COVID-19 and acute limb ischemia: latest hypotheses of pathophysiology and molecular mechanisms.

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; Hui LU

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COVID-19 and acute limb ischemia: latest hypotheses of pathophysiology and molecular mechanisms.

Author: Chengjun YAO ¹ ; Yanzhao DONG ¹ ; Haiying ZHOU ¹ ; Xiaodi ZOU ¹ ; Ahmad ALHASKAWI ¹ ; Sohaib Hasan Abdullah EZZI ² ; Zewei WANG ¹ ; Jingtian LAI ¹ ; Vishnu Goutham KOTA ² ; Mohamed Hasan Abdulla Hasan ABDULLA ² ; Zhenfeng LIU ² ; Sahar Ahmed ABDALBARY ³ ; Olga ALENIKOVA ⁴ ; Hui LU ⁵
Author Information

1. Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
2. Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
3. Department of Orthopaedic Physical Therapy, Faculty of Physical Therapy, Nahda University, Beni Suef 2711860, Egypt.
4. Republic Scientific Practical Center of Neurology and Neurosurgery, Ministry of Health of the Republic of Belarus, Minsk 220004, Belarus.
5. Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. huilu@zju.edu.cn.
Publication Type:Review
Keywords: Acute limb ischemia (ALI); Angiotensin-converting enzyme 2 (ACE2); Coronavirus disease 2019 (COVID-19) infection complication; Hypercoagulability; Hypoxia-inducible factor 1α (HIF-1α); Thrombosis; Tocilizumab; Type I interferon (IFN-I); Vasospasm
MeSH: Humans; COVID-19/physiopathology*; Ischemia/etiology*; SARS-CoV-2; Extremities/blood supply*; Risk Factors; Interleukin-6/antagonists & inhibitors*; Acute Disease; Angiotensin-Converting Enzyme 2
From: Journal of Zhejiang University. Science. B 2025;26(4):333-352
CountryChina
Language:English
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.