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

To the Editor Myocarditis, pericarditis, and myopericarditis are inflammatory heart conditions recognized as adverse events linked to COVID-19 mRNA vaccines, but their population-level clinical outcomes remain underdocumented. In a recent JAMA article, Ms Semenzato and colleagues provided valuable insights by comparing different myocarditis etiologies; the exclusion of pericarditis is notable. Accurate identification of myocarditis is crucial for both diagnosis and management. Case definitions from the Centers for Disease Control and Prevention and the Brighton Collaboration offer structured criteria, especially for vaccine-related cases. In the study by Semenzato and colleagues, myocarditis occurring within 7 days of vaccination was classified as postvaccine myocarditis, while myocarditis occurring within 30 days of SARS-CoV-2 infection was labeled post–COVID-19 myocarditis. In contrast, the Brighton Collaboration’s definitions, widely used in Canada for evaluating myocarditis and pericarditis after vaccination, include graduated levels of diagnostic certainty (definite, probable, possible) and consider events occurring within 6 weeks of vaccination as likely vaccine-associated. The Centers for Disease Control and Prevention reports onset of myocarditis symptoms ranging from 0 to 40 days after vaccination. while data from the Vaccine Adverse Event Reporting System, one of the largest global systems for tracking vaccine-associated adverse events, suggest that onset of myocarditis and pericarditis can extend beyond 120 days after vaccination. The study’s 7-day window may underestimate vaccine-associated myocarditis.

Objectives
Despite widespread vaccination programmes and consensus recommendations, the understanding of the durability of COVID-19 vaccination against ensuing infection and transmission at the individual level is incomplete. The objective of this study was to estimate the effects of time-varying covariates including time since vaccination and symptoms on subsequent positive SARS-CoV-2 test results and assess the stability of these effects between March 2020 and April 2022.

Design
Prospective cohort study.

Setting
Urban university in the USA.

Participants
Drexel University students, faculty, and staff (n=15 527) undergoing mandatory COVID-19 symptom tracking, testing and vaccinations.

Intervention
Systematic symptom tracking and SARS-COV-2 testing starting in September 2020 and mandatory COVID-19 vaccination starting in September 2021.

Main outcomes and measures
COVID-19 vaccine effectiveness modified by time since vaccination and symptoms.

Results
Using fit-for-purpose digitally based symptom and vaccine tracking and mandatory comprehensive testing for SARS-CoV-2 infection, we estimate the time-dependent effects of vaccination, symptoms and covariates on the risk of infection with a Cox proportional hazards model based on calendar time scale. We found a strong protective effect of vaccination against symptomatic infection. However, there was strong evidence of a protective effect against infection only in the first 90 days after completed vaccination, and only against symptomatic versus asymptomatic infection. The overall estimated effect of vaccination within 30 days, including asymptomatic infections, was 37.3% (95% CI 26%, 47%). Vaccine effect modification by reported symptoms and time period was estimated, revealing the protective effect of vaccination within 90 days against symptomatic infection that varied from 90% (95% CI 84%, 94%) to 49%(95% CI –77%, 85%) across time periods.

Conclusions
This study is among the first to prospectively capture complete COVID-19 symptom, testing and vaccination data over a multiyear period. Overall effectiveness of the COVID-19 vaccine against subsequent infection, including transmissible asymptomatic infections, is modest and wanes after 90 days. Vaccination policies may need to take these issues into account.

Objectives
This study aimed to compare mortality rates and length of hospital stay between patients with critical COVID-19 transferred to another hospital due to capacity constraints and those who remained at their initial admission hospital.

Design
Single-centre cohort study.

Setting and participants
665 patients were treated for SARS-CoV-2 at two intensive care units (ICUs) in Stockholm, Sweden, from 1 March 2020 to 30 June 2021. Data on interhospital transfers (IHTs) were retrieved from medical records and patient data management systems according to predefined protocols.

Main outcome measures
The outcomes were 30-day and 90-day mortality, days alive and out of ICU. HR with 95% CI were calculated using Cox proportional hazard models with adjustments for age, sex, body mass index, severity of illness, comorbidity, invasive ventilation, treatment limitations and pandemic waves.

