Risultati per: Long COVID: principali risultati, meccanismi e raccomandazioni

Stroke, Volume 53, Issue Suppl_1, Page ATMP13-ATMP13, February 1, 2022. Introduction:Coronavirus Disease 2019 (COVID-19) is associated with an increased risk of stroke and worse stroke outcomes. A clinical score that can identify high-risk patients could enable closer monitoring and targeted preventative strategies.Methods:We used data from the AHA’s COVID-19 CVD Registry to create a clinical score to predict the risk of stroke among patients hospitalized with COVID-19. We included patients aged >18 years who were hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our score, we used demographics, preexisting comorbidities, home medications, and vital sign and lab values at admission. The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, TIA, or cerebral vein thrombosis. We used two separate analytical approaches to build the score. First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable (p

Stroke, Volume 53, Issue Suppl_1, Page ATMP21-ATMP21, February 1, 2022. Background:Although hospital admissions for stroke declined in 2020 during the COVID-19 pandemic, patients with comorbid COVID-19 and stroke had increased mortality. We explored stroke mortality in 2020 and its association with COVID-19 prevalence and state-level hospital capacities.Methods:We analyzed CDC National Vital Statistics System and COVID Data Tracker data from 2017-2020. The primary outcome was age-adjusted stroke (ischemic and hemorrhagic) mortality rate per 100,000. The secondary outcome was % change in state-level stroke mortality rates in 2020 (vs. 2017-19); we report its correlation with state-level 1) prevalence of confirmed COVID-19 infections by 12/31/2021, 2) total COVID mortality by 12/31/20, and the 2020 average state-level % of 3) hospital and 4) ICU beds occupied by COVID-19 patients.Results:Figure 1A shows the typical seasonal decline in stroke mortality in quarters 2/3 was attenuated in 2020. The % change in state-level stroke mortality in 2020 (Figure 1B) was not correlated with prevalence of COVID-19 infection (rho=0.05, p=0.74), mortality (rho=0.10, p=0.49), or the % of ICU beds occupied by COVID-19 patients (rho=0.24, p=0.09). There was a correlation with % of hospital beds occupied by COVID-19 patients (rho=0.35, p=0.01) (Figure 2).Conclusion:Overall stroke mortality increased in 2020, particularly in Q2/3, the early-to-mid phase of the COVID-19 pandemic. At the state level, the average % of all hospital beds occupied by COVID-19 patients in 2020 was the only COVID-19 metric associated with change in stroke mortality. Future work should determine if this association was due to decreased hospital capacity to deliver standard stroke care.

Stroke, Volume 53, Issue Suppl_1, Page A20-A20, February 1, 2022. Introduction:Identification of key molecules that control conversion of resting microglia/macrophages (Mi/MΦ) to a detrimental or beneficial phenotype may help develop novel therapies to ischemic stroke. The transcription factor STAT1 contributes to acute (< 24h) neuronal death after brain ischemia/reperfusion (I/R), but its role in Mi/MΦ and impact on long term stroke outcome remain unknown.Hypothesis:Activation of STAT1 dictates proinflammatory responses of Mi/MΦ at subacute stage (3-5 d) after I/R. Selective deletion of STAT1 reprograms Mi/MΦ into an inflammation-resolving phenotype and improves long term stroke outcome.Methods:We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1. Brain injury, inflammation and various behavioral deficits were assessed after 1 h MCAO and 1-35 d reperfusion. Mi/MΦ phenotype was examinedin vivo(FACS followed by RNA-seq) andin vitro(primary microglia).Results:STAT1 was activated (phosphorylated) in Mi/MΦ 3 d after I/R in WT but not in STAT1 mKO mice. STAT1 mKO did not alter 24-h infarct size (TTC; p >0.05, n=8), but attenuated Mi/MΦ release of HMGB1 and increased arginase 1-producing Mi/MΦ 3d after I/R (immunostain, n=6), suggesting boosted inflammation-resolving responses of Mi/MΦ. RNA-seq further revealed downregulated proinflammatory genes and a concomitant elevation of phagocytosis-related genes in STAT1 mKO Mi/MΦ 3d after I/R (n=3, FDR

