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

New England Journal of Medicine, Ahead of Print.

Researchers have confirmed two specific variations in immune response that might lead to preventive and treatment interventions for COVID-19.

Objectives
Studies have reported high incidences of stroke in patients hospitalised with SARS-CoV-2, but the impact of disease severity is unexplored. We aimed to estimate the risk of incident ischaemic stroke in SARS-CoV-2 test-positive individuals compared with test-negative individuals stratified by disease severity during acute infection and post infection.

Design
A register-based cohort study.

Setting
A Danish nationwide study.

Participants
All Danish adults who had PCR tests for SARS-CoV-2 performed between 1 March 2020 and 30 November 2021. Test-positive individuals were included at their first positive test. For individuals tested prior to 30 November 2021, we randomly sampled an index date from the distribution of test dates among SARS-CoV-2 test-positive individuals. Test-positive individuals were followed during the acute phase of infection (days 0–14) and post infection (180 days after the acute phase). Test-negative individuals were followed in equivalent time periods.

Primary and secondary outcome measures
Incident ischaemic stroke risk in SARS-CoV-2 test-positive individuals compared with test-negative individuals during acute infection and post infection. We calculated subdistribution HRs (SHR) with death as a competing risk using propensity score weighting as confounder control. The risk was stratified according to disease severity: community managed, hospitalised, or admission to the intensive care unit.

Results
Among 3 910 219 SARS-CoV-2 PRC-tested individuals, 356 421 test-positive and 3 067 456 test-negative individuals were included. A positive SARS-CoV-2 test was associated with an SHR of 3.32 (95% CI 2.60 to 4.25) overall for stroke compared with test negative in the acute phase. In the postinfection period, the risk of stroke remained increased in individuals hospitalised during the acute phase (SHR 1.85, 95% CI 1.45 to 2.37). Individuals with community-managed SARS-CoV-2 had no increased long-term risk of stroke (SHR 1.01, 95% CI 0.88 to 1.16).

Conclusion
SARS-CoV-2 infection is associated with increased stroke risk. Disease severity seems to be an important factor. Individuals with community-managed SARS-CoV-2 had no increased stroke risk.

Annals of Internal Medicine, Ahead of Print.

The recent publication by Ng et al titled ‘Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events’ provides valuable insights on gut microbiota in modulating immune responses to both inactivated (CoronaVac) and mRNA (BNT162b2) SARS-CoV-2 vaccines. The authors identified specific gut microbiota markers influenced immunity and vaccine efficacy, suggesting that microbiota-targeted interventions could potentially enhance vaccine effectiveness in adults.1 Expanding on Ng et al’s research, our study further investigates the associations between gut microbial taxa, metabolites and immune response to inactivated vaccines. Our findings establish a connection between maternal gut microbiota/metabolites and the efficacy of mother-to-infant antibody transfer, providing a potential protective strategy for infants against COVID-19 symptoms. We conducted a prospective, observational investigation involving 97 vaccinated pregnant women in Guangdong, China, and profiled gut microbiota and metabolome using shotgun metagenomics and non-targeted metabolomics. All participants received two doses of inactivated SARS-CoV-2 vaccine, including…

Objective
In order to predict at hospital admission the prognosis of patients with serious and life-threatening COVID-19 pneumonia, we sought to understand the clinical characteristics of hospitalised patients at admission as the SARS-CoV-2 pandemic progressed, document their changing response to the virus and its variants over time, and identify factors most importantly associated with mortality after hospital admission.

Design
Observational study using a prospective hospital systemwide COVID-19 database.

Setting
15-hospital US health system.

Participants
26 872 patients admitted with COVID-19 to our Northeast Ohio and Florida hospitals from 1 March 2020 to 1 June 2022.

Main outcome measures
60-day mortality (highest risk period) after hospital admission analysed by random survival forests machine learning using demographics, medical history, and COVID-19 vaccination status, and viral variant, symptoms, and routine laboratory test results obtained at hospital admission.

