Contribution of CD4+T cell-mediated inflammation to diarrhea in patients with COVID-19

Objectives: This study aimed to explore the role of CD4+ T cells in the mechanisms of COVID-19 related diarrhea. Methods: We analyzed lymphocyte subsets in patients with COVID-19 and the expression of angiotensinconverting enzyme 2 (ACE2), the transmembrane protease serine 2, and CD4+ T cell-related indicators in the colon were compared between patients with and without diarrhea. Correlation analyses were performed forand other indicators to identify the relationship between SARS-CoV-2 infection and CD4+ mediated inflammation. The expression and distribution of CD4+ T cell-associated chemokines and their receptors were detected to determine the possibility of migration of CD4+ T cells to inflammation sites. Results: The CD4+ T cell counts and percentages and CD4/CD8 ratio showed the most significant differences between the 2 groups. The diarrhea group expressed higher levels of ACE2, T-box expressed in T cells (Tbet), and tumor necrosis factor-alpha (TNF alpha) at both the mRNA and protein levels, with no difference from the nondiarrhea group for the percentage of ACE2 + TNF alpha+ cells, indicating an indirect association between ACE2 and TNF alpha. The mRNA expression of CXCL10, CXCL11, and CXCR3 and the number of CD4 + CXCR3 + T cells were increased in the diarrhea group. Conclusions: CD4+ T cell-mediated inflammation may contribute to COVID-19 related diarrhea. CXCR3+ mediated migration of CD4+ T cells into the gut may perpetuate inflammation. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.