Characteristics of a COVID-19 Cohort With Large Vessel Occlusion: A Multicenter International Study.

BACKGROUND: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke. OBJECTIVE: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort. METHODS: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020. RESULTS: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates.

International controlled study of revascularization and outcomes following COVID-positive mechanical thrombectomy.

BACKGROUND AND PURPOSE: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates.

Ethical Management of COVID-19 Pandemic at a Neurological Hospital: The Ethicovid report.

BACKGROUND: During the first wave of the coronavirus disease-2019 (COVID-19) pandemic, it was necessary to prepare for the possibility of triaging patients who could benefit from access to an intensive care unit (ICU). In our neuroscience institution, the challenge was to continue to manage usual neurological emergencies as well as the influx of COVID-19 patients. METHODS: We report the experience of an ethical consulting unit to support care clinical decisions during the first wave of the pandemic (March 16 to April 30, 2020). Three objective evaluation criteria were defined: 2 of these criteria, patient's factors and general disease severity (Simplified Acute Physiology Score II), were common to all patients, and the third was the specific severity of the disease (neurological for brain injury, respiratory for COVID-19). Given our scarce resources, we used a high probability of a 3-month modified Rankin Scale ≤3 as the criterion for further resuscitation and management. RESULTS: A total of 295 patients were admitted during the first pandemic wave; 111 with COVID-19 and 184 with neurological emergencies. The ethical unit's expertise was sought for 75 clinical situations in 56 patients (35 COVID-19 and 21 neurological). Decisions were as follows: 11% no limitation on care, 5% expectant care with reassessment (maximum therapy to assess possible progress pending decision), 67% partial limitation (no intensification of care or no transfer to ICU), and 17% limitation of curative care. At no time did a lack of availability of ICU beds require the ethical unit to advise against admission to the ICU. CONCLUSIONS: Our ethical consulting unit allowed for collegial ethical decision-making in line with international recommendations. This model could be easily transferred to other triage situations, provided it is adapted to the local context.

Impact of COVID-19 on thrombus composition and response to thrombolysis: Insights from a monocentric cohort population of COVID-19 patients with acute ischemic stroke.

BACKGROUND: Resistance to fibrinolysis, levels of procoagulant/antifibrinolytic neutrophil extracellular traps (NETs), and the severity of acute ischemic stroke (AIS) are increased by COVID-19. Whether NETs are components of AIS thrombi from COVID-19 patients and whether COVID-19 impacts the susceptibility of these thrombi to thrombolytic treatments remain unknown, however. OBJECTIVES: We aimed to characterize AIS thrombi from COVID-19 patients by immunohistology and to compare their response to thrombolysis to that of AIS thrombi from non-COVID-19 patients. PATIENTS/METHODS: For this monocentric cohort study, 14 thrombi from COVID-19 AIS patients and 16 thrombi from non-COVID-19 patients, all recovered by endovascular therapy, were analyzed by immunohistology or subjected to ex vivo thrombolysis by tissue-type plasminogen (tPA)/plasminogen. RESULTS: COVID-19 AIS thrombi were rich in neutrophils and contained NETs, but not spike protein. Thrombolysis assays revealed a mean resistance profile to tPA/plasminogen of COVID-19 AIS thrombi similar to that of non-COVID-19 AIS thrombi. The addition of DNase 1 successfully improved thrombolysis by potentiating fibrinolysis irrespective of COVID-19 status. Levels of neutrophil, NETs, and platelet markers in lysis supernatants were comparable between AIS thrombi from non-COVID-19 and COVID-19 patients. CONCLUSIONS: These results show that COVID-19 does not impact NETs content or worsen fibrinolysis resistance of AIS thrombi, a therapeutic hurdle that could be overcome by DNase 1 even in the context of SARS-CoV-2 infection.

Global impact of COVID-19 on stroke care.

BACKGROUND: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. AIMS: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). METHODS: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. RESULTS: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. CONCLUSION: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.

European Multicenter Study of ET-COVID-19.

BACKGROUND AND PURPOSE: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. METHODS: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. SECONDARY OUTCOMES: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0-1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. RESULTS: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59-79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11-21) and 8 (interquartile range, 7-9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3-87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20-39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8-29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7-12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21-5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22-5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43-12.91] per SD-log increase in LDH). CONCLUSIONS: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient's profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04406090.

Early Brain Imaging Shows Increased Severity of Acute Ischemic Strokes With Large Vessel Occlusion in COVID-19 Patients.

