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Background The objective of the present work was to assess the reactogenicity and immunogenicity of heterologous COVID-19 vaccination regimens in clinical trials and observational studies. Methods PubMed, Cochrane Library, Embase, MedRxiv, BioRxiv databases were searched in September 29, 2021. The PRISMA instruction for systemic review was followed. Two reviewers independently selected the studies, extracted the data and assessed risk of bias. The quality of studies was evaluated using the New Castle-Ottawa and Cochrane risk of instrument. The characteristics and study outcome (e.g., adverse events, immune response, and variant of concern) were extracted. Results Nineteen studies were included in the final data synthesis with 5 clinical trials and 14 observational studies. Heterologous vaccine administration showed a trend toward more frequent systemic reactions. However, the total reactogenicity was tolerable and manageable. Importantly, the heterologous prime-boost vaccination regimens provided higher immunogenic effect either vector/ mRNA-based vaccine or vector/ inactivated vaccine in both humoral and cellular immune response. Notably, the heterologous regimens induced the potential protection against the variant of concern, even to the Delta variant. Conclusions The current findings provided evidence about the higher induction of robust immunogenicity and tolerated reactogenicity of heterologous vaccination regimens (vector-based/mRNA vaccine or vector-based/inactivated vaccine). Also, this study supports the application of heterologous regimens against COVID-19 which may provide more opportunities to speed up the global vaccination campaign and maximize the capacity to control the pandemic.

Rationale Although households of tuberculosis cases represent a setting for intense transmission of M. tuberculosis, household exposure accounts for less than 20% of transmission within a community. Objectives To estimate excess risk of M. tuberculosis infection among household and extra-household contacts of index cases. Methods We performed a cross-sectional study in Kampala, Uganda, to delineate social networks of tuberculosis cases and matched controls without tuberculosis. We estimated the age-stratified prevalence difference of tuberculous infection between case and control networks, partitioned as household and extra-household contacts. Results We enrolled 123 index cases, 124 index controls, and 2415 first-degree network contacts. The prevalence of infection was highest among household contacts of cases (61.5%), lowest among household contacts of controls (25.2%), and intermediary among extra-household tuberculosis contacts (44.9%) and extra-household control contacts (41.2%). The age-adjusted prevalence difference between extra-household contacts of cases and their controls was 5.4%. The prevalence of infection was similar among the majority of extra-household case contacts and corresponding controls (47%). Conclusions Most first-degree social network members of tuberculosis cases do not have adequate contact with the index case to experience additional risk for infection but appear instead to acquire infection through unrecognized exposures with infectious cases in the community.