Single-cell-resolved interspecies comparison shows a shared inflammatory axis and a dominant neutrophil-endothelial program in severe COVID-19
Stefan Peidli,
Geraldine Nouailles,
Emanuel Wyler,
Julia M. Adler,
Sandra Kunder,
Anne Voß,
Julia Kazmierski,
Fabian Pott,
Peter Pennitz,
Dylan Postmus,
Luiz Gustavo Teixeira Alves,
Christine Goffinet,
Achim D. Gruber,
Nils Blüthgen,
Martin Witzenrath,
Jakob Trimpert,
Markus Landthaler,
Samantha D. Praktiknjo
Affiliations
Stefan Peidli
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Berlin, Germany; Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany
Geraldine Nouailles
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases, Respiratory Medicine and Critical Care, Berlin, Germany
Emanuel Wyler
Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
Julia M. Adler
Institut für Virologie, Freie Universität Berlin, Berlin, Germany
Sandra Kunder
Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany
Anne Voß
Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany
Julia Kazmierski
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
Fabian Pott
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
Peter Pennitz
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases, Respiratory Medicine and Critical Care, Berlin, Germany
Dylan Postmus
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
Luiz Gustavo Teixeira Alves
Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
Christine Goffinet
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
Achim D. Gruber
Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany
Nils Blüthgen
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Pathology, Berlin, Germany; Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany
Martin Witzenrath
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases, Respiratory Medicine and Critical Care, Berlin, Germany; German Center for Lung Research (DZL), Berlin, Germany
Jakob Trimpert
Institut für Virologie, Freie Universität Berlin, Berlin, Germany; Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
Markus Landthaler
Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
Samantha D. Praktiknjo
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany; Corresponding author
Summary: A key issue for research on COVID-19 pathogenesis is the lack of biopsies from patients and of samples at the onset of infection. To overcome these hurdles, hamsters were shown to be useful models for studying this disease. Here, we further leverage the model to molecularly survey the disease progression from time-resolved single-cell RNA sequencing data collected from healthy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected Syrian and Roborovski hamster lungs. We compare our data to human COVID-19 studies, including bronchoalveolar lavage, nasal swab, and postmortem lung tissue, and identify a shared axis of inflammation dominated by macrophages, neutrophils, and endothelial cells, which we show to be transient in Syrian and terminal in Roborovski hamsters. Our data suggest that, following SARS-CoV-2 infection, commitment to a type 1- or type 3-biased immunity determines moderate versus severe COVID-19 outcomes, respectively.
