Sheerin Dylan, Peton Nashied, Vo William, Allison Cody Charles, Wang Xutao, Johnson W Evan, Coussens Anna Kathleen
Infectious Diseases and Immune Defence Division, The Walter & 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.
iScience. 2022 May 25;25(6):104464. doi: 10.1016/j.isci.2022.104464. eCollection 2022 Jun 17.
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 - and -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 validated that SARS-CoV-2 infection is increased in human macrophages cultured in the inflammatory milieu of -infected macrophages, correlating with , , , , , and induction.
目前及既往的结核病会增加新型冠状病毒肺炎（COVID-19）死亡及重症风险。为确定COVID-19与结核病之间免疫病理相互作用的机制，我们对来自全血、外周血单个核细胞（PBMCs）和支气管肺泡灌洗液（BALF）、涵盖疾病严重程度的COVID-19转录组特征进行了系统综述和患者水平的荟萃分析。在来自853名处于结核病感染谱不同阶段个体的1181个RNA测序样本上分析了35个符合条件的特征。在三个独立队列中，与未进展者和未感染对照相比，13个COVID-19基因特征在活动性结核病和潜伏性结核病进展者中具有显著更高的“COVID-19风险评分”（p<0.005）。综合单细胞RNA测序分析确定了在重症COVID-19的BALF和活动性结核病血液中富集的表达 和 的巨噬细胞。基因本体论和蛋白质-蛋白质相互作用网络确定了COVID-19与结核病之间的12基因疾病加重热点。最后，我们验证了在 感染的巨噬细胞的炎性环境中培养的人巨噬细胞中，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染增加，这与 、 、 、 、 和 的诱导相关。
