Risultati per: Scoperti anticorpi che bloccano l’infezione da SARS-CoV-2 nelle cellule

Stroke, Volume 53, Issue Suppl_1, Page A51-A51, February 1, 2022. Introduction:Cerebral Venous Sinus Thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of SARS-CoV-2 vaccination. The estimated background rate of CVST in adults is around 1 case per million per month, and CVST with thrombocytopenia accounts for 8% of all CVST. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination.Methods:We estimated the absolute risk of any CVST, CVST with thrombocytopenia, and CVST without thrombocytopenia, within 28 days of first dose SARS-CoV-2 vaccination, using data from the European Medicines Agency’s EudraVigilance database (until 13 June 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category.Results:The absolute risk of CVST within 28 days of first dose vaccination was 7.5 (95%CI 6.9-8.3), 0.7 (95%CI 0.2-2.4), 0.6 (95%CI 0.5-0.7) and 0.6 (95%CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2 and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95%CI 3.9-4.9), 0.7 (95%CI 0.2-2.4), 0.0 (95%CI 0.0-0.1) and 0.0 (95%CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2 and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the risk of CVST, both with and without thrombocytopenia, was the highest in the 18-24 years age group (7.3 per million, 95%CI 2.8-18.8 and 3.7, 95%CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia was the lowest in ChAdOx1 nCov-19 recipients ≥70 years (0.2, 95%CI 0.0-1.3). Age

Stroke, Volume 53, Issue Suppl_1, Page ATMP14-ATMP14, February 1, 2022. Background:Undiagnosed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may be seen in acute stroke patients. Rapid screening is important to reduce exposure to medical professionals and other patients during acute assessment and treatment. Chest computed tomographic (CT) scan may be another time-sensitive option for identification of SARS-CoV-2 infection in acute stroke patients.Objective:We report our experience of incorporating chest CT scan in the initial neuroimaging protocol for evaluation of acute stroke patients.Methods:All acute stroke patients underwent chest CT scan concurrent to CT head, CT angiogram of head and neck and CT perfusion for 10 months. We identified patients who had chest CT scan findings that were suggestive of SARS-CoV-2 infection including bilateral, multilobar ground glass opacification with a peripheral or posterior distribution, and/or consolidation. All patients subsequently underwent polymerase chain reaction (PCR) testing using nasopharyngeal specimen for identification of SARS-CoV-2 with contact isolation. Sensitivity, specificity, and likelihood ratios were calculated.Results:A total of 530 consecutive acute stroke patients (mean age in years 65.6± SD; 15.4; 280 were men) underwent neuroimaging with concurrent chest CT scan. The chest CT scan identified findings suggestive of SARS-CoV-2 infection in 34 (6.4%) patients. Subsequent PCR testing confirmed the diagnosis of SARS-CoV-2 infection in 21 of 34 patients. Among 491 patients in whom chest CT scan did not identify any findings suggestive of SARS-CoV-2 infection, 387 underwent PCR tests; PCR testing confirmed the diagnosis of SARS-CoV-2 infection in 13 of 34 patients. Sensitivity and specificity of chest CT scan for detecting SARS-CoV-2 infection was 61.9% and 96.2%, respectively. Positive and negative likelihood ratio of chest CT scan for detecting SARS-CoV-2 infection is 16.26 and 0.39, respectively.Conclusions:Although specificity was high, the relatively low sensitivity of chest CT scan in identifying SARS-CoV-2 infection limits the value of adding this imaging to standard neuroimaging in acute stroke patients. At our institution, we have subsequently discontinued the protocol.

Stroke, Volume 53, Issue Suppl_1, Page ATMP17-ATMP17, February 1, 2022. Background:Studies have shown that patients with ischemic stroke (IS) and concurrent COVID-19 have increased stroke severity. These analyses were limited by use of prepandemic era controls or by utilization of a sample from the early pandemic period when stroke care delivery was affected by lockdown. Studies on the severity of hemorrhagic stroke (HS) in patients with concurrent COVID-19 are few and limited by small sample sizes.Methods:Using the National Institute of Health (NIH) National COVID Cohort Collaborative (N3C) database, we identified patients diagnosed with stroke between Mar 1, 2020 – Feb 28, 2021. Hospitalized stroke patients with concurrent COVID-19 (stroke within 3 months after or one week prior to positive SARS-COV-2 PCR or AG lab test) were matched to all other hospitalized stroke patients in a 1:3 ratio. Nearest neighbor matching with a caliper of 0.25 was used for most clinical and demographic factors; exact matching for race/ethnicity and site. Within our matched sample, we used Poisson regression to calculate stroke severity incident rate ratio (IRR).Results:Our query identified 10,394 patients hospitalized with IS with available NIHSS scores upon admission (802 with concurrent COVID-19 and 9,592 without) and 2138 patients hospitalized with HS (181 with concurrent COVID-19 and 1957 without). Average NIHSS was greater in concurrent groups with both IS and HS (11.1 vs 7.68, p < 0.001 and 15.7 vs 11.7, p < 0.001 respectively). Propensity matched analysis also demonstrated that stroke patients with concurrent COVID-19 had increased initial NIHSS (IS: IRR = 1.4, 95% CI:1.3-1.5, p-value < 0.001; HS: IRR = 1.3, 95% CI:1.2-1.5, p < 0.001). Average NIHSS in both IS and HS patients was greater in the Mar-Apr 2020 epoch than in all other 2 month epochs studied in these respective groups.Conclusions:This analysis suggests that the association between increased stroke severity and concurrent COVID-19 that was observed during the early pandemic was present throughout the pandemic as stroke care utilization normalized. Further work will center on the interaction between COVID-19 illness severity and stroke severity.

