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Viral and Symptom Rebound in Untreated COVID-19 Infection

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  • Viral and Symptom Rebound in Untreated COVID-19 Infection


    Viral and Symptom Rebound in Untreated COVID-19 Infection
    Rinki Deo, Manish C Choudhary, Carlee Moser, Justin Ritz, Eric S Daar, David A Wohl, Alexander L Greninger, Joseph J Eron, Judith S Currier, Michael D Hughes, Davey M Smith, Kara W Chew, Jonathan Z Li
    This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.


    Background: There 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. Methods: The 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). Findings: In 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. Interpretation: Viral 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. Funding: This study was supported by the National Institute of Allergy and Infectious Diseases; ACTIV-2/A5401 number NCT04518410.