Intestinal mucosal abnormalities shed light on ‘viral persistence’ of long COVID-19
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SAN DIEGO — Patients who recovered from COVID-19 infection demonstrated significant differences in mucosal immune cell populations compared with non-infected controls, according to data presented at Digestive Disease Week 2022.
“Our group previously published evidence for the presence of viral proteins in the gut mucosa, not only in patients with acute COVID-19 but also months after recovery, suggesting persistence of virus in the tissue,” Hadar Meringer, MD, of the Icahn School of Medicine at Mount Sinai in New York City, told Healio. “Together with persistence of symptoms in a fraction of recovered patients, also known as the long COVID, we were interested in exploring which cells are involved in the immune response of these patients and to evaluate their association with viral persistence.”
Meringer and colleagues analyzed 30 patients with confirmed COVID-19 diagnosis a median of 4 months prior (range, 1-10 months) and a control group of 40 individuals with no previous COVID-19 diagnosis.
Patients underwent colonic and small intestinal biopsies, which were analyzed using multiparameter flow cytometry to assess mucosal immune cell populations, including myeloid cells, T cells, B cells and NK cells.
Results showed that the COVID group had higher frequencies of CD14+ monocytes in both the colon and the small bowel. Moreover, significantly higher frequencies of several other cell types were found in the COVID-19 group compared with controls, including conventional dendritic cells (cDC)1 (lin–HLA-DRhiCD14–CD11c+CD141+) and cDC2 (lin-HLA–DRhiCD14–CD11c+CD1c+), according to findings.
In NK subsets, significantly higher levels of CD56bright CD16– NK cells were observed in the colon of patients in the COVID group compared with controls.
For the T cell subsets, CD8+ tissue resident memory T cells (CD8+CD69+CD103+) were significantly elevated in the colon of COVID patients compared with controls.
Among B cell subsets, plasma cells (CD3–CD27+CD38hi) were not significantly higher, while populations of mucosal B cells (CD3–CD19+) were significantly lower in the terminal ileum of post-COVID-19 patients compared with controls.
“Abnormalities were seen in both the innate and the adaptive immune cells. We believe the changes in the adaptive immune cells were more pronounced than in the innate immune cells,” Meringer said. “Memory responses are known to be responsible for future protection from reinfection. The abnormalities we observed may signify a noneffective immune response, possibly due to continuous presentation of viral antigens in the mucosa and persistent immune cell activation.”
Immunofluorescence microscopy findings showed SARS-CoV-2 nucleocapsid protein in more than one-third of individuals in the post-COVID arm at follow-up.
“One of our aims in this study was to assess the persistence of viral antigens in the mucosa using immunostaining for the SARS-CoV-2 nucleocapsid protein,” Meringer said. “This staining was shown to be specific by our group. We found positive staining in 35% of recovered patients, but as staining appears to be patchy and sporadic, this number is probably an underestimation of the real positivity.”
Meringer added that positive staining was observed in recovered patients, long after the acute infection. “Two patients were found to be positive after over 18 months, both reported had long COVID gastrointestinal symptoms,” she said. “The possible association with long COVID needs to be further studied — comparing recovered patients suffering from long COVID symptoms to those without.”
On the potential broader applicability of these findings, Meringer added: “I believe that this will enhance our understanding of other post-infectious-gut-brain disorders as we see regularly in our clinic and enable future therapies.”
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Meringer H, et al. Abstract 1161. Presented at: Digestive Disease Week; May 21-24, 2022; San Diego (hybrid meeting).
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