Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

• Published in: Cell Vol. 181; no. 5; pp. 1036 - 1045.e9
• Main Authors: Blanco-Melo, Daniel, Nilsson-Payant, Benjamin E., Liu, Wen-Chun, Uhl, Skyler, Hoagland, Daisy, Møller, Rasmus, Jordan, Tristan X., Oishi, Kohei, Panis, Maryline, Sachs, David, Wang, Taia T., Schwartz, Robert E., Lim, Jean K., Albrecht, Randy A., tenOever, Benjamin R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.05.2020
• Subjects: animal models; Animals; Betacoronavirus - physiology; blood serum; Cells, Cultured; chemokines; Chemokines - genetics; Chemokines - immunology; Coronavirus; Coronavirus infections; Coronavirus Infections - genetics; Coronavirus Infections - immunology; COVID-19; Disease Models, Animal; ferret; Host-Pathogen Interactions; Humans; IL6; Immunity, Innate; inflammation; Inflammation - virology; interferon; interferons; Interferons - genetics; Interferons - immunology; interleukin-6; pandemic; Pandemics; patients; Pneumonia, Viral - genetics; Pneumonia, Viral - immunology; RNA Viruses - classification; RNA Viruses - immunology; SARS-CoV-2; transcription (genetics); Transcription, Genetic; transcriptomics; virus-host interactions; viruses; COVID-19; SARS-CoV-2; IL6; Coronavirus; virus-host interactions; transcriptomics; interferon; chemokines; ferret
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2020.04.026

Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19. [Display omitted] •SARS-CoV-2 infection induces low IFN-I and -III levels with a moderate ISG response•Strong chemokine expression is consistent across in vitro, ex vivo, and in vivo models•Low innate antiviral defenses and high pro-inflammatory cues contribute to COVID-19 In comparison to other respiratory viruses, SARS-CoV-2 infection drives a lower antiviral transcriptional response that is marked by low IFN-I and IFN-III levels and elevated chemokine expression, which could explain the pro-inflammatory disease state associated with COVID-19.