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

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

Objectives
The study aim was to evaluate vaccine effectiveness (VE) of COVID-19 vaccines in preventing symptomatic COVID-19 among healthcare workers (HCWs) in Zambia. We sought to answer the question, ‘What is the vaccine effectiveness of a complete schedule of the SARS-CoV-2 vaccine in preventing symptomatic COVID-19 among HCWs in Zambia?’

Design/setting
We conducted a test-negative case–control study among HCWs across different levels of health facilities in Zambia offering point of care testing for COVID-19 from May 2021 to March 2022.

Participants
1767 participants entered the study and completed it. Cases were HCWs with laboratory-confirmed SARS-CoV-2 and controls were HCWs who tested SARS-CoV-2 negative. Consented HCWs with documented history of vaccination for COVID-19 (vaccinated HCWs only) were included in the study. HCWs with unknown test results and unknown vaccination status, were excluded.

Primary and secondary outcome measures
The primary outcome was VE among symptomatic HCWs. Secondary outcomes were VE by: SARS-CoV-2 variant strains based on the predominant variant circulating in Zambia (Delta during May 2021 to November 2021 and Omicron during December 2021 to March 2022), duration since vaccination and vaccine product.

Results
We recruited 1145 symptomatic HCWs. The median age was 30 years (IQR: 26–38) and 789 (68.9%) were women. Two hundred and eighty-two (24.6%) were fully vaccinated. The median time to full vaccination was 102 days (IQR: 56–144). VE against symptomatic SARS-CoV-2 infection was 72.7% (95% CI: 61.9% to 80.7%) for fully vaccinated participants. VE was 79.4% (95% CI: 58.2% to 90.7%) during the Delta period and 37.5% (95% CI: –7.0% to 63.3%) during the Omicron period.

Conclusions
COVID-19 vaccines were effective in reducing symptomatic SARS-CoV-2 among Zambian HCWs when the Delta variant was circulating but not when Omicron was circulating. This could be related to immune evasive characteristics and/or waning immunity. These findings support accelerating COVID-19 booster dosing with bivalent vaccines as part of the vaccination programme to reduce COVID-19 in Zambia.

Purpose
The RESPIRA cohort aims to describe the nature, magnitude, time course and efficacy of the immune response to SARS-CoV-2 infection and vaccination, population prevalence, and household transmission of COVID-19.

Participants
From November 2020, we selected age-stratified random samples of COVID-19 cases from Costa Rica confirmed by PCR. For each case, two population-based controls, matched on age, sex and census tract were recruited, supplemented with hospitalised cases and household contacts. Participants were interviewed and blood and saliva collected for antibodies and PCR tests. Participants will be followed for 2 years to assess antibody response and infection incidence.

Findings to date
Recruitment included 3860 individuals: 1150 COVID-19 cases, 1999 population controls and 719 household contacts from 304 index cases. The age and regional distribution of cases was as planned, including four age strata, 30% rural and 70% urban. The control cohort had similar sex, age and regional distribution as the cases according to the study design. Among the 1999 controls recruited, 6.8% reported at enrolment having had COVID-19 and an additional 12.5% had antibodies against SARS-CoV-2. Compliance with visits and specimens has been close to 70% during the first 18 months of follow-up. During the study, national vaccination was implemented and nearly 90% of our cohort participants were vaccinated during follow-up.

Future plans
RESPIRA will enable multiple analyses, including population prevalence of infection, clinical, behavioural, immunological and genetic risk factors for SARS-CoV-2 acquisition and severity, and determinants of household transmission. We are conducting retrospective and prospective assessment of antibody levels, their determinants and their protective efficacy after infection and vaccination, the impact of long-COVID and a series of ancillary studies. Follow-up continues with bimonthly saliva collection for PCR testing and biannual blood collection for immune response analyses. Follow-up will be completed in early 2024.

Trial registration number
NCT04537338.

