基於 TriNetX 資料庫之研究：COVID-19 疫苗接種既有周邊血管疾病患者之下肢截肢率與死亡率相關性

研究目的：本研究旨在利用 TriNetX 多中心電子病歷資料庫，探討周邊動脈阻塞性疾病（PAOD）患者於感染 SARS-CoV-2 前接受 COVID-19 疫苗接種，是否與降低下肢截肢率及全因死亡率相關，並評估疫苗在高風險血管疾病族群中的臨床保護效益與預後影響。研究方法及資料：本研究採回溯性世代研究設計，使用 TriNetX 美國多中心電子病歷資料庫，納入2015–2019年間具有周邊動脈阻塞性疾病（PAOD）病史，且於2020–2023年間感染 SARS-CoV-2 之成年患者。依感染前是否接受 COVID-19 疫苗接種分組，並以1:1傾向分數配對（PSM）平衡年齡、性別、共病及醫療利用等基線特徵。主要分析3年內下肢截肢與全因死亡風險，並以 Cox 比例風險模型與 Kaplan–Meier 曲線進行統計分析。研究結果：流行病學研究顯示，COVID-19患者合併動脈血栓或急性肢體缺血（ALI）平均年齡大多介於60至75歲之間，性別方面，多數研究均呈現男性比例較高，男性約占52.4%至90%。死亡率約為23.3%至40%；在合併嚴重呼吸症狀與下肢動脈血栓者，死亡率可達38%。截肢率方面，相關研究報告約為25%至30%。本研究共納入57,012名感染 SARS-CoV-2 的PAOD患者，經1:1傾向分數配對後，疫苗接種組與未接種組各11,822人。結果顯示，COVID-19疫苗接種與較低之3年全因死亡率及下肢截肢風險顯著相關；其中全因死亡風險下降約14%（HR = 0.857），下肢截肢風險下降約28%（HR = 0.716）。然而，兩組在缺血性中風風險方面則無顯著差異。Kaplan–Meier曲線亦顯示接種疫苗者具有較佳長期預後。結論與建議：本研究顯示，於感染 SARS-CoV-2 前接受 COVID-19 疫苗接種之周邊動脈阻塞性疾病（PAOD）患者，其3年全因死亡率與下肢截肢風險均顯著降低，顯示疫苗接種可能對高風險血管疾病族群具有臨床保護效益。研究結果支持 COVID-19 疫苗除降低感染重症外，亦可能減少血栓相關併發症與不良預後。然而，本研究屬回溯性觀察研究，無法直接推論因果關係，且仍可能存在未測量干擾因子。未來建議進一步結合前瞻性研究、多國資料庫及生物標誌物分析，以驗證其機轉與臨床應用價值。

Objective：To evaluate whether prior COVID-19 vaccination is associated with reduced risks of lower limb amputation and all-cause mortality in patients with peripheral arterial occlusive disease (PAOD) following SARS-CoV-2 infection. Methods and Materials：This retrospective cohort study utilized the TriNetX United States collaborative network. Adult patients with PAOD who developed SARS-CoV-2 infection between 2020 and 2023 were identified. Patients were categorized according to prior COVID-19 vaccination status. One-to-one propensity score matching was performed to balance demographics, comorbidities, lifestyle factors, and healthcare utilization. The primary outcomes were 3-year risks of lower limb amputation and all-cause mortality. Kaplan–Meier analysis and Cox proportional hazards models were applied for statistical analysis. Results：Epidemiological studies have shown that COVID-19 patients complicated by acute limb ischemia (ALI) were mostly older adults, with a mean age generally ranging from 60 to 75 years. In terms of sex distribution, most studies reported a higher proportion of male patients, ranging from approximately 52.4% to 90%. The reported mortality rate ranged from 23.3% to 40%; among patients with severe respiratory symptoms and lower-extremity arterial thrombosis, mortality reached 38%. Regarding limb outcomes, the reported amputation rate was approximately 25% to 30%. After propensity score matching, 11,822 vaccinated patients were compared with 11,822 unvaccinated patients. COVID-19 vaccination was associated with significantly lower risks of 3-year all-cause mortality (HR = 0.857, 95% CI 0.796–0.922) and lower limb amputation (HR = 0.716, 95% CI 0.587–0.873). Kaplan–Meier analysis also demonstrated lower cumulative incidences of mortality and amputation in the vaccinated cohort. However, no significant difference in ischemic stroke risk was observed between the two groups. These findings suggest that prior COVID-19 vaccination may be associated with improved long-term outcomes in patients with PAOD following SARS-CoV-2 infection.Conclusion and Suggestion：Prior COVID-19 vaccination was associated with lower risks of all-cause mortality and lower limb amputation in patients with PAOD following SARS-CoV-2 infection. These findings suggest that COVID-19 vaccination may provide potential protective effects in high-risk vascular populations beyond reducing severe infection alone. However, this retrospective observational study cannot establish causality, and residual confounding factors may still exist despite propensity score matching. Future prospective studies, external validation across different populations, and integration of inflammatory or thrombotic biomarkers are warranted to further clarify the underlying mechanisms and evaluate the clinical applicability of vaccination-associated prognostic benefits in patients with PAOD.