Stroke, Volume 53, Issue Suppl_1, Page ATMP20-ATMP20, February 1, 2022. Background:Neurologic complications of Coronavirus Disease 2019 (COVID-19) may be associated with neurotropism of the virus or secondary brain injury from systemic inflammation. Acute respiratory distress syndrome (ARDS) is associated with cerebrovascular injury, including both ischemia and hemorrhage. We aimed to compare brain MRI findings of COVID-19 associated ARDS with non-COVID-19 ARDS.Methods:A registry of patients with COVID-19 from March 2020 through July 2021 from a hospital network was reviewed. Patients who met criteria for ARDS by Berlin definition and underwent MRI during their hospitalization were included. These patients were matched 1:1 by age and sex with patients who underwent MRI from another registry of patients of ARDS in the same hospital between 2010 and 2018. Cerebrovascular injury was classified as either acute cerebral ischemia (ischemic infarct or hypoxic ischemic brain injury) or intracranial hemorrhage (ICH) including intraparenchymal hemorrhage, subarachnoid hemorrhage, subdural hematoma, and cerebral microbleeds (CMBs).Results:Of 13,319 patients with COVID-19 infection, 26 patients had ARDS and MRI. Sixty-six of 678 non-COVID-19 ARDS patients had an MRI and were matched 1:1 by age and sex resulting in 23 matched pairs. The median age was 66 and 59% of patients were male. Patients with COVID-19 ARDS were more likely to have hypertension and chronic kidney disease but otherwise baseline medical characteristics were similar. ARDS severity as determined by PaO2/FiO2 ratio at ICU admission was similar between both groups. No difference was seen in the prevalence of cerebrovascular injury (52% vs 61%, p=0.8), cerebral ischemia (35% vs 43%, p=0.8), ICH (43% vs 48%, p=1.0), or CMBs (43% vs 39% p=1.0) on MRI between the COVID-19 and non-COVID-19 cohorts. However, two unique patterns of injury were seen only among COVID-19 patients: hemorrhagic leukoencephalitis (3 patients, 12%) and bilateral cerebral peduncular ischemia with microhemorrhage (2 patients, 8%).Conclusion:Cerebrovascular injury was common in both COVID-19 and non-COVID-19 ARDS without significant frequency difference. However, COVID-19 ARDS had unique neuroimaging patterns that may indicate distinct patterns of brain injury of COVID-19.

Stroke, Volume 53, Issue Suppl_1, Page ATP91-ATP91, February 1, 2022. There is limited information on long-term risk of acute medical events after acute ischemic stroke (AIS) treatment with tissue plasminogen activator (tPA) or mechanical thrombectomy (MT). We sought to determine the incidence of seven acute medical events at 1 and 5 years after AIS treatment using an administrative database. The Optum Clinformatics Data Mart database was used to construct the cohort of patients aged 30+ years with AIS diagnosis (ICD-10 I63 or ICD-9 433.x1, 434.x1, 436 or DRG 061-063) during the period: 01/01/2015-06/30/2020 with at least 1-year observation prior to cohort entry. Using procedure coding (CPT or ICD-9/10), patients were grouped as tPA only, MT only, tPA+MT, or untreated. Excluded were patients with an acute event in year preceding first AIS treatment, or first AIS diagnosis for untreated patients. Acute medical events were assessed at 1 and 5 years. The denominator was calculated as the person-years (PY) (per 100) from AIS diagnosis date or treatment, until event occurrence date or database end. The Charlson-comorbidity score (CCS) was used to measure concomitant illness severity.The 313,756-patient AIS cohort was mostly male, had a mean age of 72 years, with 8% receiving intervention. In the first year, cardiovascular event rates were highest in the tPA+MT group for recurrent AIS (10.9/100 PY), myocardial infarction (4.8/100 PY), and venous thromboembolism (4.3/100 PY). All-cause mortality (35.2/100 PY) and urinary tract infections (31.4/100 PY) were highest in the tPA+MT group. The tPA group had the highest rate for pneumonia (18.6/100 PY). The untreated group had the lowest rate for all events. All event rates decreased at 5 years, with the largest decline (-34%) in recurrent AIS.Stroke patients remain at significant risk of morbidity in the first year after stroke, in spite of treatment, but rates of acute medical events decrease over time possibly related to prevention strategies.

