BACKGROUND: The impact of antiviral therapies, including Paxlovid, on post-acute sequelae of COVID-19 (PASC) remains inconclusive.
METHODS: We analyzed data from 19,413 patients (age > 18) from a validated PASC research cohort in New England who experienced at least one COVID-19 infection episode between January 1, 2022, and June 7, 2022, totaling 22,094 episodes. Multivariable logistic regression with inverse probability weights was used to infer the causal effects of Paxlovid treatment during acute infection and the risk of PASC overall (primary outcome), stratified by age group and organ system.
RESULTS: Across all age groups, Paxlovid shows no statistically significant effect in lowering overall PASC risk. Stratification by organ system reveals a 37% reduction in gastrointestinal PASC (OR: 0.63; 95% CI: [0.468, 0.850]; p < 0.05) but a 97.4% increase in the risk of eye and ear-related PASC (OR: 1.974; 95% CI: [1.048, 3.718]; p < 0.05). Among patients aged 65 to 75 years who were not hospitalized, Paxlovid is associated with a 16.8% reduction in PASC risk (OR: 0.832; 95% CI: [0.7, 0.989]; p < 0.05). No statistically significant effects is observed for other organ-specific outcomes.
CONCLUSIONS: Paxlovid demonstrates organ-specific effects on the risk of PASC, with a reduction in gastrointestinal symptoms and an increased risk of eye and ear-related symptoms. In older, non-hospitalized patients, Paxlovid modestly reduces overall PASC risk. These findings highlight the complexity of antiviral therapy's long-term impact and underscore the need for further research to clarify the mechanisms underlying these outcomes.