Virological, serological and clinical outcomes in chronic hepatitis B virus infection: development and validation of the HEPA-B simulation model

Objectives
Detailed simulation models are needed to assess strategies for prevention and treatment of hepatitis B virus (HBV) infection, the world’s leading cause of liver disease. We sought to develop and validate a simulation model of chronic HBV that incorporates virological, serological and clinical outcomes.

Methods
We developed a novel Monte Carlo simulation model (the HEPA-B Model) detailing the natural history of chronic HBV. We parameterised the model with epidemiological data from the Western Pacific and sub-Saharan Africa. We simulated the evolution of HBV DNA, ‘e’ antigen (HBeAg) and surface antigen (HBsAg). We projected incidence of HBeAg loss, HBsAg loss, cirrhosis, hepatocellular carcinoma (HCC) and death over 10-year and lifetime horizons. We stratified outcomes by five HBV DNA categories at the time of HBeAg loss, ranging from HBV DNA106 copies/mL. We tested goodness of fit using intraclass coefficients (ICC).

Results
Model-projected incidence of HBeAg loss was 5.18% per year over lifetime (ICC, 0.969 (95% CI: 0.728 to 0.990)). For people in HBeAg-negative phases of infection, model-projected HBsAg loss ranged from 0.78% to 3.34% per year depending on HBV DNA level (ICC, 0.889 (95% CI: 0.542 to 0.959)). Model-projected incidence of cirrhosis was 0.29–2.09% per year (ICC, 0.965 (95% CI: 0.942 to 0.979)) and HCC incidence was 0.06–1.65% per year (ICC, 0.977 (95% CI: 0.962 to 0.986)). Over a lifetime simulation of HBV disease, mortality rates were higher for people with older age, higher HBV DNA level and liver-related complications, consistent with observational studies.

Conclusions
We simulated HBV DNA-stratified clinical outcomes with the novel HEPA-B Model and validated them to observational data. This model can be used to examine strategies of HBV prevention and management.

Leggi
Gennaio 2024

Risk factors for SARS-CoV-2 infection: a test-negative case-control study with additional population controls in Norway

Objectives
This study aims to assess risk factors for SARS-CoV-2 infection by combined design; first comparing positive cases to negative controls as determined by PCR testing and then comparing these two groups to an additional prepandemic population control group.

Design and setting
Test-negative design (TND), multicentre case–control study with additional population controls in South-Eastern Norway.

Participants
Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls and additional age-matched population controls.

Primary outcome measures
The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR-positive cases and PCR-negative controls. Using subgroup analysis, the risk factors for both PCR-positive and PCR-negative participants were compared with a population control group.

Results
In total, 400 PCR-positive cases, 719 PCR-negative controls and 14 509 population controls were included. Male sex was associated with the risk of SARS-CoV-2 infection only in the TND study (OR 1.9, 95% CI 1.4 to 2.6), but not when PCR-positive cases were compared with population controls (OR 1.2, 95% CI 0.9. to 1.5). Some factors were positively (asthma, wood heating) or negatively (hypertension) associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but lacked convincing association in the TND study. Smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.6, 95% CI 0.4 to 0.8).

Conclusions
Male sex was a possible risk factor for SARS-CoV-2 infection only in the TND study, whereas smoking was negatively associated with SARS-CoV-2 infection in both the TND study and when using population controls. Several factors were associated with SARS-CoV-2 infection when PCR-positive cases were compared with population controls, but not in the TND study, highlighting the strength of combining case–control study designs during the pandemic.

Leggi
Gennaio 2024

Inflammation-associated gut microbiome in postacute sequelae of SARS-CoV-2 points towards new therapeutic targets

We read with interest the recent report by Liu et al1 describing faecal microbiome differences with postacute sequelae of SARS-CoV-2 (PASC), commonly referred to as ‘Long-COVID’. We have previously reported elevated levels of SARS-CoV-2-specific T cells with PASC compared with resolved COVID-19 (RC; no lingering symptoms at the time of sample collection) that correlated with increased levels of the inflammatory marker IL-6, suggesting that elevated inflammation in PASC may be related to immune response to residual virus.2 Although several studies have reported gut microbiome differences during acute COVID-19,3 PASC has received less attention. We, thus, sought to characterise gut microbiome differences in PASC versus RC using faecal samples from our study2 and to relate these differences to inflammation. The faecal microbiome was evaluated using 16S rRNA gene sequencing. Plasma levels of inflammatory markers IL-6 and C reactive protein (CRP) were measured…

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Gennaio 2024

Seroprevalence of anti-SARS-CoV-2 antibodies and risk of viral exposure among healthcare workers in the South Kivu province, eastern Democratic Republic of the Congo: a cross-sectional study

Objectives
Healthcare workers (HCWs) are on the frontline of combating COVID-19, hence are at elevated risk of contracting an infection with SARS-CoV-2. The present study aims to measure the impact of SARS-CoV-2 on HCWs in central sub-Saharan Africa.

Setting
A cross-sectional serological study was conducted at six urban and five rural hospitals during the first pandemic wave in the South Kivu province, Democratic Republic of the Congo (DRC).

Participants
Serum specimens from 1029 HCWs employed during the first pandemic wave were collected between August and October 2020, and data on demographics and work-related factors were recorded during structured interviews.

Primary and secondary outcome measures
The presence of IgG antibodies against SARS-CoV-2 was examined by ELISA. Positive specimens were further tested using a micro-neutralisation assay. Factors driving SARS-CoV-2 seropositivity were assessed by multivariable analysis.

Results
Overall SARS-CoV-2 seroprevalence was high among HCWs (33.1%), and significantly higher in urban (41.5%) compared with rural (19.8%) hospitals. Having had presented with COVID-19-like symptoms before was a strong predictor of seropositivity (31.5%). Personal protective equipment (PPE, 88.1% and 11.9%) and alcohol-based hand sanitizer (71.1% and 28.9%) were more often available, and hand hygiene was more often reported after patient contact (63.0% and 37.0%) in urban compared with rural hospitals, respectively. This may suggest that higher exposure during non-work times in high incidence urban areas counteracts higher work protection levels of HCWs.

Conclusions
High SARS-CoV-2 seropositivity indicates widespread transmission of the virus in this region of DRC. Given the absence of publicly reported cases during the same time period at the rural sites, serological studies are very relevant in revealing infection dynamics especially in regions with low diagnostic capacities. This, and discrepancies in the application of PPE between urban and rural sites, should be considered in future pandemic response programmes.

Leggi
Gennaio 2024

Changing epidemiology, microbiology and mortality of bloodstream infections in patients with haematological malignancies before and during SARS-CoV-2 pandemic: a retrospective cohort study

Objective
This study was to explore the changes in bacterial bloodstream infection (BSI) in patients with haematological malignancies (HMs) before and during SARS-CoV-2 pandemic.

Design
Retrospective cohort study between 2018 and 2021.

Setting
The largest haematological centre in southern China.

Results
A total of 599 episodes of BSI occurring in 22 717 inpatients from January 2018 to December 2021 were analysed. The frequencies of the total, Gram-negative and Gram-positive BSI before and during the pandemic were 2.90% versus 2.35% (p=0.011), 2.49% versus 1.77% (p

Leggi
Dicembre 2023