Integrated Metagenomic and Metatranscriptomic Characterization of Inflammatory Chronic Rhinosinusitis Endotypes

SUMMARY The SARS-CoV-2 pandemic demands a swift response to address a broad range of medical and scientific questions to mitigate harm to populations and slow and eventually eliminate the epidemic. To understand the course, history, and pathogenesis that will lead to effective therapies and vaccines it is critical to answer several fundamental scientific questions longitudinally: Viral, genetic, ecological factors and co-morbidity/co- infections risk factors need to be identified for 1) symptomatic and asymptomatic infection; 2) prolonged shedding; and 3) acute and chronic sequelae. In particular we must define correlates of reduced viral load in upper airways early in disease, and the host-viral response that defines later severe lower respiratory disease and ARDS that is prefaced by cytokine storm. We hypothesize that a combination of viral (high viral load, specific viral signature of virulence, respiratory viral co-infection and virome), ecological (such as, microbiome community structure/function) and host (local mucosal immune response) factors will predict disease outcomes and severity. Below are our specific aims to address our hypothesis: Aim 1: Determine longitudinal kinetics of SARS-CoV2 viral load to establish association between nasal viral load and viral shedding with disease severity. Aim 2: Characterize how SARS-CoV2 infection changes nasal microbiome composition, structure and secondary bacterial infection during Covid-19. Aim 3: To examine if nasal microbiome patterns during SARS-CoV2 infection are associated with local immune responses and cytokine storm. Collectively, this study will identify determinants of SARS-CoV2 viral kinetics, persistence, virus-host and microbiome interactions. Specifically, our proposal will advance our understanding of the role of the upper airway microbiome in Covid-19 and establish its role in programming of the local immune response upon SARS-CoV2 infection and effects on Covid-19 outcomes.