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

doi:10.1631/jzus.B2300512

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Review | Updated：2025-04-23

COVID-19 and acute limb ischemia: latest hypotheses of pathophysiology and molecular mechanisms
COVID-19 and acute limb ischemia: latest hypotheses of pathophysiology and molecular mechanisms
COVID-19和急性肢体缺血：病理生理学和分子机制的最新假说
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 4, Pages: 333-352(2025)
Affiliations：

1.Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
2.Zhejiang University School of Medicine, Hangzhou 310058, China
3.Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, China
4.Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
5.Department of Orthopaedics, Third Xiangya Hospital, Central South University, Changsha 410013, China
6.Department of Orthopaedic Physical Therapy, Faculty of Physical Therapy, Nahda University, Beni Suef 2711860, Egypt
7.Republic Scientific Practical Center of Neurology and Neurosurgery, Ministry of Health of the Republic of Belarus, Minsk 220004, Belarus
Funds：
DOI：10.1631/jzus.B2300512
CLC：
CSTR：
Received：21 July 2023，

Revised：01 January 2024，

Published Online：19 February 2025，

Published：23 April 2025
Accepted：

姚成俊,董延钊,周海英等.COVID-19和急性肢体缺血：病理生理学和分子机制的最新假说[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(04):333-352.

Chengjun YAO, Yanzhao DONG, Haiying ZHOU, et al. COVID-19 and acute limb ischemia: latest hypotheses of pathophysiology and molecular mechanisms[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(4): 333-352.
姚成俊,董延钊,周海英等.COVID-19和急性肢体缺血：病理生理学和分子机制的最新假说[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(04):333-352. DOI： 10.1631/jzus.B2300512.

Chengjun YAO, Yanzhao DONG, Haiying ZHOU, et al. COVID-19 and acute limb ischemia: latest hypotheses of pathophysiology and molecular mechanisms[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(4): 333-352. DOI： 10.1631/jzus.B2300512.

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。

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.

关键词

Keywords

references

Abou-Ismail MY , Diamond A , Kapoor S , et al. , 2020 . The hypercoagulable state in COVID-19: incidence, pathophysiology, and management . Thromb Res , 194 : 101 - 115 . https://doi.org/10.1016/j.thromres.2020.06.029 https://doi.org/10.1016/j.thromres.2020.06.029

Agrawal A , 2013 . Mechanisms and implications of age-associated impaired innate interferon secretion by dendritic cells: a mini-review . Gerontology , 59 ( 5 ): 421 - 426 . https://doi.org/10.1159/000350536 https://doi.org/10.1159/000350536

Ahmetaj-Shala B , Peacock TP , Baillon L , et al. , 2020 . Resistance of endothelial cells to SARS-CoV-2 infection in vitro . bioRxiv , preprint. https://doi.org/10.1101/2020.11.08.372581 https://doi.org/10.1101/2020.11.08.372581

Aikawa T , Ogino J , Oyama-Manabe N , et al. , 2022 . Vasospastic angina: a cause of post-acute COVID-19 syndrome . Intern Med , 61 ( 17 ): 2693 - 2695 . https://doi.org/10.2169/internalmedicine.0137-22 https://doi.org/10.2169/internalmedicine.0137-22

Al Yacoub R , Patel J , Solanky N , et al. , 2022 . Acute limb ischaemia due to vasospasm: a rare presentation . BMJ Case Rep , 15 ( 1 ): e246495 . https://doi.org/10.1136/bcr-2021-246495 https://doi.org/10.1136/bcr-2021-246495

Algahtani H , Subahi A , Shirah B , 2016 . Neurological complications of middle east respiratory syndrome coronavirus: a report of two cases and review of the literature . Case Rep Neurol Med , 2016 : 3502683 . https://doi.org/10.1155/2016/3502683 https://doi.org/10.1155/2016/3502683

Ali YM , Ferrari M , Lynch NJ , et al. , 2021 . Lectin pathway mediates complement activation by SARS-CoV-2 proteins . Front Immunol , 12 : 714511 . https://doi.org/10.3389/fimmu.2021.714511 https://doi.org/10.3389/fimmu.2021.714511

Alitter QT , Jarrar A , Alsoud F , et al. , 2023 . Unilateral limb is chemia in a COVID-19 patient: a case report. Cureus , 15 ( 1 ): e34464 . https://doi.org/10.7759/cureus.34464 https://doi.org/10.7759/cureus.34464

Alonso MN , Mata-Forte T , García-León N , et al. , 2020 . Incidence, characteristics, laboratory findings and outcomes in acro-ischemia in COVID-19 patients . Vasc Health Risk Manag , 16 : 467 - 478 . https://doi.org/10.2147/VHRM.S276530 https://doi.org/10.2147/VHRM.S276530

Anderson CL , Chacko GW , Osborne JM , et al. , 1995 . The Fc receptor for immunoglobulin G (FcγRII) on human platelets . Semin Thromb Hemost , 21 ( 1 ): 1 - 9 . https://doi.org/10.1055/s-2007-1000374 https://doi.org/10.1055/s-2007-1000374

Althaus K , Marini I , Zlamal J , et al. , 2021 . Antibody-induced procoagulant platelets in severe COVID-19 infection . Blood , 137 ( 8 ): 1061 - 1071 . https://doi.org/10.1182/blood.2020008762 https://doi.org/10.1182/blood.2020008762

Angeli F , Reboldi G , Verdecchia P , 2021a . Ageing, ACE2 deficiency and bad outcome in COVID-19 . Clin Chem Lab Med , 59 ( 10 ): 1607 - 1609 . https://doi.org/10.1515/cclm-2021-0658 https://doi.org/10.1515/cclm-2021-0658

Angeli F , Spanevello A , Reboldi G , et al. , 2021b . SARS-CoV-2 vaccines: lights and shadows . Eur J Intern Med , 88 : 1 - 8 . https://doi.org/10.1016/j.ejim.2021.04.019 https://doi.org/10.1016/j.ejim.2021.04.019

Antoniak S , Mackman N , 2014 . Multiple roles of the coagulation protease cascade during virus infection . Blood , 123 ( 17 ): 2605 - 2613 . https://doi.org/10.1182/blood-2013-09-526277 https://doi.org/10.1182/blood-2013-09-526277