Results
Of 665 patients, 133 (20%) were transferred to another hospital. The mortality rate of transferred patients compared with non-transferred patients at 30 days was 19% vs 26% (p=0.13) and at 90 days 26% vs 30% (p=0.43). In the adjusted Cox regression analysis, IHT was associated with a lower mortality risk at 30 days (HR 0.47, 95% CI 0.30 to 0.76) and 90 days (HR 0.52, 95% CI 0.34 to 0.79). However, the number of days alive and out of ICU was significantly lower for the IHT group at 30 days.

Conclusion
In our study, IHT due to capacity constraints among critically ill COVID-19 patients was not associated with a higher mortality risk. The suitability for transfer was likely associated with lower mortality, although residual confounding cannot be ruled out. The requirement for invasive ventilation among transferred patients might account for the extended length of ICU stay, rather than the transfer itself. However, the difficulty in studying this issue lies in the fact that while patients are likely exposed to risks during transfer, they are simultaneously the patients stable enough to be transported.

Objective brain injury and associated cognitive impairment were noted as long as 1 year after infection with SARS-CoV-2.

Objectives
This study aims to characterise the diversity of post-COVID-19 physical and mental health outcomes, known as the post-COVID-19 condition (PCC), and the determining factors 3–6 months after acute SARS-CoV-2 infection.

Design
This is a prospective cohort study.

Setting
This study took place at the European Hospital of Marseille, France.

Participants
Participants include patients with acute COVID-19 treated as inpatients or outpatients.

Interventions
Interventions include face-to-face assessment of physical and mental health symptoms.

Main outcome measures
Main outcome measures include symptom scores and scales, as well as paraclinical elements (thoracic CT scan, pulmonary functional tests). Multiple component analysis was used to identify clinical phenotypic clusters of PCC patients, as well as their initial comorbidity groups. A multinomial regression model was used to evaluate the association between the initial comorbidities and disease severity with PCC phenotype.

Results
A total of 210 patients agreed to participate, of which 157 (75%) reported at least one symptom at the 3–6 months visit; mostly asthenia, dyspnoea, psychiatric disorders such as anxiety, depression, post-traumatic stress disorder and cognitive disorders. Four PCC clusters were recognised: (1) paucisymptomatic PCC (n=82, 39%); (2) physical sequelae PCC (n=39, 18.6%), (3) pre-existing pulmonary comorbidities PCC (n=29, 13.8%); and (4) functional somatic and/or mental symptoms PCC (n=60, 28.6%). In addition to their PCC symptoms, the patients in these clusters differed in terms of their demographic characteristics (sex), comorbidities and severity of COVID-19.

Conclusions
The four identified PCC clusters corresponded to distinct and coherent clinical and paraclinical entities, making it possible to consider adapted and personalised prognosis and therapeutic interventions.

Objective
The aim of this analysis was to describe the epidemiology, demographics and characteristics of children and young people (CYP) who died of SARS-CoV-2 infection in England during the first 2 years of the pandemic.

Design
The cohort investigated in this study is all CYP, born alive at, or after, 22 weeks of gestation, who died before their 18th birthday between 1 February 2020 and 31 March 2022 in England. All cases were reviewed to identify if SARS-CoV-2 probably, or possibly, contributed to death. Mortality rates were calculated, assuming a Poisson distribution, for the whole population, and split by demographics and patient characteristics.

Setting
England.

Participants
6389 CYP deaths in England reported to the National Child Mortality Database (NCMD).

Main outcome
Risk of death.