The first study to investigate potential associations between gut microbiota composition and SARS-CoV-2 vaccine immunogenicity was recently published in Gut.1 This study demonstrated a statistically significant reduction in alpha diversity and a shift in gut microbiota composition following BNT162b2 vaccination, characterised by reductions in Actinobacteriota, Blautia, Dorea, Adlercreutzia, Asacchaobacter, Coprococcus, Streptococcus, Collinsella and Ruminococcus spp and an increase in Bacteroides cacaae and Alistipes shahii. Our prospective observational study (n=52; figure 1A, ) similarly showed a shift in gut microbiota after the first BNT162b2 vaccine dose (p=0.016; ), including a reduction in Actinobacteria, Blautia spp (p

SARS-CoV-2 binds to ACE2 receptors and enters cells. The symptoms are cough, breathlessness, loss of taste/smell and X-ray evidence of infiltrates on chest imaging initially caused by oedema, and subsequently by a lymphocytic pneumonitis. Coagulopathy, thrombosis and hypotension occur. Worse disease occurs with age, obesity, ischaemic heart disease, hypertension and diabetes.
These features may be due to abnormal activation of the contact system. This triggers coagulation and the kallikrein-kinin system, leading to accumulation of bradykinin and its derivatives, which act on receptors B1R and B2R. Receptor activation causes cough, hypotension, oedema and release of the cytokine interleukin-6 (IL-6) which recruits lymphocytes. These effects are core features seen in early SARS CoV-2 infection.
Methods and analysis
In this study, hypoxic patients with COVID-19 with symptom onset ≤7 days will be randomised to either a bradykinin inhibitor (icatibant) or placebo. Patients and investigators will be blinded. The primary outcome will be blood oxygenation, measured by arterial blood sampling. The secondary outcome will be cardiovascular status. Retinal imaging will be performed to assess vessel size. Blood samples will be taken for measurement of inflammatory analyses including IL-6. As a separate substudy, we will also take comparator blood inflammatory samples from a COVID-19-negative cohort.

Ethics and dissemination
The study has received the following approvals: West Midlands–Edgbaston Research Ethics Committee. Medicines and Healthcare products Regulatory Agency has issued a clinical trial authorisation. Belfast Health and Social Care Trust is the study sponsor. Results will be made available to participants upon request and findings will be presented and published.

Trial registration number
NCT05407597

Objectives
The coronavirus is continuously mutating and creating new SARS-CoV-2 variants. Public awareness about SARS-CoV-2 mutation is essential for effective preventive measures. The present study aimed to assess the knowledge, attitude and practices (KAP) towards SARS-CoV-2 variants among the general population in Bangladesh.

Design
We conducted this online survey between 9 April 2021 and 10 May 2021 using structured questionnaires to collect the information.

Setting
We distributed the survey link among the participants from all 64 districts of Bangladesh using social media platforms.

Participants
A total of 1,090 respondents completed this survey. After careful evaluation, we excluded 18 responses due to partial or incomplete information, and 1,072 responses entered into the final analysis.

Primary outcome
The KAP of participants towards SARS-CoV-2 variants depends on their demographic backgrounds. Associations between demographic characteristics and the likelihood of having adequate KAP were estimated using adjusted logistic regressions.

Results
Among the participants, 42% had a poor knowledge level, 4% had a low attitude level and 14% had a poor practice score. The average knowledge, attitude and practice score were 2.65, 4.194 and 4.464 on a scale of 5, respectively. Only 51.8% of the participants knew about mutant strains, and only 47.6% knew about the effectiveness of vaccines against new variants. The key factors associated with poor knowledge levels were educational levels, area of residence, geographic location, and concern regarding COVID-19. Sociodemographic factors for poor attitude levels were geographic location, vaccination and concern regarding COVID-19. The pivotal factors in determining poor practice scores were the residence area of people and concern regarding COVID-19.

Conclusions
The knowledge level and positive attitude are associated with better preventive measures against SARS-CoV-2 variants. Based on these findings, we recommended several awareness programmes on SARS-CoV-2 mutations and variants for the rural population in Bangladesh to increase overall awareness levels.

New England Journal of Medicine, Volume 389, Issue 22, Page 2105-2107, November 2023.

To the Editor A recent Research Letter examined COVID-19 treatment rates in US nursing homes from May 31, 2021, through December 25, 2022, and found that only 1 in 4 nursing home residents with COVID-19 had been treated with antiviral treatments and that more than 40% of nursing homes reported never administering any oral antiviral or monoclonal antibody treatment in the 19-month study window. As a practicing nursing home attending physician and medical director, I wish to elaborate on some of the barriers to treatment in nursing homes to highlight policy changes that could improve treatment rates in future pandemics.

