Abstract
Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
摘要
2019 冠状病毒病 (COVID-19) 作为一种多系统疾病, 可导致各种严重并发症。 急性肢体缺血 (ALI) 被认为是与 COVID-19 相关的一种并发症, 通常预示着不良预后。 但目前人们对 COVID-19 相关 ALI 的病理生理和分子机制仍知之甚少, 高凝状态和血栓形成被认为是重要机制。 本文强调了血管痉挛、缺氧和酸中毒在疾病发病中的作用, 血管紧张素转化酶2 (ACE2) 途径、炎症和血小板激活可能是 COVID-19 诱导上述病理变化的重要分子机制。 此外, 本文从遗传、年龄和性别角度对 COVID-19 相关 ALI 危险因素的假说进行了讨论和分析, 并对治疗方法如使用白细胞介素-6 (IL-6) 拮抗剂托珠单抗、钙通道拮抗剂和血管紧张素转化酶抑制剂等进行总结, 以期为治疗冠状病毒相关肢体缺血性疾病提供新见解。
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This work was supported by the Zhejiang Provincial Medical Scientific Research Program (No. 2022RC136), China.
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Hui LU, Olga ALENIKOVA, Sahar Ahmed ABDALBARY and Zhenfeng LIU designed the study. Chengjun YAO, Yanzhao DONG, Haiying ZHOU, Xiaodi ZOU, Ahmad ALHASKAWI, Sohaib Hasan Abdullah EZZI, Zewei WANG, Jingtian LAI, Vishnu Goutham KOTA, and Mohamed Hasan Abdulla Hasan ABDULLA performed the literature collection and analyzed the results. Chengjun YAO, Yanzhao DONG, Haiying ZHOU, Xiaodi ZOU, and Ahmad ALHASKAWI drafted the manuscript. Chengjun YAO, Sahar Ahmed ABDALBARY, Zewei WANG, Jingtian LAI, Vishnu Goutham KOTA, and Mohamed Hasan Abdulla Hasan ABDULLA critically revised the manuscript. All authors have read and approved the final manuscript.
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Chengjun YAO, Yanzhao DONG, Haiying ZHOU, Xiaodi ZOU, Ahmad ALHASKAWI, Sohaib Hasan Abdullah EZZI, Zewei WANG, Jingtian LAI, Vishnu Goutham KOTA, Mohamed Hasan Abdulla Hasan ABDULLA, Zhenfeng LIU, Sahar Ahmed ABDALBARY, Olga ALENIKOVA, and Hui LU declare that they have no conflicts of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (The First Affiliated Hospital of Zhejiang University School of Medicine, China) and with the Helsinki Declaration of 1975, as revised in 2013. Informed consent was obtained from all patients included in the study. Additional informed consent was obtained from all patients for whom identifying information is included in this article.
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Yao, C., Dong, Y., Zhou, H. et al. COVID-19 and acute limb ischemia: latest hypotheses of pathophysiology and molecular mechanisms. J. Zhejiang Univ. Sci. B 26, 333–352 (2025). https://doi.org/10.1631/jzus.B2300512
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DOI: https://doi.org/10.1631/jzus.B2300512
Key words
- Acute limb ischemia (ALI)
- Coronavirus disease 2019 (COVID-19) infection complication
- Hypercoagulability
- Thrombosis
- Vasospasm
- Hypoxia-inducible factor 1α (HIF-1α)
- Angiotensin-converting enzyme 2 (ACE2)
- Type I interferon (IFN-I)
- Tocilizumab