Arman M , Krauel K , Tilley DO , et al. , 2014 . Amplification of bacteria-induced platelet activation is triggered by FcγRIIA, integrin αIIbβ3, and platelet factor 4 . Blood , 123 ( 20 ): 3166 - 3174 . https://doi.org/10.1182/blood-2013-11-540526 https://doi.org/10.1182/blood-2013-11-540526

Arning C , Schrattenholzer A , Lachenmayer L , 1998 . Cervical carotid artery vasospasms causing cerebral ischemia: detection by immediate vascular ultrasonographic investigation . Stroke , 29 ( 5 ): 1063 - 1066 . https://doi.org/10.1161/01.str.29.5.1063 https://doi.org/10.1161/01.str.29.5.1063

Assinger A , Kral JB , Yaiw KC , et al. , 2014 . Human cytomegalovirus-platelet interaction triggers Toll-like receptor 2-dependent proinflammatory and proangiogenic responses . Arterioscler Thromb Vasc Biol , 34 ( 4 ): 801 - 809 . https://doi.org/10.1161/ATVBAHA.114.303287 https://doi.org/10.1161/ATVBAHA.114.303287

Baker AT , Boyd RJ , Sarkar D , et al. , 2021 . ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome . Sci Adv , 7 ( 49 ): eabl8213 . https://doi.org/10.1126/sciadv.abl8213 https://doi.org/10.1126/sciadv.abl8213

Bautista-Vargas M , Bonilla-Abadía F , Cañas CA , 2020 . Potential role for tissue factor in the pathogenesis of hypercoagulability associated with in COVID-19 . J Thromb Thrombolysis , 50 ( 3 ): 479 - 483 . https://doi.org/10.1007/s11239-020-02172-x https://doi.org/10.1007/s11239-020-02172-x

Bellosta R , Luzzani L , Natalini G , et al. , 2020 . Acute limb ischemia in patients with COVID-19 pneumonia . J Vasc Surg , 72 ( 6 ): 1864 - 1872 . https://doi.org/10.1016/j.jvs.2020.04.483 https://doi.org/10.1016/j.jvs.2020.04.483

Bellosta R , Piffaretti G , Bonardelli S , 2021 . Regional survey in lombardy, northern italy, on vascular surgery intervention outcomes during the COVID-19 pandemic . Eur J Vasc Endovasc Surg , 61 ( 4 ): 688 - 697 . https://doi.org/10.1016/j.ejvs.2021.01.037 https://doi.org/10.1016/j.ejvs.2021.01.037

Blanco-Rivero J , Cachofeiro V , Lahera V , et al. , 2005 . Participation of prostacyclin in endothelial dysfunction induced by aldosterone in normotensive and hypertensive rats . Hypertension , 46 ( 1 ): 107 - 112 . https://doi.org/10.1161/01.HYP.0000171479.36880.17 https://doi.org/10.1161/01.HYP.0000171479.36880.17

Bory M , Mattei M , Egre A , et al. , 1979 . Acute ischemic syndrome and apparently spontaneous spasms of the lower leg arteries . Coeur Med Interne , 18 ( 4 ): 607 - 611 .

Bouck EG , Denorme F , Holle LA , et al. , 2021 . COVID-19 and sepsis are associated with different abnormalities in plasma procoagulant and fibrinolytic activity . Arterioscler Thromb Vasc Biol , 41 ( 1 ): 401 - 414 . https://doi.org/10.1161/ATVBAHA.120.315338 https://doi.org/10.1161/ATVBAHA.120.315338

Brill A , Fuchs TA , Savchenko AS , et al. , 2012 . Neutrophil extracellular traps promote deep vein thrombosis in mice . J Thromb Haemost , 10 ( 1 ): 136 - 144 . https://doi.org/10.1111/j.1538-7836.2011.04544.x https://doi.org/10.1111/j.1538-7836.2011.04544.x

Buie JNJ , Oates JC , 2014 . Role of interferon alpha in endothelial dysfunction: insights into endothelial nitric oxide synthase-related mechanisms . Am J Med Sci , 348 ( 2 ): 168 - 175 . https://doi.org/10.1097/MAJ.0000000000000284 https://doi.org/10.1097/MAJ.0000000000000284

Cappel , MA , Cappel , JA , Wetter , DA , 2021 . Pernio (chilblains), SARS-CoV-2, and COVID toes unified through cutaneous and systemic mechanisms . Mayo Clin Proc , 96 ( 4 ): 989 - 1005 . https://doi.org/10.1016/j.mayocp.2021.01.009 https://doi.org/10.1016/j.mayocp.2021.01.009

Centers for Disease Control and Prevention , 2023 . Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19: Information for Healthcare Professionals . https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fscience%2Fscience-briefs%2Funderlying-evidence-table.html https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fscience%2Fscience-briefs%2Funderlying-evidence-table.html [ Accessed on Apr. 5, 2023 ] .

Chang Y , Wei W , 2015 . Angiotensin II in inflammation, immunity and rheumatoid arthritis . Clin Exp Immunol , 179 ( 2 ): 137 - 145 . https://doi.org/10.1111/cei.12467 https://doi.org/10.1111/cei.12467

Chen T , Wu D , Chen HL , et al. , 2020 . Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study . BMJ , 368 : m1091 . https://doi.org/10.1136/bmj.m1091 https://doi.org/10.1136/bmj.m1091

Chen ZW , Tsai CH , Pan CT , et al. , 2019 . Endothelial dysfunction in primary aldosteronism . Int J Mol Sci , 20 ( 20 ): 5214 . https://doi.org/10.3390/ijms20205214 https://doi.org/10.3390/ijms20205214

Chou CH , Hung CS , Liao CW , et al. , 2018 . IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis . Cardiovasc Res , 114 ( 5 ): 690 - 702 . https://doi.org/10.1093/cvr/cvy013 https://doi.org/10.1093/cvr/cvy013

Conway EM , Mackman N , Warren RQ , et al. , 2022 . Understanding COVID-19-associated coagulopathy . Nat Rev Immunol , 22 ( 10 ): 639 - 649 . https://doi.org/10.1038/s41577-022-00762-9 https://doi.org/10.1038/s41577-022-00762-9

