W133 - Identification and Treatment of CD8 T Cell Exhaustion and Symptoms in Myalgic Encephalomyelitis/chronic Fatigue Syndrome (ME/CFS) and Long COVID with Inspiritol in a Case Based Study

George Hoag; John Salerno; Mady Hornig; Nancy Klimas; Liisa Selin

Abstract Text: Patients with Long COVID, the new pandemic, have a symptom complex highly analogous to ME/CFS, suggesting that at least a subset may have the same disorder. There is an urgent need for diagnostic tools and treatment strategies for these two related poorly understood devastating disorders. Here, we hypothesize that Long COVID and ME/CFS maybe due to an aberrant response to an immunological trigger like infection, which results in a dysregulated immune system dominated by CD8 T cell exhaustion. We treated 4 ME/CFS and 4 Long COVID patients in an open-label study with Inspiritol, a compounded drug taken by nebulizer that has the potential to relieve oxidative stress, attenuate NF-κB signaling, and act directly against pathogens. First, we show that CD8 T cells were functionally exhausted in production of IFN and TNF by intracellular cytokine assays in ME/CFS (n=12) and Long COVID (n=8) patients compared to healthy donors (n=10). Then we used this assay and our symptom severity questionnaire to track disease outcome during Inspiritol therapy. Here, we present two observations fundamental to the pathogenesis and treatment of Long COVID and ME/CFS: 1) both diseases are characterized by exhausted T cells with severe deficiencies in their abilities to produce IFN and TNF; 2) a new immune-modulatory and anti-oxidant reagent, Inspiritol, corrects this immune deficiency and improves health of the patients. This work provides evidence of a new treatment and a biomarker useful for diagnosis and tracking of treatment outcomes that can help expedite clinical trials in both Long COVID and ME/CFS.