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When started within 5 days after symptom onset, molnupiravir lowered risk for post-acute death and long-COVID sequelae regardless of vaccination status or reinfection.
Long COVID is a multifaceted condition with persistent post-acute and chronic sequelae. Previous reports indicated that full vaccination and antiviral treatment with nirmatrelvir/ritonavir (Paxlovid) were both associated with significantly lower risk for long COVID (NEJM JW Gen Med May 1 2023 and JAMA Intern Med 2023 Mar 23; [e-pub]). Now, Xie et al. conducted a retrospective cohort study between January 2022 and January 2023 in the VA network to determine whether treatment with the antiviral molnupiravir also reduced long-COVID symptoms. Participants comprised >229,000 individuals with at least one risk factor for severe COVID-19. Of these, 11,472 were started on molnupiravir within 5 days of a positive SARS-CoV-2 test.
Compared with those who received no treatment, molnupiravir recipients had lower risk for post-acute mortality (hazard ratio, 0.62) and post-acute hospital admission (HR, 0.86). Furthermore, molnupiravir use was associated with significant risk reduction in 8 of 13 post-acute long-COVID sequelae (dysrhythmia, pulmonary embolism, thrombosis, fatigue and malaise, liver disease, acute kidney injury, muscle pain, and neurocognitive impairment; HR vs. no treatment, 0.86). Molnupiravir’s effectiveness was independent of age, race, sex, vaccination or prior COVID-19 infection, immunodeficiency, or comorbidities.
It’s generally acknowledged that risk for long COVID is associated with disease severity during the acute phase. The lower mortality and reduced risk for long-term sequelae associated with molnupiravir treatment appear to support this concept and are in line with the findings of a similar study by the same researchers on Paxlovid in the acute phase of COVID-19. However, as the pathogenesis of long COVID remains obscure, unmeasured confounders cannot be fully excluded. Furthermore, the effectiveness of Paxlovid appears to be slightly higher than that of molnupiravir. While a head-to-head comparison is still lacking, Paxlovid remains a first-line choice followed by molnupiravir if Paxlovid cannot be given because of drug interactions.
Xie Y et al. Molnupiravir and risk of post-acute sequelae of covid-19: Cohort study. BMJ 2023 Apr 25; 381:e074572. (https://doi.org/10.1136/bmj-2022-074572. opens in new tab)