SARS-CoV-2 causes gastric damage: structural and ultrastructural evaluation

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infects the gastrointestinal tract; however, its effects on the stomach and underlying mechanisms remain unknown. The presence of ACE2 (angiotensin-converting enzyme 2) receptors in the gastric mucosa suggests that the stomach is vulnerable to infection. This study is the first to examine SARS-CoV-2's impact on distinct cell types within gastric tissue, alongside the involvement of protective mechanisms and cell death pathways. K18-hACE2 transgenic mice (n = 20) were divided into control and SARS-CoV-2 groups, and their gastric tissues were analyzed on day 8 post-infection to represent the acute phase. Epithelial degeneration, hemorrhage, glandular cell damage, inflammatory infiltration, and muscle injury were assessed and scored, alongside apoptosis, pyroptosis, necroptosis, and Galectin-3 expression levels. Ultrastructural changes were identified using transmission electron microscopy. The SARS-CoV-2 group exhibited significant epithelial desquamation, extensive tissue damage (P < 0.0001), diminished mucin content, elevated apoptosis (P = 0.0279) and pyroptosis (P = 0.0265), and reduced Galectin-3 expression (P = 0.0211). Parietal cells showed pronounced structural damage and strong SARS-CoV-2 positivity, highlighting their susceptibility and potential role in gastric dysfunction during infection. Virus-like particles (70-110 nm) were observed within cells and in vesicles. Enteroendocrine cells displayed heightened activity. SARS-CoV-2 infection caused significant damage to gastric epithelial and parietal cells through inflammatory, apoptotic, and pyroptotic mechanisms, likely exacerbated by reduced Galectin-3 expression and consequent impairment of gastric protection. This damage may amplify susceptibility to secondary infections, such as H. pylori, and could contribute to clinical symptoms such as nausea, dyspepsia, and unexplained gastric complaints observed in SARS-CoV-2 cases.