TY - JOUR
T1 - Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity
AU - Human Cell Atlas Lung Biological Network
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 - Misharin, Alexander V.
AU - Tsankov, Alexander M.
AU - Spira, Avrum
AU - Barbry, Pascal
AU - Brazma, Alvis
AU - Samakovlis, Christos
AU - Shepherd, Douglas P.
AU - Rawlins, Emma L.
AU - Theis, Fabian J.
AU - Griffonnet, Jennifer
AU - Lee, Haeock
AU - Schiller, Herbert B.
AU - Hofman, Paul
AU - Powell, Joseph E.
AU - Schultze, Joachim L.
AU - Whitsett, Jeffrey
AU - Choi, Jiyeon
AU - Lundeberg, Joakim
AU - Ordovas-Montanes, Jose
AU - Rajagopal, Jayaraj
AU - Meyer, Kerstin B.
AU - Krasnow, Mark A.
AU - Saeb‐Parsy, Kourosh
AU - Zhang, Kun
AU - Lafyatis, Robert
AU - Leroy, Sylvie
AU - Haniffa, Muzlifah
AU - Nawijn, Martijn C.
AU - Nikolić, Marko Z.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
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.
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.
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U2 - 10.1038/s41467-021-24467-0
DO - 10.1038/s41467-021-24467-0
M3 - Article
C2 - 34262047
AN - SCOPUS:85111779796
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4314
ER -