Evaluation of the impact of COVID-19 on hepatitis B in Henan Province and its epidemic trend based on Bayesian structured time series model (preprint)

Background There may be evidence that COVID-19 affects illness patterns. This study aimed to estimate epidemiological trends in China and to assess the effects of COVID-19 epidemic on the declines in hepatitis B (HB) case notifications.Methods The Bayesian structured time series (BSTS) method was used to investigate the causal effect of COVID-19 on the decline in HB cases based on the monthly incidence of HB from January 2013 to September 2022. To assess how well the BSTS algorithm performs predictions, we split the observations into various training and testing ranges.Results The incidence of HB in Henan was generally declining with periodicity and seasonality. The seasonal index in September and February was the smallest (0.91 and 0.93), and that in March was the largest (1.19). Due to the COVID-19 pandemic, the monthly average number of notifications of HB cases decreased by 38% (95% credible intervals [CI]: -44% ~ -31%) from January to March 2020, by 24% (95% CI: -29% ~ -17%) from January to June 2020, by 15% (95% CI: -19% ~ -9.2%) from January to December 2020, by 11% (95% CI: -15% ~ -6.7%) from January 2020 to June 2021, and by 11% (95% CI: -15% ~ -7.3%) from January 2020 to December 2021. From January 2020 to September 2022, it decreased by 12% (95% CI: -16% ~ -8.1%). From 2021 to 2022, the impact of COVID-19 on HB was attenuated. In both training and test sets, the average absolute percentage error (10.03%) generated by the BSTS model was smaller than that generated by the ARIMA model (14.4%). It was also found that the average absolute error, root mean square error, and root mean square percentage error generated by the BSTS model were smaller than ones generated by the ARIMA model. The trend of HB cases in Henan from October 2022 to December 2023 predicted by the BSTS model remained stable, with a total number of 81,650 cases (95% CI: 47,372 ~ 115,391).Conclusions After COVID-19 intervention, the incidence of HB in Henan decreased and exhibited clear seasonal and cyclical trends. The BSTS model outperformed the ARIMA model in predicting the HB incidence trend in Henan. This information may serve as a reference and provide technical assistance for developing strategies and actions to prevent and control HB. Take additional measures to accelerate the progress of eliminating HB.

Inhalable SARS-CoV-2 vaccines for single-dose dry-powder aerosol immunization and orchestrated mucosal/systemic immune responses (preprint)

The ongoing coronavirus disease pandemic has fostered major advances in vaccination technologies; however, there are urgent needs of mucosal immune responses and single-dose, non-invasive administration. Here, we develop a SARS-CoV-2 vaccine for single-dose, dry-powder aerosol inhalation that induces potent systemic and mucosal immune responses. Our vaccine encapsulates proteinaceous cholera toxin B subunit-assembled nanoparticles displaying the SARS-CoV-2 RBD antigen (R-CNP) within microcapsules of optimal aerodynamic size, and such unique nano-micro coupled structure supports efficient alveoli delivery, sustained R-CNP release, and antigen presenting cell uptake, which are favorable for invocation of immune responses. Moreover, our vaccine successfully induces robust serological IgG and secretory IgA production, collectively conferring effective protection from SARS-CoV-2 challenge (including pseudovirus and the authentic virus) in mice, hamsters, and non-human primates. Finally, we also demonstrate a “mosaic iteration” of our vaccine that co-displays ancestral and Omicron’s antigens, thus extending the breadth of antibody response against co-circulating strains and transmission of Omicron variant. These findings support our inhalable vaccine as a promising candidate to prevent SARS-CoV-2 infection, disease, and transmission.

