Delaysin thrombolysis during COVID-19 are associated with worse neurological outcomes: the Society of Vascular and Interventional Neurology Multicenter Collaboration

Objective: To investigate whether delays in intravenous thrombolysis (IVT) administration during the Coronavirus (COVID-19) pandemic for patients with suspected acute ischemic stroke are associated with worse neurologic outcomes. Background: The COVID-19 pandemic has had a deleterious impact on health care systems across the world. Delays in presentation and management of emergent medical conditions like myocardial infarction, and stroke have been reported with a recent multicenter cohort study demonstrating that the COVID-19 pandemic has led to delays in IVT administration. It is unknown if these delays contribute to meaningful differences in short-term outcomes. Design/Methods: This was a nested observational cohort study of adult acute ischemic stroke patients receiving IVT from 9 comprehensive stroke centers in 7 states across the United States. Patients admitted prior to the pandemic (1/1/2019-2/19/2020) were compared to those admitted during the early pandemic (3/1/2020-7/31/2020). The effect of delay in IVT administration on death and discharge destination was estimated using multivariable logistic regression model. Results: There were 676 patients who received IVT with a median age of 70 (IQR 58-81) years and median NIHSS of 8 (IQR 4-16). 313 patients (46.3%) were female. During the early COVID19 period, longer treatment delays were observed (median 46 versus 38 minutes, p=0.01) that were associated with higher in-hospital death or hospice discharge (OR per hour 1.08, 95% CI 1.01-1.17, p = 0.03). After multivariable adjustment, this effect was strengthened (aOR 1.15, 95% CI 1.07-1.24, p < 0.001). Each hour delay in IVT administration was also associated with 7% lower odds of being discharged home or to a rehabilitation facility (aOR 0.93, 95% CI 0.89-0.97, p < 0.001). Conclusions: Treatment delays observed during the COVID-19 pandemic led to worse shortterm outcomes with higher rates of mortality and hospice care along with lower rates of discharge to home or rehabilitation facility.

Ischemic stroke in COVID-19: A need for early identification and management

Objective: We aimed to describe the clinical and radiographic characteristics of patients who were admitted with COVID-19 and had an acute ischemic stroke. Background: In the setting of the Coronavirus Disease 2019 (COVID-19) global pandemic caused by SARS-CoV-2, a potential association of this disease with stroke has been suggested. Design/Methods: This is a case series of PCR-confirmed COVID-19 patients with ischemic stroke admitted to an academic health system in Atlanta, Georgia (USA) between March 24th, 2020 and July 17th, 2020. Demographic, clinical, and radiographic characteristics were described. Results: Of 396 ischemic stroke patients admitted during this study period, 13 (2.5%) were also diagnosed with COVID-19. The mean age of patients was 61.6 ± 10.8 years, 10 (76.9%) male, 8 (61.5%) were Black Americans, mean time from last normal was 4.97 ± 5.1 days, and only one received acute reperfusion therapy. All 13 patients had at least one stroke-associated comorbidity. The predominant pattern of ischemic stroke was embolic with 4 explained by atrial fibrillation. COVID-19 patients had a significantly higher rate of cryptogenic stroke than nonCOVID-19 patients during the study period (69% vs 17%, p=0.0001). 4 patients (30.7%) died by the end of the study period. Conclusions: In our case series, ischemic stroke affected COVID-19 patients with traditional stroke risk factors, but mainly affecting males and Black Americans. We observed a predominantly embolic pattern of stroke with a higher than expected rate of cryptogenic strokes, a prolonged median time to presentation and symptom recognition limiting the use of acute reperfusion treatments along with a high mortality. These results highlight the need for increased community awareness, early identification, and management of AIS in COVID-19 patients. Further studies to determine the effects of COVID-19 associated coagulopathy on ischemic stroke risk as well as the interactions between COVID-19 and other known stroke risk factors are warranted.

Cardio-cerebral infarction, intraluminal carotid thrombosis and hyperperfusion in COVID-19