Results
88 of the 6389 deaths of CYP were identified as deaths probably due to COVID-19. Thus, COVID-19 was responsible for 1.4% of all deaths of CYP in this 26-month period. Overall mortality rate due to COVID-19 in CYP was 3.59 (2.88–4.42) per 1 000 000 person years, being highest in the youngest (< 5 years; 4.68 (3.16–6.68)) and oldest (16/17 years; 4.83 (2.57–8.26)) CYP. Asian and Black CYP had higher mortality than those from white backgrounds (p

Introduction
Postacute sequelae of SARS-CoV-2 infection (PASC) are extensive. Also known as long COVID, primary outcomes reported are neurologic, cardiac and respiratory in nature. However, several studies have also reported an increase in gastrointestinal (GI) symptoms and syndromes following COVID-19. This study of PASC will include extensive analyses of GI symptoms, determine if people with pre-existing irritable bowel syndrome (IBS) are at higher risk of developing PASC generally or PASC-GI, and which biomarkers are impacted and to what degree. This R01 study is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK135483-01) from 2023 to 2028.

Methods and analyses
This study combines a longitudinal epidemiologic cohort study and in-depth, novel biologic analyses. In collaboration with a pre-existing study, the Arizona CoVID-19 Cohort (CoVHORT)-GI will recruit participants based on the history of COVID infection(s), new or ongoing GI symptoms 3–6 months postinfection, and pre-existing or incident IBS diagnosis to represent five study groups for comparison and analyses. A subset (n=1000) of those recruited will submit both stool and blood samples. Both samples will undergo a novel method to quantitate humoral and mucosal immune responses to host-derived faecal communities in conjunction with magnetic bead-based separation and high-depth shotgun microbial sequencing. Stool samples will also undergo traditional microbiome analyses (diversity and abundance) and faecal calprotectin assays. Additional serum analyses will aim to determine if a proteomics-based signature exists that differentiates a unique biomarker compositional signature discriminating PASC-GI versus no PASC. All laboratory data will be linked with in-depth epidemiologic data on demographics, symptoms and chronic conditions.

Ethics and dissemination
This study involves human participants and was approved by the University of Arizona Institutional Review Board (IRB (#00002332) and has been deemed minimal risk. Participants gave informed consent to participate in the study before taking part. All publications from the study will be shared back to participants along with alternative lay summaries and webinars to communicate key findings. The data management plan has been published and is publicly available online, including protocols for data requests.

Stroke, Volume 56, Issue Suppl_1, Page ATMP46-ATMP46, February 1, 2025. Background:The modified Rankin Scale (mRS) is a key measure of functional outcomes in stroke trials. To minimize variability and uphold trial integrity, structured tools like the Rankin Focused Assessment (RFA) and central adjudication are recommended. This study compares local versus centrally adjudicated mRS scores in the Multi-arm Optimization of Stroke Thrombolysis (MOST) trial.Methods:MOST was a Phase 3, single-blind trial evaluating argatroban, eptifibatide, or placebo in addition to standard IV thrombolysis. The primary outcome, the 90-day mRS score, was gathered through in-person video recordings by blinded local personnel. The RFA was encouraged and recordings were sent to central adjudicators for final scoring. During the trial, in-person visits became limited due to the SARS-CoV-2 pandemic; thus, remote telephone or video interviews were allowed. We hypothesized that local mRS scores would be moderately associated with central scores, with no trial outcome differences between local and central mRS. Fleiss-Cohen’s quadratic weighted kappa statistics were used to determine the strength of agreement between local and central scores, as well as by assessment mode, RFA usage, and baseline mRS scores.Results:Out of 514 enrolled subjects, 386 subjects had recorded 90-day visits available; 57 died, 8 withdrew consent, 1 terminated early, 26 were lost to follow-up, 33 lacked recorded video/audio, and 3 recordings could not be scored. Of the 386, 122 were in-person video, 157 remote video, and 101 remote audio-only (Table 1). Local assessors were blinded 97.3% of the time and 85.4% of visits used the RFA (Table 2). Overall agreement between local and central mRS scores was very good (weighted Kappa 0.86, 95% CI: 0.82-0.90). However, strength of agreement decreases for those with a baseline mRS greater than zero, (baseline mRS=0: 0.87, 95% CI: 0.83-0.90 versus baseline mRS≠0: 0.80, 95% CI: 0.68-0.91). Agreement by mode of assessment was 0.87 (95% CI: 0.81-0.92) for in-person video, 0.87 (95% CI: 0.82-0.92) for remote video, and 0.86 (95% CI: 0.76-0.95) for remote audio. Trial outcomes were unchanged when utilizing the local mRS versus central adjudication.Conclusion:Local mRS scores demonstrated strong agreement with central scores across all assessment modes (in-person video, remote video and audio). Caution remains necessary in patients whose baseline mRS is not zero. Central mRS adjudication in acute stroke clinical trials may not be necessary.

