Saurabh Mehandru, MD, Professor and Vice Chair of Research Division of Gastroenterology Department of Medicine, Icahn School of Medicine at Mount Sinai
David Putrino, PhD, Director of Rehabilitation Innovation for the Mt Sinai Health System, Associate Professor of Rehabilitation Medicine at the Icahn School of Medicine
Marcelo Freire, PhD, DDS, Associate professor in the Genomic Medicine and Infectious Disease The J. Craig Venter Institute
Christopher Dupont, PhD, Associate Professor in the Genomic Medicine, Environment & Sustainability, and Synthetic Biology groups, The J. Craig Venter Institute
Amy Proal, PhD, President, Research Director, PolyBio Research Foundation
This collaborative study uses advanced complementary methods to determine if SARS-CoV-2 or its proteins can persist for long periods of time in the gastrointestinal tract of patients with Long COVID. Intestinal tissue is being collected via colonoscopy from individuals with Long COVID and from individuals with prior COVID but no long-haul symptoms. Three forms of advanced microscopy are being used to probe for SARS-CoV-2 and its proteins in intestinal tissue samples. Spatial transcriptomics is being used to localize SARS-CoV-2 RNA and protein in tissue samples, and to document the gene expression of nearby immune cells and host epithelium tissue. The team is also characterizing both the microbiome of stool and intestinal tissue (using metatranscriptomics) to see if changes in microbiome activity correlate with potential SARS-CoV-2 persistence in tissue.
If SARS-CoV-2 is identified in intestinal tissue, the team will further study divergence of the virus from nasopharyngeal strains to determine if viral persistence in the gastrointestinal tract can lead to the emergence of new viral variants. Blood samples are also being collected from study participants to analyze T cell, B cell, macrophage, natural killer, and other immune cells, to determine if immunological responses potentially generated in response to SARS-CoV-2 in intestinal tissue can be measured in plasma, and to document the presence of potential autoantibodies. In the case that SARS-CoV-2 RNA or protein are not identified in any intestinal tissue samples analyzed, the project will still provide valuable data on immune cell activity and other inflammatory parameters that may themselves contribute to the Long COVID disease process.
A straightforward possibility for Long COVID development is that patients do not fully “clear” the SARS-CoV-2 virus after initial acute illness. Instead, a small amount of virus may persist in patient tissue, where it continues to provoke the immune system or disturb gut/tissue microbiome balance. These low-levels of persistent SARS-CoV-2 are called a viral reservoir. Intestinal tissue is a likely potential reservoir site for SARS-CoV-2 in Long COVID, because it is dense with the ACE2 receptors the virus uses for cell entry. Indeed, study co-principal investigator Dr. Saurabh Mehandru is a member of one of the first research teams in the world to demonstrate SARS-CoV-2 persistence in intestinal tissue. More specifically, the team identified SARS-CoV-2 antigens & immunoreactivity in intestinal tissue samples obtained from 7 asymptomatic individuals ~4 months after their COVID-19 onset. The current study is an extension of these important early findings: intestinal tissue is now being specifically collected from Long COVID patients for analysis so that identification of SARS-CoV-2 in samples can be correlated with Long COVID symptoms. The Long COVID intestinal tissue project should clarify if antivirals or other medications that impact the immune response in tissue might benefit patients with Long COVID.