Author:
Deo Rinki,Choudhary Manish C.,Moser Carlee,Ritz Justin,Daar Eric S.,Wohl David A.,Greninger Alexander L.,Eron Joseph J.,Currier Judith S.,Hughes Michael D.,Smith Davey M.,Chew Kara W.,Li Jonathan Z.,
Abstract
SummaryBackgroundThere are reports of viral RNA and symptom rebound in people with COVID-19 treated with nirmatrelvir/ritonavir. Since the natural course of viral and symptom trajectories of COVID-19 has not been well described, we evaluated the incidence of viral and symptom rebound in untreated outpatients with mild-moderate COVID-19.MethodsThe study population included 568 participants enrolled in the ACTIV-2/A5401 platform trial who received placebo. Anterior nasal swabs were collected for SARS-CoV-2 RNA testing on days 0-14, 21 and 28. Participants recorded the severity of 13 targeted symptoms daily from day 0 to 28. Viral rebound was defined as ≥0.5 log10 viral RNA copies/mL increase and symptom rebound was defined as a 4-point total symptom score increase from baseline. Baseline was defined as study day 4 (primary analysis) or 8 days from symptom onset (secondary analysis).FindingsIn both the primary and secondary analyses, 12% of participants had viral rebound. Viral rebounders were older than non-rebounders (median 54 vs 47 years, P=0.04). Symptom rebound occurred in 27% of participants after initial symptom improvement and in 10% of participants after initial symptom resolution. The combination of high-level viral rebound to ≥5.0 log10 RNA copies/mL and symptom rebound after initial improvement was observed in 1-2% of participants.InterpretationViral RNA rebound or symptom relapse in the absence of antiviral treatment is common, but the combination of high-level viral and symptom rebound is rare.FundingThis study was supported by the National Institute of Allergy and Infectious Diseases; ACTIV-2/A5401 ClinicalTrials.gov number NCT04518410.
Publisher
Cold Spring Harbor Laboratory