Search Results for: Identificate le origini evolutive di SARS-CoV-2

Stroke, Volume 55, Issue Suppl_1, Page ATP314-ATP314, February 1, 2024. Introduction:Although SARS-CoV-2 infection can cause a wide range of mild to severe symptoms, the pathophysiology of acute and long-term neurological manifestations remains elusive. The arginine-glycine-aspartic acid motif of the viral spike protein may use to bind integrins receptors in the CNS, which play an important role in cerebrovascular integrity. Here we investigate the role of integrin α5β1 in mediating brain endothelial damage and inflammation during SARS-CoV-2 infection.Method:Mouse brain microvascular endothelial cells (bEnd.3) were treated with SARS-CoV-2 (Isolate USA-WA1/2020) or delta variant spike protein for 24h then later exposed to hypoxia for 6h (to model the effects of in vivo pulmonary infection). Cells were pretreated with ATN-16, 1h before SARS-CoV-2 and hypoxia challenge. Further, BALB/c mice were inoculated intranasally with 2×104-PFU of the MA-10 strain of SARS-CoV-2 and treated with 1mg/kg of ATN-161, an α5β1 integrin inhibitor, retro-orbitally. The brains were collected 3 days post-infection for neuropathological evaluation.Results:SARS-CoV-2 and delta variant spike protein inoculations induced integrin α5 and decreased claudin-5 expression in bEnd.3 cells in a dose-dependent manner. SARS-CoV-2 spike protein challenge at 0.5 μg for 24h followed by hypoxia for 6h 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 bEnd.3 cells. Theinvivostudies showed a significant increase in the pro-inflammatory response as measured by cytokine IL-6 expression and a decrease in barrier integrity by tight junction claudin-5 expression in the brains of MA10-infected mice compared to mock controls. ATN-161 treatment decreased IL-6 expression and increased claudin 5 expression in infected mice.Conclusion:Therefore, we propose that targeting integrin α5β1 through inhibitors such as ATN-161 offers a promising therapeutic strategy for attenuating SARS-CoV-2 and its immunological impact on brain vasculature. This approach may be pivotal in reducing both acute and chronic neurological morbidities associated with COVID-19.

Stroke, Volume 55, Issue Suppl_1, Page A17-A17, February 1, 2024. COVID-19 doubles the risk for acute ischemic stroke in patients with cardiovascular disorders, yet, the molecular mechanisms are unclear and remain unresolved medical challenges. We hypothesize that SARS-CoV-2 spike protein exacerbates stroke and neurovascular complications via increasing coagulation and decreasing fibrinolysis by disrupting the renin-angiotensin-aldosterone system (RAAS) balance.Methods:MCA/FeCl3thromboembolic model was induced in humanized ACE2 knock-in mice. hACE2 mice were treated with Losartan, an angiotensin receptor blocker, after one day of SARS-CoV-2 spike protein injection. Cerebral blood flow was measured using a Laser speckle imager. Infarct size was compared using TTC stain. Vascular-induced cognitive function and dementia (VCID) were assessed using a Novel object recognition test. D-dimmer, Tissue factor -3 (TF-3), and Plasminogen activator inhibitor-1 (PAI-1) were measured using ELISA and Western blot to assess coagulation and fibrinolysis. Human brain microvascular endothelial cells (HBMEC) were exposed to hypoxia with/without SARS-Co-V2 spike protein and were assessed for coagulation factors, inflammation, and RAAS balance.Results:SARS-CoV-2 spike protein increased neuronal death and decreased cognitive function after MCA/FeCl3thromboembolic occlusion. hACE2 mice subjected to SARS-CoV-2 spike protein showed diminished cerebral blood flow compared to control groups. SARS-CoV-2 spike protein increased coagulation factors (increased TF-3, P

Stroke, Volume 55, Issue Suppl_1, Page A112-A112, February 1, 2024. Introduction:The Vascular effects of Infection in Pediatric Stroke (VIPS II) study aimed to confirm prior findings that viral infection can trigger childhood arterial ischemic stroke (AIS). The COVID-19 pandemic developed midway through VIPS II enrollment, creating an opportunity to assess its impact.Methods:At 22 North American sites, we enrolled 205 children (28 days-18 years) with AIS (12/2016 – 1/2022), collected serum samples up to 7 days post-stroke, and measured clinical infection via parental interview. We defined the COVID-19 pandemic epoch as 1/2020-1/2022. We collected serum samples on 40 stroke-free controls (median [IQR] age 13.2 years [6.4, 16.5]) during the pandemic. We measured SARS-CoV2 spike IgG antibodies (present after vaccination or infection) and nucleocapsid IgG total antibodies (present after infection only; elevated for months).Results:The sites saw 117 AIS cases in 2019 (51 enrolled), 122 (44) in 2020, and 109 (52) in 2021. Comparing the pre-pandemic (N=105) and pandemic (N=100) cohorts, pandemic cases were less likely to report a recent infection (Table). Evidence of SARS-CoV2 infection was seen in 4 (10%) of controls and 26 (25%) of 100 pandemic cases (p=0.065); 10 of the 26 COVID positive cases reported a recent infection, and 7 of the 10 had a clinical diagnosis of COVID. Median (IQR) nucleocapsid IgG titers were 18.8 (12.0, 101) in the positive controls and 50.1 (26.9, 95.3) in the positive cases (p=0.33).Conclusions:The COVID19 pandemicreducedthe proportion of childhood AIS cases with preceding infection, likely reflecting decreased infectious exposures while “stay at home” and masking policies were in effect. A quarter of cases in the pandemic era had positive antibodies consistent with prior SARS-CoV2 infection. Like other childhood respiratory viruses, SARS-CoV2 may act as a trigger for childhood AIS, but further investigation is needed to establish a causal role.

