A higher rate of stroke has been reported in adults with COVID-19 compared to a cohort of patients with influenza. A retrospective study published in JAMA Neurology concludes that around 1.6% of adults with COVID-19 who visited the emergency department or who were hospitalised experienced an ischaemic stroke.
The authors, Alexander E Merkler and colleagues, from Weill Cornell Medicine, New York, USA, call for additional studies to confirm these findings, and write: “Clinicians should be vigilant for symptoms and signs of acute ischaemic stroke in patients with COVID-19, so that time-sensitive interventions can be instituted if possible to reduce the burden of long-term disability.” They add that in the meantime, further elucidation of thrombotic mechanisms in patients with COVID-19 may “yield better strategies” to prevent disabling thrombotic complications like stroke.
Discussing the rationale behind comparing cohorts of patients with COVID-19 and influenza, Merkler and the team note that while recent publications from China, France, and New York point to the possibility that COVID-19 may increase the risk of ischaemic stroke, the studies lacked appropriate control groups.
“To evaluate whether COVID-19 is associated with a higher rate of ischaemic stroke than would generally be expected from a respiratory infection, we compared the likelihood of acute ischaemic stroke in patients with COVID-19 with patients with influenza, a known risk factor,” the investigators state.
This retrospective cohort study was conducted at two academic hospitals in New York, and included adult patients with emergency department visits or hospitalisations with COVID-19 from 4 March 2020, through to 2 May. The comparison cohort included adults with emergency department visits or hospitalisations with influenza A/B from 1 January 2016 to 31 May 2018 (spanning moderate and severe influenza seasons).
A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. “We used logistic regression to compare the proportion of patients with COVID-19 with ischaemic stroke versus the proportion among patients with influenza,” note Merkler and colleagues.
They reported that among 1,916 patients with emergency department visits or hospitalisations with COVID-19, 31 (1.6%; 95% CI, 1.1–2.3) had an acute ischemic stroke. The median age of patients with stroke was 69 years, and 18 (58%) were men. Stroke was the reason for hospital presentation in eight cases (26%). In comparison, three of 1,486 patients with influenza (0.2%; 95% CI, 0.0–0.6) had an acute ischaemic stroke.
According to the authors, the findings demonstrated that after adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3–25.2). “The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission,” Merkler and team add.
However, they report: “Our understanding of the neurological complications of COVID-19 is limited.”
Discrepancies in the rate of stroke
Merkler and colleagues write that among 214 patients hospitalised with COVID-19 infection in Wuhan, China, 3% had a stroke. Yet, among 13 patients with COVID-19 infection who underwent brain magnetic resonance imaging (MRI) in France, 23% had an ischaemic stroke.
More recently, Merkler and team say, investigators found that of the 3,556 patients hospitalised with COVID-19 in New York, 0.9% had an ischaemic stroke, while among the 1,916 patients in this study with emergency department visits or hospitalisations with COVID-19 infection, 1.6% received a diagnosis of ischaemic stroke.
They add: “The rate of ischaemic stroke among patients hospitalised with COVID-19 in this study was 1.8%, which is similar to that observed in the Wuhan cohort, but higher than that observed in the study by Yaghi et al in New York.”
In their paper, Merkler and the team proceed to discuss reasons for these discrepancies in the rate of stroke. First, they write, the method of stroke ascertainment varied across studies, and thus some patients with ischaemic stroke may have been missed. Secondly, the team acknowledged that many hospitalised patients with COVID-19 infection are severely ill, which makes acquiring brain imaging challenging and at times impractical. “As a consequence,” they state, “the threshold to obtain brain imaging may have varied between institutions.”
Lastly, the team highlights that the demographic composition of patients included in these cohorts varied, and data suggest that races of colour appear to be at heightened risk for severe disease.