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

iScience

Abhimanyu¹  Anna Kathleen Coussens¹  Cody Charles Allison¹  Xutao Wang²  W. Evan Johnson³  Dylan Sheerin³  William Vo³  Nashied Peton⁴ 

[1] Eliza Hall Institute of Medical Research, Parkville 3279, VIC, Australia;Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, Observatory, 7925 Western Cape, South Africa;;Infectious Diseases and Immune Defence Division, The Walter &Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, Observatory, 7925 Western Cape, South Africa;

关键词: Pathophysiology;    Immunology;    Virology;    Transcriptomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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, IFNA1, IFNB1, IFNG, TNF, and IL1B induction.

【 授权许可】

Unknown