The 4 Ms of COVID-19-Related Stroke Epidemiology

The mechanisms, magnitude, manifestations, and management of stroke during the pandemic.

Since the beginning of the pandemic, investigators have been trying to learn more about the connection between the COVID-19 virus and stroke. While the story is still unraveling, radiologists do know now that the link exists, and understanding more about the prevalence and appearance of stroke can impact patient care.

In a Nov. 30 session during this year’s Radiological Society of North America (RSNA) annual meeting, Ajay Gupta, M.D., professor of radiology and neuroscience at Weill Cornell Medicine, outlined what he dubbed the “4 Ms” of COVID-19-related stroke: mechanisms, magnitude, manifestations, and management.


Increasing, Gupta said, COVID-19 is being viewed as an endothelial cell disease in addition to being involved with the lungs. It causes significant deregulation in the immune system, leading to cytokine release syndrome.

“Within the blood vessels, this cytokine release, in the form of IL-6 and TNF-alpha, resulted in a vicious cycle of inflammation and thrombosis,” he said. “It’s this increase in inflammation that really can increase the risk of vascular events.”


A bit of uncertainty exists around the epidemiology of COVID-19-related stroke, he said, because in the initial phases of the pandemic, medical data and literature show a significant dip in the number of stroke cases reported. This was likely prompted by patients’ fear of coming to the hospital at that time.

“Without the true estimate, it’s hard to know how much excess stroke we have seen and what the risk is with COVID-19,” he explained. “But, we know we saw a precipitous drop in stroke cases reported during March and April – close to 50 percent. So, you would expect the number of strokes to increase.”

In addition, research in the past few months has shown a spotlight on how COVID-19 should not be compared to the flu, particularly in context of the risk of stroke. By comparing patients who were hospitalized for the flu between January 2016 to March 2018 to patients who were hospitalized for COVID-19 earlier this year, Gupta said, investigators determined that patients hospitalized for COVID-19 have an 8-fold increased risk of suffering a stroke while hospitalized.

“This underscores the argument that healthcare providers have been making,” he said. “COVID-19 really isn’t the flu. It is a much more serious disease.”


Do not expect a COVID-19-related stroke to appear differently on imaging than the strokes that typically show up in reading rooms, however. When it comes to presentation, these strokes are unremarkable, making them roughly indistinguishable from ischemic or other forms of stroke that occur in patients who are not positive for the virus.

Overall, patients mostly present with cryptogenic stroke without any known etiology, as well as some cardioembolic and large-vessel occlusion strokes.

But, when it comes to patients who are hospitalized for COVID-19, there is a distinct difference in the incidence and effect of stroke. In a paper published recently in Neurology, Gupta said, between 1.5 percent of patients in this group experience an ischemic stroke, and 1.8 percent of patients have some type of stroke event. This leads to a roughly 35-percent to 45-percent mortality rate. These findings can be particularly disturbing for younger patients who test positive because nearly 40 percent who suffer a stroke have no prior risk factors, and approximately 50 percent are largely asymptomatic for the disease.

Additionally, he said, pre-existing stroke history has been identified as an independent risk factor for a COVID-19-related stroke, as well.


While there has been very little official guidance for managing these patients, Gupta did offer three recommendations:

  • Continue to adhere to guidelines, following best practices for treatment, such as providing mechanical thrombectomy and endovascular therapy.
  • Use telemedicine to assess stroke severity, not only to maximize social distancing, but also to provide evaluation for a patient who may be unable to come to the hospital.
  • Rely on teamwork. Reach out to other neuroradiologists and interventional radiologists who have worked with this patient population.

“For those who went through those harrowing times in March and April,” he said, “we know that working closely and collegially with all providers is key to being able to take care of patients during this difficult time.”

For more RSNA coverage, click here.