Regulatory Role of the VCL/ICAM-1 Pathway in Inflammatory Exudative Damage to the Gas-Blood Barrier in SARS-CoV-2 Infection: New Insights from the Omicron Paradigm

ABSTRACT: Infections by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranging from the initial Wildtype (WT) variant in Wuhan, China, to later variants including Omicron, have showcased a diverse spectrum of symptoms. This diversity underscores the need for ongoing exploration into the virus's elusive pathogenesis. This study employs multi-omics and collaborative validation methods to comprehensively understand SARS-CoV-2's pathology, offering insights that remain pertinent as the virus evolves. Through proteomic analysis, we have identified signaling pathways associated with damage to the vascular system. Importantly, the vinculin (VCL) pathway has been identified as a distinctive feature in Omicron infections, representing a key mechanism causing lung exudation. Metabolomic analysis uncovered disruptions in immune functions, cell membrane stability, and metabolic shifts. Integrated analysis highlighted the involvement of VCL in processes such as inflammation, cell adhesion, and extravasation. A validation cohort confirmed VCL and ICAM1 as Omicron-associated biomarkers. Our mouse model studies not only corroborated these findings but also indicated therapeutic potential of targeting VCL. In contrast to genomic studies highlighting host immunity and infection susceptibility in COVID-19, our research sheds light on the evolving physiological impacts induced by the Omicron variant via the VCL pathway. By our elucidation of key molecular mechanisms involved, provides a strategic direction for developing therapies to address emerging SARS-CoV-2 variants, emphasizing the need for continuous adaptation in combating viral challenges.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Mingshan Xue  

LAB HEAD: Mingshan Xue

PROVIDER: PXD054443 | Pride | 2025-05-07

REPOSITORIES: Pride