Increased stroke severity and mortality in patients with SARS-CoV-2 infection: An analysis from the N3C database.

BACKGROUND: Studies from early in the COVID-19 pandemic showed that patients with ischemic stroke and concurrent SARS-CoV-2 infection had increased stroke severity. We aimed to test the hypothesis that this association persisted throughout the first year of the pandemic and that a similar increase in stroke severity was present in patients with hemorrhagic stroke. METHODS: Using the National Institute of Health National COVID Cohort Collaborative (N3C) database, we identified a cohort of patients with stroke hospitalized in the United States between March 1, 2020 and February 28, 2021. We propensity score matched patients with concurrent stroke and SARS-COV-2 infection and available NIH Stroke Scale (NIHSS) scores to all other patients with stroke in a 1:3 ratio. Nearest neighbor matching with a caliper of 0.25 was used for most factors and exact matching was used for race/ethnicity and site. We modeled stroke severity as measured by admission NIHSS and the outcomes of death and length of stay. We also explored the temporal relationship between time of SARS-COV-2 diagnosis and incidence of stroke. RESULTS: Our query identified 43,295 patients hospitalized with ischemic stroke (5765 with SARS-COV-2, 37,530 without) and 18,107 patients hospitalized with hemorrhagic stroke (2114 with SARS-COV-2, 15,993 without). Analysis of our propensity matched cohort revealed that stroke patients with concurrent SARS-COV-2 had increased NIHSS (Ischemic stroke: IRR=1.43, 95% CI:1.33-1.52, p<0.001; hemorrhagic stroke: IRR=1.20, 95% CI:1.08-1.33, p<0.001), length of stay (Ischemic stroke: estimate = 1.48, 95% CI: 1.37, 1.61, p<0.001; hemorrhagic stroke: estimate = 1.25, 95% CI: 1.06, 1.47, p=0.007) and higher odds of death (Ischemic stroke: OR 2.19, 95% CI: 1.79-2.68, p<0.001; hemorrhagic stroke: OR 2.19, 95% CI: 1.79-2.68, p<0.001). We observed the highest incidence of stroke diagnosis on the same day as SARS-COV-2 diagnosis with a logarithmic decline in counts. CONCLUSION: This retrospective observational analysis suggests that stroke severity in patients with concurrent SARS-COV-2 was increased throughout the first year of the pandemic.

Stroke Associated with COVID-19 Vaccines.

OBJECTIVES: Development of safe and effective vaccines against coronavirus disease 2019 (COVID-19) remains the cornerstone of controlling this pandemic. However, there are increasing reports of various types of stroke including ischemic stroke, and hemorrhagic stroke, as well as cerebral venous sinus thrombosis (CVST) after COVID-19 vaccination. This paper aims to review reports of stroke associated with COVID-19 vaccines and provide a coherent clinical picture of this condition. MATERIALS AND METHODS: A literature review was performed with a focus on data from recent studies. RESULTS: Most of such patients are women under 60 years of age and who had received ChAdOx1 nCoV-19 vaccine. Most studies reported CVST with or without secondary ischemic or hemorrhagic stroke, and some with Vaccine-induced Thrombotic Thrombocytopenia (VITT). The most common clinical symptom of CVST seen after COVID-19 vaccination was headache. The clinical course of CVST after COVID-19 vaccination may be more severe than CVST not associated with COVID vaccination. Management of CVST following COVID-19 vaccination is challenging and may differ from the standard treatment of CVST. Low molecular weight heparin is commonly used in the treatment of CVST; however, it may worsen outcomes in CVST associated with VITT. Furthermore, administration of intravenous immunoglobulin and high-dose glucocorticoids have been recommended with various success rates. CONCLUSION: These contradictory observations are a source of confusion in clinical decision-making and warrant further study and development of clinical guidelines. Clinicians should be aware of clinical presentation, diagnosis, and management of stroke associated with COVID-19 vaccination.

Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection.

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.

Ambient air pollution and the risk of ischaemic and haemorrhagic stroke.

Stroke is a leading cause of disability and the second most common cause of death worldwide. Increasing evidence suggests that air pollution is an emerging risk factor for stroke. Over the past decades, air pollution levels have continuously increased and are now estimated to be responsible for 14% of all stroke-associated deaths. Interpretation of previous literature is difficult because stroke was usually not distinguished as ischaemic or haemorrhagic, nor by cause. This Review summarises the evidence on the association between air pollution and the different causes of ischaemic stroke and haemorrhagic stroke, to clarify which people are most at risk. The risk for ischaemic stroke is increased after short-term or long-term exposure to air pollution. This effect is most pronounced in people with cardiovascular burden and stroke due to large artery disease or small vessel disease. Short-term exposure to air pollution increases the risk of intracerebral haemorrhage, a subtype of haemorrhagic stroke, whereas the effects of long-term exposure are less clear. Limitations of the current evidence are that studies are prone to misclassification of exposure, often rely on administrative data, and have insufficient clinical detail. In this Review, we provide an outlook on new research opportunities, such as those provided by the decreased levels of air pollution due to the current COVID-19 pandemic.

