COVID-19 and stroke

Authors: R. Herzig 1;  R. Mikulík 2;  A. Tomek 3;  J. Neumann 4;  D. Školoudík 5
Authors‘ workplace: Neurologická klinika, Komplexní cerebrovaskulární centrum, LF UK a FN Hradec Králové 1;  Neurologická klinika FN u sv. Anny, Brno 2;  Neurologická klinika 2. LF UK a FN Motol, Praha 3;  Neurologické oddělení, Krajská zdravotní, a. s. – Nemocnice Chomutov, o. z. 4;  Centrum zdravotnického výzkumu, LF OU, Ostrava 5
Published in: Cesk Slov Neurol N 2021; 84/117(1): 31-37
Category: Review Article


The aim of this work is to provide an overview of the relationship between COVID-19 and stroke. The work deals with the risk of stroke and its mechanisms in patients with COVID-19, as well as the prognosis, impact on the organization of care and the treatment of stroke itself due to the COVID-19 pandemic. The COVID-19 pandemic has led to a reduction in acute care for stroke patients in a number of countries, but in the Czech Republic there was no significant deterioration in the provision of this care during the spring wave in 2020. The incidence of stroke in patients with COVID-19 ranges from 0.9 to 6%, but may be higher. Patients with stroke should be tested for COVID-19, especially if they do not have typical cardiovascular risk factors. The clinical manifestation of a stroke in patients with COVID-19 is moderate to severe, with a high percentage of these patients having large artery occlusion. Most patients with COVID-19 and stroke are older and have typical cardiovascular risk factors, but stroke may also occur in young patients without risk factors. Stroke develops on average within 11 days of the development of COVID-19 symptoms (severe COVID-19 infection may be complicated by an early cytokine storm, followed by a prothrombotic condition and frequent venous and arterial thromboembolic complications), but stroke may develop also in the early phase of infection. Patients with COVID-19 and stroke have a worse clinical outcome and higher mortality than patients with stroke without COVID-19. COVID-19 stroke patients should receive standard treatment. Prophylactic or therapeutic anticoagulation could also be beneficial.


COVID-19 – stroke – risk – development mechanisms – prognosis – care organization – therapy


1. Mao L, Jin H, Wang M et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020; 77 (6): 683–690. doi: 10.1001/jamaneurol.2020.1127.

2. Morelli N, Rota E, Terracciano C et al. The baffling case of ischemic stroke disappearance from the casualty department in the COVID-19 era. Eur Neurol 2020; 83 (2): 213–215. doi: 10.1159/000507666.

3. Tan YK, Goh C, Leow AST et al. COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature. J Thromb Thrombolysis 2020; 50 (3): 587–595. doi: 10.1007/s11239-020-02228-y.

4. Oxley TJ, Mocco J, Majidi S et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020; 382 (20): e60. doi: 10.1056/NEJMc2009 787.

5. Viguier A, Delamarre L, Duplantier J et al. Acute ischemic stroke complicating common carotid artery thrombosis during a severe COVID-19 infection. J Neuroradiol 2020; 47 (5): 393–394. doi: 10.1016/j.neurad.2020.04.003.

6. Ellul MA, Benjamin L, Singh B et al. Neurological associations of COVID-19. Lancet Neurol 2020; 19 (9): 767–783. doi: 10.1016/S1474-4422 (20) 30221-0.

7. Belani P, Schefflein J, Kihira S et al. COVID-19 is an independent risk factor for acute ischemic stroke. AJNR Am J Neuroradiol 2020; 41 (8): 1361–1364. doi: 10.3174/ajnr.A6650.

8. Merkler AE, Parikh NS, Mir S et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza. JAMA Neurol 2020; 77 (11): 1–7. doi: 10.1001/jamaneurol.2020.2730.

9. Iba T, Levy JH, Warkentin TE et al. Dia­gnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost 2019; 17 (11): 1989–1994. doi: 10.1111/jth.14578.

10. Tang N, Bai H, Chen X et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020; 18 (5): 1094–1099. doi: 10.1111/jth.14817.

11. Mehta P, McAuley DF, Brown M et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395 (10229): 1033–1034. doi: 10.1016/S0140-6736 (20) 30628-0.

12. Zhang Y, Xiao M, Zhang S et al. Coagulopathy and antiphospholipid antibodies in patients with covid-19. N Engl J Med 2020; 382 (17): e38. doi: 10.1056/NEJMc2007575.

13. Zhou P, Yang XL, Wang XG. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579 (7798): 270–273. doi: 10.1038/s41586-020-2012-7.

14. Hoffmann M, Kleine-Weber H, Schroeder S et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181 (2): 271–280. doi: 10.1016/j.cell.2020.02.052.

15. Xu P, Sriramula S, Lazartigues E. ACE2/ANG- (1-7) /Mas pathway in the brain: the axis of good. Am J Physiol Regul Integr Comp Physiol 2011; 300 (4): R804–R817. doi: 10.1152/ajpregu.00222.2010.