Stroke, Volume 55, Issue Suppl_1, Page AWP324-AWP324, February 1, 2024. COVID-19 neurological complications such as strokes and cognitive impairment have been reported. Yet the molecular mechanisms are under investigation. A mild and reproducible thromboembolic model will be a helpful tool for investigating COVID-thromboembolic complications. The aim of this study is to investigate the middle cerebral artery/ferric chloride (MCA/FeCl3) thromboembolic model as an easily and reproducible model for COVID-19-induced cerebrovascular embolic complications.Methods:SARS-CoV-2 spike-protein of the alpha variant were injected intravenously (4 ug/animal) in K18 (transgenic knock-in humanized ACE2 in epithelial cells). Seven days later, MCA/FeCl3thromboembolic model was induced in K18 mice by exposing the MCA and placing filter paper wet with FeCl3. Laser speckle imaging was used for the assessment of blood flow and recanalization after 1,2,6, and 24 hrs. TTC was used to assess the infarct volume. Cognitive function was assessed using a novel object recognition test. Cerebral vascular density and blood-brain barrier (BBB) were assessed by immunohistochemistry staining using Iso-B4 lectin and Occludin-5 antibody.Results:SARS-CoV-2 spike-protein caused a significant increase in the time required for vascular recanalization as detected by laser speckle imaging compared to control K18 mice. (P

Stroke, Volume 55, Issue Suppl_1, Page AWP326-AWP326, February 1, 2024. Introduction:The coagulation cascade in mammalian blood consists of a series of enzyme activation events in which proteins are activated in the next step of the cascade via limited proteolysis, resulting in polymerization of fibrin and the activation of platelets. The extrinsic, intrinsic, and common pathways are well-described. While typically protective, these pathways may also promote pathologic thrombosis, which is a leading cause of death and disability. An emerging concept is that COVID-induced endothelial injury initiates systemic activation of the extrinsic pathway, marked by direct protein-protein interactions with soluble fibrinogen molecules. In controlled in vitro settings, microclots can be induced using an array of substances including SARS-CoV-2 S1 spike protein. In this study, scanning electron microscopy (SEM) was used to visually demonstrate the detailed features of microclot interaction with erythrocytes at an ultrastructural level.Methods:SEM was performed on citrated whole blood of healthy individuals and patients with Long COVID. Whole blood smears from healthy controls and patients with Long COVID were placed on a glass coverslip, fixed in 4% formaldehyde, dehydrated in serial alcohol steps, coated with carbon and viewed with a scanning electron microscope (Carl Zeiss, Germany).Results:Proteolytic resistant fibrin microclots, spanning a size range of submicron to 200 μm, have a profound effect on the structure and function of erythrocytes (Figure 1).Conclusion:Long COVID microclots are characterized by an anomalous form of fibrin that is resistant to proteolysis (fibrinolysis). In addition to the possibility of microvascular ischemia, persistent microclots alter erythrocyte structure and may also entrap other proteins and stimulate production of various autoantibodies. Further study on the mechanism for microclot formation in Long COVID may lead to desperately needed novel treatment strategies.