Dang EV , Barbi J , Yang HY , et al. , 2011 . Control of T H 17/T reg balance by hypoxia-inducible factor 1 . Cell , 146 ( 5 ): 772 - 784 . https://doi.org/10.1016/j.cell.2011.07.033 https://doi.org/10.1016/j.cell.2011.07.033

de Masson A , Bouaziz JD , Sulimovic L , et al. , 2020 . Chilblains is a common cutaneous finding during the COVID-19 pandemic: a retrospective nationwide study from france . J Am Acad Dermatol , 83 ( 2 ): 667 - 670 . https://doi.org/10.1016/j.jaad.2020.04.161 https://doi.org/10.1016/j.jaad.2020.04.161

Demir Ş , Akin Ş , Tercan F , et al. , 2010 . Ergotamine-induced lower extremity arterial vasospasm presenting as acute limb ischemia . Diagn Interv Radiol , 16 ( 2 ): 165 - 167 . https://doi.org/10.4261/1305-3825.DIR.1931-08.2 https://doi.org/10.4261/1305-3825.DIR.1931-08.2

Deng Y , Liu W , Liu K , et al. , 2020 . Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study . Chin Med J (Engl) , 133 ( 11 ): 1261 - 1267 . https://doi.org/10.1097/CM9.0000000000000824 https://doi.org/10.1097/CM9.0000000000000824

Deshotels MR , Xia HJ , Sriramula S , et al. , 2014 . Angiotensin II mediates angiotensin converting enzyme type 2 internalization and degradation through an angiotensin II type I receptor-dependent mechanism . Hypertension , 64 ( 6 ): 1368 - 1375 . https://doi.org/10.1161/HYPERTENSIONAHA.114.03743 https://doi.org/10.1161/HYPERTENSIONAHA.114.03743

Döring Y , Soehnlein O , Weber C , 2017 . Neutrophil extracellular traps in atherosclerosis and atherothrombosis . Circ Res , 120 ( 4 ): 736 - 743 . https://doi.org/10.1161/CIRCRESAHA.116.309692 https://doi.org/10.1161/CIRCRESAHA.116.309692

Dotan A , Shoenfeld Y , 2021 . Perspectives on vaccine induced thrombotic thrombocytopenia . J Autoimmun , 121 : 102663 . https://doi.org/10.1016/j.jaut.2021.102663 https://doi.org/10.1016/j.jaut.2021.102663

Escher R , Breakey N , Lämmle B , 2020 . Severe COVID-19 infection associated with endothelial activation . Thromb Res , 190 : 62 . https://doi.org/10.1016/j.thromres.2020.04.014 https://doi.org/10.1016/j.thromres.2020.04.014

Fan BE , 2020 . Hematologic parameters in patients with COVID‐19 infection: a reply . Am J Hematol , 95 ( 8 ): E215 . https://doi.org/10.1002/ajh.25847 https://doi.org/10.1002/ajh.25847

Fiebeler A , Schmidt F , Müller DN , et al. , 2001 . Mineralocorticoid receptor affects AP-1 and nuclear factor-κB activation in angiotensin II-induced cardiac injury . Hypertension , 37 ( 2 ): 787 - 793 . https://doi.org/10.1161/01.HYP.37.2.787 https://doi.org/10.1161/01.HYP.37.2.787

Foley JH , Conway EM , 2016 . Cross talk pathways between coagulation and inflammation . Circ Res , 118 ( 9 ): 1392 - 1408 . https://doi.org/10.1161/CIRCRESAHA.116.306853 https://doi.org/10.1161/CIRCRESAHA.116.306853

Forrester SJ , Booz GW , Sigmund CD , et al. , 2018 . Angiotensin II signal transduction: an update on mechanisms of physiology and pathophysiology . Physiol Rev , 98 ( 3 ): 1627 - 1738 . https://doi.org/10.1152/physrev.00038.2017 https://doi.org/10.1152/physrev.00038.2017

Galván Casas C , Català A , Carretero Hernández G , et al. , 2020 . Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases . Br J Dermatol , 183 ( 1 ): 71 - 77 . https://doi.org/10.1111/bjd.19163 https://doi.org/10.1111/bjd.19163

Gheblawi M , Wang KM , Viveiros A , et al. , 2020 . Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2 . Circ Res , 126 ( 10 ): 1456 - 1474 . https://doi.org/10.1161/CIRCRESAHA.120.317015 https://doi.org/10.1161/CIRCRESAHA.120.317015

Giamarellos-Bourboulis EJ , Netea MG , Rovina N , et al. , 2020 . Complex immune dysregulation in COVID-19 patients with severe respiratory failure . Cell Host Microbe , 27 ( 6 ): 992 - 1000.e3 . https://doi.org/10.1016/j.chom.2020.04.009 https://doi.org/10.1016/j.chom.2020.04.009

Giannis D , Ziogas IA , Gianni P , 2020 . Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past . J Clin Virol , 127 : 104362 . https://doi.org/10.1016/j.jcv.2020.104362 https://doi.org/10.1016/j.jcv.2020.104362

Goeijenbier M , van Wissen M , van de Weg C , et al. , 2012 . Review: viral infections and mechanisms of thrombosis and bleeding . J Med Virol , 84 ( 10 ): 1680 - 1696 . https://doi.org/10.1002/jmv.23354 https://doi.org/10.1002/jmv.23354

Goldman IA , Ye K , Scheinfeld MH , 2020 . Lower-extremity arterial thrombosis associated with COVID-19 is characterized by greater thrombus burden and increased rate of amputation and death . Radiology , 297 ( 2 ): E263 - E269 . https://doi.org/10.1148/radiol.2020202348 https://doi.org/10.1148/radiol.2020202348

Gomez-Arbelaez D , Ibarra-Sanchez G , Garcia-Gutierrez A , et al. , 2020 . COVID-19-related aortic thrombosis: a report of four cases . Ann Vasc Surg , 67 : 10 - 13 . https://doi.org/10.1016/j.avsg.2020.05.031 https://doi.org/10.1016/j.avsg.2020.05.031