Stroke, Volume 53, Issue Suppl_1, Page ATMP19-ATMP19, February 1, 2022. Patients with significant cerebrovascular comorbidities (e.g. brain ischemia, vascular dementia) are more affected and are more likely to have worsened post-acute neurologic sequelae after SARS-CoV-2 infection. This may be due to viral invasion and propagation in brain endothelial cells (BECs) and disruption of the blood-brain barrier (BBB). Viral spike protein used to bind and infect host cells encodes an arginine-glycine-aspartic acid (RGD) motif that it may use to bind integrins cell receptors that play an important role in cerebrovascular integrity. Therefore, integrins may represent an acute and post-acute SARS-CoV-2 therapeutic target. However, the interplay between vascular dysregulation, integrin function, and COVID-19 is unclear. As we have previously demonstrated that activation of the integrin α5 plays a key role in BBB breakdown, stroke injury, OGD/R, SARS-CoV-2 infection, and its inhibition with the clinically validated peptide ATN-161 is therapeutic in these conditions, we hypothesize that SARS-CoV-2 alters BEC α5 integrin (and associated tight junction protein) expression as a means of infecting and altering cerebrovascular integrity, and this can be prevented by ATN-161.Methods:Mouse BECs (bEnd3) were inoculated with heat-inactivated SARS-CoV-2 (Isolate USA-WA1/2020) or delta variant of SARS-CoV-2 spike protein for 24 h then later exposed to hypoxia for 6h to model the effects ofin vivopulmonary infection. Cells were pretreated with ATN-161 (1, 5, and 10μM) 1h before SARS-CoV-2 challenge and during hypoxia. α5 and claudin-5 proteins were analyzed by immunoblotting.Results:Both SARS-CoV-2 inoculations induced integrin α5 and decreased claudin-5 expression (delta > SARS-CoV-2) in a dose-dependent fashion, although higher doses of SARS-CoV-2 (2.5 and 5 μg) had no effect on these proteins. SARS-CoV-2 spike protein challenge at 0.5 μg followed by hypoxia resulted in increased α5 and decreased claudin-5 expression in either hypoxia or SARS-CoV-2+hypoxia combination. ATN-161 (10μM) pretreatment inhibited SARS-CoV-2+hypoxia-induced α5 upregulation and restored claudin-5 loss. In addition to its demonstrated anti-viral effects, ATN-161 may be an important therapy for SARS-CoV-2-mediated cerebrovascular injury.

Stroke, Volume 53, Issue Suppl_1, Page AWP27-AWP27, February 1, 2022. Introduction:Recent studies have shown patients with coronavirus disease 2019 (COVID-19) develop significant coagulopathy with thromboembolic complications including ischemic stroke. However, data are sparse regarding the clinical characteristics, stroke mechanism, and patient outcomes.Methods:We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 2020 and June 2021, within at a Regional Medical Center serving three large counties in South Carolina. We further investigated clinical and demographic characteristics, stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS), and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria among patients with COVID-19 who also suffered from an acute ischemic stroke.Results:During the study period, out of 1087 hospitalized patients with a diagnosis of COVID-19 infection, 18 patients (1.6%) had an imaging-proven ischemic stroke. Of these 18 patients, 10 (56%) were men, 16 were African-Americans (89%), 2 (11.1%) patients were

Stroke, Volume 53, Issue Suppl_1, Page AWP25-AWP25, February 1, 2022. Objectives:Acute ischemic stroke patients with severe acute respiratory syndrome coronavirus maybe candidates for acute revascularization treatments (intravenous thrombolysis and/or mechanical thrombectomy).Materials and Methods:We analyzed the data from 62 healthcare facilities to determine the odds of receiving acute revascularization treatments in severe acute respiratory syndrome coronavirus infected patients and odds of composite of death and non-routine discharge with severe acute respiratory syndrome coronavirus infected and non-infected patients undergoing acute revascularization treatments after adjusting for potential confounders.Results:Acute ischemic stroke patients with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments (odds ratio 0.6, 95% confidence interval 0.5-0.8, p=0.0001). Among ischemic stroke patients who received acute revascularization treatments, severe acute respiratory syndrome coronavirus infection was associated with increased odds of death or non-routine discharge (odds ratio 3.0, 95% confidence interval 1.8-5.1). The higher odds death or non-routine discharge (odds ratio 2.1, 95% confidence interval 1.9-2.3) with severe acute respiratory syndrome coronavirus infection were observed in all ischemic stroke patients without any modifying effect of acute revascularization treatments (interaction term for death (p=0.9) or death or non-routine discharge (p=0.2).Conclusions:Patients with acute ischemic stroke patients with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments. Severe acute respiratory syndrome coronavirus infection was associated with a significantly higher rate of death or non-routine discharge among acute ischemic stroke patients receiving revascularization treatments.