Abstract This proposal would allow us to compare EBV and SARS-CoV-2 immune markers and metabolomics on the samples from our unique data sets. Immune and metabolomic analyses are interesting discovery tools and an important aspect of the integrative approach we will use, with their broad and flexible potential for studying post-viral fatigue. We have also shown that college students with post-IM ME/CFS have an inflammatory profile, even at baseline, different from those who recover from IM (Jason, Cotler, et al., 2021). In addition, metabolomics has emerged as a novel tool for analyzing post-viral fatigue. Multiple studies have reported detectable changes in metabolic pathways related to energy production, amino acids, nucleotides, nitrogen, lipids, and neurotransmitters in patients with post-viral fatigue (Armstrong et al., 2014; Germain, Ruppert, Levine, & Hanson., 2017; Nagy-Szakal et al., 2018; Naviaux et al., 2016). Our study of immunology and metabolomics hopes to identify possible biosignatures for PASC and ME/CFS. Our primary aims are to determine immunologic and metabolomic risk factors for the development of PASC following SARS CoV-2 infection and ME/CFS following IM. We hypothesize that altered host immune and metabolomic profiles will be associated with post-viral fatigue following primary EBV and SARS-CoV-2 infection, in contrast to healthy controls. In addition, qualitative in-depth interviews will explore perceptions of the following: major life changes, fluctuations in employment status, changes in somatic symptoms, changes in coping strategies, changes in physical and mental status, and the evolution of support systems, to determine which if any of these factors are also important for the development and maintenance of PASC and ME/CFS.

Project Narrative Our study will identify underlying biological mechanisms of PASC versus ME/CFS among an adolescent and college age sample.