Stroke, Volume 55, Issue Suppl_1, Page ATP203-ATP203, February 1, 2024. Introduction:The outcomes of endovascular thrombectomy (EVT) in SARS-CoV2 positive patients with acute ischemic stroke (AIS) are not well studied. In the large Florida Stroke Registry we compared in hospital and discharge outcomes of patients with target vessel occlusions treated endovascularly with versus without a SARS-CoV2 positive infection status during their hospitalization.Methods:Data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from March 2020 to December 2022 were reviewed. EVT patients with coding for SARS-CoV2 testing during their hospital stay were categorized into SARS-CoV2 positive or negative groups. Associations between SARS-CoV2 status and favorable EVT outcomes of good mRS (0-2) at discharge, discharge to home or to rehabilitation centre, and independent ambulation at discharge were examined using multivariate logistic regression modeling adjusting for demographics, vascular risk factors, and clinical characteristics with generalized estimating equations (GEE). Temporal analyses compared outcomes across the years 2020-2022.Results:A total of 8,778 patients underwent EVT, of these, 193 (2.25%) were SARS-CoV2 positive. The odds of mRS 0-2 and independent ambulation at discharge were OR 0.194 (CI 0.035,1.077) and OR 0.794 (CI 0.168,3.75) in SARS-CoV2 positive relative to negative EVT patients. Outcomes of mRS 0-2 (OR 0.194, CI 0.035,1.077) and ambulation at discharge (OR 0.794, CI 0.168,3.75) were shy of statistical significance. Accounting for baseline differences SARS-CoV2 positive patients were less likely to be discharged home or to a rehabilitation centre (OR 0.671, CI 0.488,0.921) in multivariable analysis with GEE. Temporal analysis of SARS-CoV2 positive patients showed no significant differences across the years studied.Conclusions:In this large muliticentre stroke registry the results suggest that favorable outcomes post thrombectomy may be negatively impacted by SARS-CoV2 infection. Temporal assessment showed similar results across the years studied. These findings provide novel insight from a large database to add to the emerging literature examining outcomes of concurrent SARS-CoV2 infection in the setting of EVT for target vessel occlusion AIS.

Objectives
Understanding disease seasonality can help predict the occurrence of outbreaks and inform public health planning. Respiratory diseases typically follow seasonal patterns; however, knowledge regarding the seasonality of COVID-19 and its impact on the seasonality of influenza remains limited. The objective of this study was to provide more evidence to understand the circulation of SARS-CoV-2, the virus responsible for COVID-19, in an endemic scenario to guide potential preventive strategies.

Design
In this study, a descriptive analysis was undertaken to describe seasonality trends and/or overlap between COVID-19 and influenza in 12 low-income and middle-income countries using Our World in Data and FluMart data sources. Plots of COVID-19 and influenza cases were analysed.

Setting
Singapore, Thailand, Malaysia, the Philippines, Argentina, Brazil, Mexico, South Africa, Morocco, Bahrain, Qatar and Saudi Arabia.

Outcome measures
COVID-19 cases and influenza cases.

Results
No seasonal patterns of SARS-CoV-2 or SARS-CoV-2/influenza cocirculation were observed in most countries, even when considering the avian influenza pandemic period.

Conclusions
These results can inform public health strategies. The lack of observed seasonal behaviour highlights the importance of maintaining year-round vaccination rather than implementing seasonal campaigns. Further research investigating the influence of climate conditions, social behaviour and year-round preventive measures could be fundamental for shaping appropriate policies related to COVID-19 and respiratory viral disease control in low-income and middle-income countries as COVID-19 variant data and epidemiologic patterns accrue over time.

SARS-CoV-2 vaccine response may be reduced in seniors (age 65+) with inflammatory bowel disease (IBD) and those on anti-TNF therapy. A challenge of the COVID-19 era has been conveying rapid-evolving health information, especially for groups with higher risk of poor outcomes of COVID-19 such as seniors and immunocompromised individuals.

Post-COVID-19 conditions (PCC) is an umbrella term that encompasses a range of signs, symptoms and conditions present weeks after the acute phase of a SARS-CoV-2 infection. This systematic literature review summarises the heterogeneous methodology used to measure PCC across real-world studies and highlights trends by region, age group, PCC follow-up period and data source.
Methods
Medline, EMBASE and the Cochrane Library were searched and supplemented with conference and grey literature searches. Eligible studies included individuals with (1) PCC or (2) a positive SARS-CoV-2 test or COVID-19 diagnosis who were followed over time. Included studies were published in English between 1 January 2020 and 14 November 2022.

Findings
Of 291 publications included, 175 (60%) followed individuals with confirmed COVID-19 over time for PCC and 116 (40%) used a prespecified PCC definition. There was substantial heterogeneity in study design, geography, age group, PCC conditions/symptoms assessed and their classification and duration of follow-up. Among studies using a prespecified PCC definition, author-defined criteria (51%) were more common than criteria recommended by major public health organisations (19%). Measurement periods for PCC outcomes from date of acute COVID-19 test were primarily 3 to

This Medical News article discusses 2 new observational studies that examined associations with SARS-CoV-2 antiviral medications and long COVID.

Collecting both nasal and throat specimens from people with COVID-19 symptoms resulted in more sensitive rapid antigen testing than when collecting only a nasal specimen, according to findings involving about 2900 participants aged 16 years or older in Denmark.

Objectives
In the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients’ referral to acute care and prevent overcrowding of medical centres. We sought to evaluate the impact of such a programme, the COVID-19 Home Care Team (CHCT) programme.

Design
Retrospective cohort.

Setting
Kaiser Permanente Northern California.

