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Long-Term Stroke and Mortality Risk Reduction Associated With Acute-Phase Paxlovid Use in Mild-to-Moderate COVID-19
Cheng-Hsun Chuang1,2,3, Yu-Hsun Wang1,4, Liang-Tsai Yeh5,6,7
1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Journal of Medical Virology
|April 14, 2025
Summary
Paxlovid (nirmatrelvir/ritonavir) use in acute COVID-19 significantly lowers the risk of long COVID-related stroke and mortality. This antiviral treatment offers crucial protection against long-term cerebrovascular events and death post-infection.
Area of Science:
- Neurology
- Infectious Diseases
- Pharmacology
Background:
- Long COVID, a condition occurring more than 3 months post-COVID-19 diagnosis, can include cerebrovascular events like stroke.
- The effectiveness of antiviral treatments, such as Paxlovid (nirmatrelvir/ritonavir), in mitigating long-term COVID-19 complications remains an area of active investigation.
Purpose of the Study:
- To determine if Paxlovid administration during the acute phase of mild-to-moderate COVID-19 reduces the risk of ischemic or hemorrhagic stroke in the long COVID period.
- To assess the impact of Paxlovid on all-cause mortality in patients with long COVID.
Main Methods:
- Retrospective cohort study using TriNetX electronic health records (118 million patients).
- Adults with COVID-19 (2022-2023) were divided into Paxlovid (within 5 days of diagnosis) and non-Paxlovid groups.
- Propensity score matching (1:1 ratio) controlled for confounders; stroke and mortality analyzed using survival curves and Cox models.
Main Results:
- Paxlovid use was associated with a significantly reduced risk of ischemic and hemorrhagic stroke (HR 0.85; 95% CI: 0.80-0.89) and all-cause mortality (HR 0.68; 95% CI: 0.63-0.73) in the long COVID period (>90 days post-diagnosis).
- Protective effects were consistent across subgroups, including older adults and individuals with metabolic conditions like obesity, and were independent of vaccination status.
Conclusions:
- Paxlovid use during acute COVID-19 significantly reduces the risk of long-term cerebrovascular events and mortality.
- These findings underscore the critical role of Paxlovid in mitigating long-term complications associated with COVID-19, including neurological sequelae.
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