The immune response to SARS-CoV-2: Friend or Foe?

The novel SARS-CoV-2 coronavirus is responsible for worldwide pandemic that has infected over 8 million people resulting in close to 500,000 deaths. The immune response to SARS-CoV-2 involves both innate and adaptive responses and it appears that the timing and magnitude of these responses are important factors in determining the outcome of the infection. For the vast majority of those infected by SARS-CovV-2 the clinical course is mild, with a significant proportion of individuals experiencing asymptomatic infection. In mild cases, it appears that classic anti- viral immunity, manifested by early type 1 interferon production, virus-specific CD8 T cells and the generation of neutralizing antibodies, is responsible for rapid viral clearance. However, the picture is very different for the 10% of infected individuals who develop serious disease, which can lead to respiratory failure, multi-organ failure and death. This is associated with a hyperinflammatory state, with high levels of circulating cytokines, and a failure of the adaptive immune response. New data are emerging concerning the factors, both genetic and environmental, that determine the clinical outcome of disease. In this talk we will examine the host and viral factors that lead either to rapid viral clearance or to severe clinical disease. Deeper understanding of the immune response to SARS-CoV-2 will lead to the development of novel therapeutics that can be tested in a modeling framework.