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.
【저자키워드】 Adaptive immunity, viral infection, Innate immunity, Mechanisms of disease, 【초록키워드】 COVID-19, SARS-CoV-2, Macrophage, proteomics, COVID19, immune response, macrophages, T cells, SARS-COV-2 infection, disease severity, Infection, lung, Lung injury, viral clearance, Moderate COVID-19, Anti-viral, monocyte, T cell, Cytotoxic T cells, Viral, IgM antibodies, endothelial cells, immune responses, Lungs, Therapeutic strategies, epithelial cells, dataset, hamster, expression, scRNA-seq, COVID-19 patients, Pathomechanism, longitudinal analysis, Endothelial cell, Evidence, epithelial cell, Cytotoxic T cell, Cellular responses, Pathomechanisms, Subtypes, Blood samples, IgM antibody, blood sample, functions, cellular mechanisms, transcriptional response, datasets, Pro-inflammatory genes, post infection, Monocyte-derived macrophages, pro-inflammatory, inflammatory lung injury, Genes, Cell, identify, cellular mechanism, alterations, 【제목키워드】 response, hamster, cellular, Analysis, Temporal,