Integrated Metagenomic and Metatranscriptomic Characterization of Inflammatory Chronic Rhinosinusitis Endotypes

SUMMARYThe SARS-CoV-2 pandemic demands a swift response to address a broad range of medical and scientificquestions to mitigate harm to populations and slow and eventually eliminate the epidemic. To understand thecourse, history, and pathogenesis that will lead to effective therapies and vaccines it is critical to answerseveral 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) prolongedshedding; and 3) acute and chronic sequelae. In particular we must define correlates of reduced viral loadin upper airways early in disease, and the host-viral response that defines later severe lowerrespiratory disease and ARDS that is prefaced by cytokine storm. We hypothesize that a combination ofviral (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 willpredict 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 andviral shedding with disease severity. Aim 2: Characterize how SARS-CoV2 infection changes nasalmicrobiome composition, structure and secondary bacterial infection during Covid-19. Aim 3: To examine ifnasal microbiome patterns during SARS-CoV2 infection are associated with local immune responses andcytokine 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 ofthe upper airway microbiome in Covid-19 and establish its role in programming of the local immune responseupon SARS-CoV2 infection and effects on Covid-19 outcomes.