Cell
Volume 181, Issue 5, 28 May 2020, Pages 1036-1045.e9
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Article
Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

https://doi.org/10.1016/j.cell.2020.04.026Get rights and content
open access

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

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.

Keywords

SARS-CoV-2
COVID-19
interferon
Coronavirus
transcriptomics
virus-host interactions
chemokines
IL6
ferret

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9

These authors contributed equally

10

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