{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:34:06Z","timestamp":1762342446640,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Unvaccinated individuals with peripheral arterial occlusive disease (PAOD) are more likely to develop acute limb ischemia (ALI) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We assessed the protective effect of the COVID-19 vaccine in preventing ALI in PAOD patients with SARS-CoV-2 infection. Methods: This retrospective cohort study was conducted using the United States TriNetX (Cambridge, MA, USA), using patients with PAOD who were diagnosed with SARS-CoV-2 infection between 1 November 2020 and 31 December 2023. Propensity score matching was performed to adjust for demographic variables, lifestyle factors, medical utilization, and comorbidities. Cox proportional hazards models were used to compare the two matched cohorts. Kaplan\u2013Meier analysis estimated the 3-year cumulative probability of lower limb amputation incidence. We selected 12,948 PAOD patients who received the COVID-19 vaccine and 44,064 PAOD patients who were unvaccinated against COVID-19. Results: A total of 11,822 pairs of COVID-19 vaccinated PAOD patients and unvaccinated individuals were compared. The mean (SD) age was 66.5 (14.1) years; there were 4849 male patients (41%) and 6569 female (55.6%) compared to unvaccinated PAOD patients, and those who received the COVID-19 vaccine had a significantly lower risk of 3-year all-cause mortality (log-rank test, p &lt; 0.001; hazard ratio (HR) was 0.857; 95% CI, 0.796\u20130.922) and lower limb amputation (log-rank test, p = 0.001, HR = 0.716; 95% CI, 0.587\u20130.873), though there was no significant difference in ischemic stroke (log-rank test, p = 0.174; HR = 0.958; 95% CI, 0.902\u20131.019). Conclusions: This study found that patients who received the COVID-19 vaccine had a significantly lower risk of 3-year all-cause mortality and lower limb amputation, though there was no significant difference in ischemic stroke.<\/jats:p>","DOI":"10.3390\/vaccines13090969","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T12:34:03Z","timestamp":1757680443000},"page":"969","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["COVID-19 Vaccination Reduces Lower Limb Amputation Rates and Mortality Rate in Patients with Pre-Existing Peripheral Vascular Disease Based on TriNetX Database"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2392-0824","authenticated-orcid":false,"given":"Shiuan-Tzuen","family":"Su","sequence":"first","affiliation":[{"name":"Department of Surgery, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung 40201, Taiwan"},{"name":"School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Hsuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asia University Hospital, Taichung 40201, Taiwan"},{"name":"Department of Optometry, Asia University, Taichung 40201, Taiwan"},{"name":"School of Medicine, College of Medicine, China Medical University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0794-9388","authenticated-orcid":false,"given":"Jing-Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Health Data Science, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.-C.","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"Graduate Institute of Integrated Medicine, China Medical University, Taichung 40201, Taiwan"},{"name":"Office of Research and Development, Asia University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hu, P.J., Chen, C.H., Wong, C.S., Chen, T.T., Wu, M.Y., and Sung, L.C. (2021). Influenza vaccination reduces incidence of peripheral arterial occlusive disease in elderly patients with chronic kidney disease. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-84285-8"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.amjcard.2012.04.059","article-title":"Frequency of coronary artery disease in patients undergoing peripheral artery disease surgery","volume":"110","author":"Hur","year":"2012","journal-title":"Am. J. Cardiol."},{"key":"ref_3","first-page":"729","article-title":"The diagnosis and treatment of peripheral arterial vascular disease","volume":"113","author":"Lawall","year":"2016","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.jvs.2022.12.002","article-title":"COVID-associated acute limb ischemia during the Delta surge and the effect of vaccines","volume":"77","author":"Xie","year":"2023","journal-title":"J. Vasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1016\/j.jvs.2020.04.483","article-title":"Acute limb ischemia in patients with COVID-19 pneumonia","volume":"72","author":"Bellosta","year":"2020","journal-title":"J. Vasc. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.mayocp.2020.11.018","article-title":"Arterial thrombotic events in adult inpatients with COVID-19","volume":"96","author":"Fournier","year":"2021","journal-title":"Mayo. Clin. Proc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1001\/jama.2020.13372","article-title":"Thrombosis in hospitalized patients with COVID-19 in a New York City health system","volume":"324","author":"Bilaloglu","year":"2020","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jvs.2020.07.089","article-title":"Early experience with arterial thromboembolic complications in patients with COVID-19","volume":"73","author":"Indes","year":"2021","journal-title":"J. Vasc. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1093\/eurheartj\/ehaa623","article-title":"COVID-19 is, in the end, an endothelial disease","volume":"41","author":"Libby","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/j.jvs.2020.06.008","article-title":"Acute limb ischemia in COVID-19 patients: Could aortic floating thrombus be the source of embolic complications?","volume":"72","author":"Silingardi","year":"2020","journal-title":"J. Vasc. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.avsg.2020.05.031","article-title":"COVID-19-related aortic thrombosis: A report of four cases","volume":"67","year":"2020","journal-title":"Ann. Vasc. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.avsg.2020.12.005","article-title":"Acute limb ischemia in a Peruvian cohort infected by COVID-19","volume":"72","author":"Sanchez","year":"2021","journal-title":"Ann. Vasc. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E263","DOI":"10.1148\/radiol.2020202348","article-title":"Lower-extremity arterial thrombosis associated with COVID-19 is characterized by greater thrombus burden and increased rate of amputation and death","volume":"297","author":"Goldman","year":"2020","journal-title":"Radiology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s11239-020-02176-7","article-title":"Incidence and consequences of systemic arterial thrombotic events in COVID-19 patients","volume":"50","author":"Cantador","year":"2020","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_16","first-page":"112","article-title":"Mortality of COVID-19 patients with vascular thrombotic complications","volume":"156","author":"Ansuategui","year":"2021","journal-title":"Med. Clin."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.jvs.2020.08.038","article-title":"Acute thrombotic manifestations of coronavirus disease 2019 infection: Experience at a large New York City health care system","volume":"73","author":"Ilonzo","year":"2021","journal-title":"J. Vasc. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/jmv.26232","article-title":"The cytokine storm and COVID-19","volume":"93","author":"Hu","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1001\/jama.2020.21753","article-title":"Older adults and the mental health effects of COVID-19","volume":"324","author":"Vahia","year":"2020","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.avsg.2020.08.085","article-title":"Acute arterial thromboembolism in patients with COVID-19 in the New York City area","volume":"70","author":"Etkin","year":"2021","journal-title":"Ann. Vasc. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.thromres.2020.04.041","article-title":"Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis","volume":"191","author":"Klok","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1002\/rth2.12439","article-title":"Risk of venous thromboembolism in patients with COVID-19: A systematic review and meta-analysis","volume":"4","author":"Nopp","year":"2020","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e15267","DOI":"10.1111\/1756-185X.15267","article-title":"Computed tomography imaging-based radiologic evaluation of pulmonary artery thrombosis in a series of patients with Behcet\u2019s disease","volume":"27","author":"Germe","year":"2024","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1111\/1756-185X.14875","article-title":"SARS-CoV-2 infection and increasing autoimmune disorders among ICU-hospitalized COVID-19 Patients","volume":"26","author":"Mosavat","year":"2023","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s10096-020-04138-6","article-title":"COVID-19: Angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection","volume":"40","author":"Beyerstedt","year":"2021","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1042\/CS20200483","article-title":"Brain angiotensin converting enzyme-2 in central cardiovascular regulation","volume":"134","author":"Mohammed","year":"2020","journal-title":"Clin. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101619","DOI":"10.1016\/j.eclinm.2022.101619","article-title":"Long-term cardiovascular outcomes in COVID-19 survivors among non-vaccinated populations: A retrospective cohort study from the TriNetX US collaborative networks","volume":"53","author":"Wang","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1001\/jama.2024.1059","article-title":"Stroke risk after COVID-19 bivalent vaccination among US older adults","volume":"331","author":"Lu","year":"2024","journal-title":"JAMA"},{"key":"ref_30","first-page":"542","article-title":"COVID-19 and acute limb ischemia: A systematic review","volume":"62","author":"Attisani","year":"2021","journal-title":"J. Cardiovasc. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"371","DOI":"10.4244\/EIJ-D-20-00052","article-title":"Validation of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria in patients undergoing percutaneous coronary intervention and comparison with contemporary bleeding risk scores","volume":"16","author":"Ueki","year":"2020","journal-title":"EuroIntervention"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1182\/blood-2016-10-746479","article-title":"Elevated hematocrit enhances platelet accumulation following vascular injury","volume":"129","author":"Walton","year":"2017","journal-title":"Blood"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/9\/969\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:44:28Z","timestamp":1760035468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/9\/969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":32,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["vaccines13090969"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13090969","relation":{},"ISSN":["2076-393X"],"issn-type":[{"type":"electronic","value":"2076-393X"}],"subject":[],"published":{"date-parts":[[2025,9,12]]}}}