COVID-19-Associated Ischemic Strokes Are More Severe, Study Suggests

George Ntaios, MD, MSc, PhD

Data from a case-series study comparing the severity of strokes in patients with and without COVID-19 suggest that ischemic strokes associated with the viral infection are more severe with worse functional outcomes and higher mortality rates than non-COVID-19 ischemic strokes.

In a 1:1 matched sample of 336 patients with COVID-19 and without COVID-19, the median National Institute of Health Stroke Scale (NIHSS) score was higher in patients with COVID-19 (10; interquartile range (IQR), 4—18) compared to those without (6; IQR, 3–14) for an odds ratio (OR) of 1.69 (95% CI, 1.08–2.65; P = .03). The study was led by George Ntaios, MD, MSc, PhD, assistant professor, University of Thessaly, Greece.

Among the 48 patient (27.6%) deaths during the study, 22 were attributed to COVID-19 and 26 to stroke. Severe disability at discharge occurred in 49 (51%) of the 96 survivors with available information about disability status.

When discussing the potential explanations for the relationship between COVID-19 associated ischemic strokes and increased severity, the study authors noted,” It was proposed that viral infections may cause a direct vasculopathic effect (endotheliopathy) or potentiate the prothrombotic milieu via several mechanisms including immune-mediated platelet activation, dehydration, and infection-induced cardiac arrhythmias.”

They continued by detailing that it is unclear whether the finding of increased severity applies to all ischemic stroke types or if it is mainly driven by an increase in large-vessel occlusion strokes. Additionally, the possibility of patients staying at home in fear of the virus may have prevented patients with acute stroke with smaller deficits from presenting to the hospital sooner or at all.

In the propensity score-matched population (n = 330), patients with COVID-19 had higher risk for severe disability (COVID-19: median modified Rankin Scale [mRS] score, 4 [IQR, 2—6]; non-COVID-19: mRS score, 2 [IQR, 1–4]; P <.001) and death (OR, 4.3; 95% CI, 2.22—8.30) compared with patients without COVID-19.

The main stroke symptoms observed were motor (67.8%), dysarthria (46%), and sensory (42%). In 93 of 163 patients with available information, the middle cerebral artery was the most frequently affected vascular territory.

The study used a 1:1 propensity score matching analyses of COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. A total of 174 patients (median age 71.2 years; 37.9% female) with COVID-19 and acute ischemic stroke were hospitalized between January 27, 2020, and May 19, 2020.

Within the matched database, 132 of 168 patients with COVID-19 had a complete diagnostic workup towards stroke cause. Of those 132 patients, 30 (22.7%) and 10 (7.6%) had a large-artery or a lacunar stroke, respectively. Notably, 22 (13.1%) and 17 (10.2%) patients had large-artery atherosclerosis and lacunar stroke within the non-COVID matched cohort.

“The increased stroke severity at admission in COVID19 associated stroke patients compared with the non-COVID-19 cohort may explain the worse outcomes,” Ntaios and colleagues added. “The broad multi-system complications of COVID-19 including acute respiratory distress syndrome, cardiac arrhythmias, acute cardiac injury, shock, pulmonary embolism, cytokine release syndrome and secondary infection, probably contribute further to the worse outcomes including higher mortality in these patients.”

Previous studies have mainly looked at the association between COVID-19 and neurological manifestations, but not necessarily the severity of stroke. One of the first multi-case studies of COVID-19 demonstrated complex central nervous system involvement, including neurologic symptoms such as peripheral nervous system and skeletal muscular manifestations commonly reported.²

Additionally, NeurologyLive recently spoke Shadi Yaghi, MD, associate professor of neurology at NYU Grossman School of Medicine; director of Clinical Vascular Neurology Research at NYU Langone Health; and director of Vascular Neurology at NYU Langone Hospital-Brooklyn on a study he conducted which explored the difficulties of understanding patients with stroke and COVID-19.³ His colleague and co-author on the study, Jennifer Frontera, MD, professor of neurology, NYU Langone, also discussed the overlap surrounding neurologic symptoms, including stroke, that may or may not have been triggered by COVID-19 in this interview.

REFERENCES

1. Ntaios G, Michel P, Georgiopoulos G, et al. Characteristics and outcomes in patients with COVID-19 and acute ischemic stroke. Stroke. Published July 8, 2020. doi: 10.1161/STROKEAHA.120.031208

2. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. Published online April 10, 2020. doi:10.1001/jamaneurol.2020.1127

3. Yaghi, S, Koto I, Torres J, et al. SARS2-CoV-2 and Stroke in a New York Healthcare System. Stroke. 2020;51:00—00. doi: 10.1161/STROKEAHA.120.030335