Immunopathogenic overlap between COVID-19 and tuberculosis identified from transcriptomic meta-analysis and human macrophage infection

Sheerin, D; Abhimanyu,; Peton, N; Vo, W; Allison, CC; Wang, X; Johnson, WE; Coussens, AK

Author(s): Sheerin, D; Abhimanyu,; Peton, N; Vo, W; Allison, CC; Wang, X; Johnson, WE; Coussens, AK;
Details: Publication Year 2022-05-25,Volume 25,Issue #6,Page 104464
Journal Title: iScience
Abstract: Current and previous tuberculosis (TB) increase the risk of COVID-19 mortality and severe disease. To identify mechanisms of immunopathogenic interaction between COVID-19 and TB, we performed a systematic review and patient-level meta-analysis of COVID-19 transcriptomic signatures, spanning disease severity, from whole blood, PBMCs and BALF. 35 eligible signatures were profiled on 1181 RNA-seq samples from 853 individuals, across the spectrum of TB infection. Thirteen COVID-19 gene-signatures had significantly higher "COVID-19 risk scores" in active TB and latent TB progressors compared with non-progressors and uninfected controls (p<0·005), in three independent cohorts. Integrative single-cell-RNAseq analysis identified FCN1- and SPP1-expressing macrophages enriched in severe COVID-19 BALF and active TB blood. Gene ontology and protein-protein interaction networks identified 12-gene disease-exacerbation hot-spots between COVID-19 and TB. Finally, we in vitro validated that SARS-CoV-2 infection is increased in human macrophages cultured in the inflammatory milieu of Mtb-infected macrophages, correlating with TMPRSS2, interferon, TNF, and IL1B induction.
Publisher: Elsevier
Keywords: SARS-CoV-2; Tb; epigenetic regulation; interferon; macrophage; neutrophil; progression; scRNA-seq; severity; treatment
Research Division(s): Infectious Diseases And Immune Defence
PubMed ID: 35634577
Publisher's Version: https://doi.org/10.1016/j.isci.2022.104464
Open Access at Publisher's Site: https://doi.org/ 10.1016/j.isci.2022.104464
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2022-06-17 09:28:53

Last Modified: 2022-06-17 09:58:02