Journal Article

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

Balzer, Felix, Laudi, Sven, Pott, Fabian, Schneider, Stefan, Müller-Redetzky, Holger, Lukassen, Soeren, Sander, Leif-Erik, Hocke, Andreas, Ishaque, Naveed, Hennig, Bianca P., Debnath, Olivia, Loske, Jennifer, Eils, Roland, Schmidt, Sein, Wendisch, Daniel, Drosten, Christian, Lehmann, Irina, Twardziok, Sven, Machleidt, Felix, Liebig, Johannes, Witzenrath, Martin, Suttorp, Norbert, Timmermann, Bernd, Maier, Melanie, Eils, Jürgen, Trump, Saskia, Liebert, Uwe Gerd, Kurth, Florian, Thürmann, Loreen, Chua, Robert Lorenz, Conrad, Christian, Goffinet, Christine, Völker, Maria Theresa, Krannich, Alexander, von Kalle, Christof, Kazmierski, Julia

2020

Overview

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. Single-cell analysis of COVID-19 patient samples identifies activated immune pathways that correlate with severe disease.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/255/2514 / 631/337/2019 / 692/308/174 / 692/699/255/2514 / ACE2 / Adult / Aged / Agriculture / Airway (Medicine) / Angiotensin-Converting Enzyme 2 / Bioinformatics / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Biomedicine / Biotechnology / Bronchoalveolar Lavage Fluid - virology / CC chemokine receptors / CCL20 protein / CCL3 protein / CCR1 protein / CCR5 protein / Cell Communication / Cell Differentiation / Cell interaction / Cell interactions / Coronaviridae / Coronavirus Infections - pathology / Coronavirus Infections - physiopathology / Coronavirus Infections - virology / Coronaviruses / COVID-19 / CXCL10 protein / Epithelial cells / Epithelial Cells - pathology / Epithelial Cells - virology / Epithelium / Female / Gene sequencing / Genetic aspects / Health aspects / Humans / Immune response / Immune system / Immune System - pathology / Inflammation / Inflammation - immunology / Inflammation - pathology / Interferon / Interleukin 1 / Interleukin 8 / Life Sciences / Longitudinal Studies / Macrophages / Male / Middle Aged / Monocyte chemoattractant protein 1 / Nasopharynx - virology / Pandemics / Peptidyl-Dipeptidase A - genetics / Pneumonia, Viral - pathology / Pneumonia, Viral - physiopathology / Pneumonia, Viral - virology / Receptors / Respiratory diseases / Respiratory failure / Respiratory System - immunology / Respiratory System - pathology / Respiratory System - virology / Respiratory tract / Ribonucleic acid / RNA / Severe acute respiratory syndrome coronavirus 2 / Severity of Illness Index / Single-Cell Analysis / Transcription / Transcriptome / Tumor necrosis factor / Viral diseases