SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease

Luxenburger H, Thimme R. SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease. Gut 2023;72:1783-94
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Effect of booster vaccination on the adaptive immune response in LTR and AIH patients (A) Booster vaccination significantly improves the SARS-CoV- 2-specific antibody response in AIH, while the frequency of T cells remains stable. (B) Booster vaccination significantly improves the SARS-CoV-2- specific antibody response in LTR, while the frequency of T cells remains stable. (C) After two RNA vaccine doses, the CD4+T cell subset distribution is altered in LTR with lower frequencies of TFH cells, however, the frequencies increase after booster infection. AIH, autoimmune hepatitis; LTR, liver transplant recipients; TFH cells: T follicular helper cells.

Leggi
Marzo 2024

Impact and cost-effectiveness of SARS-CoV-2 self-testing strategies in schools: a multicountry modelling analysis

Objectives
To determine the most epidemiologically effective and cost-effective school-based SARS-CoV-2 antigen-detection rapid diagnostic test (Ag-RDT) self-testing strategies among teachers and students.

Design
Mathematical modelling and economic evaluation.

Setting and participants
Simulated school and community populations were parameterised to Brazil, Georgia and Zambia, with SARS-CoV-2 self-testing strategies targeted to teachers and students in primary and secondary schools under varying epidemic conditions.

Interventions
SARS-CoV-2 Ag-RDT self-testing strategies for only teachers or teachers and students—only symptomatically or symptomatically and asymptomatically at 5%, 10%, 40% or 100% of schools at varying frequencies.

Outcome measures
Outcomes were assessed in terms of total infections and symptomatic days among teachers and students, as well as total infections and deaths within the community under the intervention compared with baseline. The incremental cost-effectiveness ratios (ICERs) were calculated for infections prevented among teachers and students.

Results
With respect to both the reduction in infections and total cost, symptomatic testing of all teachers and students appears to be the most cost-effective strategy. Symptomatic testing can prevent up to 69·3%, 64·5% and 75·5% of school infections in Brazil, Georgia and Zambia, respectively, depending on the epidemic conditions, with additional reductions in community infections. ICERs for symptomatic testing range from US$2 to US$19 per additional school infection averted as compared with symptomatic testing of teachers alone.

Conclusions
Symptomatic testing of teachers and students has the potential to cost-effectively reduce a substantial number of school and community infections.

Leggi
Febbraio 2024

Viral shedding of SARS-CoV-2 in body fluids associated with sexual activity: a systematic review and meta-analysis

Objective
To identify and summarise the evidence on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection and persistence in body fluids associated with sexual activity (saliva, semen, vaginal secretion, urine and faeces/rectal secretion).

Eligibility
All studies that reported detection of SARS-CoV-2 in saliva, semen, vaginal secretion, urine and faeces/rectal swabs.

Information sources
The WHO COVID-19 database from inception to 20 April 2022.

Risk of bias assessment
The National Institutes of Health tools.

Synthesis of results
The proportion of patients with positive results for SARS-CoV-2 and the proportion of patients with a viral duration/persistence of at least 14 days in each fluid was calculated using fixed or random effects models.

Included studies
A total of 182 studies with 10 023 participants.

Results
The combined proportion of individuals with detection of SARS-CoV-2 was 82.6% (95% CI: 68.8% to 91.0%) in saliva, 1.6% (95% CI: 0.9% to 2.6%) in semen, 2.7% (95% CI: 1.8% to 4.0%) in vaginal secretion, 3.8% (95% CI: 1.9% to 7.6%) in urine and 31.8% (95% CI: 26.4% to 37.7%) in faeces/rectal swabs. The maximum viral persistence for faeces/rectal secretions was 210 days, followed by semen 121 days, saliva 112 days, urine 77 days and vaginal secretions 13 days. Culturable SARS-CoV-2 was positive for saliva and faeces.

Limitations
Scarcity of longitudinal studies with follow-up until negative results.

Interpretation
SARS-CoV-2 RNA was detected in all fluids associated with sexual activity but was rare in semen and vaginal secretions. Ongoing droplet precautions and awareness of the potential risk of contact with faecal matter/rectal mucosa are needed.

PROSPERO registration number
CRD42020204741.

Leggi
Febbraio 2024

Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study

Objective
Patients receiving immunosuppressives have been excluded from trials for SARS-CoV-2 vaccine efficacy. Investigation of immunosuppressants’ impact on effectiveness of vaccines, particularly in patients with immune-mediated inflammatory diseases (IMID), is therefore required.

Design
We performed a nationwide cohort study to assess the risk of COVID-19 infection in vaccinated patients with IMID exposed to immunosuppressives compared with IMID unexposed to immunosuppressives. Exposure to immunosuppressives in the 120 days before receiving the second SARS-CoV-2 mRNA vaccination was assessed. Patients were followed from date of second vaccination and weighted Cox models were used to estimate the risk of infection associated with immunosuppressives. Secondary outcomes included hospitalisation and death associated with a positive SARS-CoV-2 test. Risk of infection by immunosuppressant drug class was also analysed.

Setting
This study used population-representative data from Danish national health registries in the period from 1 January to 30 November 2021.

