{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T23:26:45Z","timestamp":1773444405107,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This retrospective cohort study investigated whether Paxlovid (nirmatrelvir\/ritonavir) use during the acute phase of mild\u2010to\u2010moderate COVID\u201019 reduces the risk of ischemic or hemorrhagic stroke occurring more than 3 months post\u2010diagnosis, a condition classified as long COVID. Utilizing TriNetX electronic health records comprising 118 million patients in the United States, adults aged 18 years or older with confirmed COVID\u201019 diagnoses from 2022 to 2023 were categorized into Paxlovid (administered within 5 days of diagnosis) and non\u2010Paxlovid groups. Exclusion criteria included prior cerebrovascular disease, mortality within 3 months, use of specific antivirals, and severe clinical conditions such as ICU admission, intubation, mechanical support, SpO\u2082 &lt;\u200990%, respiratory rate &gt;\u200930\/min, sepsis, systemic inflammatory response syndrome, and acute respiratory distress syndrome. The index date was the initial COVID\u201019 diagnosis. Propensity score matching in a 1:1 ratio controlled for confounding factors, and stroke (ischemic or hemorrhagic) and mortality were analyzed using Kaplan\u2013Meier survival curves and Cox proportional hazards models. Among 181\u2009992 matched pairs, Paxlovid use was associated with a significantly reduced risk of ischemic and hemorrhagic stroke (hazard ratio [HR] 0.85; 95% confidence interval [CI]: 0.80\u20130.89) and all\u2010cause mortality (HR 0.68; 95% CI: 0.63\u20130.73) during the long COVID period, defined as more than 90 days post\u2010diagnosis. Subgroup analyses demonstrated consistent protective effects across age, sex, BMI, comorbidities such as hypertension, diabetes, and hyperlipidemia, and vaccination status. Notably, older adults (HR 0.81; 95% CI: 0.76\u20130.86) and individuals with metabolic conditions, including obesity (HR 0.86; 95% CI: 0.78\u20130.96), exhibited pronounced benefits, and the protective effects were observed irrespective of vaccination status. These findings highlight that Paxlovid use during the acute phase of COVID\u201019 significantly reduces the risk of long\u2010term cerebrovascular events and mortality, emphasizing its critical role in mitigating long\u2010term complications associated with COVID\u201019.<\/jats:p>","DOI":"10.1002\/jmv.70351","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T06:02:31Z","timestamp":1744610551000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Long\u2010Term Stroke and Mortality Risk Reduction Associated With Acute\u2010Phase Paxlovid Use in Mild\u2010to\u2010Moderate COVID\u201019"],"prefix":"10.1002","volume":"97","author":[{"given":"Cheng\u2010Hsun","family":"Chuang","sequence":"first","affiliation":[{"name":"Institute of Medicine Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Emergency Medicine, School of Medicine Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Emergency Medicine Chung Shan Medical University Hospital  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Hsun","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicine Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Medical Research Chung Shan Medical University Hospital  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang\u2010Tsai","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Changhua Christian Hospital Changhua Taiwan"},{"name":"School of Medicine Chung Shan Medical University Taichung Taiwan"},{"name":"Department of Post\u2010Baccalaureate Medicine, College of Medicine National Chung Hsing University Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3978-5576","authenticated-orcid":false,"given":"Chao\u2010Bin","family":"Yeh","sequence":"additional","affiliation":[{"name":"Institute of Medicine Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Emergency Medicine, School of Medicine Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Emergency Medicine Chung Shan Medical University Hospital  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsb2408466"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.10.006"},{"issue":"2","key":"e_1_2_9_4_1","first-page":"61","article-title":"Multi\u2010Organ Systems Involvement in COVID\u201019 Is Associated With a Worse 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