16. Mecca AP, Regenhardt RW, O‘Connor TE et al. Cerebroprotection by angiotensin- (1-7) in endothelin-1-induced ischaemic stroke. Exp Physiol 2011; 96 (10): 1084–1096. doi: 10.1113/expphysiol.2011.058578.

17. Regenhardt RW, Desland F, Mecca AP et al. Anti-inflammatory effects of angiotensin- (1-7) in ischemic stroke. Neuropharmacology 2013; 71: 154–163. doi: 10.1016/j.neuropharm.2013.03.025.

18. Regenhardt RW, Mecca AP, Desland F et al. Centrally administered angiotensin- (1-7) increases the survival of stroke-prone spontaneously hypertensive rats. Exp Physiol 2014; 99 (2): 442–453. doi: 10.1113/expphysiol.2013.075242.

19. Arendse LB, Jan Danser AH, Poglitsch M et al. Novel therapeutic approaches targeting the renin-angiotensin system and associated peptides in hypertension and heart failure. Pharmacol Rev 2019; 71 (4): 539–570. doi: 10.1124/pr.118.017129.

20. Doobay MF, Talman LS, Obr TD et al. Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol 2007; 292 (1): R373–R381. doi: 10.1152/ajpregu.00292.2006.

21. Chen J, Xiao X, Chen S et al. Angiotensin-converting enzyme 2 priming enhances the function of endothelial progenitor cells and their therapeutic efficacy. Hypertension 2013; 61 (3): 681–689. doi: 10.1161/HYPERTENSIONAHA.111.00202.

22. Chen J, Zhao Y, Chen S et al. Neuronal over-expression of ACE2 protects brain from ischemia-induced damage. Neuropharmacology 2014; 79: 550–558. doi: 10.1016/j.neuropharm.2014.01.004.

23. Xie X, Chen J, Wang X et al. Age- and gender-related difference of ACE2 expression in rat lung. Life Sci 2006; 78 (19): 2166–2171. doi: 10.1016/j.lfs.2005.09.038.

24. Wang M, Monticone RE, Lakatta EG et al. Proinflammation of aging central arteries: a mini-review. Gerontology 2014; 60 (6): 519–529. doi: 10.1159/000362548.

25. Hess DC, Eldahshan W, Rutkowski E. COVID-19-related stroke. Transl Stroke Res 2020; 11 (3): 322–325. doi: 10.1007/s12975-020-00818-9.

26. Akhmerov A, Marbán E. COVID-19 and the heart. Circ Res 2020; 126 (10): 1443–1455. doi: 10.1161/CIRCRESAHA.120.317055.

27. Markus HS, Brainin M. COVID-19 and stroke – a global World Stroke Organization perspective. Int J Stroke 2020; 15 (4): 361–364. doi: 10.1177/174749302 0923472.

28. Aggarwal G, Lippi G, Henry BM. Cerebrovascular disease is associated with an increased disease severity in patients with coronavirus disease 2019 (COVID-19): A pooled analysis of published literature. Int J Stroke 2020; 15 (4): 385–389. doi: 10.1177/1747493020921664.

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

30. Ntaios G, Michel P, Georgiopoulos G et al. Characte- ristics and outcomes in patients with COVID-19 and acute ischemic stroke: the Global COVID-19 Stroke Registry. Stroke 2020; 51 (9): e254–e258. doi: 10.1161/STROKEAHA. 120.031208.

31. Yaghi S, Ishida K, Torres J et al. SARS-CoV-2 and stroke in a New York healthcare system. Stroke 2020; 51 (7): 2002–2011. doi: 10.1161/STROKEAHA.120.030335.

32. Baracchini C, Pieroni A, Viaro F et al. Acute stroke management pathway during coronavirus-19 pandemic. Neurol Sci 2020; 41 (5): 1003–1005. doi: 10.1007/s10072-020-04375-9.

33. Školoudík D, Mijajlović M. Neurosonology during the COVID-19 pandemic (editorial commentary from the chairs of the ultrasound panel of the European Academy of Neurology). Eur J Neurol 2020; 27 (9): 1774–1775. doi: 10.1111/ene.14410.

34. Baracchini C, Pieroni A, Kneihsl M et al. Practice recommendations for neurovascular ultrasound investigations of acute stroke patients in the setting of the COVID-19 pandemic: an expert consensus from the European Society of Neurosonology and Cerebral Hemodynamics. Eur J Neurol 2020; 27 (9): 1776–1780. doi: 10.1111/ene.14334.

35. Bersano A, Kraemer M, Touzé E et al. Stroke care during the COVID-19 pandemic: experience from three large European countries. Eur J Neurol 2020; 27 (9): 1794–1800. doi: 10.1111/ene.14375.