Stroke, Volume 53, Issue Suppl_1, Page ATP10-ATP10, February 1, 2022. Objective:There is a high prevalence of progressive cognitive impairment in intracerebral hemorrhage (ICH) survivors. We sought to identify gene expression changes, in association with long-term neurodegeneration, among patients 12-24 months post-ICH.Methods:TheRecovery and Outcomes from StrokE (ROSE)study prospectively recruits patients with spontaneous, supratentorial ICH, collecting baseline peripheral blood samples and MRI with diffusion tract imaging (DTI). TheRecovery of StrokE-Longitudinal Assessment with Neuroimaging (ROSE-LAWN)study performs long term follow-up at 12-24 months on cases enrolled in ROSE. We report on the first five cases enrolled in the ROSE-LAWN study from December 2020 to March 2021. Controls were matched to an overall ICH population by age, sex, and race. RNA-sequencing, aligned to human genome assembly GRCh38, was tested for differential gene expression. Canonical pathway enrichment and network analyses were computed for differentially expressed genes using Ingenuity Pathway Analysis, STRING and MCODE.Results:RNA-seq analysis of 5 ICH cases [male, 80%; median age, 61 (45 – 73); black, 40%; ICH volume, 14.88cc ± 13.07] and 13 controls [male, 54%; median age, 74 (69 – 79); black, 15%] identified 554 differentially expressed genes (genomic control adjusted p < 0.01), of which 24 met the false discovery rate correction for multiple comparisons (FDR < 0.05). The most significant difference was observed in hypoxia up-regulated 1 (HYOU1),a heat shock protein related gene (p = 2.64E-11). Pathway analysis identified enrichment of dopamine and serotonin receptor signaling (p = 8.74E-03, 2.23E-02), cell cycle regulation (p = 1.75E-02) and agranulocyte adhesion pathways (p = 2.18E-02). Comparison of baseline and follow-up MRI DTI demonstrated extensive cortical tract degeneration, beyond the initial injury.Conclusion:These results provide novel evidence of significant gene expression changes occurring years after the initial ICH. Despite resolution of the ICH, persistent inflammation may correlate with progressive neurodegeneration and subsequent cognitive impairment in ICH survivors. Future studies with greater sample sizes are supported by this work.

Stroke, Volume 53, Issue Suppl_1, Page ATP23-ATP23, February 1, 2022. Background:Coronavirus disease 2019 (COVID-19) is a viral disease that has primarily been known to cause respiratory symptoms; however, there has also been an association of COVID-19 with neurological symptoms, including acute ischemic stroke (AIS). There is a lack of data on the characteristics of AIS patients with COVID-19 from the stroke belt. We aim to describe the characteristics of patients with COVID-19 and AIS and compare the characteristics of those who required intensive care unit (ICU) admission versus ward-only.Methods:Single center, retrospective cohort study of adult patients admitted in a tertiary academic center from March 1-December 31, 2020. The institutional COVID database was utilized for data collection. Demographic, clinical and laboratory data were collected. Primary outcome measure was mortality. Secondary outcomes included hospital length of stay (LOS) and discharge disposition.Results:Both COVID-19 and AIS were found in 2.4% (n=75) of patients out of 3,031 patients with COVID-19, during the study period. These patients were male (45, 60%), African American (43, 57%), 65±12 years old, with hypertension (69, 92%) and Diabetes Mellitus type 2 (50, 67%). We noted a 20% (n=15) overall in-patient mortality rate among patients with both COVID-19 and AIS. Among these patients, 23% (n=17) required ICU admission. Demographic, clinical and laboratory characteristics were comparable among ICU versus ward-only patients except for higher LDH (476.12±189.70 vs 276.17±88.35 U/L, p==0.0003); and lower relative lymphocytic count (3.57±3.56 vs 8.93±7.83 103cells/μL, p=0.0160) among those admitted into the ICU. Mortality (13, 68% vs 6, 32%, p

Stroke, Ahead of Print. Background:Connectome analysis of neuroimaging data is a rapidly expanding field that offers the potential to diagnose, characterize, and predict neurological disease. Animal models provide insight into biological mechanisms that underpin disease, but connectivity approaches are currently lagging in the rodent.Methods:We present a pipeline adapted for structural and functional connectivity analysis of the mouse brain, and we tested it in a mouse model of vascular dementia.Results:We observed lacunar infarctions, microbleeds, and progressive white matter change across 6 months. For the first time, we report that default mode network activity is disrupted in the mouse model. We also identified specific functional circuitry that was vulnerable to vascular stress, including perturbations in a sensorimotor, visual resting state network that were accompanied by deficits in visual and spatial memory tasks.Conclusions:These findings advance our understanding of the mouse connectome and provide insight into how it can be altered by vascular insufficiency.

Stroke, Volume 53, Issue 2, Page e64-e64, February 1, 2022.

Comunicato del 21/01/2022 n°2