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

Daniel Blanco-Melo; Benjamin E Nilsson-Payant; Wen-Chun Liu; Skyler Uhl; Daisy Hoagland; Rasmus Møller; Tristan X Jordan; Kohei Oishi; Maryline Panis; David Sachs; Taia T Wang; Robert E Schwartz; Jean K Lim; Randy A Albrecht; Benjamin R tenOever

doi:10.1016/j.cell.2020.04.026

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

Cell. 2020 May 28;181(5):1036-1045.e9. doi: 10.1016/j.cell.2020.04.026. Epub 2020 May 15.

Authors

Affiliations

¹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Virus Engineering Center for Therapeutics and Research, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁴ Divison of Infectious Diseases, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
⁵ Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA. Electronic address: res2025@med.cornell.edu.
⁶ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: jean.lim@mssm.edu.
⁷ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: randy.albrecht@mssm.edu.
⁸ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Virus Engineering Center for Therapeutics and Research, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: benjamin.tenoever@mssm.edu.

Abstract

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.

Keywords: COVID-19; Coronavirus; IL6; SARS-CoV-2; chemokines; ferret; interferon; transcriptomics; virus-host interactions.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Betacoronavirus / physiology*
COVID-19
Cells, Cultured
Chemokines / genetics
Chemokines / immunology
Coronavirus Infections / genetics
Coronavirus Infections / immunology*
Disease Models, Animal
Host-Pathogen Interactions
Humans
Immunity, Innate
Inflammation / virology
Interferons / genetics
Interferons / immunology
Pandemics
Pneumonia, Viral / genetics
Pneumonia, Viral / immunology*
RNA Viruses / classification
RNA Viruses / immunology*
SARS-CoV-2
Transcription, Genetic

Substances

Chemokines
Interferons

Abstract

Publication types

MeSH terms

Substances

Grants and funding