Ischemic Strokes More Severe, Deadlier in COVID-19

Acute ischemic strokes that occur in conjunction with COVID-19 are more severe and carry greater disability than those in patients who don’t have the viral disease, data from the Global COVID-19 Stroke Registry show.

“The association between COVID-19 and severe stroke highlights the urgent need for studies aiming to uncover the underlying mechanisms and is relevant for prehospital stroke awareness and in-hospital acute stroke pathways during the current and future pandemics, since severe strokes have typically poor prognosis and can potentially be treated with recanalization techniques,” George Ntaios, MD, PhD (University of Thessaly, Larissa, Greece), and colleagues write in their paper, published recently in Stroke.

Earlier case series, including one from New York City, have suggested worse outcomes and higher mortality, Ntaios noted in an email to TCTMD. “Our study confirmed this in a large international multicenter cohort.”

More research is needed to understand these patterns, he said. “Potential explanations include a direct effect of the virus on the vascular endothelium and a prothrombotic tendency induced by immune-mediated platelet activation, dehydration, and infection-induced cardiac arrhythmias.”

American Heart Association President Mitchell Elkind, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), said that stroke is a known complication of COVID-19, pointing out that previous research has suggested a rate of around 1% to 2% patients hospitalized with the illness. “Thankfully it’s rare, but it does happen,” most often due to hypercoaguability, he told TCTMD. With COVID-19, large-vessel strokes are also being seen in younger people without as many risk factors as would be typical.

As to why the fallout from stroke appears worse with COVID-19, Elkind said: “One way I think of it is that stroke is a bad disease, COVID is a bad disease—and you put them together and you’re going to do worse. So if you just have a stroke and you don’t have COVID, that’s bad but it may not be as bad as having serious respiratory illness on top of it. That seems a little bit self-evident to me, . . . but it’s important to know that in caring for these people.”

Also on the plus side, he added, is that this report represents one of the largest collections so far of strokes in COVID-19.

Matthew Fink, MD (NewYork-Presbyterian/Weill Cornell Medicine, New York, NY), also said the findings, while informative, come as no surprise. “We know that anyone with ischemic stroke that has severe comorbidities with it, and those comorbidities are usually things like pneumonia, urinary tract infections, underlying diabetes, and other organ system illnesses—they all do worse. We’ve known that. That’s not new. And COVID affects multiple organ systems, particularly the lungs.” With pulmonary involvement, there’s severe hypoxemia, which “is the worse thing you can have possibly have for a stroke,” he said. “That’s why the strokes are so bad.”

One way I think of it is that stroke is a bad disease, COVID is a bad disease—and you put them together and you’re going to do worse. Mitchell Elkind

Ntaios et al pooled data on all 174 patients (median age 71.2 years; 37.9% women) hospitalized with acute ischemic stroke and lab-confirmed COVID-19 at 28 sites in 16 countries between January 27 and May 19, 2020. The median number of patients per site was 12.

Patient age varied, with approximately one-quarter being older than 80 and one-quarter younger than 64. Stroke risk factors included hypertension (68.4%), obesity (37.4%), and diabetes (31.0%), and 11.5% had had a prior stroke. On average, the strokes occurred at 7 days after the onset of COVID-19 symptoms, most commonly fever (55.2%), cough (53.5%), and dyspnea (43.7%). Stroke therapy included alteplase (19.7%) and endovascular thrombectomy (12.1%).

Ultimately, 48 (27.6%) of the COVID-19 patients died, with 54% of those deaths due to stroke and the rest attributed to the viral disease.

Patients in the COVID-19 registry were propensity matched 1:1 to non-COVID-19 patients hospitalized for acute ischemic stroke in Lausanne, Switzerland, between 2003 and 2019. The prevalence of large-artery and lacunar stroke didn’t differ between the two groups. Compared with the patients without COVID-19, those with the disease had a higher median National Institutes of Health Stroke Scale score (10 vs 6; P = 0.03) and, after their stroke, had a higher median modified Rankin Scale score (4 vs 2;  P < 0.001). Notably, the risk of death was much higher in the COVID-19 context, with an odds ratio of 4.3 (95% CI 2.2-8.3).

Another Comorbidity or Something More?

Beyond being yet another comorbidity, there does seem to be something unique about COVID-19, Fink commented. For example, he co-authored a retrospective cohort study, recently published in JAMA Neurology, showing that in New York City, “stroke occurred eight times more often in COVID patients than in influenza patients” treated before the pandemic—this despite the fact that influenza itself is known to elevate stroke risk.

As such, in the COVID-19 era, “we are very aggressive with anticoagulation now . . . to try to prevent thrombosis, not just in the brain [but] in the kidney, the lungs, the heart, everywhere,” Fink said. That, rather than ischemic strokes, “seems to be the thing that’s killing people: the microvascular thrombosis, which occurs everywhere.”

When ischemic strokes do happen, patients “should receive the optimal treatment, regardless if COVID-19 positive or negative,” Ntaios urged.

Elkind agreed. “When somebody comes in with a stroke, we’re going to treat them the same way” whether or not they have COVID-19, he said, with the presumption that all could potentially be positive. “We’re treating everybody with the same level of caution.”

Fortunately, Elkind added, there don’t seem to be any treatment delays arising from these precautions. “We can do as good a job now treating patients with stroke as we could before the pandemic, and I think people should feel reassured about that,” he said, stressing that patients shouldn’t be dissuaded from seeking care. “We don’t want people staying home because they’re worried about the risk of getting COVID.”