Der Zusammenhang zwischen COVID-19 und Schlaganfall: Pathophysiologie und klinische Bedeutung

Zusammenfassung

Dass COVID-19 mit einem erhöhten Risiko für das Auftreten ischämischer Schlaganfälle einhergeht, wurde bereits in den ersten Monaten nach dem weltweiten Bekanntwerden des Ausbruchs der Pandemie im Ground Zero Wuhan deutlich. Spätere Kohortenanalysen, Fallserien und Meta-Analysen bestätigten diesen Zusammenhang. Eine nicht unerhebliche geographische Variabilität der Prävalenz COVID-19-bezogener Schlaganfälle verdeutlicht allerdings den fortbestehenden Bedarf an umfassenden epidemiologischen Analysen. Im Übrigen fanden sich zunehmend Hinweise dafür, dass dem mit COVID-19 assoziierten Schlaganfall ein multifaktorieller pathophysiologischer Mechanismus zugrundeliegenden könnte. Neben einer durch die SARS-CoV-2-Infektion verursachten Hyperkoagubilität, die sowohl im mikrovaskulären System als auch in Großgefäßen thrombogen wirkt, scheinen vaskulitische arterielle Veränderungen und kardiogene Embolien infolge virusassoziierter myokardialer Schädigung bei der Ätiologie des COVID-19-assoziierten Schlaganfalls eine Rolle zu spielen. Die Versorgung von Schlaganfallpatienten/innen in Zeiten der Pandemie durch multidisziplinäre Teams scheint in insgesamt kompensierten Kliniken im Wesentlichen nicht kompromittiert zu sein. Hinweise, dass Patienten/innen mit COVID-19-assoziiertem Schlaganfall von einem intensivierten Monitoring und einer aggressiveren Sekundärprävention profitieren, bedarf klinischer Prüfung.

Abstract

The notion of an increased risk of acute ischemic stroke in patients with COVID-19 emerged during the first months after the outbreak of the COVID-19 pandemic at ground zero in Wuhan. Subsequently, this association was confirmed by multiple case reports, cohort studies and meta-analyses. However, substantial geographical variability in prevalence of COVID-19 associated stroke underscores a persistent need of encompassing epidemiological study. Accumulative evidence suggested a rather complex underlying pathophysiology. Possible mechanisms include small and large vessel thromboembolism induced by systemic hypercoagubility, vasculitis and cardiac embolism caused by virus-induced cardiomyopathy. Multidisciplinary care of acute stroke patients in general does not seem to be compromised by the pandemic in otherwise compensated hospitals. However, it remains to be answered whether more aggressive approaches of secondary prevention and intensified monitoring strategies after COVID-19 related stroke are necessary to optimize clinical outcomes.

Schlüsselwörter

COVID-19 - SARS-CoV-2 - Schlaganfall - Hyperkoagulabilität - Vaskulitis - Kardiomyopathie

Key words

COVID-19 - SARS-CoV-2 - Stroke - Hypercoagulability - Vasculitis - Cardiomyopathy