Participants
Adult members before COVID-19 vaccine availability (1 February 2020–31 January 2021) with positive SARS-CoV-2 tests.

Intervention
Virtual programme to track and treat patients with ‘CHCT programme’.

Outcomes
The outcomes were (1) COVID-19-related emergency department visit, (2) COVID-19-related hospitalisation and (3) inpatient mortality or 30-day hospice referral.

Measures
We estimated the average effect comparing patients who were and were not treated by CHCT. We estimated propensity scores using an ensemble super learner (random forest, XGBoost, generalised additive model and multivariate adaptive regression splines) and augmented inverse probability weighting.

Results
There were 98 585 patients with COVID-19. The majority were followed by CHCT (n=80 067, 81.2%). Patients followed by CHCT were older (mean age 43.9 vs 41.6 years, p

Objectives
This study aims to assess risk factors for SARS-CoV-2 infection by combined design; first comparing positive cases to negative controls as determined by PCR testing and then comparing these two groups to an additional prepandemic population control group.

Design and setting
Test-negative design (TND), multicentre case–control study with additional population controls in South-Eastern Norway.

Participants
Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls and additional age-matched population controls.

Primary outcome measures
The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR-positive cases and PCR-negative controls. Using subgroup analysis, the risk factors for both PCR-positive and PCR-negative participants were compared with a population control group.

Results
In total, 400 PCR-positive cases, 719 PCR-negative controls and 14 509 population controls were included. Male sex was associated with the risk of SARS-CoV-2 infection only in the TND study (OR 1.9, 95% CI 1.4 to 2.6), but not when PCR-positive cases were compared with population controls (OR 1.2, 95% CI 0.9. to 1.5). Some factors were positively (asthma, wood heating) or negatively (hypertension) associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but lacked convincing association in the TND study. Smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.6, 95% CI 0.4 to 0.8).

Conclusions
Male sex was a possible risk factor for SARS-CoV-2 infection only in the TND study, whereas smoking was negatively associated with SARS-CoV-2 infection in both the TND study and when using population controls. Several factors were associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but not in the TND study, highlighting the strength of combining case–control study designs during the pandemic.

We read with interest the recent report by Liu et al1 describing faecal microbiome differences with postacute sequelae of SARS-CoV-2 (PASC), commonly referred to as ‘Long-COVID’. We have previously reported elevated levels of SARS-CoV-2-specific T cells with PASC compared with resolved COVID-19 (RC; no lingering symptoms at the time of sample collection) that correlated with increased levels of the inflammatory marker IL-6, suggesting that elevated inflammation in PASC may be related to immune response to residual virus.2 Although several studies have reported gut microbiome differences during acute COVID-19,3 PASC has received less attention. We, thus, sought to characterise gut microbiome differences in PASC versus RC using faecal samples from our study2 and to relate these differences to inflammation. The faecal microbiome was evaluated using 16S rRNA gene sequencing. Plasma levels of inflammatory markers IL-6 and C reactive protein (CRP) were measured…

Objectives
Healthcare workers (HCWs) are on the frontline of combating COVID-19, hence are at elevated risk of contracting an infection with SARS-CoV-2. The present study aims to measure the impact of SARS-CoV-2 on HCWs in central sub-Saharan Africa.

Setting
A cross-sectional serological study was conducted at six urban and five rural hospitals during the first pandemic wave in the South Kivu province, Democratic Republic of the Congo (DRC).

Participants
Serum specimens from 1029 HCWs employed during the first pandemic wave were collected between August and October 2020, and data on demographics and work-related factors were recorded during structured interviews.

Primary and secondary outcome measures
The presence of IgG antibodies against SARS-CoV-2 was examined by ELISA. Positive specimens were further tested using a micro-neutralisation assay. Factors driving SARS-CoV-2 seropositivity were assessed by multivariable analysis.

Results
Overall SARS-CoV-2 seroprevalence was high among HCWs (33.1%), and significantly higher in urban (41.5%) compared with rural (19.8%) hospitals. Having had presented with COVID-19-like symptoms before was a strong predictor of seropositivity (31.5%). Personal protective equipment (PPE, 88.1% and 11.9%) and alcohol-based hand sanitizer (71.1% and 28.9%) were more often available, and hand hygiene was more often reported after patient contact (63.0% and 37.0%) in urban compared with rural hospitals, respectively. This may suggest that higher exposure during non-work times in high incidence urban areas counteracts higher work protection levels of HCWs.

Conclusions
High SARS-CoV-2 seropositivity indicates widespread transmission of the virus in this region of DRC. Given the absence of publicly reported cases during the same time period at the rural sites, serological studies are very relevant in revealing infection dynamics especially in regions with low diagnostic capacities. This, and discrepancies in the application of PPE between urban and rural sites, should be considered in future pandemic response programmes.