Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C
Alexander Preiss, Abhishek Bhatia, Chengxi Zang, Leyna V Aragon, John M Baratta, Monika Baskaran, Frank Blancero, M Daniel Brannock, Robert F Chew, Ivan Diaz, Megan Fitzgerald, Elizabeth P Kelly, Andrea G Zhou, Mark G Weiner, Thomas W Carton, Fei Wang, Rainu Kaushal, Christopher G Chute, Melissa Haendel, Richard Moffitt, Emily Pfaff
doi:10.1101/2024.01.20.24301525
Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,461 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. Our primary outcome measure was a PASC computable phenotype. Secondary outcomes were the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.99, 95% confidence interval [CI] 0.96-1.01). However, its effect varied across the cognitive (RR = 0.85, 95% CI 0.79-0.90), fatigue (RR = 0.93, 95% CI 0.89-0.96), and respiratory (RR = 0.99, 95% CI 0.95-1.02) symptom clusters, suggesting that Paxlovid treatment may help prevent post-acute cognitive and fatigue symptoms more than others.
SUPPLEMENT A -ADDITIONAL TABLES AND FIGURES sleep wake disorders, dyspnea (or shortness of breath), acute pharyngitis, hair loss, edema, fever, malaise and fatigue. 66, 67 The incident post-acute sequelae of SARS-CoV-2 (PASC) symptoms from the list above was observed during the post-acute phase (30 to 180 days after the index date), while absent during the baseline period (7 days to 3 years preceding the index date). Individuals classified as having incident PASC when he/she exhibited at least one incident PASC-related symptom during the post-acute phase. The same set of covariates as N3C were built for the adjustment analyses, including age, self-reported sex, race/ethnicity, CCI score, baseline hospitalization utilization, social-economic status and infection time. The social-economic status was quantified by the national-level area deprivation index (ADI) linked by either 9-digit zip code or geocode. The IPTW re-weighted survival analyses, including Cox proportional hazard model for the relative risk, and the Aalen-Johansen model for the cumulative incidence. Both methods considered the death to be a competing risk for the target incident outcomes. The IPTW weights were learned based on method from Zang et al. 68
Results
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