Ischemic Stroke Risk Highest Early After COVID-19 Diagnosis

Acute ischemic stroke risk is about 10 times higher in the first 3 days after a COVID-19 diagnosis and remains elevated for several more weeks, a study of Medicare beneficiaries indicates.

In the self-controlled case series study, the relationship was stronger in the youngest patients (65 to 74 years) and in those without a prior history of stroke, according to poster findings presented last week at the International Stroke Conference (ISC) 2022.

“Vaccination and other preventive measures for COVID-19 are important to reduce risk of infection and complications, including stroke,” Quanhe Yang, PhD (Division for Heart Disease and Stroke Prevention, US Centers for Disease Control and Prevention, Atlanta, GA), and colleagues report. The study was published simultaneously online in Neurology.

Commenting for TCTMD, Larry Goldstein, MD (University of Kentucky, Lexington), said “patients with COVID should be particularly alert to the symptoms of stroke and seek care immediately should any symptoms develop.”

The association between COVID-19 and stroke has not been consistent in previous studies, with stroke risk found to be higher, lower, or no different in patients infected with SARS-CoV-2. However, there are limited data focused on older patients, who have the highest risks of stroke even without a COVID-19 diagnosis, Yang et al say.

For the current study, the investigators examined claims data on 37,379 Medicare fee-for-service beneficiaries 65 and older (mean age 80.4 years; 56.7% women) who were diagnosed with COVID-19 between April 2020 and February 2021; 34% had a prior history of stroke. Hospitalizations for acute ischemic stroke were tracked between January 2019 and February 2021.

Patients served as their own controls, with stroke rates compared between certain risk periods—0-3, 4-7, 8-14, and 15-28 days after COVID-19 diagnosis—and all other periods during the study.

When strokes on the day of exposure were included in the risk period, the increase in stroke rate—evaluated with incidence rate ratios (IRRs)—was highest early after COVID-19 diagnosis:

• 0-3 days (IRR 10.3; 95% CI 9.9-10.8)
• 4-7 days (IRR 1.6; 95% CI 1.4-1.8)
• 8-14 days (IRR 1.4; 95% CI 1.3-1.6)
• 15-28 days (IRR 1.1; 95% CI 1.0-1.2)

Strokes also were more frequent in the week before patients received their COVID-19 diagnosis (IRR 1.9; 95% CI 1.8-2.1). When strokes on the day of exposure were not included in the risk period, there were still higher IRRs across all assessed time windows.

Although the relationship was stronger in the youngest beneficiaries and those without a previous stroke, there was not much variation across sex and racial/ethnic groups. Any differences that were observed “may not be clinically significant,” Yang et al note. Why the link between COVID-19 and stroke may be stronger in certain groups is not clear, they write, adding that the mechanisms at play in the overall association are likely multifactorial.

“The key proposed mechanisms suggested that SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) receptors of epithelial and endothelial cells where the immunological activation occurs that can lead to development of cytokine storm and hypercoagulability, and an increased tendency of blood clots formation, leading to increased risk of acute ischemic stroke,” they explain. “SARS-CoV-2 infection may also have direct viral injury causing viral-induced endotheliitis, potentially leading to angiopathic thrombosis.”

Ultimately, “timely diagnosis of COVID-19-associated stroke, and providing recommended treatment might play important roles in reducing the morbidity and mortality in patients with temporally COVID-19-associated stroke during the pandemic,” they write. “In addition, further studies are warranted to examine the long-term effects of COVID-19-associated stroke.”

Any infection, we know, is linked to stroke risk, probably because any infection will cause inflammation and inflammation can cause clots or thrombus. Louise McCullough

Goldstein said these results apply only to people 65 and older because of the Medicare data used, adding that it’s unclear why the younger patients in that group saw a stronger association between COVID-19 and stroke. Risk might be accentuated in those without a prior history of stroke because those who already had a cerebral event would have been taking medications to lower their risk, “but this is just speculation,” he said.

In a video commentary, Louise McCullough, MD, PhD (University of Texas Health Science Center at Houston), chair of ISC 2022, acknowledged that the study was restricted to older individuals. Still, she noted, “everyone is likely at risk for stroke after COVID. Any infection, we know, is linked to stroke risk, probably because any infection will cause inflammation and inflammation can cause clots or thrombus.”

Key to avoiding the heightened stroke risk tied to COVID-19 is to prevent the infection in the first place, McCullough said. “We have learned so much about social distancing and masking, but the best way to prevent getting seriously or critically ill from COVID, whether with stroke or other manifestations of COVID, . . . is to get vaccinated.”