ABSTRACT
Human induced pluripotent stem cell (iPSC) derived intestinal organoids (HIOs) represent an inexhaustible cellular resource that could serve as a valuable tool to study viral infections such as SARS-CoV-2 as well as other enteric viruses that infect the intestinal epithelium. Intestinal symptoms of COVID-19 are present in a significant number of patients, and include nausea, diarrhea, and viral RNA shedding in feces. Using this platform we found that SARS-CoV-2 productively infects both proximally and distally patterned HIOs, leading to the release of infectious viral particles while stimulating a robust transcriptomic response, including a significant upregulation of interferon-related genes that appeared to be conserved across multiple epithelial cell types. These findings illuminate a potential inflammatory epithelial-specific signature that may contribute to both the multisystemic nature of COVID- 19 as well as its highly variable clinical presentation. We are now expanding our studies to investigate the role of Ebola virus infection in intestinal epithelial injury.