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

Neil R. Aggarwal*, Jacquie Nordwall, Dominique L. Braun, Lucy Chung, Jordan Coslet, Tatyana Der, Nnakelu Eriobu, Adit A. Ginde, Awori J. Hayanga, Helene Highbarger, Mark Holodniy, Juan P. Horcajada, Mamta K. Jain, Kami Kim, Sylvain Laverdure, Jens Lundgren, Ven Natarajan, Hien H. Nguyen, Sarah L. Pett, Andrew PhillipsGaryphallia Poulakou, David A. Price, Philip Robinson, Angela J. Rogers, Uriel Sandkovsky, Katy Shaw-Saliba, Jeffrey M. Sturek, Barbara W. Trautner, Michael Waters, Cavan Reilly, ACTIV-3/TICO Study Group , Henrik Nielsen (Medlem af forfattergruppering), Rikke Krog Thisted (Medlem af forfattergruppering), Kristine Toft Petersen (Medlem af forfattergruppering), Maria Ruwald Juhl (Medlem af forfattergruppering)


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Background. 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. Methods. 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. Results. 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 O 2 [aHR, 1.84; 1.06–3.22]; ≥4 L O 2 [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. Conclusions. 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.

TidsskriftClinical Infectious Diseases
Udgave nummer6
Sider (fra-til)1490-1503
Antal sider14
StatusUdgivet - 15 jun. 2024

Bibliografisk note

© 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: [email protected].


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