Stroke, Volume 56, Issue Suppl_1, Page AWMP117-AWMP117, February 1, 2025. Introduction:SARS-CoV-2 causes various neurological sequelae in COVID-19 survivors including fatigue and cognitive dysfunction. Endothelial dysfunction, a key mechanism in COVID-19 illness, is also a major risk factor for vascular dementia (VaD). Clinical evidence suggests that reduced nitric oxide (NO) bioavailability is a likely pathogenic factor of endothelial dysfunction in COVID-19 patients, and eNOS levels decline with advancing age, a risk factor for both COVID-19 morbidity and VaD . We hypothesize that endothelial nitric oxide synthase (eNOS) deficiency contributes to brain endothelial dysfunction in SARS-CoV-2 infection and that SARS-CoV-2 infection accelerates the onset of VaD in eNOS-deficient mice.Methods:6-month-old eNOS+/- (pre-cognitively impaired experimental VaD) and WT male mice were infected with 1X104-pfu mouse-adapted (MA10) SARS-CoV-2 intranasally, and animals were evaluated acutely out to 3-days-postinfection (3dpi) for changes in body weight and clinical signs of illness. Viral copy numbers and nuclear capsid were also quantified in lung and brain. Quantitative PCR and immunofluorescence were used to analyze markers of brain inflammation and senescence.Results:eNOS+/- infected mice exhibited more disease-associated weight loss (~15%) than WT-infected mice (~5 %). While infected WT and eNOS+/- had comparable pulmonary viral load, neither had detectable virus in the brain. Quantitative PCR analysis of whole brain-isolated mRNA showed increases in multiple proinflammatory mediators such as CCL2 and IL-6 and senescence markers such as p53 and p21 (eNOS+/- > > WT). Similarly, immunofluorescent analysis showed increased Iba1 (microglia marker) fluorescent intensity in the cortex of infected mice (eNOS+/- > > WT).Conclusions:eNOS+/- deficiency, a clinically relevant model of VaD, worsens acute SARS-CoV-2-associated morbidity, neuroinflammation and markers of brain senescence despite comparable pulmonary viral load (to WT-infected animals) and absence of virus in the brain. While the potential effects of SARS-COV-2 on cognitive decline in this model will be assessed in future studies, this is the first experimental evidence demonstrating a link between eNOS and neuropathology associated with COVID-19.

Stroke, Volume 56, Issue Suppl_1, Page A162-A162, February 1, 2025. Background:Preceding respiratory tract infections (RTIs) caused by bacteria or viruses are associated with worse stroke outcomes, likely due to an exaggerated inflammatory immune response, endothelial dysfunction, platelet activation, and coagulopathy. Recent studies have revealed increased plasma von Willebrand factor (VWF) levels and reduced ADAMTS13 activity (the risk factors for stroke) in patients with RTIs, including COVID-19. However, it remains unclear whether an imbalance in the VWF–ADAMTS13 axis plays a causative role in the pathophysiology ofS. aureus- or COVID-19-associated stroke severity or is merely an associative marker of disease status.Objective:To examine whether an imbalance in the VWF–ADAMTS13 axis is a causal link between RTIs and stroke severity.Methods:Wild-type (WT) mice (3–4 months old) were infected intranasally with sublethal doses ofS. aureus(on days 0, 2, and 5) or mouse-adapted SARS-CoV-2 (on day 0). On day 6 (S. aureus) or day 3 (SARS-CoV-2), the infection was confirmed to be localized in the lungs (but not in the brain) and the plasma VWF levels and ADTMTS13 activity were quantified. In another set of experiments, WT,Vwf−/−, andAdamts13−/−mice (3–4 months old) with respective littermate controls were subjected to transient (30 or 45 min) cerebral ischemia (filament stroke model) followed by reperfusion. For theS. aureusexperiments, brain infarcts were assessed on day 2 post-reperfusion and functional outcomes (corner test, wire hanging test, modified neurological severity score, and rotarod test) on week 1 and 4 post-reperfusion. For the SARS-CoV-2 experiments, brain infarcts and functional outcomes (the Bederson score) were assessed on day 1 post-reperfusion.Result:We demonstrated thatS. aureusor SARS-CoV-2 infection localized to the lungs in the WT mice resulted in increased (2–3 fold) plasma VWF levels and reduced ADAMTS13 activity, concomitant with larger infarcts and worse functional outcomes (P

