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.

Patterns of emergency medical transport for suspected acute stroke, acute myocardial infarction, and other diagnoses during the COVID-19 pandemic: A retrospective analysis of a large hospital-based emergency medical services (EMS) agency

Introduction: During the initial peak of the COVID-19 pandemic, many centers globally reported a significant decrease in volumes of emergencies including acute stroke (AS) and acute myocardial infarction (AMI). While the reason for this remains unknown, pandemic-driven anxiety among patients may have resulted in unwarranted refusals to transport when deemed necessary by EMS (Emergency Medical Services) providers. We sought to study the impact of COVID-19 pandemic on the patterns of Emergency Medical transport (EMTr) and patient refusals to transport when serious medical conditions were suspected by EMS personnel. Methods: In this retrospective, observational study of Grady Health System's EMS, we compared the rates of EMTr and refusals for adult patients with suspected diagnoses of AS, AMI, and other medical conditions in the first year of the pandemic (Y1, Mar 2020-Feb 2021) with the corresponding period in the year prior (Y0). We also compared the temporal trends for these variables across the different pandemic waves (1st , Mar-May 2020;2nd , Jun-Aug 2020;3rd, Sep 2020-Feb 2021) with the corresponding periods in the year before. Results: Grady EMS responded to 207,888 calls in Y1 compared to 201,968 in Y0. The overall rate of refusals for all diagnoses was 15.5% in Y1 vs 14.1% in Y0, that for AS was 2.25% in Y1 vs 1.77% in Y0 and 7.5% in Y1 vs 5.67% in Y0 for AMI (Figure). Conclusion: There were more refusals in the first two waves of the pandemic. While refusals were higher for AS and AMI, this was not statistically significant. Our study provides valuable insight into the behavioral patterns of patients seeking emergency care during the pandemic and emphasizes a need for public education and more research. (Figure Presented).

Global impact of the COVID-19 pandemic on stroke care and intravenous thrombolysis

Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods. Background: The COVID-19 pandemic led to widespread repercussions on the delivery of health care worldwide. Design/Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by ICD-10 codes and/or classifications in stroke center databases. Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI,-11.7 to-11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI,-13.8 to-12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI,-13.7 to-10.3, p=0.001). There were greater declines in primary compared to comprehensive stroke centers (CSC) for stroke hospitalizations (-17.3% vs-10.3%, p<0.0001) and IVT (-15.5% vs-12.6%, p=0.0001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) months of the pandemic, with greater recovery in hospitals with lower COVID-19 hospitalization volume, high volume stroke center, and CSC. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722/52,026) of all stroke admissions. Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months, with greater recovery in hospitals with lower COVID-19 hospitalizations, high volume stroke centers, and CSCs.

Impact of the COVID-19 pandemic on the volumes and outcomes of acute ischemic stroke and myocardial infarction

Introduction: The COVID-19 pandemic has wreaked havoc on the presentation, care and outcomes of patients with acute cerebrovascular and cardiovascular conditions. We sought to measure the national impact of COVID-19 on the care for acute ischemic stroke (AIS) and acute myocardial infarction (AMI). Methods: In this retrospective, observational study, we used the Premier Healthcare Database to evaluate the changes in the volume of care and hospital outcomes for AIS and AMI in relation to the pandemic. The pandemic months were defined from March 1, 2020- April 30, 2020 and compared to the same period in the year prior. Outcome measures were volumes of hospitalization and reperfusion treatment for AIS and AMI (including intravenous thrombolysis [IVT] and/or mechanical thrombectomy [MT] for AIS and percutaneous coronary interventions [PCI] for AMI) as well as inhospital mortality, hospital length of stay (LOS) and hospitalization costs were compared across a 2- month period at the height of the pandemic versus the corresponding period in the prior year. Results: There were 95,453 AIS patients across 145 hospitals and 19,744 AMI patients across 126 hospitals. There was a significant nation-wide decline in the absolute number of hospitalizations for AIS (-38.94%;95%CI,-34.75% to -40.71%) and AMI (-38.90%;95%CI,-37.03% to -40.81%) as well as IVT (-30.32%;95%CI,-27.02% to -33.83%), MT (-23.54%;95%CI,-19.84% to -27.70%), and PCI (-35.05%;95%CI,-33.04% to -37.12%) during the first two months of the pandemic. This occurred across low-, mid-, and high-volume centers and in all geographic regions. Higher in-hospital mortality was observed in AIS patients (5.7% vs.4.2%, p=0.0037;OR 1.41,95%CI 1.1-1.8) but not AMI patients. A shift towards an increase in the proportion of admitted AIS and AMI patients receiving reperfusion therapies suggests a greater clinical severity among patients that were hospitalized for these conditions during the pandemic. A shorter length of stay (AIS: -17%, AMI: -20%), and decreased hospitalization costs (AIS: -12%, AMI: -19%) were observed. Conclusions: Our findings shed light on the combined health outcomes and economic impact the COVID-19 pandemic has had on acute stroke and cardiac emergency care.

