COVID-Related Strokes Especially Severe, Result in Worse Outcomes

Ischemic strokes in COVID-19 patients tended to be more severe than those in other individuals, according to a case-control study from the U.K.

Among 86 stroke patients with COVID-19, stroke characteristics and outcomes differed from uninfected stroke patients treated during the same period. The COVID-19-associated strokes:

• Were more likely to involve multiple large vessel occlusions (17.9% vs 8.1%, P<0.03)
• Were more severe (median NIH Stroke Scale score 8 vs 5, P<0.002)
• Were associated with higher D-dimer levels (3.4 vs 3.0 ng/ml on the log₁₀ scale, P<0.01)
• Resulted in more severe disability on discharge (median modified Rankin Scale score 4 vs 3, P<0.0001)
• Resulted in more deaths during index admission (19.8% vs 9.6%, P<0.0001)

"Our study provides the most compelling evidence yet that COVID-19-associated ischaemic strokes are more severe and more likely to result in severe disability or death, although the outlook is not quite as bleak as previous studies have suggested," according to a group led by Richard Perry, BM, BCh, PhD, of UCL Queen Square Institute of Neurology and the National Hospital for Neurology & Neurosurgery, London. A full manuscript was published in the Journal of Neurology, Neurosurgery & Psychiatry.

A median of 6 days elapsed from onset of COVID-19 symptoms to the onset of ischemic stroke among patients admitted to 13 centers in England and Scotland from March 9 to July 5 this year.

"The data are consistent with prior reports focused on stroke associated with COVID-19 and reinforces those findings," commented Larry B. Goldstein, MD, of University of Kentucky in Lexington.

"Large vessel strokes affect larger areas of the brain and are generally more severe, again consistent with the results of this study. This may in part be related to an increased tendency for persons with COVID-19 to form blood clots that can lead to stroke," he told MedPage Today.

Large vessel occlusion in COVID-19 may be a direct manifestation of a SARS-CoV-2-related hypercoagulable state -- as suggested by elevated D-dimers -- but levels of the biomarker varied substantially, suggesting much heterogeneity among patients, Perry and colleagues indicated.

"COVID-19 does not appear to influence stroke solely through a single mechanism; no single aetiological category of ischaemic stroke seems to have been more strongly associated with COVID-19 infection than the others," they wrote.

"We suggest that COVID-19 may provoke the onset of an ischaemic stroke through a variety of thrombotic and inflammatory mechanisms, promoting generation of thrombus in the heart or large vessels or via small vessel occlusion. Which of these mechanisms manifests in a given patient may be determined by that individual's conventional vascular risk factors such as atrial fibrillation, large vessel atheroma, hypertension or type 2 diabetes mellitus," study authors continued.

Perry's group relied on a combination of retrospective and prospective data collection for the study.

Early in the study period, SARS-CoV-2 testing was given to patients only if there was clinical suspicion of COVID-19. The proportion of asymptomatic patients tested rose progressively from 10.3% to 93.5% from the weeks of March 9 to May 11 before staying at a mean of 95.3% for the rest of the study, according to Perry and colleagues.

The 86 stroke patients had tested positive within 4 days of admission or stroke onset. They were split between 81 ischemic strokes and five intracerebral hemorrhages.

For comparison, Perry and colleagues examined records for 1,384 patients admitted during the same period who were either consistently SARS-CoV-2-negative or were never tested because they did not show symptoms or signs of COVID-19. This group counted 1,193 ischemic strokes and 191 intracerebral hemorrhages.

Overall, the cohort had a median age of 73 years, and roughly 53% were men.

Stroke patients with SARS-CoV-2 infection were not more likely to be younger or men, unlike previous reports. Rather, COVID-19 patients who had strokes were more likely to be Asian (18.8% vs 6.7% of non-COVID group, P<0.0001), Perry's team reported.

Recurrence of stroke during the patient's admission was similarly rare among COVID cases and controls (2.3% vs 1.0%).

Study authors noted that other large studies of COVID-19-associated stroke had used historical controls for comparison, biasing the results toward overestimating the influence of COVID-19 on stroke severity and any other parameters correlated with severity.

Nevertheless, their own study was subject to biases as well, given that some reports and tests were not available in all patients.

The case-control study also failed to include all consecutive cases during the study period.

"We anticipated that most centres would not be able to collect data on consecutive stroke admissions throughout the whole study period, so centres were asked to prioritise weeks during which patients with COVID-19 were admitted, and for any such week (Monday to Sunday) to include all strokes regardless of SARS-CoV-2 status," Perry's group noted.

For now, patients presenting with ischemic stroke and very elevated D-dimers with no other explanation should be tested for SARS-CoV-2 infection, the authors said. They added that people testing positive for COVID-19 may benefit from CT angiography because the finding of multiple large vessel occlusions may require a specific management strategy (i.e., mechanical thrombectomy or a different antithrombotic agent).

"On the other hand, in most patients with COVID-19-associated ischaemic stroke, very early anticoagulation is probably not warranted as a strategy to prevent inpatient stroke recurrence, as this outcome is too uncommon to justify the increased risk of secondary haemorrhage," according to the group.

"Finally, it is important to note that although less than 6% of the patients included in this report had COVID-19, because the disease affects persons of all ages, even young people need to know the symptoms of stroke and seek care immediately," Goldstein emphasized.

Disclosures

Perry and Goldstein disclosed no conflicts.

Study co-authors reported relationships with Bayer, Sanofi, Pfizer, Alnylam, and Portola.

Primary Source

Journal of Neurology, Neurosurgery & Psychiatry

Source Reference: Perry RJ, et al "Characteristics and outcomes of COVID-19-associated stroke: a UK multicentre case-control study" J Neurol Neurosurg Psychiatry 2020; DOI: 10.1136/jnnp-2020-324927.

https://www.medpagetoday.com/neurology/strokes/89509