlottesville, Virginia, USA., Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA.,
    1. Year: 2024
    2. Date: Feb 20
    3. Epub Date: 2024 02 20
  2. Journal: Clinical Infectious Diseases : an official publication of the Infectious Diseases Society of America
  4. Type of Article: Article
  5. Article Number: ciad780
  1. Abstract:

    Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials. A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models. Viral Ag =4500 ng/L (vs < 200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (< 35 000 copies/mL [aHR, 2.42; 1.09-5.34], =35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support (< 4 L O2 [aHR, 1.84; 1.06-3.22]; =4 L O2 [aHR, 4.41; 2.63-7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46-19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29-2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74-3.70] vs =5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time. Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease. © The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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  1. View Full Text
  2. DOI: 10.1093/cid/ciad780
  3. PMID: 38376212
  4. PII : 7611291

Library Notes

  1. Fiscal Year: FY2023-2024
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