Clot characteristics in mechanical thrombectomy: Interim analysis of the excellent registry

Introduction: Red blood cell (RBC) rich vs fibrin rich clots have different mechanical properties and greater knowledge about clot composition in the context of clinical, imaging, and procedural factors in mechanical thrombectomy (MT) may help with procedural optimization. The EXCELLENT Registry (NCT03685578) is a prospective, global, multi-center, observational registry of EmboTrap as the first line MT device for large vessel occlusion (LVO). We present an interim analysis of clot collected per pass in the registry. Methods: Five hundred thirty-three clot specimens from 376 subjects were collected by 20 sites and sent for analysis by independent Central Labs under standardized protocol. Analysis was interrupted by COVID-19, but the labs were fully operational as of June 2020 and on track to deliver results for 300 subjects in Q4. At the time of abstract submission, composition data for 234 clots from 163 subjects was available. All available data will be presented at the time of the conference. Results: Cardioembolic etiology (n=100) was associated with lower RBC (40.2 vs 47.2%) and higher fibrin content (31.7 vs 26.7%) compared to large artery disease (n=12). Hyperdense/vessel susceptibility sign (78+, 24-, per independent imaging core lab) corresponded to higher mean RBC content (44.4 vs 34.9%). Treatment with IV tPA (60+, 91-) had no clear impact on clot composition (42.3 vs 40.6% RBC;30.4 vs 30.0% fibrin). Notably, clots retrieved with the first 2 passes of were more RBC rich (42.1 vs 28.0%) and clots retrieved in higher passes had a higher average fibrin content (35.5 vs 29.6%) suggesting that higher fibrin content leads to greater refractoriness. Conclusions: Clot density/susceptibility on baseline imaging, stroke etiology and number ofthrombectomy passes were associated with differential clot composition. These findings may havepotential implications for the development of better MT strategies.

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.

Global impact of the COVID-19 pandemic on stroke hospitalizations and mechanical thrombectomy volumes: A society of vascular and interventional neurology COVID-19 international collaboration

Introduction: The COVID-19 pandemic led to profound changes in both the organization of health care systems and the psychosocial behavior of the population worldwide. The extent to which the COVID-19 outbreak disrupted stroke systems of care merits study from a global lens. Methods: We conducted a retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The study objectives were to measure the global impact of the pandemic on the volumes for mechanical thrombectomy (MT), stroke and intracranial hemorrhage (ICH) hospitalizations over a 3-month period at the height of the pandemic (March 1 to May 31, 2020) compared with two control 3-month periods prior (immediately preceding and one year prior). A secondary objective was to examine whether these changes in volume were impacted by COVID-19 and baseline hospital center stroke volumes. Third, we evaluated the relationships between stroke and COVID-19 diagnoses. Results: There were 26,699 stroke admissions in the 3 months immediately before compared to 21,576 admissions during the pandemic months, representing a 19.2% (95%CI,-19.7 to -18.7) decline. There were 5,191 MT procedures in the 3 months preceding compared to 4,533 procedures during the pandemic, representing a 12.7% (95%CI,-13.6 to -11.8) drop. Significant reductions were also seen in relation to the prior year control period. The decreases were noted across centers with high, intermediate, and low COVID-19 hospitalization burden, and also across high, intermediate, and low volume stroke centers. High-volume COVID-19 centers (-20.5%) had greater declines in MT volumes than mid- (-10.1%) and low-volume (-8.7%) centers. There was a 1.5% stroke rate across54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of allstroke admissions. Conclusions: The COVID-19 pandemic was associated with a global decline in the volume ofoverall stroke hospitalizations, MT procedures, ischemic stroke/TIA and ICH admission volumes.Despite geographic variations, these volume reductions were observed regardless of COVID-19hospitalization burden and pre-pandemic stroke and MT volumes. Centers with higher COVID-19inpatient volumes experienced steeper declines.

