Diarrhea is a common symptom in patients with COVID-19.
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The mechanism of diarrhea occurring in patients with COVID-19 is poorly documented.
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CD4+ T cell-mediated inflammation might contribute to COVID-19 related diarrhea.
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The occurrence and persistence of inflammation might be associated with SARS-CoV-2.
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CXCR3+ mediated migration of CD4+ T cells into the gut might perpetuate inflammation.
Abstract
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 angiotensin-converting 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 for ACE2 and 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 (TNFα) at both the mRNA and protein levels, with no difference from the nondiarrhea group for the percentage of ACE2+TNFα+ cells, indicating an indirect association between ACE2 and TNFα. 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.
