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Acute Ischemic Stroke During the Convalescent Phase of Asymptomatic COVID-2019 Infection in Men

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is the risk of acute ischemic stroke (AIS) elevated in patients in the convalescent phase of an asymptomatic COVID-19 infection?

Findings  In this case series of 18 male adults aged 50 years or younger who presented with AIS during the convalescent phase of an asymptomatic COVID-19 infection confirmed by a positive SARS-CoV-2 serological (antibodies) test result, the median onset of stroke was 2 months after the diagnosis of COVID-19.

Meaning  Results of this study suggest a persistent increased risk of AIS in individuals with asymptomatic COVID-19 months after serological diagnosis, warranting stroke units to be on alert and use SARS-CoV-2 serological testing.


Importance  Acute ischemic stroke (AIS) is a known neurological complication in patients with respiratory symptoms of COVID-19 infection. However, AIS has not been described as a late sequelae in patients without respiratory symptoms of COVID-19.

Objective  To assess AIS experienced by adults 50 years or younger in the convalescent phase of asymptomatic COVID-19 infection.

Design, Setting, and Participants  This case series prospectively identified consecutive male patients who received care for AIS from public health hospitals in Singapore between May 21, 2020, and October 14, 2020. All of these patients had laboratory-confirmed asymptomatic COVID-19 infection based on a positive SARS-CoV-2 serological (antibodies) test result. These patients were individuals from South Asian countries (India and Bangladesh) who were working in Singapore and living in dormitories. The total number of COVID-19 cases (54 485) in the worker dormitory population was the population at risk. Patients with ongoing respiratory symptoms or positive SARS-CoV-2 serological test results confirmed through reverse transcriptase–polymerase chain reaction nasopharyngeal swabs were excluded.

Main Outcomes and Measures  Clinical course, imaging, and laboratory findings were retrieved from the electronic medical records of each participating hospital. The incidence rate of AIS in the case series was compared with that of a historical age-, sex-, and ethnicity-matched national cohort.

Results  A total of 18 male patients, with a median (range) age of 41 (35-50) years and South Asian ethnicity, were included. The median (range) time from a positive serological test result to AIS was 54.5 (0-130) days. The median (range) National Institutes of Health Stroke Scale score was 5 (1-25). Ten patients (56%) presented with a large vessel occlusion, of whom 6 patients underwent intravenous thrombolysis and/or endovascular therapy. Only 3 patients (17%) had a possible cardiac source of embolus. The estimated annual incidence rate of AIS was 82.6 cases per 100 000 people in this study compared with 38.2 cases per 100 000 people in the historical age-, sex-, and ethnicity-matched cohort (rate ratio, 2.16; 95% CI, 1.36-3.48; P < .001).

Conclusions and Relevance  This case series suggests that the risk for AIS is higher in adults 50 years or younger during the convalescent period of a COVID-19 infection without respiratory symptoms. Acute ischemic stroke could be part of the next wave of complications of COVID-19, and stroke units should be on alert and use serological testing, especially in younger patients or in the absence of traditional risk factors.

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Article Information

Accepted for Publication: March 4, 2021.

Published: April 22, 2021. doi:10.1001/jamanetworkopen.2021.7498

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Tu TM et al. JAMA Network Open.

Corresponding Author: Tian Ming Tu, MRCP, Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433 (tu.tian.ming@singhealth.com.sg).

Author Contributions: Dr Tu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Tu, Seet, Umapathi.

Acquisition, analysis, or interpretation of data: Tu, Seet, Tham, Koh, Chiew, De Leon, Chua, Hui, S. S. Y. Tan, Vasoo, B. Y.-Q. Tan, Tambyah, Yeo.

Drafting of the manuscript: Tu, Seet, Koh, De Leon, Chua, B. Y.-Q. Tan, Tambyah.

Critical revision of the manuscript for important intellectual content: Tu, Tham, Chiew, Hui, S. S. Y. Tan, Vasoo, B. Y.-Q. Tan, Umapathi, Tambyah, Yeo.

Statistical analysis: Tu, De Leon, B. Y.-Q. Tan.

Administrative, technical, or material support: Tham, Koh, Chiew, Hui, S. S. Y. Tan, B. Y.-Q. Tan, Umapathi, Tambyah, Yeo.

Supervision: Umapathi, Yeo.

Conflict of Interest Disclosures: Dr Tambyah reported receiving grants paid to the institution from Roche, Shionogi, Arcturus, and Johnson and Johnson as well as honorarium paid to the institution from AJ Biologics. Dr Yeo reported receiving personal fees from Stryker and grants from the National Medical Research Council of Singapore outside the submitted work. No other disclosures were reported.

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