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 M��ller, Tristan X Jordan, Kohei Oishi, Maryline Panis, David Sachs, Taia T Wang, Robert E Schwartz, Jean K Lim, Randy A Albrecht, Benjamin R tenOever
Author Information
  1. Daniel Blanco-Melo: 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. Benjamin E Nilsson-Payant: 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.
  3. Wen-Chun Liu: 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.
  4. Skyler Uhl: 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.
  5. Daisy Hoagland: 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.
  6. Rasmus M��ller: 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.
  7. Tristan X Jordan: 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.
  8. Kohei Oishi: 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.
  9. Maryline Panis: 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.
  10. David Sachs: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  11. Taia T Wang: 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.
  12. Robert E Schwartz: Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA. Electronic address: res2025@med.cornell.edu.
  13. Jean K Lim: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: jean.lim@mssm.edu.
  14. Randy A Albrecht: 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.
  15. Benjamin R tenOever: 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

References

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Grants

  1. T32 AI007647/NIAID NIH HHS
  2. HHSN272201400008C/NIAID NIH HHS
  3. R01 AI123155/NIAID NIH HHS
  4. R01 AI145882/NIAID NIH HHS
  5. R21 AI149033/NIAID NIH HHS
  6. R01 AI110575/NIAID NIH HHS
  7. R01 DK121072/NIDDK NIH HHS
  8. U19 AI111825/NIAID NIH HHS
  9. R01 AI139119/NIAID NIH HHS
  10. R01 AI076471/NIAID NIH HHS

MeSH Term

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

Chemicals

Chemokines
Interferons