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, 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
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.
Conflict of interest statement
Declaration of Interests The authors declare no competing interests.
Copyright © 2020 Elsevier Inc. All rights reserved.
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