Post-COVID-19 Effects on Chronic Gastritis and Gastric Cellular and Molecular Characteristics in Male Mice

Abstract

BACKGROUNDS & AIMS: Since the Omicron variant emerged as a major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, COVID-19-associated mortality has decreased remarkably. Nevertheless, patients with a history of SARS-CoV-2 infection have been suffering from an aftereffect commonly known as 'long COVID,' affecting diverse organs. However, the effect of SARS-CoV-2 on gastric cells and disease progression was not previously known. We aimed to investigate whether SARS-CoV-2 infection affects stomach cells and if post-COVID-19 conditions can lead to severe gastric disease. METHODS: Stomach specimens obtained from male K18-hACE2 mice 7 days after SARS-CoV-2 infection were subjected to a transcriptomic analysis for molecular profiling. To investigate the putative role of SARS-CoV-2 in gastric carcinogenesis, K18-hACE2 mice affected by nonlethal COVID-19 were also inoculated with Helicobacter pylori SS1. RESULTS: Despite the lack of viral dissemination and pathologic traits in the stomach, SARS-CoV-2 infection caused dramatic changes to the molecular profile and some immune subsets in this organ. Notably, the gene sets related to metaplasia and gastric cancer were significantly enriched after viral infection. As a result, chronic inflammatory responses and preneoplastic transitions were promoted in these mice. CONCLUSION: SARS-CoV-2 infection indirectly leads to profound and post-acute COVID-19 alterations in the stomach at the cellular and molecular levels, resulting in adverse outcomes following co-infection with SARS-CoV-2 and H pylori. Our results show that 2 prevalent pathogens of humans elicit a negative synergistic effect and provide evidence of the risk of severe chronic gastritis in the post-COVID-19 era. (Cell Mol Gastroenterol Hepatol 2025;19:101511; https://doi.org/ 10.1016/j.jcmgh.2025.101511)