Publication History

Received: 09 February 2021

Accepted: 08 April 2021

Article published online:
21 May 2021

• Literatur

• 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 (06) : 683-690. DOI: 10.1001/jamaneurol.2020.1127.
• 2 Niazkar HR, Zibaee B, Nasimi A. et al. The neurological manifestations of COVID-19: A review article. Neurol Sci 2020; 41 (07) : 1667-1671. 10.1007/s10072-020-04486-3
• 3 Bikdeli B, Madhavan MV, Jimenez D. et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020; 75 (23) : 2950-2973. DOI: 10.1016/j.jacc.2020.04.031.
• 4 Cui S, Chen S, Li X. et al. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020; 18 (06) : 1421-1424. 10.1111/jth.14830
• 5 Lodigiani C, Iapichino G, Carenzo L. et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 2020; 191: 9-14. 10.1016/j.thromres.2020.04.024
• 6 Fridman S, Bres Bullrich M, Jimenez-Ruiz A. et al. Stroke risk, phenotypes, and death in COVID-19: systematic review and newly reported cases. Neurology 2020; 95 (24) : e3373-e3385. DOI: 10.1212/WNL.0000000000010851.
• 7 Siepmann T, Sedghi A, Simon E. et al. Increased risk of acute stroke among patients with severe COVID-19: A multicenter study and meta-analysis. Eur J Neurol 2021; 28 (01) : 238-247. 10.1111/ene.14535
• 8 Siow I, Lee KS, Zhang JJY. et al. Stroke as a neurological complication of COVID-19: a systematic review and meta-analysis of incidence, outcomes and predictors [published online ahead of print, 2020 Dec 15]. J Stroke Cerebrovasc Dis 2020; 30 (03) : 105549. DOI: 10.1016/j.jstrokecerebrovasdis.2020.105549.
• 9 Siepmann T, Sedghi A, Barlinn J. et al. Association of history of cerebrovascular disease with severity of COVID-19 [published online ahead of print, 2020 Aug 6]. J Neurol. 2020: 1-12. 10.1007/s00415-020-10121-0
• 10 Kummer BR, Klang E, Stein LK. et al. History of stroke is independently associated with in-hospital death in patients with COVID-19. Stroke 2020; 51 (10) : 3112-3114. DOI: 10.1161/STROKEAHA.120.030685.
• 11 Escalard S, Chalumeau V, Escalard C. et al. Early brain imaging shows increased severity of acute ischemic strokes with large vessel occlusion in COVID-19 patients. Stroke 2020; 51 (11) : 3366-3370. DOI: 10.1161/STROKEAHA.120.031011.
• 12 Bekelis K, Missios S, Ahmad J. et al. Ischemic stroke occurs less frequently in patients with COVID-19: a multicenter cross-sectional study. Stroke 2020; 51 (12) : 3570-3576. DOI: 10.1161/STROKEAHA.120.031217.
• 13 Merkler AE, Parikh NS, Mir S. et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza [published online ahead of print, 2020 Jul 2]. JAMA Neurol 2020; 77 (11) : 1-7. 10.1001/jamaneurol.2020.2730
• 14 Ellul MA, Benjamin L, Singh B. et al. Neurological associations of COVID-19. Lancet Neurol 2020; 19 (09) : 767-783. DOI: 10.1016/S1474-4422(20)30221-0.
• 15 Ntaios G, Michel P, Georgiopoulos G. et al. Characteristics and outcomes in patients with COVID-19 and acute ischemic stroke: the global COVID-19 stroke registry. Stroke. 2020; 51 (09) : e254-e258. DOI: 10.1161/STROKEAHA.120.031208.
• 16 Yaghi S, Ishida K, Torres J. et al. SARS-CoV-2 and stroke in a New York healthcare system [published correction appears in Stroke. 2020 Aug;51(8):e179]. Stroke 2020; 51 (07) : 2002-2011. DOI: 10.1161/STROKEAHA.120.030335.
• 17 Fifi JT, Mocco J. COVID-19 related stroke in young individuals. Lancet Neurol 2020; 19 (09) : 713-715. DOI: 10.1016/S1474-4422(20)30272-6.
• 18 Spence JD, De Freitas GR, Pettigrew LC. et al. Mechanisms of stroke in COVID-19. Cerebrovasc Dis 2020; 49 (04) : 451-458. DOI: 10.1159/000509581.