Gould TJ , Vu TT , Swystun LL , et al. , 2014 . Neutrophil extracellular traps promote thrombin generation through platelet-dependent and platelet-independent mechanisms . Arterioscler Thromb Vasc Biol , 34 ( 9 ): 1977 - 1984 . https://doi.org/10.1161/ATVBAHA.114.304114 https://doi.org/10.1161/ATVBAHA.114.304114

Herman EW , Kezis JS , Silvers DN , 1981 . A distinctive variant of pernio: clinical and histopathologic study of nine cases . Arch Dermatol , 117 ( 1 ): 26 - 28 . https://doi.org/10.1001/archderm.1981.01650010032019 https://doi.org/10.1001/archderm.1981.01650010032019

Hermidorff MM , de Assis LVM , Isoldi MC , 2017 . Genomic and rapid effects of aldosterone: what we know and do not know thus far . Heart Fail Rev , 22 ( 1 ): 65 - 89 . https://doi.org/10.1007/s10741-016-9591-2 https://doi.org/10.1007/s10741-016-9591-2

Holter JC , Pischke SE , de Boer E , et al. , 2020 . Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients . Proc Natl Acad Sci USA , 117 ( 40 ): 25018 - 25025 . https://doi.org/10.1073/pnas.2010540117 https://doi.org/10.1073/pnas.2010540117

Hubiche T , Le Duff F , Chiaverini C , et al. , 2021 . Negative SARS-CoV-2 PCR in patients with chilblain-like lesions . Lancet Infect Dis , 21 ( 3 ): 315 - 316 . https://doi.org/10.1016/S1473-3099(20)30518-1 https://doi.org/10.1016/S1473-3099(20)30518-1

Iba T , Levy JH , 2022 . The roles of platelets in COVID-19-associated coagulopathy and vaccine-induced immune thrombotic thrombocytopenia . Trends Cardiovasc Med , 32 ( 1 ): 1 - 9 . https://doi.org/10.1016/j.tcm.2021.08.012 https://doi.org/10.1016/j.tcm.2021.08.012

Iba T , Levy JH , Levi M , et al. , 2020 . Coagulopathy in COVID-19 . J Thromb Haemost , 18 ( 9 ): 2103 - 2109 . https://doi.org/10.1111/jth.14975 https://doi.org/10.1111/jth.14975

Inoue K , Makita N , Matsuo K , et al. , 2009 . OE-045 Clinical significance of aldosterone levels and C-reactive protein in patients with coronary vasospasm (OE08, atherosclerosis (clinical/diagnosis) (IHD), oral presentation (English), the 73rd Annual Scientific Meeting of the Japanese Circulation Society) . Circ J , 73 : 185 .

Jabalameli N , Rajabi F , Firooz A , et al. , 2022 . The overlap between genetic susceptibility to COVID-19 and skin diseases . Immunol Invest , 51 ( 4 ): 1087 - 1094 . https://doi.org/10.1080/08820139.2021.1876086 https://doi.org/10.1080/08820139.2021.1876086

Jahani M , Dokaneheifard S , Mansouri K , 2020 . Hypoxia: a key feature of COVID-19 launching activation of HIF-1 and cytokine storm . J Inflamm , 17 ( 1 ): 33 . https://doi.org/10.1186/s12950-020-00263-3 https://doi.org/10.1186/s12950-020-00263-3

Jain A , Reddy A , Murugesan R , et al. , 2022 . Outcomes of patients with acute limb ischemia in patients with COVID-19: a systemic review and meta-analysis . Cureus , 14 ( 7 ): e27370 . https://doi.org/10.7759/cureus.27370 https://doi.org/10.7759/cureus.27370

Kambas K , Chrysanthopoulou A , Vassilopoulos D , et al. , 2014 . Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease . Ann Rheum Dis , 73 ( 10 ): 1854 - 1863 . https://doi.org/10.1136/annrheumdis-2013-203430 https://doi.org/10.1136/annrheumdis-2013-203430

Kaneyama J , Kawarada O , Sakamoto S , et al. , 2014 . Vasospastic limb ischemia presenting acute and chronic limb ischemia . Ann Vasc Dis , 7 ( 2 ): 169 - 172 . https://doi.org/10.3400/avd.cr.13-00113 https://doi.org/10.3400/avd.cr.13-00113

Kang SJ , Kishimoto T , 2021 . Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms . Exp Mol Med , 53 ( 7 ): 1116 - 1123 . https://doi.org/10.1038/s12276-021-00649-0 https://doi.org/10.1038/s12276-021-00649-0

Kang SJ , Tanaka T , Inoue H , et al. , 2020 . IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome . Proc Natl Acad Sci USA , 117 ( 36 ): 22351 - 22356 . https://doi.org/10.1073/pnas.2010229117 https://doi.org/10.1073/pnas.2010229117

Kartikasari U , Djajalaksana S , Martini H , 2021 . Acute limb ischemia in a patient with Covid-19 pneumonia: a case report . J Thromb Thrombolysis , 52 ( 3 ): 974 - 979 . https://doi.org/10.1007/s11239-021-02434-2 https://doi.org/10.1007/s11239-021-02434-2

Keser Z , Suarez-Cedeno G , Saha RK , et al. , 2018 . An atypical presentation of varicella zoster (VZV) vasculopathy . J Vasc Interv Neurol , 10 ( 1 ): 23 - 24 .

