Risultati per: Identificate le origini evolutive di SARS-CoV-2

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 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 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.