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Principal Investigator: Jeremiah James Faith
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2020
Award: $787,826
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
PROJECT SUMMARY
In approximately 6 months, the Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in >6 million cases and led to >350K deaths
worldwide, with over 100K of these deaths in the USA alone. Although the major pathologies leading to these
deaths 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 that
enterocytes can be infected by SARS-CoV-2, analyses of the GI tract in humans have been limited to viral
RNA detection in feces or suggestions of enteric inflammation as measured by elevated levels of fecal
calprotectin in a subset of patients. Being at the forefront of COVID-19 cases in New York City, we have
recruited a cohort of >60 individuals. With a strong collaborative infra-structure supported by the parent R01
grant focusing on host-viral (HIV-1 associated) interactions in the GI tract, we are well-poised for detailed
analyses of intestinal tissues in COVID-19 patients. Specifically, as evidenced in the submitted application, we
have already generated a strong body of data, demonstrating for the first time, human enterocyte infection by
SARS-CoV-2 that is in some cases associated with evidence of intestinal inflammation as measured by fecal
calprotectin and numerous fecal cytokines. We are in the process of determining how these inflammatory
responses modulate SARS-CoV-2 specific immune responses as measured by fecal IgA. The supplementary
funds as requested will allow us to continue with the analyses of specimens that are already banked and will
enable further recruitment of patients with active and convalescent COVID-19 disease. With the proposed
studies, we aim to a) further characterize infection of GI tissues; b) determine viral persistence in the gut during
convalescence; and c) determine the generation and evolution of inflammatory and antigen-specific mucosal
immune responses. Altogether, through further development and analyses of this unique cohort, we aim to
provide important insights into the role played by the GI tract in COVID-19 pathogenesis and transmission.
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