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Abstract Background Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. Methods Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. Results Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. Conclusions These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.

Abstract Background The two inactivated SARS-CoV-2 vaccines, CoronaVac and BBIBP-CorV, have been widely used to control the COVID-19 pandemic. The influence of multiple factors on inactivated vaccine effectiveness (VE) during long-term use and against variants is not well understood. Methods We selected published or preprinted articles from PubMed, Embase, Scopus, Web of Science, medRxiv, BioRxiv, and the WHO COVID-19 database by 31 August 2022. We included observational studies that assessed the VE of completed primary series or homologous booster against SARS-CoV-2 infection or severe COVID-19. We used DerSimonian and Laird random-effects models to calculate pooled estimates and conducted multiple meta-regression with an information theoretic approach based on Akaike’s Information Criterion to select the model and identify the factors associated with VE. Results Fifty-one eligible studies with 151 estimates were included. For prevention of infection, VE associated with study region, variants, and time since vaccination; VE was significantly decreased against Omicron compared to Alpha (P = 0.021), primary series VE was 52.8% (95% CI, 43.3 to 60.7%) against Delta and 16.4% (95% CI, 9.5 to 22.8%) against Omicron, and booster dose VE was 65.2% (95% CI, 48.3 to 76.6%) against Delta and 20.3% (95% CI, 10.5 to 28.0%) against Omicron; primary VE decreased significantly after 180 days (P = 0.022). For the prevention of severe COVID-19, VE associated with vaccine doses, age, study region, variants, study design, and study population type; booster VE increased significantly (P = 0.001) compared to primary; though VE decreased significantly against Gamma (P = 0.034), Delta (P = 0.001), and Omicron (P = 0.001) compared to Alpha, primary and booster VEs were all above 60% against each variant. Conclusions Inactivated vaccine protection against SARS-CoV-2 infection was moderate, decreased significantly after 6 months following primary vaccination, and was restored by booster vaccination. VE against severe COVID-19 was greatest after boosting and did not decrease over time, sustained for over 6 months after the primary series, and more evidence is needed to assess the duration of booster VE. VE varied by variants, most notably against Omicron. It is necessary to ensure booster vaccination of everyone eligible for SARS-CoV-2 vaccines and continue monitoring virus evolution and VE. Trial registration PROSPERO, CRD42022353272.

Abstract Background The long-term impact of sexual transmission on the hepatitis B virus (HBV) infection in China remains unclear. This study aims to estimate the independent influence of sexual transmission on HBV infection. Methods Based on the natural history of HBV infection and three national serosurvey data of hepatitis B in China, we developed an age- and sex-specific discrete model to describe the transmission dynamics of HBV. The initial conditions of the model were determined according to the age- and sex-specific national serosurvey data in 1992. Based on the national survey data of hepatitis B in 1992 and 2006, by using the Markov Chain Monte Carlo (MCMC) method, we estimated the age- and sex-specific seroclearance rates of hepatitis B surface antigen (HBsAg) and the horizontal transmission rates as well as their 95% confidence intervals (CI). Then we used the age- and sex-specific national serosurvey data of hepatitis B in 2014 to test the accuracy of our model-based estimation. Finally, we evaluated the independent impact of sexual transmission on HBV infection and discussed the long-term effect of promotion of condom use in China. Results We estimated that the annual rates of HBsAg seroclearance for males and females aged 1–59 years were respectively 1.04% (95% CI, 0.49–1.59%) and 1.92% (95% CI, 1.11–2.73%). Due to sexual transmission, in 2014, the total number of chronic HBV infections in people aged 0–100 years increased 292,581, of which males increased 189,200 and females increased 103,381. In 2006, the acute HBV infections due to sexual transmission accounted for 24.76% (male: 31.33%, female: 17.94%) and in 2014, which accounted for 34.59% (male: 42.93%, female: 25.73%). However, if the condom usage rate was increased by 10% annually starting in 2019, then compared with current practice, the total number of acute HBV infections from 2019 to 2035 would be reduced by 16.68% (male: 21.49%, female: 11.93%). The HBsAg prevalence in people aged 1–59 years in 2035 would be reduced to 2.01% (male: 2.40%, female: 1.58%). Conclusions Sexual transmission has become the predominant route of acute HBV infection in China, especially for men. The promotion of condom use plays a significant role in reducing the cases of acute HBV infection.

