Abstract
Background
COVID-19-related strokes are increasingly being diagnosed across the world. Knowledge about the clinical profile, imaging findings, and outcomes is still evolving. Here we describe the characteristics of a cohort of 62 COVID-19-related stroke patients from 13 hospitals, from Bangalore city, south India.
Objective
To describe the clinical profile, neuroimaging findings, interventions, and outcomes in COVID-19-related stroke patients.
Methods
This is a multicenter retrospective study of all COVID-19-related stroke patients from 13 hospitals from south India; 1st June 2020–31st August 2020. The demographic, clinical, laboratory, and neuroimaging data were collected along with treatment administered and outcomes. SARS–CoV-2 infection was confirmed in all cases by RT-PCR testing. The data obtained from the case records were entered in SPSS 25 for statistical analysis.
Results
During the three-month period, we had 62 COVID-19-related stroke patients, across 13 centers; 60 (97%) had ischemic strokes, while 2 (3%) had hemorrhagic strokes. The mean age of patients was 55.66 ± 13.20 years, with 34 (77.4%) males. Twenty-six percent (16/62) of patients did not have any conventional risk factors for stroke. Diabetes mellitus was seen in 54.8%, hypertension was present in 61.3%, coronary artery disease in 8%, and atrial fibrillation in 4.8%. Baseline National Institutes of Health Stroke Scale score was 12.7 ± 6.44. Stroke severity was moderate (National Institutes of Health Stroke Scale 5–15) in 27 (61.3%) patients, moderate to severe (National Institutes of Health Stroke Scale 16–20) in 13 (20.9%) patients and severe (National Institutes of Health Stroke Scale 21–42) in 11 (17.7%) patients. According to TOAST classification, 48.3% was stroke of undetermined etiology, 36.6% had large artery atherosclerosis, 10% had small vessel occlusion, and 5% had cardioembolic strokes. Three (5%) received intravenous thrombolysis with tenecteplase 0.2 mg/kg and 3 (5%) underwent mechanical thrombectomy, two endovascular and one surgical. Duration of hospital stay was 16.16 ± 6.39 days; 21% (13/62) died in hospital, while 37 (59.7%) had a modified Rankin score of 3–5 at discharge. Hypertension, atrial fibrillation, and higher baseline National Institutes of Health Stroke Scale scores were associated with increased mortality. A comparison to 111 historical controls during the non-COVID period showed a higher proportion of strokes of undetermined etiology, higher mortality, and higher morbidity in COVID-19-related stroke patients.
Conclusion
COVID-19-related strokes are increasingly being recognized in developing countries, like India. Stroke of undetermined etiology appears to be the most common TOAST subtype of COVID-19-related strokes. COVID-19-related strokes were more severe in nature and resulted in higher mortality and morbidity. Hypertension, atrial fibrillation, and higher baseline National Institutes of Health Stroke Scale scores were associated with increased mortality.
Introduction
Recent evidence surfacing across the globe suggests that SARS–CoV-2 infection is associated with both ischemic and hemorrhagic strokes. Stroke appears to be one of the dangerous neurological complications of SARS–CoV-2 infection. Of late, with surges in COVID-19 cases in India, especially in the state of Karnataka, we are witnessing an increasing number of COVID-19-related strokes. The knowledge about the clinical profile, imaging findings, and outcomes of COVID-19-related strokes is still evolving. Here we have described the characteristics of COVID-19-related strokes from 13 stroke centers from Bengaluru, an urban city in the state of Karnataka, south India. We have compared these observations with a cohort of non-COVID strokes, during the same months of the previous year and analyzed the factors associated with mortality in COVID-19-related stroke patients.
Methods
This multicenter retrospective observational study was conducted in 13 stroke treatment ready hospitals in an urban city (Bengaluru) in south India from 1st June 2020 to 31st August 2020. All consecutive cases of COVID-related strokes from 13 centers were recruited during the study period. The presence of stroke was confirmed in all cases either by CT (computed tomography) or MRI (magnetic resonance imaging) of the brain. All patients underwent RT-PCR testing on the nasopharyngeal swab. Patients with strokes and positive RT-PCR for SARS–CoV 2 were enrolled for the study. Data regarding demographic variables, comorbidities, clinical features, National Institutes of Health Stroke Scale (NIHSS) and modified Rankin score (mRS) at baseline and discharge, laboratory tests, neuroimaging findings, treatment administered, and outcomes were collected. The strokes were classified according to TOAST based on clinical features and findings on either MRI brain with MR angiogram or CT brain with CT angiogram, ECG, echocardiogram, and 24-h Holter evaluation. The historical controls were selected from the stroke registry of one of the major tertiary coordinating stroke centers (St Johns National Academy of Health Sciences) in the same city, catering to the same population, during the same calendar period of the previous year (2019). All the historical controls had been evaluated in detail with either MRI brain with MR angiogram or CT brain with CT angiogram, carotid and vertebral Doppler, ECG, echocardiogram, and 24-h Holter. Descriptive statistics including mean, standard deviation, and percentages were used to summarize the data. A Pearson’s chi-squared test was performed for categorical variables, and an independence sample “t” test was performed for continuous variables for evaluation of the statistical difference between case and historical control groups. All tests were two-tailed, and a P value of .05 was considered statistically significant. All statistical analyses were conducted with the SPSS statistical package for Windows, Version 25 (IBM). Study was approved by the institutional review boards of the coordinating centers.
