COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature

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COVID‑19 and ischemic stroke: a systematic review and meta‑summary of the literature Ying‑Kiat Tan1 · Claire Goh1 · Aloysius S. T. Leow2 · Paul A. Tambyah1,3 · Alicia Ang3 · Eng‑Soo Yap4,5 · Tian‑Ming Tu6 · Vijay K. Sharma1,2 · Leonard L. L. Yeo1,2 · Bernard P. L. Chan2 · Benjamin Y. Q. Tan1,2

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean d-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated d-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis. Keywords  Antiphospholipid antibodies · COVID-19 · Hypercoagulable · Ischemic stroke · Thrombosis Ying-Kiat Tan and Claire Goh are co-first authors.

Highlights

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1123​9-020-02228​-y) contains supplementary material, which is available to authorized users.

• Incidence of acute ischemic stroke in COVID-19 patients

* Leonard L. L. Yeo [email protected]

• Stroke severity in COVID-19 patients are typically at

1



Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore

2



Division of Neurology, Department of Medicine, National University Health System, Singapore, Singapore

3

Division of Infectious Diseases, Department of Medicine, National University Health System, Singapore, Singapore

4

Department Laboratory Medicine, National University Hospital, Singapore, Singapore

5

Department of Haematology‑Oncology, National University Cancer Institute, Singapore, Sin