Abstract
Coinfection of pathogenic bacteria and viruses is associated with multiple diseases. During the COVID-19 pandemic, the co-infection of other pathogens with SARS-CoV-2 was one of the important determinants of the severity. Although primarily a respiratory virus gastric manifestation of the SARS-CoV-2 infection was widely reported. This study highlights the possible consequences of SARS-CoV-2 -Helicobacter pylori coinfection in the gastrointestinal cells. We utilized the transfection and infection model for SARS-CoV-2 spike Delta (δ) and H. pylori respectively in colon carcinoma cell line HT-29 to develop the coinfection model to study inflammation, mitochondrial function, and cell death. The results demonstrate increased transcript levels of inflammatory markers like TLR2 (p < 0.01), IL10 (p < 0.05), TNFα (p < 0.05) and CXCL1 (p < 0.05) in pre-H. pylori infected cells as compared to the control. The protein levels of the β-Catenin (p < 0.01) and c-Myc (p < 0.01) were also significantly elevated in pre-H. pylori infected group in case of co-infection. Further investigation of apoptotic and necrotic markers (Caspase-3, Caspase-8, and RIP-1) reveals a necroptotic cell death in the coinfected cells. The infection and coinfection also damage the mitochondria in HT-29 cells, further implicating mitochondrial dysfunction in the necrotic cell death process. Our study also highlights the detrimental effect of pre-H. pylori exposure in the coinfection model compared to post-exposure and lone infection of H. pylori and SARS-CoV-2. This knowledge could aid in developing targeted interventions and therapeutic strategies to mitigate the severity of COVID-19 and improve patient outcomes.