SARS-CoV-2 and Stroke Characteristics

A Report From the Multinational COVID-19 Stroke Study Group

Shima Shahjouei, MD, MPH; Georgios Tsivgoulis, MD, PhD, MSc; Ghasem Farahmand, MD; Eric Koza, MD Candidate; Ashkan Mowla, MD; Alireza Vafaei Sadr, PhD; Arash Kia, MD; Alaleh Vaghefi Far, MD; Stefania Mondello, MD, PhD, MPH; Achille Cernigliaro, PhD, MPH; Annemarei Ranta, MD, PhD; Martin Punter, PhD, MBChB; Faezeh Khodadadi, PharmD; Soheil Naderi, MD; Mirna Sabra, PhD; Mahtab Ramezani, MD; Ali Amini Harandi, MD; Oluwaseyi Olulana, MS; Durgesh Chaudhary, MBBS; Aicha Lyoubi, MD; Bruce C.V. Campbell, MD; Juan F. Arenillas, MD; Daniel Bock, MD; Joan Montaner, MD; Saeideh Aghayari Sheikh Neshin, MD; Diana Aguiar de Sousa, MD, PhD; Matthew S. Tenser, MD; Ana Aires, MD; Mercedes de Lera Alfonso, MD; Orkhan Alizada, MD; Elsa Azevedo, MD, PhD; Nitin Goyal, MD; Zabihollah Babaeepour, MD; Gelareh Banihashemi, MD; Leo H. Bonati, MD; Carlo W. Cereda, MD; Jason J. Chang, MD; Miljenko Crnjakovic, MD; Gian Marco De Marchis, MD; Massimo Del Sette, MD; Seyed Amir Ebrahimzadeh, MD, MPH; Mehdi Farhoudi, MD; Ilaria Gandoglia, MD; Bruno Gonçalves, MD; Christoph J. Griessenauer, MD; Mehmet Murat Hancı, MD; Aristeidis H. Katsanos, MD; Christos Krogias, MD; Ronen R. Leker, MD; Lev Lotman, MD; Jeffrey Mai, MD; Shailesh Male, MD; Konark Malhotra, MD; Branko Malojcic, MD, PhD; Teresa Mesquita, MD; Asadollah Mir Ghasemi, MD; Hany Mohamed Aref, MD; Zeinab Mohseni Afshar, MD; Jusun Moon, MD; Mika Niemelä, MD, PhD; Behnam Rezai Jahromi, MD; Lawrence Nolan, DO; Abhi Pandhi, MD; Jong-Ho Park, MD; João Pedro Marto, MD; Francisco Purroy, MD, PhD; Sakineh Ranji-Burachaloo, MD; Nuno Reis Carreira, MD; Manuel Requena, MD; Marta Rubiera, MD; Seyed Aidin Sajedi, MD; João Sargento-Freitas, MD; Vijay K. Sharma, MD; Thorsten Steiner, MD; Kristi Tempro, MD; Guillaume Turc, MD, PhD; Yasaman Ahmadzadeh, MD; Mostafa Almasi-Dooghaee, MD; Farhad Assarzadegan, MD; Arefeh Babazadeh, MD, MPH; Humain Baharvahdat, MD; Fabricio Buchadid Cardoso, MD, MPH; Apoorva Dev, PhD; Mohammad Ghorbani, MD; Ava Hamidi, MD; Zeynab Sadat Hasheminejad, MD; Sahar Hojjat-Anasri Komachali, MD; Fariborz Khorvash, MD; Firas Kobeissy, PhD; Hamidreza Mirkarimi, MD; Elahe Mohammadi-Vosough, MD; Debdipto Misra, MS; Ali Reza Noorian, MD; Peyman Nowrouzi-Sohrabi, PhD; Sepideh Paybast, MD; Leila Poorsaadat, MD; Mehrdad Roozbeh, MD; Behnam Sabayan, MD, PhD; Saeideh Salehizadeh, MD; Alia Saberi, MD; Mercedeh Sepehrnia, MD; Fahimeh Vahabizad, MD; Thomas Alexandre Yasuda, MD; Mojdeh Ghabaee, MD; Nasrin Rahimian, MD, MPH; Mohammad Hossein Harirchian, MD; Afshin Borhani-Haghighi, MD; Mahmoud Reza Azarpazhooh, MD; Rohan Arora, MD; Saeed Ansari, MD; Venkatesh Avula, MS; Jiang Li, MD, MPH; Vida Abedi, PhD; Ramin Zand, MD, MPH


Stroke. 2021;52(5):e117-e130. 

In This Article

Abstract and Introduction


Background and Purpose: Stroke is reported as a consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in several reports. However, data are sparse regarding the details of these patients in a multinational and large scale.

Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke, intracranial hemorrhage, and cerebral venous or sinus thrombosis among SARS-CoV-2–infected patients. We further investigated the risk of large vessel occlusion, stroke severity as measured by the National Institutes of Health Stroke Scale, and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria among patients with acute ischemic stroke. In addition, we explored the neuroimaging findings, features of patients who were asymptomatic for SARS-CoV-2 infection at stroke onset, and the impact of geographic regions and countries' health expenditure on outcomes.

Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least 1 eligible stroke patient. Of 432 patients included, 323 (74.8%) had acute ischemic stroke, 91 (21.1%) intracranial hemorrhage, and 18 (4.2%) cerebral venous or sinus thrombosis. A total of 183 (42.4%) patients were women, 104 (24.1%) patients were <55 years of age, and 105 (24.4%) patients had no identifiable vascular risk factors. Among acute ischemic stroke patients, 44.5% (126 of 283 patients) had large vessel occlusion; 10% had small artery occlusion according to the TOAST criteria. We observed a lower median National Institutes of Health Stroke Scale (8 [3–17] versus 11 [5–17]; P=0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; P<0.001) in countries with middle-to-high health expenditure when compared with countries with lower health expenditure. Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144 (37.8%) were asymptomatic at the time of admission for SARS-CoV-2 infection.

Conclusions: We observed a considerably higher rate of large vessel occlusions, a much lower rate of small vessel occlusion and lacunar infarction, and a considerable number of young stroke when compared with the population studies before the pandemic. The rate of mechanical thrombectomy was significantly lower in countries with lower health expenditures.


Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, several cases of cerebrovascular events were reported among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).[1] Studies presented the incidence and prevalence of acute ischemic stroke (AIS), intracranial hemorrhage (ICH), and cerebral venous or sinus thrombosis (CVST) in SARS-CoV-2–infected patients.[2–6]

Many studies proposed coagulopathy as the underlying pathophysiological mechanism for the cerebrovascular events.[7,8] Small case series demonstrated a higher proportion of large vessel occlusions (LVOs),[2,9] or cryptogenic strokes,[4,10] with elevated D-dimer level, liver enzymes, and inflammatory or renal failure biomarkers among the patients who experienced SARS-CoV-2 infection.[4,5] Additionally, most of the studies noted a higher severity and mortality rate among stroke patients diagnosed with SARS-CoV-2 compared with others.[4,11,12]

To present a more comprehensive overview of stroke among patients infected with SARS-CoV-2, we devised a multinational multiple-phase study. In the first phase, we estimated the risk of stroke among the SARS-CoV-2–infected hospitalized patients. [13] In the current study, we aimed to present more details on the features and characteristics of our expanded multinational stroke cohort with prior SARS-CoV-2 infection. We further investigated the risk of LVO, stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS), and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria in the entire cohort, as well as different geographic regions.