• 19 Carod-Artal FJ. Neurological complications of coronavirus and COVID-19. Complicaciones neurológicas por coronavirus y COVID-19. Rev Neurol 2020; 70 (09) : 311-322. DOI: 10.33588/rn.7009.2020179.
• 20 Franceschi AM, Ahmed O, Giliberto L. et al. Hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of COVID-19 infection. AJNR Am J Neuroradiol 2020; 41 (07) : 1173-1176. 10.3174/ajnr.A6595
• 21 Lee SG, Fralick M, Sholzberg M. Coagulopathy associated with COVID-19. CMAJ 2020; 192 (21) : E583. DOI: 10.1503/cmaj.200685.
• 22 Cristiano A, Fortunati V, Cherubini F. et al. Anti-phospholipids antibodies and immune complexes in COVID-19 patients: a putative role in disease course for anti-annexin-V antibodies [published online ahead of print, 2021 Jan 19]. Clin Rheumatol. 2021: 1-7. 10.1007/s10067-021-05580-3
• 23 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.
• 24 Hamadé A, Woehl B, Harzallah I. et al. Antiphospholipid antibodies in patients with coronavirus disease 2019 infection hospitalized in conventional unit [published online ahead of print, 2020 Dec 2]. Blood Coagul Fibrinolysis 2020 DOI: 10.1097/MBC.0000000000000963
• 25 Van Der Linden J, Almskog L, Liliequist A. et al. Thromboembolism, hypercoagulopathy, and antiphospholipid antibodies in critically ill coronavirus disease 2019 patients: a before and after study of enhanced anticoagulation. Crit Care Explor 2020; 2 (12) : e0308. DOI: 10.1097/CCE.0000000000000308.
• 26 Iba T, Levy JH, Connors JM. et al. The unique characteristics of COVID-19 coagulopathy. Crit Care 2020; 24 (01) : 360
• 27 Thachil J, Tang N, Gando S. et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020; 18 (05) : 1023-1026. DOI: 10.1111/jth.14810.
• 28 Magro C, Mulvey JJ, Berlin D. et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res 2020; 220: 1-13
• 29 Rapkiewicz AV, Mai X, Carsons SE. et al. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: a case series. EClinicalMedicine 2020; 24: 100434. Published 2020 Jun 25. DOI: 10.1016/j.eclinm.2020.100434.
• 30 Chen W, Pan JY. Anatomical and pathological observation and analysis of SARS and COVID-19: microthrombosis is the main cause of death. Biol Proced Online 2021; 23 (01) : 4
• 31 Middeldorp S, Coppens M, Van Haaps TF. et al. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020; 18 (08) : 1995-2002. DOI: 10.1111/jth.14888.
• 32 Cui S, Chen S, Li X. et al. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020; Jun; 18 (06) : 1421-1424. DOI: 10.1111/jth.14830. Epub 2020 May 6. PMID: 32271988; PMCID: PMC7262324.
• 33 Hamming I, Timens W, Bulthuis ML. et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203 (02) : 631-637. 10.1002/path.1570
• 34 Varga Z, Flammer AJ, Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395 (10234): 1417-1418. DOI: 10.1016/S0140-6736(20)30937-5.
• 35 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506. DOI: 10.1016/S0140-6736(20)30183-5.
• 36 McGonagle D, Bridgewood C, Ramanan AV. et al. COVID-19 vasculitis and novel vasculitis mimics [published online ahead of print, 2021 Jan 7]. Lancet Rheumatol 2021 DOI: 10.1016/S2665-9913(20)30420-3
• 37 Hernández-Fernández F, Sandoval Valencia H, Barbella-Aponte RA. et al. Cerebrovascular disease in patients with COVID-19: Neuroimaging, histological and clinical description. Brain 2020; 143 (10) : 3089-3103. DOI: 10.1093/brain/awaa239.
• 38 Akhmerov A, Marbán E. COVID-19 and the heart. Circ Res 2020; 126 (10) : 1443-1455
• 39 Puntmann VO, Carerj ML, Wieters I. et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19) [published correction appears in JAMA cardiol. 2020 Nov 1;5(11):1308]. JAMA Cardiol 2020; 5 (11) : 1265-1273. DOI: 10.1001/jamacardio.2020.3557.
