Mechanisms of SARS-CoV-2 transmission and pathogenesis

Abstract

The emergence of SARS-coronavirus 2 (SARS-CoV-2) marks the third highly pathogenic coronavirus to spill over into the human population. SARS-CoV-2 is highly transmissible with a broad tissue tropism that is likely perpetuating the pandemic. However, important questions remain regarding its transmissibility and pathogenesis. In this review, we summarize current SARS-CoV-2 research, with an emphasis on transmission, tissue tropism, viral pathogenesis, and immune antagonism. We further present advances in animal models that are important for understanding the pathogenesis of SARS-CoV-2, vaccine development, and therapeutic testing. When necessary, comparisons are made from studies with SARS to provide further perspectives on COVID-19, as well as draw inferences for future investigations.

Highlights

• The emergence of SARS-CoV-2 from China and the rapidity of a worldwide pandemic has promoted global collaboration, built on the body of work established from previous SARS-CoV and MERS-CoV outbreaks. These past experiences have aided the swiftness by which the research community has responded with an astonishing body of work.

• SARS-CoV-2 is a novel virus in the Betacoronavirus genus and exhibits similarities to SARS-CoV in genome structure, tissue tropism and viral pathogenesis. Yet, SARS-CoV-2 appears to be more transmissible and the diversity of immune responses are poorly understood.

• Highly pathogenic coronaviruses display potent interferon (IFN) antagonism, which is evident in cases of severe COVID-19 with reduced interferon signaling, and an overaggressive immune response compounded by heightened cytokines/chemokines.

• Animal models for SARS-CoV-2 recapitulate important aspects of human COVID-19 that are essential for evaluating current and prospective antiviral therapeutics and vaccine candidates.