Comparative Predictive Diagnostics for Infection-Associated Chronic Illnesses Through Deep Immunoinflammatory Profiling

Introduction: Understanding similarities and differences between infection-associated complex chronic conditions is very important for establishment of diagnostic, predictive, and therapeutic biomarkers. This is particularly important in overlapping syndromes such as Long COVID and ME/CFS.

Objective: This study seeks to perform deep immune, inflammatory, and senescent marker analysis to establish and compare molecular profiles of Long COVID with ME/CFS, Long COVID without ME/CFS, and ME/CFS without Long COVID.

Methods: We will perform immune and inflammatory profiling at several levels. Antibody levels will be analyzed by ratiometric MAESTRO-study based assays. Immune cell phenotypes will be determined by multidimensional spectral flow cytometry, with a special focus on senescent and dysfunctional cells. Immune responses will be analyzed against SARS-CoV-2 and against potentially reactivated herpesviruses (EBV, CMV) using intracellular cytokine staining following Ag-specific peptide stimulations, and by ELISPOT for T cells, and using total (ELISA) and neutralizing Ab (PRNT) assays. Inflammatory and thromboinflammatory markers will be analyzed by standard laboratory tests or by high-sensitivity Olink proteomics. The results will be integrated with clinical data and mined by AI/ML to distill potential subtype responses. The groups will include SARS-CoV-2-recovered controls, LC+ME/CFS-, LC+ME/CFS+, and LC-ME/CFS+ participants.

Results: Pending.

Conclusion/Discussion: Pending.

Key Topics:

• Assay and in vitro studies to gain mechanistic insights
• Biomarker, in-depth phenotyping assays and in vitro studies using tissue and other biospecimens
• Chronic immune dysfunction
• Clinical assessment and pathogenesis of clinical manifestations
• Clinical manifestations of chronic viral infections, biological pathways, immune-autoimmune disorders, systems, organs, or diseases
• Collaborative and systems biology approaches
• Comparative studies of Long COVID with other post-viral and post-infectious syndromes
• Long COVID and other chronic conditions
• Studies of vascular injury, thrombosis, and other potential mechanisms of Long COVID
• Validation of published studies on potential mechanisms of Long COVID using data and biospecimens from RECOVER cohorts
• Viral persistence/reactivation