Pathomechanism and Management of Stroke in COVID-19: Review of Immunopathogenesis, Coagulopathy, Endothelial Dysfunction, and Downregulation of ACE2

다국어 초록 (Multilingual Abstract)

Coronavirus disease 2019 (COVID-19) can reportedly manifest as an acute stroke, with most cases presenting as large vessel ischemic stroke in patients with or without comorbidities. The exact pathomechanism of stroke in COVID-19 remains ambiguous. The findings of previous studies indicate that the most likely underlying mechanisms are cerebrovascular pathological conditions following viral infection, inflammation-induced endothelial dysfunction, and hypercoagulability.
Acute endothelial damage due to inflammation triggers a coagulation cascade, thrombosis propagation, and destabilization of atherosclerosis plaques, leading to largevessel occlusion and plaque ulceration with concomitant thromboemboli, and manifests as ischemic stroke. Another possible mechanism is the downregulation of angiotensin-converting enzyme 2 as the target action of severe acute respiratory syndrome-coronavirus-2 (SARSCoV- 2). Acute stroke management protocols need to be modified during the COVID-19 pandemic in order to adequately manage stroke patients with COVID-19.

참고문헌 (Reference)

1 World Health Organization, "WHO Timeline - COVID-19" World Health Organization

2 Schurink B, "Viral presence and immunopathology in patients with lethal COVID-19 : a prospective autopsy cohort study" 1 : e290-, 2020

3 Lodigiani C, "Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy" 191 : 9-14, 2020

4 Remmelink M, "Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients"

5 Sironi L, "Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage" 23 : 322-327, 2003

6 Hamming I, "Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis" 203 : 631-637, 2004

7 Tay MZ, "The trinity of COVID-19 : immunity, inflammation and intervention" 20 : 363-374, 2020

8 Verdecchia P, "The pivotal link between ACE2 deficiency and SARS-CoV-2 infection" 76 : 14-20, 2020

9 Zhai P, "The impact of COVID-19 on ischemic stroke" 15 : 78-, 2020

10 Rothan HA, "The epidemiology and pathogenesis of coronavirus disease(COVID-19)outbreak" 109 : 102433-, 2020

11 Gunasekaran K, "Stroke in a young COVID-19 patient" 113 : 573-574, 2020

12 Al Saiegh F, "Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke" 91 : 846-848, 2020

13 Tan WYT, "Statin use is associated with lower disease severity in COVID-19 infection" 10 : 17458-, 2020

14 Yaghi S, "SARS-CoV-2 and stroke in a New York healthcare system" 51 : 2002-2011, 2020

15 de Wit E, "SARS and MERS : recent insights into emerging coronaviruses" 14 : 523-534, 2016

16 Vivas D, "Recommendations on antithrombotic treatment during the COVID-19 pandemic. Position statement of the working group on cardiovascular thrombosis of the Spanish Society of Cardiology" 73 : 749-757, 2020

17 Yoshimura S, "Randomized controlled trial of early versus delayed statin therapy in patients with acute ischemic stroke : ASSORT trial(administration of statin on acute ischemic stroke patient)" 48 : 3057-3063, 2017

18 Rossi R, "Protective role of statins in COVID 19 patients : importance of pharmacokinetic characteristics rather than intensity of action" 15 : 1573-1576, 2020

19 Khosravani H, "Protected code stroke : hyperacute stroke management during the Coronavirus Disease 2019(COVID-19)pandemic" 51 : 1891-1895, 2020

20 Assinger A, "Platelets in sepsis : an update on experimental models and clinical data" 10 : 1687-, 2019

21 Cox D, "Platelets and the innate immune system : mechanisms of bacterial-induced platelet activation" 9 : 1097-1107, 2011

22 Bryce C, "Pathophysiology of SARS-CoV-2: targeting of endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID-19 autopsy experience"

23 Xu Z, "Pathological findings of COVID-19 associated with acute respiratory distress syndrome" 8 : 420-422, 2020

24 Channappanavar R, "Pathogenic human coronavirus infections : causes and consequences of cytokine storm and immunopathology" 39 : 529-539, 2017

25 Berger C, "Neuroprotection by pravastatin in acute ischemic stroke in rats" 58 : 48-56, 2008

26 Matschke J, "Neuropathology of patients with COVID-19 in Germany : a post-mortem case series" 19 : 919-929, 2020

27 Solomon IH, "Neuropathological features of COVID-19" 383 : 989-992, 2020

28 Kantonen J, "Neuropathologic features of four autopsied COVID-19 patients" 30 : 1012-1016, 2020

29 Mao L, "Neurologic manifestations of hospitalized patients with Coronavirus Disease 2019 in Wuhan, China" 77 : 683-690, 2020