Khattab K , Kempa AT , Atas R , et al. , 2021 . Peripheral ischemic limb necrosis (Acro-ischemia) associated with severe COVID-19 patients (COVID-19 limbs): a report of three cases . Lung India , 38 ( S1 ): S58 - S60 . https://doi.org/10.4103/lungindia.lungindia_470_20 https://doi.org/10.4103/lungindia.lungindia_470_20

Kim OY , Chae JS , Paik JK , et al. , 2012 . Effects of aging and menopause on serum interleukin-6 levels and peripheral blood mononuclear cell cytokine production in healthy nonobese women . AGE , 34 ( 2 ): 415 - 425 . https://doi.org/10.1007/s11357-011-9244-2 https://doi.org/10.1007/s11357-011-9244-2

Klinger MH , Wilhelm D , Bubel S , et al. , 1995 . Immunocytochemical localization of the chemokines RANTES and MIP-1α within human platelets and their release during storage . Int Arch Allergy Immunol , 107 ( 4 ): 541 - 546 . https://doi.org/10.1159/000237097 https://doi.org/10.1159/000237097

Klok FA , Kruip MJHA , van der Meer NJM , et al. , 2020 . Incidence of thrombotic complications in critically ill ICU patients with COVID-19 . Thromb Res , 191 : 145 - 147 . https://doi.org/10.1016/j.thromres.2020.04.013 https://doi.org/10.1016/j.thromres.2020.04.013

Kolivras A , Dehavay F , Delplace D , et al. , 2020 . Coronavirus (COVID-19) infection-induced chilblains: a case report with histopathologic findings . JAAD Case Rep , 6 ( 6 ): 489 - 492 . https://doi.org/10.1016/j.jdcr.2020.04.011 https://doi.org/10.1016/j.jdcr.2020.04.011

Kuchynkova S , Chochola M , Varejka P , et al. , 2017 . A rare cause of acute limb ischemia of both upper and lower limbs caused by prolonged vasospasm . Cor Vasa , 59 ( 5 ): e503 - e506 . https://doi.org/10.1016/j.crvasa.2017.01.005 https://doi.org/10.1016/j.crvasa.2017.01.005

Kyriazopoulou E , Leventogiannis K , Norrby-Teglund A , et al. , 2017 . Macrophage activation-like syndrome: an immuno logical entity associated with rapid progression to death in sepsis. BMC Med , 15 : 172 . https://doi.org/10.1186/s12916-017-0930-5 https://doi.org/10.1186/s12916-017-0930-5

Lari E , Lari A , Alqinai S , et al. , 2020 . Severe ischemic complications in Covid-19—a case series . Int J Surg Case Rep , 75 : 131 - 135 . https://doi.org/10.1016/j.ijscr.2020.09.009 https://doi.org/10.1016/j.ijscr.2020.09.009

Lee N , Hui D , Wu AL , et al. , 2003 . A major outbreak of severe acute respiratory syndrome in Hong Kong . N Engl J Med , 348 ( 20 ): 1986 - 1994 . https://doi.org/10.1056/NEJMoa030685 https://doi.org/10.1056/NEJMoa030685

Li X , Wang LW , Yan SN , et al. , 2020 . Clinical characteristics of 25 death cases with COVID-19: a retrospective review of medical records in a single medical center, Wuhan, China . Int J Infect Dis , 94 : 128 - 132 . https://doi.org/10.1016/j.ijid.2020.03.053 https://doi.org/10.1016/j.ijid.2020.03.053

Liao MF , Liu Y , Yuan J , et al. , 2020 . Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19 . Nat Med , 26 ( 6 ): 842 - 844 . https://doi.org/10.1038/s41591-020-0901-9 https://doi.org/10.1038/s41591-020-0901-9

Limb J , Binning A , 2009 . Thrombosis associated with varicella zoster in an adult . Int J Infect Dis , 13 ( 6 ): e498 - e500 . https://doi.org/10.1016/j.ijid.2009.02.007 https://doi.org/10.1016/j.ijid.2009.02.007

Liu JY , Liu Y , Xiang P , et al. , 2020 . Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage . J Transl Med , 18 : 206 . https://doi.org/10.1186/s12967-020-02374-0 https://doi.org/10.1186/s12967-020-02374-0

Liu YM , Wang HQ , Shao ZH , 2021 . SARS-CoV-2 vaccines induced immune thrombotic thrombocytopenia . Chin J Hematol , 42 ( 7 ): 607 - 610 (in Chinese) . https://doi.org/10.3760/cma.j.issn.0253-2727.2021.07.016 https://doi.org/10.3760/cma.j.issn.0253-2727.2021.07.016

Mackman N , Grover SP , Antoniak S , 2021 . Tissue factor expression, extracellular vesicles, and thrombosis after infection with the respiratory viruses influenza a virus and coronavirus . J Thromb Haemost , 19 ( 11 ): 2652 - 2658 . https://doi.org/10.1111/jth.15509 https://doi.org/10.1111/jth.15509

Maggio M , Basaria S , Ble A , et al. , 2006 . Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men . J Clin Endocrinol Metab , 91 ( 1 ): 345 - 347 . https://doi.org/10.1210/jc.2005-1097 https://doi.org/10.1210/jc.2005-1097

Manne BK , Denorme F , Middleton EA , et al. , 2020 . Platelet gene expression and function in patients with COVID-19 . Blood , 136 ( 11 ): 1317 - 1329 . https://doi.org/10.1182/blood.2020007214 https://doi.org/10.1182/blood.2020007214

Marceau F , Bawolak MT , Fortin JP , et al. , 2018 . Bifunctional ligands of the bradykinin B 2 and B 1 receptors: an exercise in peptide hormone plasticity . Peptides , 105 : 37 - 50 . https://doi.org/10.1016/j.peptides.2018.05.007 https://doi.org/10.1016/j.peptides.2018.05.007

Maseri A , L'Abbate A , Baroldi G , et al. , 1978 . Coronary vasospasm as a possible cause of myocardial infarction—a conclusion derived from the study of preinfarction angina . N Engl J Med , 299 ( 23 ): 1271 - 1277 . https://doi.org/10.1056/NEJM197812072992303 https://doi.org/10.1056/NEJM197812072992303

Massberg S , Grahl L , von Bruehl ML , et al. , 2010 . Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases . Nat Med , 16 ( 8 ): 887 - 896 . https://doi.org/10.1038/nm.2184 https://doi.org/10.1038/nm.2184

Mast AE , Wolberg AS , Gailani D , et al. , 2021 . SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung . eLife , 10 : e64330 . https://doi.org/10.7554/eLife.64330 https://doi.org/10.7554/eLife.64330

Mazzotta F , Troccoli T , 2020 . Acute acro-ischemia in the child at the time of COVID-19 . Eur J Pediat Dermatol , 30 ( 2 ): 71 - 74 . https://doi.org/10.26326/2281-9649.30.2.2102 https://doi.org/10.26326/2281-9649.30.2.2102

