Duodenal Mucosal Expression of COVID-19-Related Genes in Health, Diabetic Gastroenteropathy, and Functional Dyspepsia

Abstract

Abstract Context SARS-CoV-2 infects the gastrointestinal tract and may be associated with symptoms that resemble diabetic gastroparesis. Why patients with diabetes who contract COVID-19 are more likely to have severe disease is unknown. Objective We aimed to compare the duodenal mucosal expression of SARS-CoV-2 and inflammation-related genes in diabetes gastroenteropathy (DGE), functional dyspepsia (FD), and healthy controls. Methods Gastrointestinal transit, and duodenal mucosal mRNA expression of selected genes were compared in 21 controls, 39 DGE patients, and 37 FD patients from a tertiary referral center. Pathway analyses were performed. Results Patients had normal, delayed (5 FD [13%] and 13 DGE patients [33%]; P = 0.03 vs controls), or rapid (5 FD [12%] and 5 DGE [12%]) gastric emptying (GE). Compared with control participants, 100 SARS-CoV-2-related genes were increased in DGE (FDR < 0.05) vs 13 genes in FD; 71 of these 100 genes were differentially expressed in DGE vs FD but only 3 between DGE patients with normal vs delayed GE. Upregulated genes in DGE include the SARS-CoV2 viral entry genes CTSL (|Fold change [FC]|=1.16; FDR < 0.05) and CTSB (|FC|=1.24; FDR < 0.05) and selected genes involved in viral replication (eg, EIF2 pathways) and inflammation (CCR2, CXCL2, and LCN2, but not other inflammation-related pathways eg, IL-2 and IL-6 signaling). Conclusion Several SARS-CoV-2-related genes were differentially expressed between DGE vs healthy controls and vs FD but not between DGE patients with normal vs delayed GE, suggesting that the differential expression is related to diabetes per se. The upregulation of CTSL and CTSB and replication genes may predispose to SARS-CoV2 infection of the gastrointestinal tract in diabetes.