High incidence of stroke and mortality in pediatric critical care patients with COVID-19 in Peru.

INTRODUCTION: Pediatric critical care patients with COVID-19 treated in Peru have higher mortality than those previously reported from other countries. Pediatric providers have reported a high number of patients without comorbidities presenting with hemorrhagic strokes associated with COVID-19. We present a study analyzing the factors associated with mortality in this setting. METHODS: Prospective case-control study that included patients <17 years old admitted to a pediatric critical care unit with a positive test confirming COVID-19. The primary outcome was mortality. Fisher's exact test and the Mann-Whitney U test were used for the analysis. RESULTS: Forty-seven patients were admitted to critical care. The mortality of our study is 21.3%. The mortality of patients with neurological presentation was 45.5%, which was significantly higher than the mortality of acute COVID-19 (26.7%) and MIS-C (4.8%), p 0.18. Other risk factors for mortality in our cohort were strokes and comorbidities. Only one patient presenting with hemorrhagic stroke had an undiagnosed comorbidity. CONCLUSION: Cerebrovascular events associated with COVID-19 in pediatric patients, including infants, must be recognized as one of the more severe presentations of this infection in pediatric patients. IMPACT: Pediatric patients with COVID-19 can present with hemorrhagic and ischemic strokes on presentation. Neurological presentation in pediatric patients with COVID-19 has high mortality. Mortality of pediatric patients with COVID-19 is associated with comorbidities. Pediatric presentation and outcomes of COVID-19 in different regions can be novel to previously described.

Neurosurgical Referral Patterns During the Coronavirus Disease 2019 Pandemic: A United Kingdom Experience.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a severe respiratory viral illness that has spread rapidly across the world. However, the United Kingdom has been particularly affected. Evidence has suggested that stroke, cardiac, and spinal presentations decreased during the pandemic as the public avoided seeking care. The effect on neurosurgical presentations and referrals during COVID-19 is unclear. Our aim, therefore, was to describe the referral patterns to a high-volume neurosurgical department in the United Kingdom during the COVID-19 pandemic. METHODS: Electronic referrals were identified from the referrals database from January 1, 2020 to May 31, 2020, inclusive, with January used as the baseline. The demographic data and referral diagnoses were captured on Excel (Microsoft, Redmond, Washington, USA). Statistical analyses were performed using SPSS, version 22 (IBM Corp., Armonk, New York, USA). Differences between referral volumes were evaluated using χ2 goodness-of-fit tests. RESULTS: A total of 2293 electronic referrals had been received during the study period. The median age was 63 years. Overall, the referrals had decreased significantly in volume during the study period [χ2(4) = 60.95; P < 0.001]. We have described the patterns in the daily referrals as the pandemic progressed. The reduction in the volume of referrals for degenerative spine cases and traumatic brain injuries was statistically significant (P < 0.001). CONCLUSIONS: The referrals for degenerative spine and traumatic brain injuries decreased significantly during the pandemic, which can be explained by the lower vehicular traffic and patient avoidance of healthcare services, respectively. The risk of neurological deterioration and increased morbidity and mortality, as a consequence, is of concern, and neurosurgeons worldwide should consider the optimal strategies to mitigate these risks as the pandemic eases.

Changed pattern of hospital admission in stroke during COVID-19 pandemic period in Iran: a retrospective study.

BACKGROUND: Some previous reports have shown a reduced number of admission in stroke cases during the coronavirus disease 2019 (COVID-19) pandemic period. The present study aimed to investigate this changing pattern and the potential causes behind it at an academic neurology and neurosurgery center in Iran. METHODS: Patients admitted to our center with the diagnosis of ischemic and hemorrhagic stroke, between March 1, 2019, Jun 1, 2019, and the similar 3-month period in 2020 (COVID-19 pandemic period), were compared in terms of clinical characteristics and outcome. Poisson regression was also conducted to assess the correlation between daily admissions and the COVID-19 pandemic period. RESULTS: A total of 210 patients with stroke (ischemic and hemorrhagic) in 2019 were compared with 106 patients in 2020. COVID-19 pandemic period was significantly associated with the decline in the number of daily admissions in ischemic stroke (IRR, 0.51 [95% CI, 0.4-0.64]). A significant reduction (P = 0.003) in time from onset to arrival at hospital from median 12 h [IQR, 5-32] in 2019 to median 6 h [IQR, 4-16] in 2020 was found in ischemic stroke cases. National Institute of Health Stroke Scale (NIHSS) was significantly increased (P < 0.001) from median 4 [IQR, 2-7] in 2019 to median 9 [IQR, 4-14] in 2020. Glasgow coma scale (GCS) was significantly decreased from 13.9 (SD, 2) in 2019 to 12.8 (SD, 2.9) in 2020 (P < 0.001). CONCLUSIONS: The present study provided new pieces of evidence regarding the changed pattern of hospital admission in stroke especially the possible reasons for its decline.

Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System.

BACKGROUND AND PURPOSE: While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. METHODS: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method. RESULTS: During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. CONCLUSION: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.