BACKGROUND AND PURPOSE: Reports are emerging regarding the association of acute ischemic strokes with large vessel occlusion and coronavirus disease 2019 (COVID-19). While a higher severity of these patients could be expected from the addition of both respiratory and neurological injury, COVID-19 patients with strokes can present with mild or none respiratory symptoms. We aimed to compare anterior circulation large vessel occlusion strokes severity between patients with and without COVID-19. METHODS: We performed a comparative cohort study between patients with COVID-19 who had anterior circulation large vessel occlusion and early brain imaging within 3 hours from onset, in our institution during the 6 first weeks of the COVID-19 outbreak and a control group admitted during the same calendar period in 2019. RESULTS: Twelve COVID-19 patients with anterior circulation large vessel occlusion and early brain imaging were included during the study period and compared with 34 control patients with anterior circulation large vessel occlusion and early brain imaging in 2019. Patients in the COVID-19 group were younger (P=0.032) and had a history of diabetes mellitus more frequently (P=0.039). Patients did not significantly differ on initial National Institutes of Health Stroke Scale nor time from onset to imaging (P=0.18 and P=0.6, respectively). Patients with COVID-19 had more severe strokes than patients without COVID-19, with a significantly lower clot burden score (median: 6.5 versus 8, P=0.016), higher rate of multivessel occlusion (50% versus 8.8%, P=0.005), lower DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Scores; median: 5 versus 8, P=0.006), and higher infarct core volume (median: 58 versus 6 mL, P=0.004). Successful recanalization rate was similar in both groups (P=0.767). In-hospital mortality was higher in the COVID-19 patients' group (41.7% versus 11.8%, P=0.025). CONCLUSIONS: Early brain imaging showed higher severity large vessel occlusion strokes in patients with COVID-19. Given the massive number of infected patients, concerns should be raised about the coming neurovascular impact of the pandemic worldwide.

Acute Stroke Management During the COVID-19 Pandemic: Does Confinement Impact Eligibility for Endovascular Therapy?

During the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended measures to mitigate the outbreak such as social distancing and confinement. Since these measures have been put in place, anecdotal reports describe a decrease in the number of endovascular therapy (EVT) treatments for acute ischemic stroke due to large vessel occlusion. The purpose of our study was to determine the effect on EVT for patients with acute ischemic stroke during the COVID-19 confinement. In this retrospective, observational study, data were collected from November 1, 2019, to April 15, 2020, at 17 stroke centers in countries where confinement measures have been in place since March 2020 for the COVID-19 pandemic (Switzerland, Italy, France, Spain, Portugal, Germany, Canada, and United States). This study included 1600 patients treated by EVT for acute ischemic stroke. Date of EVT and symptom onset-to-groin puncture time were collected. Mean number of EVTs performed per hospital per 2-week interval and mean stroke onset-to-groin puncture time were calculated before confinement measures and after confinement measures. Distributions (non-normal) between the 2 groups (before COVID-19 confinement versus after COVID-19 confinement) were compared using 2-sample Wilcoxon rank-sum test. The results show a significant decrease in mean number of EVTs performed per hospital per 2-week interval between before COVID-19 confinement (9.0 [95% CI, 7.8-10.1]) and after COVID-19 confinement (6.1 [95% CI, 4.5-7.7]), (P<0.001). In addition, there is a significant increase in mean stroke onset-to-groin puncture time (P<0.001), between before COVID-19 confinement (300.3 minutes [95% CI, 285.3-315.4]) and after COVID-19 confinement (354.5 minutes [95% CI, 316.2-392.7]). Our preliminary analysis indicates a 32% reduction in EVT procedures and an estimated 54-minute increase in symptom onset-to-groin puncture time after confinement measures for COVID-19 pandemic were put into place.

Treatment of Acute Ischemic Stroke due to Large Vessel Occlusion With COVID-19: Experience From Paris.

BACKGROUND AND PURPOSE: Higher rates of strokes have been observed in patients with coronavirus disease 2019 (COVID-19), but data regarding the outcomes of COVID-19 patients suffering from acute ischemic stroke due to large vessel occlusion (LVO) are lacking. We report our initial experience in the treatment of acute ischemic stroke with LVO in patients with COVID-19. METHODS: All consecutive patients with COVID-19 with acute ischemic stroke due to LVO treated in our institution during the 6 first weeks of the COVID-19 outbreak were included. Baseline clinical and radiological findings, treatment, and short-term outcomes are reported. RESULTS: We identified 10 patients with confirmed COVID-19 treated for an acute ischemic stroke due to LVO. Eight were men, with a median age of 59.5 years. Seven had none or mild symptoms of COVID-19 at stroke onset. Median time from COVID-19 symptoms to stroke onset was 6 days. All patients had brain imaging within 3 hours from symptoms onset. Five patients had multi-territory LVO. Five received intravenous alteplase. All patients had mechanical thrombectomy. Nine patients achieved successful recanalization (mTICI2B-3), none experienced early neurological improvement, 4 had early cerebral reocclusion, and a total of 6 patients (60%) died in the hospital. CONCLUSIONS: Best medical care including early intravenous thrombolysis, and successful and prompt recanalization achieved with mechanical thrombectomy, resulted in poor outcomes in patients with COVID-19. Although our results require further confirmation, a different pharmacological approach (antiplatelet or other) should be investigated to take in account inflammatory and coagulation disorders associated with COVID-19.