Epidemiological surveillance of the impact of the COVID-19 pandemic on stroke care using artificial intelligence

Background: The degree to which the COVID-19 pandemic has affected systems of care, in particular those for time-sensitive conditions such as stroke, remains poorly quantified. We sought to evaluate the impact of COVID-19 in the overall screening for acute stroke utilizing a commercial clinical artificial intelligence (AI) platform. Methods: Data were derived from the Viz Platform, an AI application designed to optimize the workflow of acute stroke patients. Neuroimaging data on suspected stroke patients across 97 hospitals in 20 US states were collected in real-time and retrospectively analyzed with the number of patients undergoing imaging screening serving as a surrogate for the amount of stroke care. The main outcome measures were the number of CTA, CTP, Large vessel occlusions (LVOs) (defined according to the automated software detection), and severe strokes on CTP (defined as those with hypoperfusion volumes>70mL) normalized as number of patients per day per hospital. Data from the pre-pandemic (November 4, 2019 to February 29, 2020) and pandemic (March 1 to May 10, 2020) periods were compared at national and state levels. Correlations were made between the inter-period changes in imaging screening, stroke hospitalizations, and thrombectomy procedures using state-specific sampling. Results: A total of 23,223 patients were included. The incidence of LVO on CTA and severe strokes on CTP were 11.2%(n=2,602) and 14.7%(n=1,229/8,328), respectively. There were significant declines in the overall number of CTAs (-22.8%;1.39 to 1.07 patients/day/hospital,p<0.001) and CTPs (-26.1%;0.50 to 0.37 patients/day/hospital,p<0.001) as well as in the incidence of LVO (-17.1%;0.15 to 0.13 patients/day/hospital,p<0.001) and severe strokes on CTP (-16.7%;0.12 to 0.10 patients/day/hospital, p<0.005). The sampled cohort showed similar declines in the rates of LVOs versus thrombectomy (18.8%vs.19.5%, p=0.9) and CSC hospitalizations (18.8%vs.11.0%, p=0.4). Conclusions: A significant decline in stroke imaging screening has occurred during the COVID-19 pandemic. This underscores the broader application of AI neuroimaging platforms for the real-time monitoring of stroke systems of care.

Global impact of the COVID-19 pandemic on subarachnoid hemorrhage

Introduction: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The objective was to examine whether subarachnoid hemorrhage(SAH) hospitalizations and ruptured aneurysm coiling interventions demonstrated similar declines. Methods: We conducted a global, retrospective, observational study across 6 continents, 37 countries, and 140 comprehensive stroke centers. Patients with diagnosis of SAH, ruptured aneurysm coiling interventions, COVID-19 were identified using ICD-10 codes or by prospectively maintained stroke databases. The 3-month cumulative volume, monthly volumes for SAH hospitalizations and ruptured aneurysm coiling procedures were compared for the period before (1- year and immediately before) and during the COVID-19 pandemic (March 1 to May 31, 2020). Results: There was a significant decline in SAH hospitalizations with 2,044 admissions in the 3 months immediately before and 1,585 admissions during the pandemic, representing a decline of 22.5% (95%CI, -24.3 to -20.7, p<0.0001). Embolization of ruptured aneurysms declined with 1,170 to 1,035 procedures, respectively, representing an 11.5%(95%CI, -13.5 to -9.8, p=0.002) drop. Hospitals with higher COVID-19 hospitalization burden demonstrated greater declines in SAH and ruptured aneurysm coiling compared to lower COVID-19 burden. A relative increase in coiling of ruptured aneurysms was noted in low coiling volume hospitals of 41.1% (95%CI, 32.3-50.6, p=0.008) despite a decrease in SAH admissions in this tertile. Conclusions: There was a global decrease in subarachnoid hemorrhage admissions and ruptured aneurysm embolizations during the COVID-19 pandemic. Among low-volume coiling SAH hospitals, there was an increase in the ruptured aneurysm coiling intervention. These findings in SAH are consistent with a global decrease in other emergencies such as stroke and myocardial infarction.

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.