Middleton EA , He XY , Denorme F , et al. , 2020 . Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome . Blood , 136 ( 10 ): 1169 - 1179 . https://doi.org/10.1182/blood.2020007008 https://doi.org/10.1182/blood.2020007008

Mohamedi N , Mirault T , Durivage A , et al. , 2021 . Ergotism with acute limb ischemia, provoked by HIV protease inhibitors interaction with ergotamine, rescued by multisite transluminal balloon angioplasty . J Med Vasc , 46 ( 1 ): 13 - 21 . https://doi.org/10.1016/j.jdmv.2020.12.002 https://doi.org/10.1016/j.jdmv.2020.12.002

Möhlendick B , Schönfelder K , Breuckmann K , et al. , 2021 . ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19 . Pharmacogenet Genomics , 31 ( 8 ): 165 - 171 . https://doi.org/10.1097/FPC.0000000000000436 https://doi.org/10.1097/FPC.0000000000000436

Monov D , Lilyanov N , Bogovsky S , et al. , 2022 . Cerebral vasospasm after subarachnoid hemorrhage from intracranial aneurysm rupture in SARS-CoV-2 positive patients. A retrospective review from two bulgarian hospitals . Biotechnol Biotechnol Equip , 36 ( 1 ): 413 - 417 . https://doi.org/10.1080/13102818.2022.2092421 https://doi.org/10.1080/13102818.2022.2092421

Nagata D , Takahashi M , Sawai K , et al. , 2006 . Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity . Hypertension , 48 ( 1 ): 165 - 171 . https://doi.org/10.1161/01.HYP.0000226054.53527.bb https://doi.org/10.1161/01.HYP.0000226054.53527.bb

Neumann FJ , Ott I , Marx N , et al. , 1997 . Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity . Arterioscler Thromb Vasc Biol , 17 ( 12 ): 3399 - 3405 . https://doi.org/10.1161/01.atv.17.12.3399 https://doi.org/10.1161/01.atv.17.12.3399

Ng KHL , Wu AKL , Cheng VCC , et al. , 2005 . Pulmonary artery thrombosis in a patient with severe acute respiratory syndrome . Postgrad Med J , 81 ( 956 ): e3 . https://doi.org/10.1136/pgmj.2004.030049 https://doi.org/10.1136/pgmj.2004.030049

Nicholls JM , Poon LLM , Lee KC , et al. , 2003 . Lung pathology of fatal severe acute respiratory syndrome . Lancet , 361 ( 9371 ): 1773 - 1778 . https://doi.org/10.1016/s0140-6736(03)13413-7 https://doi.org/10.1016/s0140-6736(03)13413-7

Nowroozpoor A , Bank MA , Jafari D , 2021 . Limb ischemia due to extensive arterial thrombosis in the absence of venous occlusion as an unusual complication of critical illness from COVID-19 . Case Rep Acute Med , 4 ( 1 ): 23 - 31 . https://doi.org/10.1159/000514291 https://doi.org/10.1159/000514291

Omar IM , Weaver JS , Samet JD , et al. , 2022 . Musculoskeletal manifestations of COVID-19: currently described clinical symptoms and multimodality imaging findings . RadioGraphics , 42 ( 5 ): 1415 - 1432 . https://doi.org/10.1148/rg.220036 https://doi.org/10.1148/rg.220036

Orrapin S , Reanpang T , Orrapin S , et al. , 2015 . Case series of HIV infection-associated arteriopathy: diagnosis, management, and outcome over a 5-year period at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University . Int J Low Extrem Wounds , 14 ( 3 ): 251 - 261 . https://doi.org/10.1177/1534734615598226 https://doi.org/10.1177/1534734615598226

Ozbey R , Algan MF , 2022 . Acro‐ischemic lesions in COVID‐19 patients: a case series . J Cosmet Dermatol , 21 ( 5 ):‍ 1822 - 1829 . https://doi.org/10.1111/jocd.14893 https://doi.org/10.1111/jocd.14893

Papamichalis P , Papadogoulas A , Katsiafylloudis P , et al. , 2020 . Combination of thrombolytic and immunosuppressive therapy for coronavirus disease 2019: a case report . Int J Infect Dis , 97 : 90 - 93 . https://doi.org/10.1016/j.ijid.2020.05.118 https://doi.org/10.1016/j.ijid.2020.05.118

Park SH , Kim TJ , Ko SB , et al. , 2022 . Transcranial doppler monitoring in subarachnoid hemorrhage . J Neurosonol Neuroimag , 14 ( 1 ): 1 - 9 . https://doi.org/10.31728/jnn.2022.00115 https://doi.org/10.31728/jnn.2022.00115

Peerschke EI , Yin W , Ghebrehiwet B , 2010 . Complement activation on platelets: implications for vascular inflammation and thrombosis . Mol Immunol , 47 ( 13 ): 2170 - 2175 . https://doi.org/10.1016/j.molimm.2010.05.009 https://doi.org/10.1016/j.molimm.2010.05.009

Perini P , Nabulsi B , Massoni CB , et al. , 2020 . Acute limb ischaemia in two young, non-atherosclerotic patients with COVID-19 . Lancet , 395 ( 10236 ): 1546 . https://doi.org/10.1016/S0140-6736(20)31051-5 https://doi.org/10.1016/S0140-6736(20)31051-5

Predenciuc A , Casian D , Culiuc V , 2023 . Outcomes of surgical revascularization for acute limb ischemia in COVID-19 patients comparing to noninfected cohort: a single-center observational prospective study . Ann Vasc Surg , 91 : 81 - 89 . https://doi.org/10.1016/j.avsg.2022.11.024 https://doi.org/10.1016/j.avsg.2022.11.024

Putko RM , Bedrin MD , Clark DM , et al. , 2021 . SARS-CoV-2 and limb ischemia: a systematic review . J Clin Orthop Trauma , 12 ( 1 ): 194 - 199 . https://doi.org/10.1016/j.jcot.2020.11.018 https://doi.org/10.1016/j.jcot.2020.11.018