Objective: To report a unique presentation of acute synchronous cardio-cerebral infarction with intraluminal carotid thrombus (ICT) and hyperperfusion in the setting of a recent SARS-CoV-2 infection. Background: Simultaneous acute ischemic stroke (AIS) and acute myocardial infarction (AMI), also referred to as cardio-cerebral infarction, is an extremely rare entity. Additionally, AIS due to ICT is an infrequent condition and is often associated with ipsilateral carotid stenosis or underlying hypercoagulable state. Infection with SARS-CoV-2 is thought to cause endothelial inflammation and a hypercoagulable state. Here we report a case of concurrent AIS due to a partially occlusive ICT and AMI in the setting of recent SARS-CoV-2 infection. Design/Methods: Case report and literature review. Results: A middle-aged male presented with isolated transcortical sensory aphasia. CT angiography showed a free-floating intraluminal thrombus in the clinoid segment of the left internal carotid artery. There was an increase in regional cerebral blood flow (CBF) and cerebral blood volume (CBV) as well as decreased Tmax on perfusion imaging consistent with hyperperfusion. Additionally, he was found to have an acute inferior-wall ST-elevation MI. He did report a recent COVID-19 exposure and clinical symptoms of chills with pulmonary imaging concerning for COVID-19 pneumonia. Swab-based PCR testing for COVID-19 was negative, but IgG antibody test returned positive, suggesting a recent infection. D-dimer was elevated. Magnetic resonance imaging (MRI) brain confirmed an AIS involving the left MCA territory. Conclusions: We report a unique case of simultaneous AIS from ICT and AMI in the setting of recent SARS-CoV-2 infection and with the etiology of both events attributed to a COVID-19 hypercoagulable state. Additionally, imaging studies showed a rare phenomenon of hyperperfusion that occurs when cerebral blood flow increases in the region of previous ischemia (hypoperfusion and/or infarcted brain tissue) and is thought to be a form of dysfunctional autoregulation.

Intraluminal carotid thrombosis and acute ischemic stroke associated with COVID-19

Background: Intraluminal carotid thrombi (ILT) are uncommon and present in only 0.4 to 1.5 % of patients with stroke. The endothelial inflammation and hypercoagulable state associated with COVID-19 (caused by SARS-CoV-2) poses a risk of arterial and venous thromboembolism. Herein, we present a series of stroke patients with ILT in the setting of a recent SARS-CoV-2 infection. Methods and Results: From July 9 , 2020 to August 17 , 2020, four patients were identified with acute ischemic stroke with varying thrombus burden but similar morphological patterns of ILT. All patients had evidence of recent SARS-CoV-2 infection as confirmed by PCR (n=3) or IgG antibody (n=1) in addition to clinical and radiological manifestations consistent with COVID-19. General characteristics and imaging of the patients are shown in table 1. Mean age was 55.3 ±7.7 years. Most patients (3) had at least two vascular risk factors and none had a central embolic source other than ILT. D-Dimer was profoundly elevated in 3 patients. ILT involved the cervical (3) and intracranial (1) internal carotid artery. COVID-19 symptoms ranged from mild transient respiratory symptoms to severe pneumonia requiring critical care support. None of the patients received acute reperfusion therapy either due to presentation beyond the therapeutic window or due to the absence of large vessel occlusion and/or unfavorable imaging profile. Conclusion: In this small case series of relatively young patients with acute ischemic stroke we found an association between COVID-19 infection and ILT. This suggests a distinctive pathophysiological pattern of stroke in COVID-19 patients. Further studies are necessary to elucidate the underlying pathophysiology and target specific treatment modalities. (Figure Presented).

Stroke etiologies in patients with COVID-19: the svin COVID-19 multinational registry

Background and purpose: Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology. Methods: We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID- 19 from 31 hospitals in 4 countries (3/1/20-6/16/20). Results: Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60-79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p</=0.05 for all comparisons). In a multivariable backward stepwise regression model estimating the odds of in-hospital mortality, cryptogenic stroke mechanism was associated with a fivefold greater odds in-hospital mortality than strokes due to any other mechanism (adjusted OR 5.16, 95%CI 1.41-18.87, p=0.01). In that model, older age (aOR2.05 per decade, 95%CI 1.35-3.11, p<0.01) and higher baseline NIHSS (aOR 1.12, 95%CI 1.02-1.21, p=0.01) were also independently predictive of mortality. Conclusions: Our findings suggest that cryptogenic stroke among COVID-19 patients may berelated to more severe disease and carries a significant risk of early mortality.

