The simultaneous occurrence of tuberculosis (TB) and COVID-19 posed a major public health challenge, particularly in regions heavily impacted by both diseases, due to their shared effects on the lungs, immune system dysfunction, and the possibility of more severe clinical outcomes. The role of immunopathogenesis is crucial in influencing the progression of co-infection, which is marked by heightened inflammation, immune exhaustion, weakened T-cell responses, and unregulated cytokine production. To better understand the intricate interactions between host and pathogen and the immune disruptions associated with this dual epidemic, multi-omics approaches such as genomics, transcriptomics, proteomics, metabolomics, epigenomics, and microbiomics have proven to be effective methods. These comprehensive strategies provide detailed insights into the mechanisms of disease, help identify potential biomarkers, and aid in the identification of therapeutic targets. This review emphasizes the importance of immune responses and systems biology in comprehending the TB-COVID-19 syndemic and highlights the promise of multi-omics in advancing precision medicine and enhancing disease management. 

Insights into Molecular Interplay in Tuberculosis–COVID-19 Co-infection via Integrated Multi-Omics Strategies

Abstract Infectious diseases have affected humanity for millennia and are among the strongest selective forces. Tuberculosis (TB) is an ancient disease, caused by the human-adapted members of the Mycobacterium tuberculosis complex (MTBC). The outcome of TB infection and disease is highly variable, and co-evolution between human populations and their MTBC strains may account for some of this variability. Particular human genetic ancestries have been associated with higher susceptibility to TB, but socio-demographic aspects of the disease can confound such associations. Here, we studied 1,000 TB patients from Dar es Salaam, Tanzania, together with their respective MTBC isolates, by combining human and bacterial genomics with clinical data. We found that the genetic background of the TB patient population was strongly influenced by the Bantu migrations from West Africa, which is in contrast to the corresponding MTBC genotypes that were mainly introduced from outside Africa. These findings suggest a recent evolutionary history of co-existence between the human and MTBC populations in Dar es Salaam. We detected no evidence of an effect of human genetic ancestry, or MTBC phylogenetic diversity alone, nor their interaction, on TB disease severity. Treatment-seeking, social and environmental factors are likely to be the main determinants of disease severity at the point of care in this patient population. Author Summary Tuberculosis (TB) is an ancient infectious disease that continues to challenge global health efforts. Here, we explored the interplay between human and bacterial genetics on TB in Dar es Salaam, Tanzania. We found that neither the genetic ancestry of the patient, nor the bacterial genotype alone, nor their interaction, influenced the severity of TB. Our finding indicate that in this patient population, social and environmental factors may be the main determinants of TB disease severity. 

Human genetic ancestry,Mycobacterium tuberculosisdiversity and tuberculosis disease severity in Dar es Salaam, Tanzania

The risk and prognosis of tuberculosis (TB) are affected by both human and bacterial genetic factors. To identify interacting human and bacterial genetic loci, we leveraged paired human and Mycobacterium tuberculosis (M.tb) genomic data from 1000 Tanzanian TB patients. Through a genome-to-genome approach, we identified two pairs of human and M.tb genetic variants that are significantly associated. One of the human genetic variants maps to the intron of PRDM15, a gene involved in apoptosis regulation. The other human variant maps to an intergenic region close to TIMM21 and FBXO15. In addition, we observed that a group of linked M.tb epitope variants were significantly associated with HLA-DRB1 variation. This suggests that even though epitope variation is rare in M.tb in general, specific epitopes might still be under immune selective pressure. Overall, our study pinpoints sites of genomic conflicts between humans and M.tb, suggesting bacterial escape from host selection pressure.

https://www.medrxiv.org/content/medrxiv/early/2023/05/11/2023.05.11.23289848.full.pdf

Genome-to-genome analysis reveals associations between human and mycobacterial genetic variation in tuberculosis patients from Tanzania

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Genome-to-genome analysis reveals associations between human and mycobacterial genetic variation in tuberculosis patients from Tanzania