Ramos SG , da Cruz Rattis BA , Ottaviani G , et al. , 2021 . ACE2 down-regulation may act as a transient molecular disease causing RAAS dysregulation and tissue damage in the microcirculatory environment among COVID-19 patients . Am J Pathol , 191 ( 7 ): 1154 - 1164 . https://doi.org/10.1016/j.ajpath.2021.04.010 https://doi.org/10.1016/j.ajpath.2021.04.010

Rieder M , Wirth L , Pollmeier L , et al. , 2021 . Serum ACE2, angiotensin II, and aldosterone levels are unchanged in patients with COVID-19 . Am J Hypertens , 34 ( 3 ): 278 - 281 . https://doi.org/10.1093/ajh/hpaa169 https://doi.org/10.1093/ajh/hpaa169

Rosas IO , Bräu N , Waters M , et al. , 2021 . Tocilizumab in hospitalized patients with severe Covid-19 pneumonia . N Engl J Med , 384 ( 16 ): 1503 - 1516 . https://doi.org/10.1056/NEJMoa2028700 https://doi.org/10.1056/NEJMoa2028700

Salama C , Han J , Yau L , et al. , 2021 . Tocilizumab in patients hospitalized with Covid-19 pneumonia . N Engl J Med , 384 ( 1 ): 20 - 30 . https://doi.org/10.1056/NEJMoa2030340 https://doi.org/10.1056/NEJMoa2030340

Schultz K , Wolf JM , 2020 . Digital ischemia in COVID-19 patients: case report . J Hand Surg , 45 ( 6 ): 518 - 522 . https://doi.org/10.1016/j.jhsa.2020.04.024 https://doi.org/10.1016/j.jhsa.2020.04.024

The Severe Covid-19 GWAS Group , 2020 . Genomewide association study of severe Covid-19 with respiratory failure . N Engl J Med , 383 ( 16 ): 1522 - 1534 . https://doi.org/10.1056/NEJMoa2020283 https://doi.org/10.1056/NEJMoa2020283

Shahi V , Wetter DA , Cappel JA , et al. , 2015 . Vasospasm is a consistent finding in pernio (chilblains) and a possible clue to pathogenesis . Dermatology , 231 ( 3 ): 274 - 279 . https://doi.org/10.1159/000437224 https://doi.org/10.1159/000437224

Sodhi CP , Wohlford-Lenane C , Yamaguchi Y , et al. , 2018 . Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg 9 bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration . Am J Physiol Lung Cell Mol Physiol , 314 ( 1 ): L17 - L31 . https://doi.org/10.1152/ajplung.00498.2016 https://doi.org/10.1152/ajplung.00498.2016

Souyris M , Cenac C , Azar P , et al. , 2018 . TLR7 escapes X chromosome inactivation in immune cells . Sci Immunol , 3 ( 19 ): eaap8855 . https://doi.org/10.1126/sciimmunol.aap8855 https://doi.org/10.1126/sciimmunol.aap8855

Stelzer M , Henes J , Saur S , 2021 . The role of antiphospholipid antibodies in COVID-19 . Curr Rheumatol Rep , 23 ( 9 ): 72 . https://doi.org/10.1007/s11926-021-01041-7 https://doi.org/10.1007/s11926-021-01041-7

Tanaka K , Koike Y , Shimura T , et al. , 2014 . In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model . PLoS ONE , 9 ( 11 ): e111888 . https://doi.org/10.1371/journal.pone.0111888 https://doi.org/10.1371/journal.pone.0111888

Tang N , Li DJ , Wang X , et al. , 2020 . Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia . J Thromb Haemost , 18 ( 4 ): 844 - 847 . https://doi.org/10.1111/jth.14768 https://doi.org/10.1111/jth.14768

Teixeira JG , Pitta GBB , da Silva CRA , et al. , 2022 . Diagnosis and management of patients with acute limb ischemia after Covid-19 infection: a case series . J Vasc Bras , 21 : e20220044 . https://doi.org/10.1590/1677-5449.202200441 https://doi.org/10.1590/1677-5449.202200441

Tiede A , Sachs UJ , Czwalinna A , et al. , 2021 . Prothrombotic immune thrombocytopenia after COVID-19 vaccination . Blood , 138 ( 4 ): 350 - 353 . https://doi.org/10.1182/blood.2021011958 https://doi.org/10.1182/blood.2021011958

Tobaiqy M , Elkout H , MacLure K , 2021 . Analysis of thrombotic adverse reactions of COVID-19 astrazeneca vaccine reported to eudravigilance database . Vaccines , 9 ( 4 ): 393 . https://doi.org/10.3390/vaccines9040393 https://doi.org/10.3390/vaccines9040393

Tukiainen T , Villani AC , Yen A , et al. , 2017 . Landscape of X chromosome inactivation across human tissues . Nature , 550 ( 7675 ): 244 - 248 . https://doi.org/10.1038/nature24265 https://doi.org/10.1038/nature24265

van de Veerdonk F , Netea MG , van Deuren M , et al. , 2020 . Kinins and cytokines in COVID-19: a comprehensive pathophysiological approach . Prepr ints.org, preprint. https://doi.org/10.20944/preprints202004.0023.v1 https://doi.org/10.20944/preprints202004.0023.v1

Vickers C , Hales P , Kaushik V , et al. , 2002 . Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase . J Biol Chem , 277 ( 17 ):‍ 14838 - 14843 . https://doi.org/10.1074/jbc.M200581200 https://doi.org/10.1074/jbc.M200581200

Villard O , Morquin D , Molinari N , et al. , 2020 . The plasmatic aldosterone and C-reactive protein levels, and the severity of Covid-19: the Dyhor-19 study . J Clin Med , 9 ( 7 ): 2315 . https://doi.org/10.3390/jcm9072315 https://doi.org/10.3390/jcm9072315

Walls AC , Park YJ , Tortorici MA , et al. , 2020 . Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein . Cell , 181 ( 2 ): 281 - 292.e6 . https://doi.org/10.1016/j.cell.2020.02.058 https://doi.org/10.1016/j.cell.2020.02.058

Wang DW , Hu B , Hu C , et al. , 2020 . Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China . JAMA , 323 ( 11 ): 1061 - 1069 . https://doi.org/10.1001/jama.2020.1585 https://doi.org/10.1001/jama.2020.1585