Abstract Background Monitoring hepatitis B surveillance data is important for evaluating progress towards global hepatitis B elimination goals. Accurate classification of acute and chronic hepatitis infections is essential for assessing program effectiveness. Methods We evaluated hepatitis B case-reporting at six hospitals in Fujian, Hainan and Gansu provinces in 2015 to assess the accuracy of case classification. We linked National Notifiable Disease Reporting System (NNDRS) HBV case-reports with hospital information systems and extracted information on age, gender, admission ward and viral hepatitis diagnosis from medical records. To assess accuracy, we compared NNDRS reported case-classifications with the national HBV case definitions. Multivariable logistic regression was used to identify factors associated with misclassification. Results Of the 1420 HBV cases reported to NNDRS, 23 (6.5%) of the 352 acute reports and 648 (60.7%) of the 1068 chronic reports were correctly classified. Of the remaining, 318 (22.4%) were misclassified and 431 (30.4%) could not be classified due to the lack of supporting information. Based on the multivariable analysis, HBV cases reported from Hainan (aOR = 1.8; 95% CI: 1.3–2.4) and Gansu (aOR = 12.7; 95% CI: 7.7–20.1) along with reports from grade 2 hospitals (aOR = 1.6; 95% CI:1.2–2.2) and those from non-HBV related departments (aOR = 5.3; 95% CI: 4.1–7.0) were independently associated with being ‘misclassified’ in NNDRS. Conclusions We identified discrepancies in the accuracy of HBV case-reporting in the project hospitals. Onsite training on the use of anti-HBc IgM testing as well as on HBV case definitions and reporting procedures are needed to accurately assess program effectiveness and ensure case-patients are referred to appropriate treatment and care. Routine surveillance evaluations such as this can be useful for improving data quality and monitoring program effectiveness.

Abstract Background The genetic variation and origin of Hepatitis B Virus (HBV) in Qinghai-Tibet Plateau were poorly studied. The coexistence of HBsAg and anti-HBs has been described as a puzzle and has never been reported in the indigenous population or in recombinant HBV sequences. This study aimed to report geographical distribution, genetic variability and seroepidemiology of HBV in southwest China. Methods During 2014–2017, 1263 HBsAg positive serum were identified and 183 complete genome sequences were obtained. Serum samples were collected from community-based populations by a multistage random sampling method. Polymerase chain reaction (PCR) was used to amplify the HBV complete genome sequences. Then recombination, genetic variability, and serological analysis were performed. Results (1) Of the 1263 HBsAg positive serum samples, there were significant differences between the distribution of seromarkers in Tibet and Qinghai. (2) Of 183 complete genome sequences, there were 130 HBV/CD1 (71.0%), 49 HBV/CD2 (26.8%) and four HBV/C2 isolates (2.2%). Serotype ayw2 (96.1%) was the main serological subtype. (3) Several nucleotide mutations were dramatically different in CD1 and CD2 sequences. Clinical prognosis-related genetic variations such as nucleotide mutation T1762/A1764 (27.93%), A2189C (12.85%), G1613A (8.94%), T1753C (8.38%), T53C (4.47%) T3098C (1.68%) and PreS deletion (2.23%) were detected in CD recombinants. (4) From the inner land of China to the northeast boundary of India, different geographical distributions between CD1 and CD2 were identified. (5) Twenty-seven (2.14%) HBsAg/HBsAb coexistence serum samples were identified. S protein amino acid mutation and PreS deletion were with significant differences between HBsAg/HBsAb coexistence group and control group. Conclusions HBV/CD may have a mixed China and South Asia origin. Based on genetic variations, the clinical prognosis of CD recombinant seems more temperate than genotype C strains in China. The HBsAg/HBsAb coexistence is a result of both PreS deletion and aa variation in S protein. Several unique mutations were frequently detected in HBV/CD isolates, which could potentially influence the clinical prognosis.

