Daniel Blanco-Melo 1 , 2 , 9 , Benjamin E. Nilsson-Payant 1 , 2 , 9 , Wen-Chun Liu 1 , 3 , 9 , Skyler Uhl 1 , 2 , Daisy Hoagland 1 , 2 , Rasmus Møller 1 , 2 , Tristan X. Jordan 1 , 2 , Kohei Oishi 1 , 2 , Maryline Panis 1 , 2 , David Sachs 4 , Taia T. Wang 5 , 6 , 7 , Robert E. Schwartz 8 , ∗ , Jean K. Lim 1 , ∗∗ , Randy A. Albrecht 1 , 3 , ∗∗∗ , Benjamin R. tenOever 1 , 2 , 3 , 10 , ∗∗∗∗
15 May 2020
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.
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.