TY - JOUR
T1 - COVID-19 severity correlates with airway epithelium–immune cell interactions identified by single-cell analysis
AU - Chua, Robert Lorenz
AU - Lukassen, Soeren
AU - Trump, Saskia
AU - Hennig, Bianca P.
AU - Wendisch, Daniel
AU - Pott, Fabian
AU - Debnath, Olivia
AU - Thürmann, Loreen
AU - Kurth, Florian
AU - Völker, Maria Theresa
AU - Kazmierski, Julia
AU - Timmermann, Bernd
AU - Twardziok, Sven
AU - Schneider, Stefan
AU - Machleidt, Felix
AU - Müller-Redetzky, Holger
AU - Maier, Melanie
AU - Krannich, Alexander
AU - Schmidt, Sein
AU - Balzer, Felix
AU - Liebig, Johannes
AU - Loske, Jennifer
AU - Suttorp, Norbert
AU - Eils, Jürgen
AU - Ishaque, Naveed
AU - Liebert, Uwe Gerd
AU - von Kalle, Christof
AU - Hocke, Andreas
AU - Witzenrath, Martin
AU - Goffinet, Christine
AU - Drosten, Christian
AU - Laudi, Sven
AU - Lehmann, Irina
AU - Conrad, Christian
AU - Sander, Leif Erik
AU - Eils, Roland
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.
AB - To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.
UR - http://www.scopus.com/inward/record.url?scp=85086858205&partnerID=8YFLogxK
U2 - 10.1038/s41587-020-0602-4
DO - 10.1038/s41587-020-0602-4
M3 - Article
C2 - 32591762
AN - SCOPUS:85086858205
SN - 1087-0156
VL - 38
SP - 970
EP - 979
JO - Nature Biotechnology
JF - Nature Biotechnology
IS - 8
ER -