In Reply Dr Bergman highlights a number of important potential barriers to COVID-19 antiviral treatment use in nursing homes, including rapidly evolving guidelines concerning the use of monoclonal antibodies, insufficient supply of recommended monoclonal antibodies, and high staffing needs to administer monoclonal antibodies intravenously. These factors likely contributed to the low antiviral treatment rates observed in our study, when monoclonal antibodies were the only treatment available.

Objectives
Determine the prevaccination healthcare impact of COVID-19 in patients with systemic lupus erythematosus (SLE) in England.

Design
Retrospective cohort study of adult patients with SLE from 1 May to 31 October 2020.

Setting
Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics (HES) databases from general practitioners across England combining primary care and other health-related data.

Participants
Overall, 6145 adults with confirmed SLE diagnosis ≥1 year prior to 1 May 2020 were included. Most patients were women (91.0%), white (67.1%), and diagnosed with SLE at age

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Objectives
Systematic review of SARS-CoV-2 seroprevalence studies undertaken in the WHO European Region to measure pre-existing and cumulative seropositivity prior to the roll out of vaccination programmes.

Design
A systematic review of the literature.

Data sources
We searched MEDLINE, EMBASE and the preprint servers MedRxiv and BioRxiv in the WHO ‘COVID-19 Global literature on coronavirus disease’ database using a predefined search strategy. Articles were supplemented with unpublished WHO-supported Unity-aligned seroprevalence studies and other studies reported directly to WHO Regional Office for Europe and European Centre for Disease Prevention and Control.

Eligibility criteria
Studies published before the widespread implementation of COVID-19 vaccination programmes in January 2021 among the general population and blood donors, at national and regional levels.

Data extraction and synthesis
At least two independent researchers extracted the eligible studies; a third researcher resolved any disagreements. Study risk of bias was assessed using a quality scoring system based on sample size, sampling and testing methodologies.

Results
In total, 111 studies from 26 countries published or conducted between 1 January 2020 and 31 December 2020 across the WHO European Region were included. A significant heterogeneity in implementation was noted across the studies, with a paucity of studies from the east of the Region. Sixty-four (58%) studies were assessed to be of medium to high risk of bias. Overall, SARS-CoV-2 seropositivity prior to widespread community circulation was very low. National seroprevalence estimates after circulation started ranged from 0% to 51.3% (median 2.2% (IQR 0.7–5.2%); n=124), while subnational estimates ranged from 0% to 52% (median 5.8% (IQR 2.3%–12%); n=101), with the highest estimates in areas following widespread local transmission.

Conclusions
The low levels of SARS-CoV-2 antibody in most populations prior to the start of vaccine programmes underlines the critical importance of targeted vaccination of priority groups at risk of severe disease, while maintaining reduced levels of transmission to minimise population morbidity and mortality.

Circulation, Volume 148, Issue Suppl_1, Page A15614-A15614, November 6, 2023. BackgroundObesity increases risk of death from SARS-CoV-2 infection. Excess ectopic fat may increase this risk through inflammation, hypercoagulability, and immune dysfunction. We hypothesized that greater pericardial (PAT) and visceral adipose tissue (VAT) would associate with higher risk of hospitalization or death from SARS-CoV-2.MethodsC4R collected SARS-CoV-2 outcomes from US-based cohort studies. These were linked to chest and abdominal CT scans obtained from Jackson Heart (2007-2010) and CARDIA (2010-2011) studies. We standardized PAT across cohorts and VAT within each cohort to account for differences in VAT measurement protocols. Our outcome was COVID-related hospitalization or death from March 2020 to February 2023 assessed via questionnaires, serosurvey, and record review. Logistic regression models were adjusted for age, sex, race/ethnicity, education, smoking status, and cohort. We adjusted for body mass index (BMI) at COVID assessment in secondary models.ResultsWe included 3002 subjects with mean (SD) age of 62 (6) years, of whom 62% were women, 41% White, 59% Black, 59% never smokers, and 13% current smokers. Sixty-one subjects (2%) had SARS-CoV-2 related hospitalization or death. Every 1-standard deviation (SD) increment in PAT volume was associated with 79% higher odds of hospitalization or death (95%CI 1.38-2.33, Fig A); the estimate was similar after adjusting for BMI (OR 1.71, 95%CI 1.27-2.31). Abdominal VAT was associated with higher odds of hospitalization or death (OR 1.47 per 1 SD, 95%CI 1.20-1.81, Fig B), even after adjustment for BMI (OR 1.35, 95%CI 1.05-1.72).ConclusionGreater pericardial or visceral adiposity measured 10-15 years prior to SARS-CoV-2 emergence, was associated with higher odds of hospitalization or death from SARS-CoV-2 independent of BMI. Lowering PAT and VAT may have collateral benefit for those who develop SARS-CoV-2 infection. Further study of the role of visceral adipose in viral infection is needed.

