Jeong Haengdueng, Kim Sung-Hee, Kim Jiseon, Jeon Donghun, Uhm Chanyang, Oh Heeju, Cho Kyungrae, Park In Ho, Oh Jooyeon, Kim Jeong Jin, Jeong Sang-Ho, Park Ji-Ho, Park Jun Won, Yun Jun-Won, Seo Jun-Young, Shin Jeon-Soo, Goldenring James R, Seong Je Kyung, Nam Ki Taek
Department of Biomedical Sciences, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea; Epithelial Biology Center and Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.
Department of Biomedical Sciences, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
Cell Mol Gastroenterol Hepatol. 2025 Mar 27;19(8):101511. doi: 10.1016/j.jcmgh.2025.101511.
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.
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.
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.
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 Hpylori. 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.
自奥密克戎变种成为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的主要变种以来，新冠病毒感染相关死亡率显著下降。然而，有SARS-CoV-2感染史的患者一直饱受一种俗称“长新冠”的后遗症折磨，该后遗症会影响多个器官。然而，SARS-CoV-2对胃细胞及疾病进展的影响此前尚不明确。我们旨在研究SARS-CoV-2感染是否会影响胃细胞，以及新冠康复后的状况是否会导致严重胃部疾病。
对SARS-CoV-2感染7天后的雄性K18-hACE2小鼠的胃标本进行转录组分析以进行分子谱分析。为研究SARS-CoV-2在胃癌发生中的潜在作用，还对受非致死性新冠病毒感染的K18-hACE2小鼠接种幽门螺杆菌SS1。
尽管在胃中未发现病毒传播和病理特征，但SARS-CoV-2感染导致该器官的分子谱和一些免疫亚群发生显著变化。值得注意的是，病毒感染后与化生和胃癌相关的基因集显著富集。结果，这些小鼠中慢性炎症反应和肿瘤前转变得到促进。
SARS-CoV-2感染在细胞和分子水平上间接导致胃在新冠急性感染后出现深刻变化，导致与SARS-CoV-2和幽门螺杆菌共同感染后出现不良后果。我们的结果表明，两种常见的人类病原体产生了负面协同效应，并为新冠后时代严重慢性胃炎的风险提供了证据。