Results
From 1st June 2020 to 31st August 2020, we had 62 COVID-19-related stroke patients, across 13 centers; 60 (97%) had ischemic strokes while 2 (3%) had hemorrhagic strokes. The mean age of patients was 55.66 ± 13.20 years, with 34 (77.4%) males; 90% (57/62) of the patients had one or more of the symptoms of fever, cough, fatigue, myalgia, and breathlessness preceding the stroke, for a period ranging from 1 day to 14 days (mean ± SD = 12.51 ± 5.06 days). SARS–CoV2 infection was confirmed in all patients using RT-PCR from the nasopharyngeal swab; 26% (16/62) of patients did not have any conventional risk factors for stroke. Hypertension was present in 61.3%; diabetes mellitus was seen in 54.8%, coronary artery disease in 8%, and atrial fibrillation in 4.8%. Baseline NIHSS score was 12.7 ± 6.44. Stroke severity was moderate (NIHSS 5–15) in 27 (61.3%) patients, moderate to severe (NIHSS 16–20) in 13 (20.9%) patients and severe (NIHSS 21–42) in 11(17.7%) patients.
Demographic, clinical features, treatments, and outcomes in COVID versus non-COVID strokes.
NIHSS: National Institutes of Health Stroke Scale; mRS: modified Rankin score.
Values are written as number (%) or mean ± standard deviation.
Comparison of variables between expired and survived in the COVID-19 related stroke group.
NIHSS: National Institutes of Health Stroke Scale.
Values are written as number (%) or mean ± standard deviation.
Discussion
SARS-CoV-2-related strokes are increasingly being recognized by the physicians all over the world. Incidence of stroke in major case series ranged from 1 to 6%.
1
A recent cross-sectional comparative study from New York identified a 7.5-fold higher rate of ischemic stroke in COVID-19 compared to influenza.
2
COVID-19-related strokes are more ischemic than hemorrhagic in all the studies reported.3–5 The current study is the largest from the Indian subcontinent. Previous studies suggested strokes were more common in elderly patients with severe disease, especially those with elevated levels of C-reactive protein,
Several theories have been proposed to explain the vascular complications of SARS–CoV-2 infection. SARS–CoV-2 is not only a neuroinvasive, neurotropic, neurovirulent virus but also has tropism to endothelial cells and cardiomyocytes.
10
Cerebral and cardiovascular events have been attributed to direct viral invasion and thrombo-inflammation or immune thrombosis. A direct endotheliopathy resulting from invasion of the virus through the ACE-2 receptors on the surface of endothelial cells contribute to the endothelial dysfunction and thrombosis.
8
Thrombo-inflammation is a consequence of the activation of various cells involved in immune defense by the virus and amplification of complement cascade and cytokine systems, resulting in further downstream stimulation of procoagulant pathways.
11
There is also a simultaneous depletion of antithrombotic factors like protein C, S, plasminogen activator inhibitor 1, and antithrombin III. The elevated CRP and IL-6 levels are indirect indicators of the severe inflammatory response, while the elevated
Limitations and strengths
The main limitations of the current study are its retrospective nature, possible selection bias, chance that less severe strokes, and COVID-19-related strokes with false-negative COVID tests would have been missed, lack of a concurrent prospective non-COVID stroke controls and incomplete stroke work up of COVID-19-related strokes patients due to isolation precautions and shortage of staff. However, the strengths of the current study are that it is one of the largest multicenter COVID-related stroke cohort from the Indian subcontinent, with a comparison with historical controls and assessment of risk factors associated with mortality.
Conclusion
As we are witnessing an avalanche of the deadly pandemic, there is a definite increase in the number of COVID-19-related strokes, in developing countries, like India. Stroke of undetermined etiology appears to be the most common TOAST subtype in COVID-19-related stroke patients. COVID-19-related strokes are of more severe nature and results in higher mortality and morbidity. Hypertension, atrial fibrillation, and higher baseline NIHSS scores are associated with increased mortality. The entire spectrum of COVID-19-related strokes will become clearer with more data accumulating from various centers across the globe. Meanwhile the stroke teams all over the world, especially those in developing countries should be more than prepared to manage these COVID-19-related strokes.
Footnotes
Acknowledgements
Thanks to Mr. Maria Anandan and Sister Annie George for the technical support.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