36. Kristoffersen ES, Jahr SH, Thommessen B et al. Effect of COVID-19 pandemic on stroke admission rates in a Norwegian population. Acta Neurol Scand 2020; 142 (6): 632–636. doi: 10.1111/ane.13307.

37. Pop R, Quenardelle V, Hasiu A et al. Impact of the COVID-19 outbreak on acute stroke pathways – insights from the Alsace region in France. Eur J Neurol 2020; 27 (9): 1783–1787. doi: 10.1111/ene.14316.

38. Uphaus T, Gröschel S, Hayani E et al. Stroke care within the COVID-19 pandemic – increasing awareness of transient and mild stroke symptoms needed. Front Neurol 2020; 11: 581394. doi: 10.3389/fneur.2020.581394.

39. Rudilosso S, Laredo C, Vera V et al. Acute stroke care is at risk in the era of COVID-19: experience at a Comprehensive Stroke Center in Barcelona. Stroke 2020; 51 (7): 1991–1995. doi: 10.1161/STROKEAHA.120.030329.

40. Hoyer C, Ebert A, Huttner HB et al. Acute stroke in times of the COVID-19 pandemic: a multicenter study. Stroke 2020; 51 (7): 2224–2227. doi: 10.1161/STROKEAHA. 120.030395.

41. Rinkel LA, Prick JC, Slot RE et al. Impact of the COVID-19 outbreak on acute stroke care. J Neurol 2021; 268 (2): 403–408. doi: 10.1007/s00415-020-10069-1.

42. Gdovinová Z, Vitková M, Baráková A et al. The impact of the COVID-19 outbreak on acute stroke care in Slovakia: data from across the country. Eur J Neurol 2020 Nov 13 [ahead of print]. doi: 10.1111/ene.14640.

43. Plumereau C, Cho TH, Buisson M et al. Effect of the COVID-19 pandemic on acute stroke reperfusion therapy: data from the Lyon Stroke Center Network. J Neurol 2020 Sep 9 [ahead of print]. doi: 10.1007/s00415-020-10199-6.

44. Tiedt S, Bode FJ, Uphaus T et al. Impact of the COVID--19-pandemic on thrombectomy services in Germany. Neurol Res Pract 2020; 2: 44. doi: 10.1186/s42466-020-00090-0.

45. Tejada Meza H, Lambea Gil Á, Sancho Saldaña A et al. Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain. Eur J Neurol 2020; 27 (12): 2491–2498. doi: 10.1111/ene.14467.

46. Kerleroux B, Fabacher T, Bricout N et al. Mechanical thrombectomy for acute ischemic stroke amid the COVID-19 outbreak: decreased activity, and increased care delays. Stroke 2020l; 51 (7): 2012–2017. doi: 10.1161/STROKEAHA.120.030373.

47. Coronavirus Country Comparator. [online]. Avail­able from URL: https: //

48. RES Registry of Stroke Care Quality. [online]. Available from URL: https: //

49. Wikipedia. List of countries by hospital beds. [online]. Available from URL: https: //

50. Šaňák D, Neumann J, Tomek A et al. Doporučení pro rekanalizační léčbu akutního mozkového infarktu – verze 2016. Cesk Slov Neurol N 2016; 79/112 (2): 231–234. doi: 10.14735/amcsnn2016231.

51. Šaňák D, Mikulík R, Tomek A et al. Doporučení pro mechanickou trombektomii akutního mozkového infarktu – verze 2019. Cesk Slov Neurol N 2019; 82/115 (6): 700–705. doi: 10.14735/amcsnn2019700.

52. Powers WJ, Rabinstein AA, Ackerson T et al. 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. Stroke 2019; 50 (12): e344–e418. doi: 10.1161/STR.0000 000000000211.

43. Thachil J. The versatile heparin in COVID-19. J Thromb Haemost 2020; 18 (5): 1020–1022. doi: 10.1111/jth. 14821.

44. Monteil V, Kwon H, Prado P et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020; 181 (4): 905–913. doi: 10.1016/j.cell.2020.04.004.

45. Khan A, Benthin C, Zeno B et al. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit Care 2017; 21 (1): 234. doi: 10.1186/s13054-017-1823-x.

46. Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a treatment for patients with COVID-19 (APN01-COVID-19). [online]. Available from URL: https: // show/NCT04335136.

57. Angiotensin- (1,7) treatment in COVID-19: the ATCO Trial (ATCO). [online]. Avail­able from URL: https: // NCT04332666.

48. Bozkurt B, Kovacs R, Harrington B. Joint HFSA/ACC/ AHA statement addresses concerns Re: Using RAAS antagonists in COVID-19. J Card Fail 2020; 26 (5): 370. doi: 10.1016/j.cardfail.2020.04.013.

49. Zhang P, Zhu L, Cai J et al. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res 2020; 126 (12): 1671–1681. doi: 10.1161/CIRCRESAHA.120.31713

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