Acute Ischemic Stroke and Convalescent COVID-19 in Men

Quick Takes

  • Asymptomatic COVID-19 infection may be associated with an increased risk of ischemic stroke.
  • These strokes occurred in younger patients without typical vascular risk factors, suggesting an etiologic role for prior COVID-19 infection.

Study Questions:

What is the risk of ischemic stroke in patients with asymptomatic coronavirus disease 2019 (COVID-19) infection?

Methods:

This study identified all acute ischemic stroke patients admitted to hospitals in Singapore from late spring to fall 2020, about 5 months. Most (94%) COVID-19 cases in Singapore occurred in foreign workers living in dormitories and active contact tracing occurred in this population. Patients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody test were included in the analyses. The authors excluded patients with active respiratory symptoms or a positive SARS-CoV-2 polymerase chain reaction (PCR) test. The annual stroke incidence rate in the study population was compared with historical data, matched to age, sex, and ethnicity.

Results:

There were 18 patients with ischemic stroke who had serologic evidence of prior COVID-19 and all of them had prior negative SARS-CoV-2 PCR testing. All the patients were men, the average age was 41 years, and there was a median of 54 days between the positive antibody test and acute stroke presentation. Most patients (67%) did not have a history of stroke risk factors and 56% presented with a large vessel occlusion. The most common stroke etiology was “undetermined” (72%), followed by cardioembolism (17%), and small vessel disease (11%). Four patients (22%) had elevated homocysteine levels and D-dimer was elevated in 17% of patients. There were two patients with positive lupus anticoagulant antibodies but testing for other antiphospholipid antibodies was otherwise negative.

The annual incidence rate of acute ischemic stroke in this population was 82.6 per 100,000, which is higher than the rate in adjusted historical controls, 38.2 per 100,000 (rate ratio, 2.16; 95% confidence interval, 1.36-3.48).

Conclusions:

Asymptomatic COVID-19 may be a risk factor for ischemic stroke.

Perspective:

Acute COVID-19 infection has been identified as a risk factor for ischemic stroke. Less is known about the consequences of asymptomatic infection and this study starts to fill in these gaps in knowledge. The young age of the patients and their lack of vascular risk factors suggests that COVID-19 was associated with their acute stroke. The etiology of stroke in these patients needs additional study and may differ from the mechanism of infarct during acute COVID-19 infection. It may be reasonable to look for SARS-CoV-2 seropositivity in stroke patients with an otherwise unrevealing workup. Given the worldwide burden of COVID-19, the association between ischemic stroke and asymptomatic infection has public health implications. Limitations of the study include its observational nature and the fact that most patients with COVID-19 infection in Singapore were male foreign workers, which impacts the generalizability of these findings. As this work was done before COVID-19 vaccinations were available, it is unclear how the results translate to patients who have been vaccinated, and therefore, likely have antibodies.

Clinical Topics: Prevention

Keywords: Antibodies, Asymptomatic Infections, Brain Ischemia, Contact Tracing, Coronavirus, COVID-19, Ethnic Groups, Homocysteine, Lupus Coagulation Inhibitor, Polymerase Chain Reaction, Primary Prevention, Risk Factors, SARS-CoV-2, Stroke, Vaccination, Vascular Diseases


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