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Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18–59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7–259·4 vs 15·9, 13·1–19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28). Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults. Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) has remained a tough problem in China. This study aims to identify the risk of tuberculosis transmission and to assess its characteristics. Methods: We performed a molecular epidemiological study for patients with culture-positive Mycobacterium tuberculosis (M. tuberculosis) in Shanghai, from 2009 to 2018. Demographic information was obtained from the Tuberculosis Information Management System. Whole-genome sequencing (WGS) was conducted with a threshold of 12 single-nucleotide polymorphisms (SNPs) to distinguish the genomic cluster. To analyze the characteristics of TB transmission, the contact investigation for clustered cases was performed. Results: In total, 94 (27.25%) of the 345 enrolled patients were grouped into 42 genomic clusters, indicating local transmission of M. tuberculosis strains. Compared to a health system delay <14 days, patients with a health system delay ≥14 days [adjusted odds ratios (AOR) = 2.57, 95% confidence interval (CI): 1.34–4.95] were more likely to be clustered. Patients under 65 years old (AOR = 3.11, 95% CI: 1.76–5.49), residents (AOR = 2.43, 95% CI: 1.18–4.99), and Beijing genotype strains (AOR = 3.35, 95% CI: 1.32–8.53) were associated with increased risk of clustering. Interestingly, patients with resistance to isoniazid (AOR = 2.36, 95% CI: 1.15–4.88) had a higher risk of transmission. Sixteen confirmed/probable epidemiological links were identified. Local transmission of imported cases and household transmission were prominent. Conclusion: Health system delay is a crucial factor for TB transmission. Patients with resistance to isoniazid should be priority targets for contact investigation to reduce transmission. [ABSTRACT FROM AUTHOR]