Results
Hospital mortality fell from 11% in March 2020 to 3.7% in March 2022, a 66% decrease (p

Objective
We aimed to evaluate the feasibility and utility of an unsupervised testing mechanism, in which participants pick up a swab kit, self-test (unsupervised) and return the kit to an on-campus drop box, as compared with supervised self-testing at staffed locations.

Design
University SARS-CoV-2 testing cohort.

Setting
Husky Coronavirus Testing provided voluntary SARS-CoV-2 testing at a university in Seattle, USA.

Outcome measures
We computed descriptive statistics to describe the characteristics of the study sample. Adjusted logistic regression implemented via generalised estimating equations was used to estimate the odds of a self-swab being conducted through unsupervised versus supervised testing mechanisms by participant characteristics, including year of study enrolment, pre-Omicron versus post-Omicron time period, age, sex, race, ethnicity, affiliation and symptom status.

Results
From September 2021 to July 2022, we received 92 499 supervised and 26 800 unsupervised self-swabs. Among swabs received by the laboratory, the overall error rate for supervised versus unsupervised swabs was 0.3% vs 4%, although this declined to 2% for unsupervised swabs by the spring of the academic year. Results were returned for 92 407 supervised (5% positive) and 25 836 unsupervised (4%) swabs from 26 359 participants. The majority were students (79%), 61% were female and most identified as white (49%) or Asian (34%). The use of unsupervised testing increased during the Omicron wave when testing demand was high and stayed constant in spring 2022 even when testing demand fell. We estimated the odds of using unsupervised versus supervised testing to be significantly greater among those

Introduction
SARS-CoV-2 mainly infects respiratory endothelial cells, which is facilitated through its spike protein binding to heparan sulphate. Calcium dobesilate (CaD) is a well-established, widely available vasoactive and angioprotective drug interacting with heparan sulphate, with the potential to interfere with the uptake of SARS-CoV-2 by epithelial cells. The CADOVID trial aims to evaluate the efficacy and safety of CaD in reducing the SARS-CoV-2 viral load in non-hospitalised adult patients diagnosed with COVID-19, confirmed by a positive SARS-CoV-2 PCR, including its efficacy to reduce the impact of persistent COVID-19 symptoms.

Methods and analysis
This is a randomised, placebo-controlled, double-blind, monocentric phase II trial. Enrolment began in July 2022. A total of 74 adult patients will be randomly allocated to the CaD arm or the placebo group with a 1:1 ratio, respectively. Participants in the intervention arm will receive two capsules of CaD 500 mg two times per day and the placebo arm will receive two matching capsules of mannitol 312.5 mg two times per day, with a treatment period of 7 days for both arms, followed by a 77-day observational period without treatment administration. Participants will be asked to complete secured online questionnaires using their personal smartphone or other electronic device. These include a COVID-19 questionnaire (assessing symptoms, temperature measurement, reporting of concomitant medication and adverse events), a COVID-19 persistent symptoms’ questionnaire and the Short Form 12-Item (SF-12) survey. SARS-CoV-2 PCR testing will be performed on nasopharyngeal swabs collected on days 1, 4, 8 and 21. The primary endpoint is the reduction from baseline of SARS-CoV-2 viral load determined by RT-PCR at day 4.

Ethics and dissemination
This trial has received approval by the Geneva Regional Research Ethics Committee (2022-00613) and Swissmedic (701339). Dissemination of results will be through presentations at scientific conferences and publication in scientific journals.

Trial registration number
NCT05305508; Clinicaltrials.gov; Swiss National Clinical Portal Registry (SNCTP 000004938).

Objectives
In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial.

Design
This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial.

Setting
10 Swiss paediatric hospitals (secondary and tertiary care) participated.

Participants
Paediatric patients hospitalised with PIMS-TS.

Interventions
All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event.

Results
Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like).

Conclusion
The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future.

Trial registration numbers
SNCTP000004720 and NCT 04826588.