Decline in mild stroke presentations and intravenous thrombolysis during the COVID-19 pandemic: the society of vascular and interventional neurology registry

Introduction: To evaluate overall ischemic stroke rates, specific subtypes, and clinical presentation during the COVID-19 pandemic in a multicenter observational study from eight states across US. Methods: We compared all ischemic strokes admitted between January 2019 and May 2020, grouped as;March-May 2020 (COVID-19 period), March-May 2019 (seasonal pre-COVID period) and November 2019-January 2020 (immediate pre-COVID-19 period). Primary outcome was stroke severity at admission measured by NIHSS stratified as mild (0-7), moderate (8-14), and severe (>14) symptoms. Secondary outcomes were number of large vessel occlusions (LVOs), stroke etiology, IV-tPA rates, and disposition. Results: Of the 7,969 patients diagnosed with acute stroke during the study period, 933 (12%) presented in the COVID-19 period, 1319 (17%), and 1254 (16%) presented in the seasonal pre- COVID-19 and immediate pre-COVID-19 periods, respectively. Significant decline was observed in the weekly mean volume of newly diagnosed strokes (98±7.3 vs 50±20, p<0.01 and 95±10.5 vs 50±20, p<0.01), LVOs (16.5±3.8 vs 8.3±5.9, p<0.01 and 14.3± 4.5 vs 8.3±5.9, p<0.01), and IV-tPA (5.3±2.9 vs 10.9±3.4 and 12.7±4.1, p<0.01). Mean weekly proportion of LVOs remained the same, when compared with seasonal pre-COVID-19 period (18%±5 vs 16%±7, p=0.24) and immediate pre-COVID-19 period (17.4%±4 vs. 16%±7, p=0.32). Additionally, these patients presented with less severe disease (NIHSS<14;aOR: 0.63, 95%CI: 0.41-0.97, p=0.035) during the COVID-19 period ascompared to immediate pre-COVID-19 period. Conclusions: We observed a decrease in newly diagnosed stroke cases and rates of IV-tPAadministration, while the LVO frequency remained unchanged during the COVID-19 pandemic.Additionally, these stroke patients had more severe presentations.

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: the society of vascular and interventional neurology multinational registry

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. Aims: To summarize the findings of a multinational observational cohort of patients with SARS-CoV- 2 and cerebrovascular disease. Methods: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in 4 countries (2/1/2020 - 06/16/2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). Results: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort;1130/100,000 patients, 95%CI 970- 1320/100,000), 68/171 (40.5%) of whom were female and 96/172 (55.8%) were between the ages 60-79 years. Of these, 156 had acute ischemic stroke (1.08%;1080/100,000 95%CI 920- 1260/100,000), 28 ICH (0.19%;190/100,000 95%CI 130 - 280/100,000) and 3 with CVST (0.02%;20/100,000, 95%CI 4-60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline strokeseverity, and all predictors of in-hospital mortality found in univariate regression (p<0.1: male sex,tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, andintracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p<0.01), olderage (aOR 1.78, 95%CI 1.07-2.94, p=0.03), and lower lymphocyte count on admission (aOR 0.58,95%CI 0.34-0.98 p=0.04) were the only independent predictors of mortality among patients withstroke and COVID-19. Conclusions: COVID-19 is associated with a small but significant risk of clinically relevantcerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19associated cerebrovascular complications, therefore aggressive monitoring and early interventionshould be pursued to mitigate poor outcomes.

Acute stroke care during the COVID-19 pandemic: the society of vascular and interventional neurology collaboration

Background: We sought to evaluate whether the coronavirus disease 2019 (COVID-19) pandemic may have contributed to delays in acute stroke management at Comprehensive Stroke Centers (CSCs). Methods: Pooled clinical data of consecutive adult stroke patients from 12 U.S. CSCs (1/1/2019- 5/31/2020) were queried. The rate of thrombolysis for non-transferred patients within the Target: Stroke goal of 60min was compared between patients admitted 3/1/2019-5/31/2019 (pre-COVID-19) and 3/1/2020-5/31/2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed. Results: Of the 7906 patients included, 1319 were admitted pre-COVID-19 and 933 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. There was no difference in the rate of thrombolysis within 60min during COVID-19 (OR 0.88, 95%CI 0.42-1.86, p=0.74), despite adjustment for variables associated with earlier treatment (adjusted OR 0.82, 95%CI 0.38-1.76, p=0.61). There was no significant overall delay to thrombolysis during the COVID-19 period vs. pe- COVID-19 (p=0.42), even after multivariable adjustment (p=0.63) or after comparison across months leading to COVID-19 (Figure). The only independent predictor of delayed treatment time between periods was the use of emergency medical services (adjusted β=-6.93, 95%CI -12.83 -1.04, p=0.03). There was no significant delay from hospital arrival to imaging in all patients, or imaging to skin puncture in patients who underwent thrombectomy. Conclusions: There was no independent effect of the COVID-19 period on delays in acute care with respect to thrombolysis or thrombectomy in this multicenter observational cohort. Further studies are warranted to externally validate these findings, and determine if site volume or center accreditation may mediate a collateral effect of the pandemic on stroke care paradigms.