Wang RY , Lee JH , Kim J , et al. , 2023 . SARS-CoV-2 restructures host chromatin architecture . Nat Microbiol , 8 ( 4 ): 679 - 694 . https://doi.org/10.1038/s41564-023-01344-8 https://doi.org/10.1038/s41564-023-01344-8

Winckiewicz M , Stanišić MG , Szajkowski R , et al. , 2007 . Acute lower limb ischemia in a young woman with arterial hypoplasia: a case report . Angiology , 58 ( 4 ): 494 - 497 . https://doi.org/10.1177/0003319706291154 https://doi.org/10.1177/0003319706291154

Wu ZY , Hu R , Zhang CZ , et al. , 2020 . Elevation of plasma angiotensin II level is a potential pathogenesis for the critically ill COVID-19 patients . Crit Care , 24 : 290 . https://doi.org/10.1186/s13054-020-03015-0 https://doi.org/10.1186/s13054-020-03015-0

Xavier FE , Aras-López R , Arroyo-Villa I , et al. , 2008 . Aldosterone induces endothelial dysfunction in resistance arteries from normotensive and hypertensive rats by increasing thromboxane A 2 and prostacyclin . Br J Pharmacol , 154 ( 6 ): 1225 - 1235 . https://doi.org/10.1038/bjp.2008.200 https://doi.org/10.1038/bjp.2008.200

Xie BW , Semaan DB , Binko MA , et al. , 2023 . COVID-associated acute limb ischemia during the delta surge and the effect of vaccines . J Vasc Surg , 77 ( 4 ): 1165 - 1173.e1 . https://doi.org/10.1016/j.jvs.2022.12.002 https://doi.org/10.1016/j.jvs.2022.12.002

Xie XD , Chen JZ , Wang XX , et al. , 2006 . Age- and gender-related difference of ACE2 expression in rat lung . Life Sci , 78 ( 19 ): 2166 - 2171 . https://doi.org/10.1016/j.lfs.2005.09.038 https://doi.org/10.1016/j.lfs.2005.09.038

Xing DQ , Nozell S , Chen YF , et al. , 2009 . Estrogen and mechanisms of vascular protection . Arterioscler Thromb Vasc Biol , 29 ( 3 ): 289 - 295 . https://doi.org/10.1161/ATVBAHA.108.182279 https://doi.org/10.1161/ATVBAHA.108.182279

Yeaman MR , 2014 . Platelets: at the nexus of antimicrobial defence . Nat Rev Microbiol , 12 ( 6 ): 426 - 437 . https://doi.org/10.1038/nrmicro3269 https://doi.org/10.1038/nrmicro3269

Yoon HE , Kim EN , Kim MY , et al. , 2016 . Age-associated changes in the vascular renin-angiotensin system in mice . Oxid Med Cell Longev , 2016 : 6731093 . https://doi.org/10.1155/2016/6731093 https://doi.org/10.1155/2016/6731093

Yu J , Yuan X , Chen H , et al. , 2020 . Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor d inhibition . Blood , 136 ( 18 ): 2080 - 2089 . https://doi.org/10.1182/blood.2020008248 https://doi.org/10.1182/blood.2020008248

Zhang HB , Penninger JM , Li YM , et al. , 2020 . Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target . Intensive Care Med , 46 ( 4 ): 586 - 590 . https://doi.org/10.1007/s00134-020-05985-9 https://doi.org/10.1007/s00134-020-05985-9

Zhang S , Liu YY , Wang X F , et al. , 2020 . SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19 . J Hematol Oncol , 13 : 120 . https://doi.org/10.1186/s13045-020-00954-7 https://doi.org/10.1186/s13045-020-00954-7

Zhang X , Yu J , Pan LY , et al. , 2020 . ACEI/ARB use and risk of infection or severity or mortality of COVID-19: a systematic review and meta-analysis . Pharmacol Res , 158 : 104927 . https://doi.org/10.1016/j.phrs.2020.104927 https://doi.org/10.1016/j.phrs.2020.104927

Zhang Y , Cao W , Xiao M , et al. , 2020 . Clinical and coagulation characteristics in 7 patients with critical COVID-2019 pneumonia and acro-ischemia . Chin J Hematol , 41 ( 4 ): 302 - 307 (in Chinese) . https://doi.org/10.3760/cma.j.issn.0253-2727.2020.008 https://doi.org/10.3760/cma.j.issn.0253-2727.2020.008

Zhao Y , Zhao ZX , Wang YJ , et al. , 2020 . Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2 . Am J Respir Crit Care Med , 202 ( 5 ): 756 - 759 . https://doi.org/10.1164/rccm.202001-0179LE https://doi.org/10.1164/rccm.202001-0179LE

Zhou F , Yu T , Du RH , et al. , 2020 . Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study . Lancet , 395 ( 10229 ): 1054 - 1062 . https://doi.org/10.1016/S0140-6736(20)30566-3 https://doi.org/10.1016/S0140-6736(20)30566-3

Zhu HB , Wei L , Niu P , 2020 . The novel coronavirus outbreak in Wuhan, China . Glob Health Res Policy , 5 : 6 . https://doi.org/10.1186/s41256-020-00135-6 https://doi.org/10.1186/s41256-020-00135-6

Zhu LL , Liu L , Zhang Y , et al. , 2018 . High level of neutrophil extracellular traps correlates with poor prognosis of severe influenza A infection . J Infect Dis , 217 ( 3 ): 428 - 437 . https://doi.org/10.1093/infdis/jix475 https://doi.org/10.1093/infdis/jix475

Zimmermann N , Wolf C , Schwenke R , et al. , 2019 . Assessment of clinical response to Janus kinase inhibition in patients with familial chilblain lupus and TREX1 mutation . JAMA Dermatol , 155 ( 3 ): 342 - 346 . https://doi.org/10.1001/jamadermatol.2018.5077 https://doi.org/10.1001/jamadermatol.2018.5077

Zuo Y , Yalavarthi S , Shi H , et al. , 2020 . Neutrophil extracellular traps in COVID-19 . JCI Insight , 5 ( 11 ): e138999 . https://doi.org/10.1172/jci.insight.138999 https://doi.org/10.1172/jci.insight.138999

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