Stroke, Volume 56, Issue Suppl_1, Page AWP209-AWP209, February 1, 2025. Background:COVID-19, primarily a respiratory illness caused by SARS-CoV-2, is associated with vascular complications like ischemia due to endothelial injury, hypercoagulability, and inflammation. This study examines how COVID-19 affects functional outcomes of ischemic stroke patients.Methods:Ischemic stroke patients admitted to our Joint Commission-certified primary stroke center were retrospectively analyzed from March 1, 2020, to March 1, 2022. A subgroup analysis was conducted for patients during the vaccination period (April 14, 2021, to March 1, 2022). Patients were included if they were ≥18 years old and had a stroke on admission or during hospitalization. Univariate and multivariable analyses were used, with a significance threshold of p

Stroke, Volume 56, Issue Suppl_1, Page AWP400-AWP400, February 1, 2025. SARS-COV-2 causes neurological and cognitive impairments and aggravates Alzheimer’s Disease-Related Dementia (ADRD). Yet, the molecular mechanism is not fully understood. We have previously shown that SARS-CoV-2 spike protein disturbs the brain’s renin-angiotensin system (RAS) and increases cerebrovascular inflammation. We hypothesize that SARS-CoV-2 spike protein will accelerate hypoxia-induced ADRD via augmenting cerebrovascular inflammation and impairing blood-brain-barrier (BBB) functions. We propose that the pharmacological restoration of the RAS balance using Losartan, an AT1receptor blocker, will improve SARS-CoV-2 spike protein-induced ADRD.Methods:Hypoxia-induced ADRD was produced in humanized ACE2 mice, a COVID-19 mouse model, using a permanent unilateral common carotid artery ligation (UCCL). Cerebral hypoxia was confirmed by laser speckle imaging. hACE-2 mice received either vehicle, SARS-CoV-2 spike protein via jugular vein, or spike protein with Losartan (10 mg/kg) in drinking water after UCCL. ADRD was assessed via Novel Object Recognition at baseline, seven days, and fourteen days after surgery. Cerebrovascular inflammatory markers and tight junction proteins (TNF-α, Il-6, VEGF, MMP-9, and occludin) were measured in brain homogenate using RT-PCR and Western Blots.Results:Blood flow analysis confirmed cerebrovascular hypoxia in all groups. Spike protein further decreased cerebral blood flow, which was prevented with Losartan (P

Objectives
During the COVID-19 pandemic, designated rehabilitation centres were established in the province of Québec, where strict sociosanitary measures such as isolation and mandatory personal protection equipment requirements were followed. This study aimed to describe the impact of the pandemic on rehabilitation care indicators for poststroke users with (COV+) and without (COV–) COVID-19 infection in designated rehabilitation centres compared with those admitted in the previous year (pre-COV).

Method
A retrospective analysis of 292 medical files was performed in 3 rehabilitation centres. Demographic characteristics were collected, as well as indicators routinely collected in acute care and rehabilitation such as length of stay (LOS), the Functional Independence Measure and a number of physical/occupational therapy (PT/OT) sessions. Non-parametric statistical tests were used to compare variables among the three groups.

Results
COV+ users were older than COV– and pre-COV ones (p

Objectives
COVID-19, a public health emergency affecting the world in 2019, not only greatly promoted the development and application of vaccines but also effectively shortened the publishing time of scientific papers. In view of these facts, the current situation, status, problems and development trends of vaccine research and application were explored through bibliometric analysis of highly cited papers in the vaccine field within the time frame of 2014–2024, and the countries, institutions, authors, funding agencies and other relevant information that contributed most to vaccine research and application were summarised.

