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.

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.