Host transcriptional profiling identifies B cell associated genes to be upregulated in individuals with asymptomatic COVID-19 and latent tuberculosis

Background SARS-CoV-2 infections resulted in a global pandemic with variable rates of COVID-19 morbidity worldwide. In high tuberculosis (TB) endemic regions it was observed that COVID-19 associated mortality was lower. Infection with Mycobacterium tuberculosis (MTB) has been shown to impact COVID-19 infections but the mechanisms involved are as yet unclear. Here we investigated the effect of latent MTB infection (LTBI) by studying host blood transcriptional profiles in individuals with Asymptomatic COVID-19. Methods We studied participants who had asymptomatic COVID-19 compared with those who had LTBI as well COVID (LTBI-COVID). Participants were aged 35.5 (+-9.2) years and comprised 27% females. Whole blood transcriptional profiles were investigated using RNA microarray analysis of individuals. Results Comparison of the LTBI-COVID and COVID groups revealed 58 differentially expressed genes (DEGs) of which 44 were upregulated and 13 were downregulated. Cluster profiler analysis showed upregulation of innate immunity associated genes (CLEC12A, TRIM15, FCRL3) upregulated in LTBI-COVID. A GO enrich analysis showed upregulation of B cell activation associated with (IL-7, SHLD1, TFRC, and FCRL3). There was a downregulation of RNF5 associated with the STING pathway. Conclusions B cell activation would lead to increased humoral immunity and enhanced uptake of pathogens by macrophages. CLEC12A and RNF5 are associated with dampening of excessive inflammation which reduces risks of COVID-19. These data support the protective role of latent TB infection associated with reduced severity of COVID-19.