Design
Bibliometric analysis through data analysis and visual mapping.

Data sources
Scientific articles.

Data extraction and synthesis
‘Vaccine’ and ‘vaccines’ were used in the WoS database to retrieve the publications and to adequately collect the data; Microsoft Excel was used for data analysis; and VOSviewer was used for visual description of data. Overall publication trends, countries, institutions and funding agencies, authors and articles, journals and languages, and research areas and co-occurrence keywords were analysed by bibliometrics.

Results
A total of 3258 highly cited papers were published in the field of vaccines in the past decade, from 735 different journals. With the COVID-19 pandemic in 2019, the number of highly cited papers in the field of vaccine research increased significantly from 2020 to 2024, accounting for 76.12%. The number of highly cited papers for vaccines peaked in 2021 and 2022, followed by a rapid decline. Highly cited papers came from 7133 institutions in 153 countries, and the most influential country in the field of vaccines was the USA, which published 1733 highly cited papers, accounting for 53.19% of the highly cited papers. The top 15 institutions with the largest influence were all from the USA or UK with 2567 published papers in total, accounting for 78.79% of highly cited papers. 4787 funding agencies were recognised in funding 2368 highly cited papers. A total of 30 926 authors in 90 research areas contributed significantly to global vaccine research. The most highly cited paper was ‘Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine’ from the New England Journal of Medicine, which was cited 9435 times in total. Among the 9848 co-occurrence keywords, COVID-19 (including SARS-CoV-2, 2019-COVID and SARS2) was the most frequently co-occurrence keyword. It appeared in 1720 articles, accounting for 52.79%, indicating that COVID-19 was the most popular study in the last decade.

Conclusions
This study visualised the research and application of vaccines in the world from the perspective of papers output, drew the knowledge map and identified the important research hotspots and development trends in the vaccine field in the recent 10 years (2014–2024), which is helpful for Centres for Disease Control and Prevention, clinicians, researchers and health policymakers to better understand the research status and problems in vaccine research and application and predict its future development direction.

Introduction
Despite repeated vaccinations against SARS-CoV-2 virus, patients who are immunocompromised remain at very high risk of catching SARS-CoV-2 virus and becoming unwell. AZD7442 (Evusheld) is a long-acting monoclonal antibody treatment that has been shown in clinical trials to prevent SARS-CoV-2 infection for up to a year after a single dose. Vaccines require a healthy immune system to generate protective immunity. AZD7442 may prevent SARS-CoV-2 infection in immunocompromised individuals that may not have responded to repeated vaccinations against SARS-CoV-2 virus. Unlike vaccinations, AZD7442 reaches effective levels within the body a few hours after a single dose. The RAPID-PROTECTION trial will determine the levels of immune protection that AZD7442 offers patients at the very highest risk of SARS-CoV-2 infection and whether this protection can be further enhanced by repeated vaccination against SARS-CoV-2 virus.

Methods
RAPID-PROTECTION is a multicentre, interventional and open-label adaptive platform trial that aims to recruit 350 immunocompromised participants across five UK centres. Participants will be administered AZD7442 on day 0 followed by a SARS-CoV-2 vaccination 28 days later. Participants will be randomised (1:1) to the Moderna vaccine or Pfizer/BioNTech vaccine. Participant samples will be taken at baseline and at multiple timepoints after the administration of AZD7442.

Analysis
The participant samples will be analysed to measure the function and magnitude of SARS-CoV-2 specific antibody and T-cell responses at baseline and at multiple timepoints after the administration of AZD7442. The immunological effect of the study interventions will be determined by comparison of the results of immunological assessments at baseline and subsequent timepoints.

Ethics and dissemination
The trial protocol was approved by the research ethics committee of the National Health Service (reference 22/HRA/0359), Health Research Authority and Health and Care Research Wales on 25 July 2022. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences.

Trial registration number
ISRCTN53507177.