Association Between Anterior Nasal and Plasma SARS-CoV-2 RNA Levels and Hospitalization or Death in Nonhospitalized Adults With Mild-to-Moderate COVID-19.

Abstract

BACKGROUND:

There is little information regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA as a predictor for clinical outcomes in outpatients with mild-to-moderate coronavirus disease 2019 (COVID-19).

METHODS:

Anterior nasal (AN) and plasma SARS-CoV-2 RNA data from 2115 nonhospitalized adults who received monoclonal antibodies (mAbs) or placebo in the ACTIV-2/A5401 trial were analyzed for associations with hospitalization or death.

RESULTS:

One hundred two participants were hospitalized or died through 28 days of follow-up. Higher day 0 (pretreatment) AN RNA was associated with increasing risk of hospitalization/death (risk ratio [RR], 1.24 per log10 copies/mL [95% confidence interval {CI}, 1.04-1.49]) among placebo recipients, ranging from 3% to 16% for <2 to ≥6 log10 copies/mL. Although only 1% had quantifiable levels, there was a similar trend across day 0 plasma RNA categories. Higher day 3 AN RNA was associated with subsequent hospitalization/death among placebo recipients (RR, 1.42 per log10 copies/mL [95% CI, 1.00-2.03]), but not mAb recipients (RR, 1.02 per log10 copies/mL [95% CI, 0.68-1.56]). The proportion of treatment effect (reduction in hospitalizations/deaths after day 3 for mAb vs placebo) explained by day 3 AN RNA was 8%.

CONCLUSIONS:

SARS-CoV-2 RNA levels are predictive of hospitalization/death in the natural history setting, but AN RNA levels may not be a reliable surrogate marker of mAb treatment effect in COVID-19 trials. Clinical Trials Registration. NCT04518410.

• Authors: Mark J Giganti, Kara W Chew, Joseph J Eron, Jonathan Z Li, Mauricio Pinilla, Carlee Moser, Arzhang Cyrus Javan, William A Fischer, Paul Klekotka, David Margolis, David Alain Wohl, Robert W Coombs, Eric S Daar, Davey M Smith, Judith S Currier, Michael D Hughes, ACTIV-2/A5401 Study Team
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 228 Issue Suppl 2 Pg. S117-S125 (08 31 2023) ISSN: 1537-6613 [Electronic] United States
• PMID: 37650230 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antibodies, Monoclonal
• RNA, Viral

Topics

• Adult
• Humans
• Antibodies, Monoclonal
• COVID-19
• Hospitalization
• RNA, Viral
• SARS-CoV-2 (genetics)