• 40 Madjid M, Safavi-Naeini P, Solomon SD. et al. Potential effects of coronaviruses on the cardiovascular system: a review. JAMA Cardiol 2020; 5 (07) : 831-840. DOI: 10.1001/jamacardio.2020.1286.
• 41 Hoyer C, Ebert A, Huttner HB. et al. Acute stroke in times of the COVID-19 pandemic: a multicenter study. Stroke 2020; 51 (07) : 2224-2227. 10.1161/STROKEAHA.120.030395
• 42 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 2020; 51 (07) : 2012-2017. DOI: 10.1161/STROKEAHA.120.030373.
• 43 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 (07) : 1991-1995. DOI: 10.1161/STROKEAHA.120.030329.
• 44 Abootalebi S, Aertker BM, Andalibi MS. et al. Call to action: SARS-CoV-2 and CerebrovAscular DisordErs (CASCADE). J Stroke Cerebrovasc Dis 2020; 29 (09) : 104938. DOI: 10.1016/j.jstrokecerebrovasdis.2020.104938.
• 45 Goyal M, Ospel JM, Southerland AM. et al. Prehospital triage of acute stroke patients during the COVID-19 pandemic. Stroke 2020; 51 (07) : 2263-2267. DOI: 10.1161/STROKEAHA.120.030340.
• 46 Khosravani H, Rajendram P, Notario L. et al. Protected code stroke: hyperacute stroke management during the coronavirus disease 2019 (COVID-19) pandemic. Stroke 2020; 51 (06) : 1891-1895. DOI: 10.1161/STROKEAHA.120.029838.
• 47 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. Published 2020 Nov 23. DOI: 10.1186/s42466-020-00090-0.
• 48 Hajdu SD, Pittet V, Puccinelli F. et al. Acute stroke management during the COVID-19 pandemic: does confinement impact eligibility for endovascular therapy?. Stroke 2020; 51 (08) : 2593-2596. DOI: 10.1161/STROKEAHA.120.030794.
• 49 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.
• 50 Barlinn K, Siepmann T, Pallesen LP. et al. Universal laboratory testing for SARS-CoV-2 in hyperacute stroke during the COVID-19 pandemic. J Stroke Cerebrovasc Dis 2020; Sep; 29 (09) : 105061. DOI: 10.1016/j.jstrokecerebrovasdis.2020.105061.
• 51 Baracchini C, Pieroni A. Acute stroke treatment during coronavirus disease 2019 pandemic. Curr Opin Neurol 2021; 34 (01) : 11-17. DOI: 10.1097/WCO.0000000000000886.
• 52 Friedlich D, Newman T, Bricker S. Impact of the COVID-19 pandemic on stroke epidemiology and clinical stroke practice in the US [published online ahead of print, 2021 Jan 26]. J Stroke Cerebrovasc Dis 2021; 30 (04) : 105639. DOI: 10.1016/j.jstrokecerebrovasdis.2021.105639.
• 53 Guan WJ, Ni ZY, Hu Y. et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382 (18) : 1708-1720. DOI: 10.1056/NEJMoa2002032.
• 54 MacDougall K, Spyropoulos AC. Prevention of venous thromboembolism in acutely ill medical patients: a new era [published online ahead of print, 2021 Feb 6]. Semin Respir Crit Care Med 2021 DOI: 10.1055/s-0041-1723018
• 55 Tiwari NR, Khatib KI, Dixit SB. et al. Anticoagulation in COVID - 19: an update. J Crit Care Med (Targu Mures) 2020; 6 (04) : 217-223. 10.2478/jccm-2020-0033
• 56 Lemos ACB, Do Espírito Santo DA, Salvetti MC. et al. Therapeutic versus prophylactic anticoagulation for severe COVID-19: a randomized phase II clinical trial (HESACOVID). Thromb Res 2020; Dec; 196: 359-366. DOI: 10.1016/j.thromres.2020.09.026. Epub 2020 Sep 21. PMID: 32977137; PMCID: PMC7503069.
• 57 https://www.nih.gov/news-events/news-releases/nih-activ-trial-blood-thinners-pauses-enrollment-critically-ill-covid-19-patients
• 58 Berlit P, Bösel J, Gahn G. et al. “Neurological manifestations of COVID-19” - guideline of the German society of neurology. Neurol Res Pract 2020; 2: 51. Published 2020 Dec 2. DOI: 10.1186/s42466-020-00097-7.