SARS-CoV2 infection in the intestine
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Principal Investigator: BRIAN KELSALL Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES Fiscal Year: 2024 Award: $10,914 Funding agency: National Institute of Allergy and Infectious Diseases Demonstrating where SARS-CoV-2 infects and replicates in intestinal epithelium in vivo has been difficult to demonstrate conclusively. Therefore, we stained limited intestinal tissues from infected human autopsy samples for SARS-CoV2 both by immunofluorescence using antibodies to the SARS-CoV2 spike and nuclear proteins and in situ hybridization for viral RNA using RNAscope technology. In one patient with high viral loads in other tissues, we found significant viral mRNA in colon epithelial cells, and possibly within other cells in the intestinal LP that appear to be macrophages. Furthermore, we have begun to evaluate intestinal tissues from mouse models of SARS-CoV2 as a collaborator with Dr. Philip Murphys laboratory. We have also collaborated with Drs. Brenchley in the NIAID, and Drs. Pollett, and Richard at the USUHS to address the expression of blood biomarkers associated with intestinal barrier dysfunction on the development of long-COVID in patients and controls from DoD hospitals. In a case-control study of 25 patients with long-COVID symptoms and control SARs-CoV2 infected patients without long-COVID, we explored blood markers for intestinal barrier dysfunction both and early and late time points. We found no significant evidence of intestinal barrier dysfunction in patients with long-COVID symptoms. A manuscript is in preparation. In FY 2024, we have continued the above studies. 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