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Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza

Our take —

Growing evidence suggests that COVID-19 leads to a hypercoagulable and prothrombotic state that may result in a greater risk of neurologic complications such as ischemic stroke. This study is one of the first to indicate that the risk of ischemic stroke is greater with COVID-19 than with influenza, a similar viral respiratory infection that is a known stroke risk factor. Additional investigation of the specific thrombotic mechanisms associated with COVID-19 is warranted to identify effective and timely treatment and prevention strategies.

Study design

Retrospective Cohort

Study population and setting

The objective of this study was to compare the probability of acute ischemic stroke associated with COVID-19 relative to influenza, another viral respiratory infection. This study compared adult patients (>18 years old) with laboratory-confirmed SARS-CoV-2 infection who were hospitalized or visited the emergency department between March 4 and May 2, 2020 with adults who were hospitalized or visited the emergency department with laboratory-confirmed influenza A/B between January 1, 2016 and May 31, 2018 (covering both moderate and severe seasons) at 2 NYC hospitals. Data for the participants with influenza were obtained from the Cornell Acute Stroke Academic Registry (CAESAR). Acute ischemic stroke was confirmed by CT or MRI for both COVID-19 and influenza cohorts. Data on demographics, risk factor, presenting symptoms, illness severity (i.e. ICU admission), treatments, and laboratory and imaging results were obtained by electronic medical records.

Summary of Main Findings

A total of 1916 patients (median age: 64; 57% male) with laboratory-confirmed SARS-CoV-2 infection presented to the two hospitals during the period of study. Of these, 17% required mechanical ventilation and 1.6% (n=31; median age: 69 years) had an acute ischemic stroke. The median duration from symptom onset to stroke was 16 days with an inpatient mortality of 32% (14% among those without stroke). A total of 1486 patients (median age: 62 years; 45% male) with influenza were included; 3% required mechanical ventilation and 3 patients (0.2%) had an acute ischemic stroke. After adjusting for age, sex, and race, patients with COVID-19 were significantly more likely to experience an acute ischemic stroke than the patients with influenza (OR: 7.6; 95% CI: 2.3-25.2). This persisted after adjusting for vascular risk factors and illness severity (OR: 4.6; 95% CI: 1.4-15.7).

Study Strengths

This is one of the first studies to indicate that COVID-19 is associated with a greater likelihood of acute ischemic stroke than other viral respiratory illnesses, specifically influenza, after accounting for other potential risk factors. The study reports that diagnosis of acute ischemic stroke was the same for the COVID-19 and influenza cohorts; both were based on clinical and imaging data. Numerous sensitivity analyses were conducted reinforcing the robustness of the findings.

Limitations

Given the use of historical comparison groups, it is likely there were differences in the criteria for hospital admission, ascertainment of infection status, and diagnosis of ischemic stroke that may have influenced the results; given the prevailing interest in neurologic complications among COVID-19 patients, it is possible they were more often screened for and, thus, diagnosed with ischemic stroke than influenza patients of years past, which could partially explain the observed increased rate of stroke among COVID-19 patients relative to influenza patients. Additionally, the testing criteria for COVID-19 changed considerably over the course of the study period, and hospital burden during the COVID-19 pandemic may have resulted in a population of sicker patients than previous influenza seasons. These measurement and selection issues could result in either an over or under-estimation of the observed differences in stroke outcomes between COVID-19 and influenza. The study population was limited to 2 hospitals in New York City, potentially limiting generalizability. Data are limited to ill patients who visited an ER or were hospitalized and findings may not be generalizable to patients with less severe disease. Only 34 patients combined had the outcome of interest, and adjustment for covariates may overfit the data and overestimate the magnitude of the association. Additionally, the use of logistic regression does not account for censoring due to death or hospital discharge.

Value added

This is one of the first and largest studies (to date) to compare the burden of ischemic stroke associated with COVID-19 relative to influenza by drawing on stroke outcomes among patients with influenza from previous influenza seasons (including both moderate and severe seasons).

This review was posted on: 22 July 2020