Circulation, Volume 148, Issue Suppl_1, Page A15709-A15709, November 6, 2023. Background:SARS-CoV-2 (COVID-19) transmits a multi-systemic disease that can lead to acute respiratory distress syndrome. Growth hormone-releasing hormone receptor (GHRH-R) and its splice variant are expressed in murine and human lung and heart. GHRH-R antagonist, MIA-602, has been shown to regulate inflammation in animal models and immune cell responses to bleomycin lung injury. Using a BSL2-compatible recombinant VSV-eGFP-SARS-CoV-2-S virus (rVSV-SARS-CoV-2-S) which mimics native SARS-CoV-2 infection in K18 hACE2tg mice, we tested our hypothesis that MIA-602 attenuates COVID-19-induced cardiopulmonary injury by reducing inflammation.Methods:Male and female K18-hACE2tg mice were infected with SARS-CoV-2/USA-WA1/2020, rVSV-SARS-CoV-2-S, or PBS and lung viral load, weight-loss and histopathology were compared (N=8). Mice infected with rVSV-SARS-CoV-2-S were subject to daily subcutaneous injections of 10 μg MIA-602 or vehicle (control) starting at 24h post-infection. Pulmonary function was measured via whole-body plethysmography on day 0, day 3, and day 5 (n=7). Five days after viral infection mice were sacrificed, and blood and tissues collected for histopathological analyses, H&E staining, RNA and protein work. Heart and lung tissues were used for RNASeq (n=3 per group). T-test or One-way ANOVA-test was used for statistical analysis.Results:SARS-CoV-2 and rVSV-SARS-CoV-2-S presented similar pathology for weight loss, infectivity (~60%) and histopathologic changes. Daily treatment with MIA-602 ameliorated weight loss, reduced lung inflammation, pneumonia and pulmonary dysfunction evidenced by rescued respiratory rate, expiratory parameters, and dysregulated airway parameters (p

Circulation, Volume 148, Issue Suppl_1, Page A12759-A12759, November 6, 2023. Introduction:Scattered studies suggest that SARS-CoV-2 spike protein (SP) promotes platelet activation, though the exact mechanism is unknown. Thymidine phosphorylase (TYMP), which facilitates platelet activation and thrombosis, is significantly increased in the plasma and lungs of COVID-19 patients, suggesting that TYMP may play a role in the COVID-19 milieu.Hypothesis:We hypothesize that TYMP enhances SP/platelet factor 4 (PF4) complex formation and inhibition of TYMP attenuates SP-induced thrombosis and/or inflammation.Methods:BEAS-2B cells were treated with SP- or its receptor binding domain (RBD)-containing COS-7 cell lysate, or control cell lysate (p3.1) and TYMP and STAT3 expression were determined by western blot. The effect of SP on thrombosis was examined in K18-hACE2 and K18-hACE2/Tymp-/-mice using the ferric chloride-induced carotid artery injury thrombosis model. SP-, TYMP-, or PF4-encoding plasmids were co-transfected into COS-7 and their protein interactions were assessed using co-IP, Blue Native-PAGE, and immunocytochemistry.Results:SP increased expression of TYMP and pY705-STAT3 in BEAS-2B. siRNA-mediated knockdown of TYMP reduced STAT3 activation. SP significantly enhanced thrombosis in the K18-hACE2 mice, which was inhibited by simultaneously treating mice with tipiracil, a selective TYMP inhibitor (Figure). K18-hACE2/Tymp-/-mice were resistant to SP-enhanced thrombosis. For the first time, we found that SP, PF4, and TYMP form a complex whose formation is dose-dependently enhanced by TYMP.Conclusions:Our studies suggest that SARS-CoV-2 SP enhances TYMP expression and is prothrombotic and proinflammatory. TYMP inhibition, either via genetic knockout or by its chemical inhibitor, attenuates SP-enhanced thrombosis. TYMP promotes the formation of a PF4/SP complex, which provides a novel insight into COVID-19-associated thrombosis. TYMP could be a novel therapeutic target for COVID-19-associated sequelae.