Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity.

Bui LT, Winters NI, Chung MI, Joseph C, Gutierrez AJ, Habermann AC, Adams TS, Schupp JC, Poli S, Peter LM, Taylor CJ, Blackburn JB, Richmond BW, Nicholson AG, Rassl D, Wallace WA, Rosas IO, Jenkins RG, Kaminski N, Kropski JA, Banovich NE, Human Cell Atlas Lung Biological Network

Nat Commun 12 (1) 4314 [2021-07-14; online 2021-07-14]

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.

PubMed 34262047

DOI 10.1038/s41467-021-24467-0

Crossref 10.1038/s41467-021-24467-0

pmc: PMC8280215
pii: 10.1038/s41467-021-24467-0