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Use of nirmatrelvir/ritonavir (N/R; Paxlovid), the recommended treatment for mild-to-moderate COVID-19, has lowered rates of hospitalization and death. For patients already taking drugs with N/R contraindications, molnupiravir is recommended and has also reduced both outcomes. Still, uptake of these antivirals has fallen short of the hoped-for goal — and this lack of acceptance is thought to be due to public belief that COVID-19 rebound (recurrence of symptoms or a newly positive SARS-CoV-2 test after recovery) is related to such drugs.
Now, CDC has published two reports: A meta-analysis of data from seven studies comparing rebound rates with and without antiviral use, and a retrospective analysis of two placebo-controlled trials of N/R. Overall, the studies yielded no statistically significant evidence that treatment with any of the approved anti–COVID-19 drugs raised risk for symptomatic or viral rebound. When rebound did occur, it generally affected patients who were immunocompromised or who had significant comorbidities, and it was not associated with increased mortality or hospitalization.
Smith DJ et al. SARS-CoV-2 rebound with and without use of COVID-19 oral antivirals. MMWR Morb Mortal Wkly Rep 2023 Dec 22; 72:1357. (https://doi.org/10.15585/mmwr.mm7251a1)
Harrington PR et al. Evaluation of SARS-CoV-2 RNA rebound after nirmatrelvir/ritonavir treatment in randomized, double-blind, placebo-controlled trials — United States and international sites, 2021–2022. MMWR Morb Mortal Wkly Rep 2023 Dec 22; 72:1365. (https://doi.org/10.15585/mmwr.mm7251a2)
Comment
Medical rumors die hard, and those surrounding the prevention and treatment of COVID-19 are no exception. However, for individuals who rely on data for decision making, these two studies provide ample evidence in favor of the currently approved drugs for mitigating severe SARS-CoV-2 infection without significantly increasing incidence of rebound, thereby diminishing the likelihood of hospitalization and death.