Abstract Background To determine the treatment behaviors among a community-based cohort of chronic hepatitis B virus (HBV)-infected persons and to examine the disease progression among non-antiviral-treated HBV-infected cases after 5 years of follow-up. Methods We conducted a community-based prospective study on people with chronic HBV infection in mainland China from 2009 to 2014. In 2009, we recruited participants who were identified as HBV infected in 2006 in a national sero-survey. A face-to-face follow-up investigation was completed in 2014, and the personal information, the clinical diagnosis provided at the last hospital visit, the HBV antiviral treatment history, and the insurance type was collected for each patient for analysis. Multivariable logistic regression was used to identify factors that are associated with active medical care- seeking and antiviral treatments. Results Among the 2422 chronic HBV-infected patients recruited in 2009, 1784 (73.7%) were followed-up to 2014, and 638 (35.8%) had sought medical care in hospitals; among them, 140 (21.9%) received antiviral treatments. The lowest medical care-seeking rate (26%) was in participants over 50-year old. We determined that the frequency of medical care-seeking was higher among those participants living in urban areas (aRR = 1.3, 95% CI:1.0–1.6), those in 0–19-year old (aRR = 1.5, 95% CI:1.1–2.1), 20–39-year old (aRR = 2.2, 95% CI:1.7–3.0) and 40–49-year old (aRR = 1.5, 95% CI:1.1–2.0), and persons with insurance of the type Urban residents’ basic medical insurance (URBMI) or Commercial health insurance (CHI) (aRR = 2.5, 95% CI:1.7–3.6) and New Rural Cooperative Medical System (NRCMS) (aRR = 1.9, 95% CI:1.4–2.6). Patients were more likely to receive antiviral treatment if they were 20–39-year old (aRR = 0.4, 95% CI:0.3–0.7), had insurance of the type URBMI or CHI (aRR = 2.6, 95% CI:1.1–6.3) or NRCMS (aRR = 3.0, 95% CI:1.3–6.9) and were treated at prefecture and above-level hospitals (aRR = 2.0, 95% CI:1.4–3.0). Among non-antiviral-treated HBV-infected cases, we found the annual rates for HBsAg sero-clearance, progress to cirrhosis and HCC were 1.0, 0.6 and 0.2%, respectively. Conclusion The rates of medical care-seeking and antiviral treatment were low among community-based chronic HBV-infected persons, thus we recommend improving the insurance policies for HBV-infected persons to increase the antiviral treatment rate, and conducting extensive education to promote HBV-infected patients actively seeking medical care from hospitals.

Abstract Background Persons with chronic hepatitis B (CHB) infection were reported to suffer severe disease after hepatitis E virus (HEV) superinfection, but the studies regarding HEV seroprevalence in this population were limited. A recent study in Vietnam found higher HEV seroprevalence among CHB patients compared with healthy controls. Methods A community-based case-control study was conducted in two counties of Shandong province, China, where hepatitis E incidence was at the highest (Rushan) and lowest (Zhangqiu) in the province based on data from routine public health surveillance. Four townships were selected randomly from each county and all residents in these townships were tested for hepatitis B surface antigen (HBsAg). Those tested positive for HBsAg (CHB group) and the 1:1 age and sex-matched HBsAg-negative residents (control group) were included. Anti-HEV IgM and IgG were tested and positive rates of IgG and IgM were compared between the CHB group and the control group. Results In total, 2048 CHB participants and 2054 controls were included in the study. In the CHB group, HEV IgG seroprevalence was 9.16% (95% CI: 7.47–11.09) in Zhangqiue and 38.06% (95% CI: 35.07–41.19) in Rushan (P

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