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

• Published in: Nature communications Vol. 12; no. 1; p. 4314
• Main Authors: Bui, Linh T., Winters, Nichelle I., Chung, Mei-I, Joseph, Chitra, Gutierrez, Austin J., Habermann, Arun C., Adams, Taylor S., Schupp, Jonas C., Poli, Sergio, Peter, Lance M., Taylor, Chase J., Blackburn, Jessica B., Richmond, Bradley W., Nicholson, Andrew G., Rassl, Doris, Wallace, William A., Rosas, Ivan O., Jenkins, R. Gisli, Kaminski, Naftali, Kropski, Jonathan A., Banovich, Nicholas E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 38/39; 45; 45/91; 631/114; 631/250/255/2514; 631/250/256; 692/420/2780; 692/699/255/2514; Adaptive immunity; Alveolar Epithelial Cells - metabolism; Alveolar Epithelial Cells - pathology; Angiotensin-Converting Enzyme 2 - genetics; Angiotensin-Converting Enzyme 2 - metabolism; Chronic Disease; Chronic infection; Coronaviruses; COVID-19; COVID-19 - genetics; COVID-19 - pathology; Epithelium; Gene expression; Health risks; Humanities and Social Sciences; Humans; Idiopathic Pulmonary Fibrosis - genetics; Idiopathic Pulmonary Fibrosis - pathology; Immune response; Immune system; Immunity, Innate - genetics; Inflammation; Inflammation - genetics; Innate immunity; Lung - metabolism; Lung - pathology; Lung diseases; Lung Diseases - genetics; Lung Diseases - pathology; Lungs; Microenvironments; multidisciplinary; SARS-CoV-2 - pathogenicity; SARS-CoV-2 - physiology; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Tobacco smoke; Transcriptome; Transcriptomes; Viral diseases; Virus Internalization; Virus Replication - genetics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-24467-0

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. Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 and poor outcomes. Here the authors compare the transcriptomes of single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in these patients.