TY - JOUR
T1 - Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity
AU - Human Cell Atlas Lung
AU - Bui, Linh T.
AU - Winters, Nichelle I.
AU - Chung, Mei-I
AU - Joseph, Chitra
AU - Gutierrez, Austin J.
AU - Habermann, Arun C.
AU - Adams, Taylor S.
AU - Schupp, Jonas C.
AU - Poli, Sergio
AU - Peter, Lance M.
AU - Taylor, Chase J.
AU - Blackburn, Jessica B.
AU - Richmond, Bradley W.
AU - Nicholson, Andrew G.
AU - Rassl, Doris
AU - Wallace, William A.
AU - Rosas, Ivan O.
AU - Jenkins, R. Gisli
AU - Kaminski, Naftali
AU - Kropski, Jonathan A.
AU - Banovich, Nicholas E.
AU - Nawijn, Martijn
PY - 2021/7/14
Y1 - 2021/7/14
N2 - 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.
AB - 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.
KW - RECEPTOR ACE2
KW - COVID-19
U2 - 10.1038/s41467-021-24467-0
DO - 10.1038/s41467-021-24467-0
M3 - Article
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4314
ER -