The regulatory effect of VCL/ICAM-1 pathway on the mechanism of inflammatory exudative damage of gas-blood barrier in SARS-CoV-2 patients

Infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from original Wildtype (WT) variant in Wuhan China to the recent Omicron variant, present diverse and unconventional symptoms and need to further explore the potential pathogenesis that has not yet been discovered. This study employs multi-omics and collaborative validation methods to comprehensively understand SARS-CoV-2's pathology. The primary mechanism of viral damage is immune-mediated inflammation, with a direct correlation between viral load and clinical severity. Immune dysfunction leads to uncontrolled inflammation, causing lung and vascular damage, potentially resulting in organ failure and thrombosis. Inflammatory markers and organ damage indicators were elevated in both Omicron and WT-infected patients, pointing to extrapulmonary organ dysfunction. Omicron patients showed milder respiratory symptoms, while WT patients exhibited severe inflammation. The VCL pathway was a distinguishing feature in Omicron using proteomic, indicating lung exudation mechanisms remained active. Metabolomic analysis showed disruptions in inflammation, cell membrane stability, and metabolic shifts. Correlation analysis revealed VCL's role in inflammation, adhesion, and extravasation functions. Animal experiments supported these findings, revealing alveolar damage and restoration. In conclusion, multi-omics approaches provide a comprehensive understanding of Omicron's pathology, with a focus on the VCL pathway as a key mechanism in lung exudation and inflammation. This study advances our knowledge of Omicron's unique impact on the human body.