Imbalanced host response to SARS-CoV-2 drives development of COVID-19

Authors: Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, Jordan TX, Oishi K, Panis M, Sachs D, Wang TT, Schwartz RE, Lim JK, Albrecht RA, Oever B

Publication: Cell; April 2020

Affiliations: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA; Virus Engineering Center for Therapeutics and Research, Icahn School of Medicine at Mount Sinai, New York, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Medicine, Division of Infectious Diseases, and Department of Microbiology and Immunology; Sanford University School of Medicine, Stanford, California, USA; Chan Zuckerberg Biohub, San Francisco, California, USA; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine

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 indepth analysis of the transcriptional response to SARS-CoV-2 as it compares to other respiratory viruses. Cell and animal models of SARS-CoV-2 infections, 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. Taken together, we propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving feature of COVID-19.