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

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

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Abstract

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.

Original language	English
Pages (from-to)	1036-1045.e9
Journal	Cell
Volume	181
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2020.04.026
State	Published - 28 May 2020

Keywords

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

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10.1016/j.cell.2020.04.026

Cite this

@article{182c0426c5bb4a6fb3044ac38be49148,

title = "Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19",

abstract = "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.",

keywords = "COVID-19, Coronavirus, IL6, SARS-CoV-2, chemokines, ferret, interferon, transcriptomics, virus-host interactions",

author = "Daniel Blanco-Melo and Nilsson-Payant, {Benjamin E.} and Liu, {Wen Chun} and Skyler Uhl and Daisy Hoagland and Rasmus M{\o}ller and Jordan, {Tristan X.} and Kohei Oishi and Maryline Panis and David Sachs and Wang, {Taia T.} and Schwartz, {Robert E.} and Lim, {Jean K.} and Albrecht, {Randy A.} and tenOever, {Benjamin R.}",

note = "Funding Information: This work was funded by generous support from the Marc Haas Foundation, the National Institutes of Health, and DARPA's PREPARE Program (HR0011-20-2-0040). The views, opinions, and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. government. We are also indebted to the Kaiser Santa Clara testing facility, which provided the clinical serum samples. We thank Julie Parsonnet and Jeffrey M. Schapiro for provision of clinical samples and Dr. D. Bogunovic for kindly sharing the JAK1/2 inhibitor ruxolitinib. Support for T.T.W. was received from Stanford University, the Chan Zuckerberg Biohub, and the Searle Scholars Program. The research reported in this publication was supported in part by National Institutes of Health 5U19AI111825-07 (to T.T.W.) and 5R01AI139119-02 (to T.T.W.). In addition, partial salary support was provided by the National Institutes of Health (R01DK121072 to R.E.S. R01AIAI145882 and R01AI110575 to B.T. and R21AI149033 to J.K.L.). R.A.A. and W.C.L. were supported by CRIP (Center for Research on Influenza Pathogenesis), a NIAID-funded Center of Excellence for Influenza Research and Surveillance (CEIRS; contract HHSN272201400008C). D.H. was supported in part by USPHS Institutional Research Training Award T32-AI07647. Postdoctoral fellowship support for T.X.J. is provided by the NIH (R01 AI123155). D.B.-M. is an Open Philanthropy Fellow of the Life Sciences Research Foundation. We also thank Dr. T. Moran for providing the SARS-CoV-2 Spike and N antibodies used in this study. Conceptualization, D.B.-M. B.E.N.-P. and B.R.T.; Methodology, D.B.-M. B.E.N.-P. W.-C.L. J.K.L. R.A.A. and B.R.T.; Software, D.B.-M. and D.S.; Validation, B.E.N.-P. S.U. D.H. and J.K.L.; Formal Analysis, D.B.-M. D.S. and B.R.T.; Investigation, D.B.-M. B.E.N.-P. W.-C.L. S.U. D.H. R.M. T.X.J. K.O. M.P. D.S. J.K.L. and R.A.A.; Resources, W.-C.L. T.T.W. R.E.S. J.K.L. and R.A.A.; Data Curation, D.B.-M.; Writing – Original Draft, D.B.-M. B.E.N.-P. B.T.O.; Writing – Review & Editing, D.B.-M. B.E.N.-P. J.K.L. and B.R.T.; Visualization, D.B.-M. D.S. B.E.N.-P. S.U. D.H. and B.R.T.; Supervision, R.A.A. and B.R.T.; Project Administration, R.A.A. and B.R.T.; Funding, B.R.T. The authors declare no competing interests. Funding Information: This work was funded by generous support from the Marc Haas Foundation , the National Institutes of Health , and DARPA {\textquoteright}s PREPARE Program ( HR0011-20-2-0040 ). The views, opinions, and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. government. We are also indebted to the Kaiser Santa Clara testing facility, which provided the clinical serum samples. We thank Julie Parsonnet and Jeffrey M. Schapiro for provision of clinical samples and Dr. D. Bogunovic for kindly sharing the JAK1/2 inhibitor ruxolitinib. Support for T.T.W. was received from Stanford University , the Chan Zuckerberg Biohub , and the Searle Scholars Program . The research reported in this publication was supported in part by National Institutes of Health 5U19AI111825-07 (to T.T.W.) and 5R01AI139119-02 (to T.T.W.). In addition, partial salary support was provided by the National Institutes of Health ( R01DK121072 to R.E.S., R01AIAI145882 and R01AI110575 to B.T., and R21AI149033 to J.K.L.). R.A.A. and W.C.L. were supported by CRIP (Center for Research on Influenza Pathogenesis), a NIAID -funded Center of Excellence for Influenza Research and Surveillance (CEIRS; contract HHSN272201400008C ). D.H. was supported in part by USPHS Institutional Research Training Award T32-AI07647 . Postdoctoral fellowship support for T.X.J. is provided by the NIH ( R01 AI123155 ). D.B.-M. is an Open Philanthropy Fellow of the Life Sciences Research Foundation. We also thank Dr. T. Moran for providing the SARS-CoV-2 Spike and N antibodies used in this study. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = may,

day = "28",

doi = "10.1016/j.cell.2020.04.026",

language = "English",

volume = "181",

pages = "1036--1045.e9",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

AU - Blanco-Melo, Daniel

AU - Nilsson-Payant, Benjamin E.

