Genomics

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Ena-DATASET-DKFZ-03-08-2020-18:14:14:560-2122 - samples


ABSTRACT: To investigate the immune response and mechanisms associated with severe COVID-19, we performed single-cell RNA-seq on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from 5 healthy controls. We identified airway epithelial cell types and states vulnerable to SARS-CoV-2 infection. In COVID-19 patients, epithelial cells showed an average threefold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared with 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 with 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 may suppress immune hyperactivation in critical COVID-19.

PROVIDER: EGAD00001006339 | EGA |

REPOSITORIES: EGA

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Publications

COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis.

Chua Robert Lorenz RL   Lukassen Soeren S   Trump Saskia S   Hennig Bianca P BP   Wendisch Daniel D   Pott Fabian F   Debnath Olivia O   Thürmann Loreen L   Kurth Florian F   Völker Maria Theresa MT   Kazmierski Julia J   Timmermann Bernd B   Twardziok Sven S   Schneider Stefan S   Machleidt Felix F   Müller-Redetzky Holger H   Maier Melanie M   Krannich Alexander A   Schmidt Sein S   Balzer Felix F   Liebig Johannes J   Loske Jennifer J   Suttorp Norbert N   Eils Jürgen J   Ishaque Naveed N   Liebert Uwe Gerd UG   von Kalle Christof C   Hocke Andreas A   Witzenrath Martin M   Goffinet Christine C   Drosten Christian C   Laudi Sven S   Lehmann Irina I   Conrad Christian C   Sander Leif-Erik LE   Eils Roland R  

Nature biotechnology 20200626 8


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 ave  ...[more]

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