The use and development of exploratory multi-omic analysis for complex disease: A COVID-19 proof-of-concept

INTRODUCTION This thesis established integrative multi-omic pipelines to investigate the molecular mechanisms driving Post-Acute Sequelae of SARS-CoV-2 (PASC). METHOD We profiled a longitudinal Belgian cohort with plasma proteomics and metabolomics, RNA-seq, WES, and nasopharyngeal metagenomics. Novel network biology methos integrated omic layers to compare interaction profiles of recovered versus PASC patients. RESULTS Metagenomics associated Dolosigranulum pigrum and Corynebacterium species to lower PASC risk. Multi-omic networks suggested persistent low-grade complement and coagulation activation in PASC with dysregulated activity around central pathway proteins. CONCLUSIONS PASC appears driven by thrombo-inflammatory loops involving complement-coagulation crosstalk and acute-phase microbial dysbiosis. Future interventions may benefit from targeting the complement-coagulation-platelet axis.