Determination of mucosal immune responses to, and infection of the gastrointestinal tract by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

PROJECT SUMMARYIn approximately 6 months, the Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe acuterespiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in >6 million cases and led to >350K deathsworldwide, with over 100K of these deaths in the USA alone. Although the major pathologies leading to thesedeaths are cardiovascular and pulmonary in nature, COVID-19 is a multi-system disease and gastrointestinal(GI) symptoms are frequently reported. While animal studies and in-vitro experiments demonstrate thatenterocytes can be infected by SARS-CoV-2, analyses of the GI tract in humans have been limited to viralRNA detection in feces or suggestions of enteric inflammation as measured by elevated levels of fecalcalprotectin in a subset of patients. Being at the forefront of COVID-19 cases in New York City, we haverecruited a cohort of >60 individuals. With a strong collaborative infra-structure supported by the parent R01grant focusing on host-viral (HIV-1 associated) interactions in the GI tract, we are well-poised for detailedanalyses of intestinal tissues in COVID-19 patients. Specifically, as evidenced in the submitted application, wehave already generated a strong body of data, demonstrating for the first time, human enterocyte infection bySARS-CoV-2 that is in some cases associated with evidence of intestinal inflammation as measured by fecalcalprotectin and numerous fecal cytokines. We are in the process of determining how these inflammatoryresponses modulate SARS-CoV-2 specific immune responses as measured by fecal IgA. The supplementaryfunds as requested will allow us to continue with the analyses of specimens that are already banked and willenable further recruitment of patients with active and convalescent COVID-19 disease. With the proposedstudies, we aim to a) further characterize infection of GI tissues; b) determine viral persistence in the gut duringconvalescence; and c) determine the generation and evolution of inflammatory and antigen-specific mucosalimmune responses. Altogether, through further development and analyses of this unique cohort, we aim toprovide important insights into the role played by the GI tract in COVID-19 pathogenesis and transmission.