Autonomic PASC Syndromes Arising from Functional Autoantibodies against G-protein Coupled Receptors

Introduction: Cumulative viral infections, such as herpesvirus infections and recurrent respiratory viral infections, may affect the risk and/or severity of Long COVID, though data is limited. We will use epitope level immune scanning with VirScan to longitudinally and quantitatively assess immune responses to multiple viruses associated with acute and latent infectious events as risk factors for different phenotypes of Long COVID.

Objective: To characterize high-dimensional, longitudinal immune response signatures of multiple viruses with VirScan in SARS-CoV-2 acutely infected or reinfected persons and correlate findings with Long COVID clinical phenotypes, severity, and trajectory.

Methods: This case-control study selects 400 persons within RECOVER with three distinct phenotypes of Long COVID (fatigue/post-exertional malaise, neurocognitive dysfunction, and orthostatic intolerance, n=100 for each phenotype) or matched controls who have recovered from acute COVID-19 (n=100). Using samples within 1-month after SARS-CoV-2 infection, and 3, 6, and 12 months later, we perform epitope level immune scanning with VirScan human virome (Vir3) library. Immune response signatures are analyzed with epitope hits (overall, highly immunogenic, diversity) and antibody binding affinity and correlated with Long COVID outcomes overall and in each specific sub-phenotype. In Specific Aim #1, we assess cumulative herpesvirus reactivation events as a risk factor for specific PASC sub-phenotypes, severity, and trajectory, focusing on latent herpesvirus (e.g., EBV, CMV, HHV-6) epitope expansion kinetics after SARS-CoV-2 infection. In Specific Aim #2, we correlate humoral immune responses to SARS-CoV-2 and endemic common cold coronaviruses with risk of Long COVID sub-phenotypes and disease severity.

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
• 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
• Effect of reinfection and/or emerging variants on the risk for Long COVID
• Viral persistence/reactivation