Acceptance of coronavirus disease 2019 (COVID-19) vaccines among healthcare workers: A meta-analysis

Background The coronavirus disease 2019 (COVID-19) pandemic has posed increasing challenges to global health systems. Vaccination against COVID-19 can effectively prevent the public, particularly healthcare workers (HCWs), from being infected by this disease. Objectives We aim to understand the factors influencing HCWs' acceptance of COVID-19 vaccines. Methods We searched PubMed, Embase and Web of Science to collect literature published before May 15, 2022, about HCWs' acceptance of COVID-19 vaccines. The Newcastle–Ottawa quality assessment scale was used to assess the risk of bias and the quality of the included studies. We utilized Stata 14.0 software for this meta-analysis with a random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were reported. This meta-analysis was conducted in alignment with the preferred reporting items for systematic review and meta-analysis (PRISMA) guideline. Results Our meta-analysis included 71 articles with 93,508 HCWs involved. The research showed that the acceptance of vaccines had significantly increased among HCWs compared to non-HCWs (OR = 1.91, 95% CI: 1.16–3.12). A willingness to undergo COVID-19 vaccination was observed in 66% (95% CI: 0.61–0.67) of HCWs. Among the HCWs involved, doctors showed a generally increased intention to be vaccinated compared with nurses (OR = 2.22, 95% CI: 1.71–2.89). Additionally, males were found to hold more positive attitudes toward vaccination than females (OR = 1.81, 95% CI: 1.55–2.12). When the effectiveness of COVID-19 vaccines was improved, the vaccination acceptance of HCWs was greatly increased accordingly (OR = 5.03, 95% CI: 2.77–9.11). The HCWs who were willing to vaccinate against seasonal influenza showed an increased acceptance of COVID-19 vaccines (OR = 3.52, 95% CI: 2.34–5.28). Our study also showed that HCWs who were willing to be vaccinated against COVID-19 experienced a reduced rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (OR = 0.78, 95% CI: 0.66–0.92). Conclusions Our analysis revealed that the five factors of occupation, gender, vaccine effectiveness, seasonal influenza vaccines, and SARS-CoV-2 infection presumably affected the acceptance of COVID-19 vaccines among HCWs. It is essential to boost the confidence of HCWs in COVID-19 vaccines for the containment of the epidemic.

Phase 1 safety and pharmacokinetics studies of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies (preprint)

Background. BRII-196 and BRII-198 are two anti-SARS-CoV-2 monoclonal neutralizing antibodies with modified Fc region that extends half-life and are being developed as cocktail therapy for the treatment of COVID-19. Safety, tolerability, pharmacokinetics, and immunogenicity of BRII-196 and BRII-198 were investigated in healthy adults. Methods. Single ascending doses of BRII-196 and BRII-198 were evaluated in parallel in the first-in-human, placebo-controlled phase 1 studies. A total of 32 healthy adults were randomized and received a single intravenous infusion of 750, 1500, and 3000 mg of BRII-196 (n=12), BRII-198 (n=12), or placebo (n=8) and were followed for 180 days. Results. All infusions were well tolerated at infusion rates between 0.5 mL/min to 4 mL/min with no dose-limiting adverse events, deaths, serious adverse events, or any systemic or local infusion reactions. Most treatment-emergent adverse events were isolated asymptomatic laboratory abnormalities of Grade 1-2 in severity. Each mAb displayed pharmacokinetics expected of Fc-engineered human IgG1 with mean terminal half-lives of approximately 46 days and 76 days, respectively, with no evidence of significant anti-drug antibody development. Conclusions. BRII-196 and BRII-198 were well-tolerated. Clinical results support further development as therapeutic or prophylactic options for SARS-CoV-2 infection.

An Antioxidant Enzyme Therapeutic for COVID-19 (preprint)

The COVID-19 pandemic has taken a significant toll on people worldwide, and there are currently no specific antivirus drugs or vaccines. We report herein a therapeutic based on catalase, an antioxidant enzyme that can effectively breakdown hydrogen peroxide and minimize the downstream reactive oxygen species, which are excessively produced resulting from the infection and inflammatory process. Catalase assists to regulate production of cytokines, protect oxidative injury, and repress replication of SARS-CoV-2, as demonstrated in human leukocytes and alveolar epithelial cells, and rhesus macaques, without noticeable toxicity. Such a therapeutic can be readily manufactured at low cost as a potential treatment for COVID-19.