Studies of respiratory and systemic immune responses in human influenza A virus and SARS-CoV-2 infection to understand what dictates disease severity

Emerging viruses like influenza A virus (IAV) and SARS-CoV-2, and their unpredictable pathogenicity, transmissibility, and pandemic potentials are a major threat to human health. This is because we still do not fully understand what dictates pathogenesis and disease severity. Human studies are crucial to understand pathogenesis in humans.

We have studied patients with influenza-like symptoms or confirmed respiratory virus infection for many years and have the infrastructure along with expertise and established methods to conduct high resolution immunological analyses to study viral pathogenesis. This proposal aims to dissect what immune parameters dictate influenza and COVID-19 disease severity.

We propose that disease severity is linked to the magnitude and type of immune response mounted to the virus, and that this is dictated by the initial local immune response at the site of infection.

A unique aspect of our work is that we sample and study the airways, affected in almost all COVID-19 patients but understudied, as well as blood.

By comparing samples from patients with influenza and COVID-19, we propose that we will understand even more about the two individual diseases than if we studied only one of them.

To make us better prepared to handle this and future outbreaks in a systematic, scientific way, productive collaborations between clinical and basic scientists like ours are critical to shorten the distance between experimental discovery and clinical implementation.