Journal Article

Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19

Wienhold, Sandra-Maria, Postmus, Dylan, Sawitzki, Birgit, Pott, Fabian, Gruber, Achim D., Sander, Leif E., Obermayer, Benedikt, Hoefler, Thomas, Trimpert, Jakob, Drosten, Christian, Landthaler, Markus, Farztdinov, Vadim, Witzenrath, Martin, Suttorp, Norbert, Vladimirova, Daria, Pennitz, Peter, Wyler, Emanuel, Nouailles, Geraldine, Dietert, Kristina, Andreotti, Sandro, Muelleder, Michael, Beule, Dieter, Goffinet, Christine, Kazmierski, Julia, Ralser, Markus

2021

Overview

In COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate COVID-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exert the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence for productive infection, endothelial cells react, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies precede viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters thus identifies cell type-specific effector functions, providing detailed insights into pathomechanisms of COVID-19 and informing therapeutic strategies. The immune response is key in determining disease severity of COVID19. Here Nouailles et al., apply bulk proteomics and scRNA-Seq of lung and blood samples of SARS-CoV-2 infected Syrian hamsters and provide a temporal atlas of the systemic and pulmonary cellular responses.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/51 / 14 / 14/63 / 38 / 38/39 / 38/79 / 38/91 / 42 / 49 / 59 / 631/250/2152 / 631/250/255/2514 / 631/250/262 / 631/80/304 / 692/699/255/2514 / Alveolar Epithelial Cells - immunology / Animals / Antibodies / Antiviral agents / Antiviral drugs / Coronaviruses / COVID-19 / COVID-19 - immunology / Cricetinae / Cytokines - genetics / Cytokines - immunology / Cytotoxicity / Disease Models, Animal / Endothelial cells / Endothelial Cells - immunology / Epithelial cells / Epithelium / Genes / Hamsters / Humanities and Social Sciences / Humans / Immune clearance / Immune response / Immune system / Immunoglobulin M / Immunoglobulin M - immunology / Infections / Inflammation / Lung - immunology / Lungs / Lymphocytes / Lymphocytes T / Macrophages / Macrophages - immunology / Mesocricetus / Monocytes / Monocytes - immunology / multidisciplinary / Proteomics / Recruitment / Rodents / SARS-CoV-2 - immunology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Signal Transduction / T-Lymphocytes, Cytotoxic - immunology / Toll-Like Receptors - immunology / Transcription / Viral diseases