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


Collaborators from 136 tertiary centers of 32 countries participated in this prospective study. Among them, 71 centers from 17 countries had at least 1 stroke patient eligible included in this study. One center in the Middle East could not provide data by the deadline. The rest of the centers did not have stroke patients who met our inclusion criteria (Document I in the Data Supplement). We received data on 432 patients—America: 114 (26.4%), Europe: 82 (19.0%), Middle East: 228 (52.8%), and Asia: 8 (1.9%). Among them, 203 (47.0%) patients were from countries with middle-to-high health expenditure. The mean age for the entire cohort was 65.7±15.7 years. Of 432 patients, the majority were men—249 (57.6%), P<0.001. A total of 144 (37.8%) of 380 patients with a known interval of stroke and infection presented to the hospital with chief complaints of stroke-related symptoms, with asymptomatic or SARS-CoV-2 infection. Among the 430 patients with complete comorbidity profiles, 105 (24.4%) patients had no identifiable vascular risk factors at the time of stroke incidence. Demographic characteristics under each stroke subtype are presented in Table 1.

Overall, 323 (74.8%) patients had AIS, 91 (21.1%) ICH, and 18 (4.2%) CVST. Among the patients with ICH (Table 2), 3 (3.3%) had simultaneous SAH and IPH without any evidence of aneurysm, and 4 (4.4%) were presented with simultaneous intraventricular hemorrhage and IPH. Isolated SAH occurred in 23 (25.3%) and isolated IPH in 61 (67%) of the patients with hemorrhagic stroke. Among 23 patients with isolated SAH, 16 (69.5%) had no evidence of aneurysm. Among the 18 patients with CVST, 5 (27.8%) had multiple cerebral sinuses and veins involvements.

The distribution of AIS subtypes according to the TOAST classification was the following: large artery atherosclerosis (33%), cardioembolism (27%), small vessel occlusion (SVO; 10%), other determined etiology (8%), and undetermined etiology (22%; Table 3). The subgroups of the patients according to the TOAST classification were different in terms of age, sex, the prevalence of LVO, imaging patterns, and need for mechanical ventilation. We observed a lower median of D-dimer among patients with large artery atherosclerosis compared with those with cardioembolic strokes (486.5 [371.5–1422.5] versus 1100.0 [955.0–2355.0] ng/mL; P=0.04). There were no significant differences in terms of lactate dehydrogenase or fibrinogen among the TOAST subgroups.

Of 283 AIS patients with confirmed data on the site of vascular occlusion, 126 (44.5%) had LVO (Table 4). In comparison with those without LVO, patients with LVO had higher prevalence of large artery atherosclerosis based on TOAST criteria (58.2% versus 9.6%), higher embolic/large vessel atherothromboembolism (88.4% versus 73.3%), and lower lacunar pattern (1.8% versus 17%) on imaging. Patients with LVO also had higher rates of IVT (22.2% versus 8.9%) and mechanical thrombectomy (19% versus 0%).

The median of NIHSS among AIS patients was 9 (4–17; Table 1). The risk of LVO increased from 8.3% among patients with no stroke symptoms (NIHSS score, 0) to 75.6% among patients with severe stroke (NIHSS score, >21; Table 4). IVT (31.4%) and mechanical thrombectomy (25.4%) were more prevalent among patients with moderate-to-severe stroke (NIHSS score, 16–20). The need for mechanical ventilation increased from 10% among patients with no stroke symptoms to 63% among patients with severe stroke.

We observed similar rates of LVOs and IVT in various geographic regions (Tables II and III in the Data Supplement). However, the rate of mechanical thrombectomy was significantly lower in the Middle Eastern countries and countries with lower health expenditure—2.6% in the Middle East versus 21.1% in Europe (P<0.001) and 2% in countries with lower health expenditure versus 12.4% in countries with higher health expenditure (P<0.001). We also detected a higher NIHSS in countries with lower health expenditure (11.0 [5.0–17.0] versus 8.0 [3.0–17.0]; P=0.02). Similarly, when comparing different regions, patients in America and Europe had a lower NIHSS than those in the Middle East (7.0 [0.0–16.0] in America and 8.0 [4.0–18.0] in Europe versus 12.0 [6.0–17.0] in the Middle East; P=0.06).

AIS patients were grouped based on sex and age (Tables IV through VI in the Data Supplement). Of 323 patients with AIS, 59.8% were men, and 36.2% were <55 years of age. Women had a lower rate of smoking and chronic kidney disease and higher NIHSS. Patients above 55 years had a higher proportion of hypertension, atrial fibrillation, ischemic heart disease, and carotid stenosis. Patients >65 years of age also had a higher rate of cardiac ejection fraction of <40%. Patients who were asymptomatic for SARS-CoV-2 infection at the stroke onset had a higher in-hospital mortality and a higher median of D-dimer (Table VII in the Data Supplement). The subgroups of AIS patients based on neuroimaging findings were different in terms of the proportion of LVO, TOAST criteria, and NIHSS categories (Table VIII in the Data Supplement).