30 Wu Y, "Nervous system involvement after infection with COVID-19 and other coronaviruses" 87 : 18-22, 2020

31 Li X, "Molecular immune pathogenesis and diagnosis of COVID-19" 10 : 102-108, 2020

32 Jaunmuktane Z, "Microvascular injury and hypoxic damage : emerging neuropathological signatures in COVID-19" 140 : 397-400, 2020

33 Amin-Hanjani S, "Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice" 32 : 980-986, 2001

34 Bazaz R, "Mechanistic links between acute respiratory tract infections and acute coronary syndromes" 66 : 1-17, 2013

35 Fara MG, "Macrothrombosis and stroke in patients with mild COVID-19 infection" 18 : 2031-2033, 2020

36 Oxley TJ, "Large-vessel stroke as a presenting feature of COVID-19 in the young" 382 : e60-, 2020

37 S. Al‐Sarraj, "Invited Review: The spectrum of neuropathology in COVID‐19" Wiley 47 (47): 3-16, 2021

38 Co COC, "Intravenous thrombolysis for stroke in a COVID-19 positive Filipino patient, a case report" 77 : 234-236, 2020

39 Schouten M, "Inflammation, endothelium, and coagulation in sepsis" 83 : 536-545, 2008

40 Thachil J, "ISTH interim guidance on recognition and management of coagulopathy in COVID-19" 18 : 1023-1026, 2020

41 Hanley B, "Histopathological findings and viral tropism in UK patients with severe fatal COVID-19 : a post-mortem study" 1 : e245-, 2020

42 Dogra S, "Hemorrhagic stroke and anticoagulation in COVID-19" 29 : 104984-, 2020

43 Kawashima S, "HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats" 34 : 157-163, 2003

44 Powers WJ, "Guidelines for the early management of patients with acute ischemic stroke : 2019 update to the 2018 Guidelines for the early management of acute ischemic stroke : a guideline for healthcare professionals from the American Heart Association/American Stroke Association" 50 : e344-, 2019

45 Lu R, "Genomic characterisation and epidemiology of 2019 novel coronavirus : implications for virus origins and receptor binding" 395 : 565-574, 2020

46 Su S, "Epidemiology, genetic recombination, and pathogenesis of coronaviruses" 24 : 490-502, 2016

47 Smith MS, "Endovascular therapy for patients with acute ischemic stroke during the COVID-19 pandemic : a proposed algorithm" 51 : 1902-1909, 2020

48 Pan CH, "Downregulation of angiotensin converting enzyme II is associated with pacing-induced sustained atrial fibrillation" 581 : 526-534, 2007

49 Jin H, "Consensus for prevention and management of coronavirus disease(COVID-19)for neurologists" 5 : 146-151, 2020

50 Tunç A, "Coexistence of COVID-19 and acute ischemic stroke report of four cases" 77 : 227-229, 2020

51 Huang C, "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China" 395 : 497-506, 2020

52 Zhou F, "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China : a retrospective cohort study" 395 : 1054-1062, 2020

53 Wang D, "Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China" 323 : 1061-1069, 2020

54 Beyrouti R, "Characteristics of ischaemic stroke associated with COVID-19" 91 : 889-891, 2020

55 Goldberg MF, "Cerebrovascular disease in COVID-19" 41 : 1170-1172, 2020

56 Paniz-Mondolfi A, "Central nervous system involvement by Severe Acute Respiratory Syndrome Coronavirus-2(SARS-CoV-2)" 92 : 699-702, 2020

57 Avula A, "COVID-19 presenting as stroke" 87 : 115-119, 2020

58 Saggese CE, "COVID-19 and stroke : casual or causal role?" 49 : 341-344, 2020

59 Levi M, "Bidirectional relation between inflammation and coagulation" 109 : 2698-2704, 2004

60 Sandercock PA, "Anticoagulants for acute ischaemic stroke" 2015 : CD000024-, 2015

61 Tang N, "Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy" 18 : 1094-1099, 2020

62 Bernstein KE, "Angiotensin-converting enzyme in innate and adaptive immunity" 14 : 325-336, 2018

63 Xia H, "Angiotensin-converting enzyme 2 in the brain : properties and future directions" 107 : 1482-1494, 2008

64 Xia H, "Angiotensin-converting enzyme 2 : central regulator for cardiovascular function" 12 : 170-175, 2010

65 Mehta PK, "Angiotensin II cell signaling : physiological and pathological effects in the cardiovascular system" 292 : C82-, 2007

66 Sharma D, "Anesthetic management of endovascular treatment of acute ischemic stroke during COVID-19 pandemic : consensus statement from Society for Neuroscience in Anesthesiology & Critical Care(SNACC)" 32 : 193-201, 2020

67 Ferrario CM, "Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7)in regulation of cardiovascular function" 289 : H2281-, 2005

68 Baracchini C, "Acute stroke management pathway during Coronavirus-19 pandemic" 41 : 1003-1005, 2020