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

Authors

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 Phillips
Garyphallia Poulakou
David A Price
Philip Robinson
Angela J Rogers
Uriel Sandkovsky
Katy Shaw-Saliba
Jeffrey M Sturek
Barbara W Trautner
Michael Waters
Cavan Reilly

Publication Date

6-14-2024

Journal

Clinical Infectious Diseases

DOI

10.1093/cid/ciad780

PMID

38376212

PMCID

PMC11175705

PubMedCentral® Posted Date

2-20-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, COVID-19, Female, Male, Middle Aged, SARS-CoV-2, Aged, Hospitalization, Interleukin-6, Adult, Antiviral Agents, RNA, Viral, COVID-19 Drug Treatment, Antibodies, Viral, Antigens, Viral, acute COVID-19, viral factors, host response

Abstract

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/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (/mL [aHR, 2.42; 1.09-5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support ([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.

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.