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

We read with interest the article by Luxenburger and Thimme, summarising current knowledge about hepatic sequelae in the context of SARS-CoV-2 infection.1 As acute liver injury is observed in one-third of the patients with hospitalised COVID-192 3 and chronic liver disease is associated with higher mortality rates,4 a detailed understanding of hepatic susceptibility and dysfunction in the context of SARS-CoV-2 infection is of utmost importance. Previous studies have provided evidence of hepatic infection,5–7 however, the molecular mechanisms underlying acute liver injury associated with SARS-CoV-2 infection are not well understood. Here we show that primary human hepatocytes (PHH) can be productively infected with SARS-CoV-2. Donor-specific production kinetics were observed, with de novo viral secretion from PHH increasing in a time-dependent manner for four out of six donors (figure 1A). To explore virus replication and…

This randomized clinical trial evaluates the efficacy of oral nirmatrelvir-ritonavir for treatment of moderate to severe postacute sequelae of SARS-CoV-2 infection of 3 months or longer duration.

Objectives
To assess the seroprevalence of infection-acquired SARS-CoV-2 and the mental health of school/daycare staff in the months after reopening of schools in Montreal, Quebec (Canada) in the Fall of 2020 and whether these varied by school and participant characteristics.

Design
A cross-sectional design based on a convenience sample of schools/daycares and staff was used as the originally planned longitudinal design was no longer feasible due to obstacles in recruitment, for example, teacher’s strike.

Setting
Forty-nine schools/daycares in four Montreal neighbourhoods from March to October 2021.

Participants
Three-hundred and sixty-two participants completed both questionnaires and serology tests.

Primary and secondary outcome measures
SARS-CoV-2 seroprevalence and prevalence of anxiety, depression, resilience and burnout/emotional exhaustion.

Results
The seroprevalence estimate made representative to the Quebec population of educators was 8.6% (95% CI 5.2 to 13.0). The adjusted seroprevalence in high school was 20% that of elementary school (aRR=0.20, 95% CI 0.07 to 0.58). Thirty per cent of seropositive staff were exposed to a household member with confirmed COVID-19. Prevalence of high emotional exhaustion/burnout was 35%, 44% and 53% in daycare, elementary school and high school staff, respectively. However, moderate/severe anxiety and depression and low resilience did not exceed 18%. After adjusting for confounders, being very afraid of catching COVID-19 at school was associated with moderate–severe anxiety, moderate–severe depression and high emotional exhaustion (aRR=4.4, 95% CI 2.2 to 8.9; aRR=2.8, 95% CI 1.5 to 5.4; aRR=2.2, 95% CI 1.6 to 3.0, respectively).

Conclusion
The seroprevalence, anxiety and depression among school/daycare staff were comparable to the reported levels in the adult population of Quebec. The prevalence of emotional exhaustion/burnout was high across all school levels and exceeding the average across all occupations in the USA and in teachers in Germany.

Annals of Internal Medicine, Volume 177, Issue 9, Page 1209-1221, September 2024.

Annals of Internal Medicine, Ahead of Print.

A large retrospective Scandinavian study shows no excess risk.

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).