1. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19
- Author
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Daisy A. Hoagland, Kohei Oishi, Wen-Chun Liu, Maryline Panis, Benjamin E. Nilsson-Payant, Daniel Blanco-Melo, Taia T. Wang, Jean K. Lim, Tristan X. Jordan, David H. Sachs, Robert E. Schwartz, Rasmus Møller, Benjamin R. tenOever, Randy A. Albrecht, and Skyler Uhl
- Subjects
Chemokine ,Transcription, Genetic ,viruses ,medicine.medical_treatment ,Pneumonia, Viral ,Cell ,chemokines ,medicine.disease_cause ,Article ,General Biochemistry, Genetics and Molecular Biology ,Transcriptome ,transcriptomics ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,Interferon ,Pandemic ,medicine ,Animals ,Humans ,RNA Viruses ,ferret ,Pandemics ,Cells, Cultured ,virus-host interactions ,030304 developmental biology ,Coronavirus ,Inflammation ,0303 health sciences ,biology ,SARS-CoV-2 ,COVID-19 ,interferon ,biology.organism_classification ,IL6 ,Immunity, Innate ,Disease Models, Animal ,Cytokine ,medicine.anatomical_structure ,Host-Pathogen Interactions ,Immunology ,biology.protein ,Interferons ,Coronavirus Infections ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Summary 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., Graphical Abstract, Highlights • 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.
- Published
- 2020