AU - Liu, Wen Chun

AU - Uhl, Skyler

AU - Hoagland, Daisy

AU - Møller, Rasmus

AU - Jordan, Tristan X.

AU - Oishi, Kohei

AU - Panis, Maryline

AU - Sachs, David

AU - Wang, Taia T.

AU - Schwartz, Robert E.

AU - Lim, Jean K.

AU - Albrecht, Randy A.

AU - tenOever, Benjamin R.

N1 - Funding Information: This work was funded by generous support from the Marc Haas Foundation, the National Institutes of Health, and DARPA's PREPARE Program (HR0011-20-2-0040). The views, opinions, and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. government. We are also indebted to the Kaiser Santa Clara testing facility, which provided the clinical serum samples. We thank Julie Parsonnet and Jeffrey M. Schapiro for provision of clinical samples and Dr. D. Bogunovic for kindly sharing the JAK1/2 inhibitor ruxolitinib. Support for T.T.W. was received from Stanford University, the Chan Zuckerberg Biohub, and the Searle Scholars Program. The research reported in this publication was supported in part by National Institutes of Health 5U19AI111825-07 (to T.T.W.) and 5R01AI139119-02 (to T.T.W.). In addition, partial salary support was provided by the National Institutes of Health (R01DK121072 to R.E.S. R01AIAI145882 and R01AI110575 to B.T. and R21AI149033 to J.K.L.). R.A.A. and W.C.L. were supported by CRIP (Center for Research on Influenza Pathogenesis), a NIAID-funded Center of Excellence for Influenza Research and Surveillance (CEIRS; contract HHSN272201400008C). D.H. was supported in part by USPHS Institutional Research Training Award T32-AI07647. Postdoctoral fellowship support for T.X.J. is provided by the NIH (R01 AI123155). D.B.-M. is an Open Philanthropy Fellow of the Life Sciences Research Foundation. We also thank Dr. T. Moran for providing the SARS-CoV-2 Spike and N antibodies used in this study. Conceptualization, D.B.-M. B.E.N.-P. and B.R.T.; Methodology, D.B.-M. B.E.N.-P. W.-C.L. J.K.L. R.A.A. and B.R.T.; Software, D.B.-M. and D.S.; Validation, B.E.N.-P. S.U. D.H. and J.K.L.; Formal Analysis, D.B.-M. D.S. and B.R.T.; Investigation, D.B.-M. B.E.N.-P. W.-C.L. S.U. D.H. R.M. T.X.J. K.O. M.P. D.S. J.K.L. and R.A.A.; Resources, W.-C.L. T.T.W. R.E.S. J.K.L. and R.A.A.; Data Curation, D.B.-M.; Writing – Original Draft, D.B.-M. B.E.N.-P. B.T.O.; Writing – Review & Editing, D.B.-M. B.E.N.-P. J.K.L. and B.R.T.; Visualization, D.B.-M. D.S. B.E.N.-P. S.U. D.H. and B.R.T.; Supervision, R.A.A. and B.R.T.; Project Administration, R.A.A. and B.R.T.; Funding, B.R.T. The authors declare no competing interests. Funding Information: This work was funded by generous support from the Marc Haas Foundation , the National Institutes of Health , and DARPA ’s PREPARE Program ( HR0011-20-2-0040 ). The views, opinions, and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. government. We are also indebted to the Kaiser Santa Clara testing facility, which provided the clinical serum samples. We thank Julie Parsonnet and Jeffrey M. Schapiro for provision of clinical samples and Dr. D. Bogunovic for kindly sharing the JAK1/2 inhibitor ruxolitinib. Support for T.T.W. was received from Stanford University , the Chan Zuckerberg Biohub , and the Searle Scholars Program . The research reported in this publication was supported in part by National Institutes of Health 5U19AI111825-07 (to T.T.W.) and 5R01AI139119-02 (to T.T.W.). In addition, partial salary support was provided by the National Institutes of Health ( R01DK121072 to R.E.S., R01AIAI145882 and R01AI110575 to B.T., and R21AI149033 to J.K.L.). R.A.A. and W.C.L. were supported by CRIP (Center for Research on Influenza Pathogenesis), a NIAID -funded Center of Excellence for Influenza Research and Surveillance (CEIRS; contract HHSN272201400008C ). D.H. was supported in part by USPHS Institutional Research Training Award T32-AI07647 . Postdoctoral fellowship support for T.X.J. is provided by the NIH ( R01 AI123155 ). D.B.-M. is an Open Philanthropy Fellow of the Life Sciences Research Foundation. We also thank Dr. T. Moran for providing the SARS-CoV-2 Spike and N antibodies used in this study. Publisher Copyright: © 2020 Elsevier Inc.

PY - 2020/5/28

Y1 - 2020/5/28

N2 - 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.

AB - 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.

KW - COVID-19

KW - Coronavirus

KW - IL6

KW - SARS-CoV-2

KW - chemokines

KW - ferret

KW - interferon

KW - transcriptomics

KW - virus-host interactions

UR - http://www.scopus.com/inward/record.url?scp=85084438244&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2020.04.026

DO - 10.1016/j.cell.2020.04.026

M3 - Article

C2 - 32416070

AN - SCOPUS:85084438244

SN - 0092-8674

VL - 181

SP - 1036-1045.e9

JO - Cell

JF - Cell

IS - 5

ER -

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

Abstract

Keywords

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