Overly Exuberant Innate Immune Response to SARS-CoV-2 Infection

Abstract

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection has posed a severe threat to global public health. It is unclear how the human immune system responds to the virus infection. Here, we profiled the immune transcriptome signatures by metatranscriptome sequencing for the bronchoalveolar lavage fluid from eight COVID-19 cases. The expression of the proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases as compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection caused hypercytokinemia. Contrasting with SARS-CoV, which is thought to induce inadequate interferon (IFN) response, SARS-CoV-2 robustly triggered the expression of myriad IFN-inducible genes (ISGs). These ISGs exhibit immunopathogenic potentials, characterized by the overrepresentation of genes involved in inflammation. Collectively, we profiled the molecular signatures of the host response to SARS-CoV-2 infection, which could help to understand the disease pathogenesis and provided clues for tailored antiviral strategies, such as IFN therapy.

Keywords: SARS-CoV-2, COVID-19, Innate immune response, Interferon, Interferon-stimulated gene, hypercytokinemia, immunopathogenesis