Results
Overall, 152 440 patients were followed over 19 341 person years. Immunosuppressants were associated with a significantly increased risk of infection across IMID (HR: 1.4, 95% CI 1.2 to 1.5), in inflammatory bowel disease (IBD) (HR: 1.6, 95% CI 1.4 to 1.9) and arthropathy (HR: 1.3, 95% CI 1.1 to 1.4) but not psoriasis (HR: 1.1, 95% CI 0.9 to 1.4). Immunosuppressants were also associated with an increased risk of hospitalisation across IMID (HR: 1.4, 95% CI 1.1 to 2.0), particularly in IBD (HR: 2.1, 95% CI 1.0 to 4.1). No significantly increased risk of death in immunosuppressant exposed patients was identified. Analyses by immunosuppressant drug class showed increased COVID-19 infection and hospitalisation with anti-tumour necrosis factor (TNF), systemic corticosteroid, and rituximab and other immunosuppressants in vaccinated patients with IMID.

Conclusion
Immunosuppressive therapies reduced effectiveness of mRNA SARS-CoV-2 vaccination against infection and hospitalisation in patients with IMID. Anti-TNF, systemic corticosteroids, and rituximab and other immunosuppressants were particularly associated with these risks.

Leggi
Febbraio 2024

Prevalence of hepatitis B virus infection among general population of Armenia in 2021 and factors associated with it: a cross-sectional study

Objectives
This study sought to determine the prevalence and associated factors of hepatitis B virus (HBV) infection ever in life and chronic HBV infection in Armenia.

Design
A population-based cross-sectional seroprevalence study combined with a phone survey of tested individuals.

Setting
All administrative units of Armenia including 10 provinces and capital city Yerevan.

Participants
The study frame was the general adult population of Armenia aged ≥18 years.

Primary and secondary outcome measures
The participants were tested for anti-HBV core antibodies (anti-HBc) and HBV surface antigen (HBsAg) using third-generation enzyme immunoassays. In case of HBsAg positivity, HBV DNA and hepatitis D virus (HDV) RNA PCR tests were performed. Risk factors of HBV infection ever in life (anti-HBc positivity) and chronic HBV infection (HBsAg positivity) were identified through fitting logistic regression models.

Results
The seroprevalence study included 3838 individuals 18 years and older. Of them, 90.7% (3476 individuals) responded to the phone survey. The prevalence of anti-HBc positivity was 14.1% (95% CI 13.1% to 15.2%) and HBsAg positivity 0.8% (95% CI 0.5% to 1.1%). The viral load was over 10 000 IU/mL for 7.9% of HBsAg-positive individuals. None of the participants was positive for HDV. Risk factors for HBsAg positivity included less than secondary education (aOR=6.44; 95% CI 2.2 to 19.1), current smoking (aOR=2.56; 95% CI 1.2 to 5.6), and chronic liver disease (aOR=8.44; 95% CI 3.0 to 23.7). In addition to these, risk factors for anti-HBc positivity included age (aOR=1.04; 95% CI 1.04 to 1.05), imprisonment ever in life (aOR=2.53; 95% CI 1.41 to 4.56), and poor knowledge on infectious diseases (aOR=1.32; 95% CI 1.05 to 1.67), while living in Yerevan (vs provinces) was protective (aOR=0.74; 95% CI 0.59 to 0.93).

Conclusion
This study provided robust estimates of HBV markers among general population of Armenia. Its findings delineated the need to revise HBV testing and treatment strategies considering higher risk population groups, and improve population knowledge on HBV prevention.

Leggi
Febbraio 2024

Seroprevalence of Japanese encephalitis virus-specific antibodies in Australia following novel epidemic spread: protocol for a national cross-sectional study

Introduction
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on the Australian mainland for the first time. This study will determine the prevalence of JEV-specific antibodies in human blood with a focus on populations at high risk of JEV exposure and determine risk factors associated with JEV seropositivity by location, age, occupation and other factors.

Method
Samples are collected using two approaches: from routine blood donors (4153 samples), and active collections targeting high-risk populations (convenience sampling). Consent-based sampling for the latter includes a participant questionnaire on demographic, vaccination and exposure data. Samples are tested for JEV-specific total antibody using a defined epitope-blocking ELISA, and total antibody to Australian endemic flaviviruses Murray Valley encephalitis and Kunjin viruses.

Analysis
Two analytic approaches will occur: descriptive estimates of seroprevalence and multivariable logistic regression using Bayesian hierarchical models. Descriptive analyses will include unadjusted analysis of raw data with exclusions for JEV-endemic country of birth, travel to JEV-endemic countries, prior JEV-vaccination, and sex-standardised and age-standardised analyses. Multivariable logistic regression will determine which risk factors are associated with JEV seropositivity likely due to recent transmission within Australia and the relative contribution of each factor when accounting for effects within the model.

Ethics
National Mutual Acceptance ethical approval was obtained from the Sydney Children’s Hospitals Network Human Research Ethics Committee (HREC). Local approvals were sought in each jurisdiction. Ethical approval was also obtained from the Australian Red Cross Lifeblood HREC.

Dissemination
Findings will be communicated to participants and their communities, and human and animal health stakeholders and policy-makers iteratively and after final analyses. Understanding human infection rates will inform procurement and targeted allocation of limited JEV vaccine, and public health strategies and communication campaigns, to at-risk populations.

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Febbraio 2024

CDC Warns of Low Vaccination Rates Amid Spike in Respiratory Diseases

From November to December 2023, US hospitalization rates increased by 200% for influenza, 51% for COVID-19, and 60% for respiratory syncytial virus (RSV) among all age groups, according to a Centers for Disease Control and Prevention (CDC) advisory. Amid growing concern, the CDC issued the advisory about the low vaccination rates for all 3 respiratory illnesses and developed a vaccination conversation guide with talking points to help clinicians encourage uptake.

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Febbraio 2024

Abstract TP203: Effect of SARS-CoV2 Infection on Endovascular Thrombectomy Outcomes – Data From the Florida Stroke Registry

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.

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Febbraio 2024