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

Annals of Internal Medicine, Ahead of Print.

This Medical News story discusses JN.1, recently classified as a SARS-CoV-2 “variant of interest” by the World Health Organization.

This study uses data from 3 prospective cohort studies conducted in the US to assess vaccine effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents.

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 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.

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

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.

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
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.

This cohort study compares the mortality and hospitalization risks among patients with vs without solid cancer and diagnosed with COVID-19 during the period when the Omicron variant was dominant.

Objective
This study was to explore the changes in bacterial bloodstream infection (BSI) in patients with haematological malignancies (HMs) before and during SARS-CoV-2 pandemic.

Design
Retrospective cohort study between 2018 and 2021.

Setting
The largest haematological centre in southern China.

Results
A total of 599 episodes of BSI occurring in 22 717 inpatients from January 2018 to December 2021 were analysed. The frequencies of the total, Gram-negative and Gram-positive BSI before and during the pandemic were 2.90% versus 2.35% (p=0.011), 2.49% versus 1.77% (p

Objectives
The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant and its sublineages.

Design
Systematic review and meta-analysis.

Data sources
Electronic databases and other resources (PubMed, Embase, CENTRAL, MEDLINE, CINAHL PLUS, APA PsycINFO, Web of Science, Scopus, ScienceDirect, MedRxiv and bioRxiv) were searched until December 2022.

Study eligibility criteria
We included studies that assessed the effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the subvariant.

Data extraction and synthesis
Estimates of vaccine effectiveness (VE) at different time points after the third-dose and fourth-dose vaccination were extracted. Random-effects meta-analysis was used to compare VE of the third dose versus the primary series, no vaccination and the fourth dose at different time points. The certainty of the evidence was assessed by Grading of Recommendations, Assessments, Development and Evaluation approach.

Results
This review included 50 studies. The third-dose VE, compared with the primary series, against SARS-CoV-2 infection was 48.86% (95% CI 44.90% to 52.82%, low certainty) at ≥14 days, and gradually decreased to 38.01% (95% CI 13.90% to 62.13%, very low certainty) at ≥90 days after the third-dose vaccination. The fourth-dose VE peaked at 14–30 days (56.70% (95% CI 50.36% to 63.04%), moderate certainty), then quickly declined at 61–90 days (22% (95% CI 6.40% to 37.60%), low certainty). Compared with no vaccination, the third-dose VE was 75.84% (95% CI 40.56% to 111.12%, low certainty) against BA.1 infection, and 70.41% (95% CI 49.94% to 90.88%, low certainty) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and maintained 79.30% (95% CI 58.65% to 99.94%, moderate certainty) at 91–120 days. The fourth-dose VE up to 60 days was 67.54% (95% CI 59.76% to 75.33%, moderate certainty) for hospitalisation and 77.88% (95% CI 72.55% to 83.21%, moderate certainty) for death.

Conclusion
The boosters provided substantial protection against severe COVID-19 outcomes for at least 6 months, although the duration of protection remains uncertain, suggesting the need for a booster dose within 6 months of the third-dose or fourth-dose vaccination. However, the certainty of evidence in our VE estimates varied from very low to moderate, indicating significant heterogeneity among studies that should be considered when interpreting the findings for public health policies.

PROSPERO registration number
CRD42023376698.

Annals of Internal Medicine, Volume 176, Issue 12, December 2023.