Correlating neutrophil function and plasma cytokine profiles with progression of ME/CFS and Long-Covid/PASC

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SUMMARY Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS) is a complex chronic condition associated with prolonged inflammatory signaling. Long Covid/Post-Acute Sequelae of Covid (PASC) has been noted as a relatively common outcome of SARS-CoV-2 infection, and appears to mirror many of the features of ME/CFS, suggesting that the etiology of these conditions might be shared [1, 2]. Neutrophils are the most common immune cells in the circulation and are exquisitely sensitive to changes in inflammatory signaling. We have developed a unique panel of microfluidic assays that probe neutrophil function from a drop of fresh blood. We recently used these assays on fresh fingerpick blood obtained from 6 ICC-diagnosed ME/CFS subjects and 1 PASC subject and found preliminary evidence that multiple neutrophil functions were altered in ME/CFS relative to progression of disease. Strikingly, the PASC subject exhibited changes in neutrophil function most similar to early-stage ME/CFS. The goal of our project is to use these microfluidic assays to probe neutrophil function in a larger cohort of ICC-ME/CFS, PASC subjects, and healthy controls. We will characterize neutrophil motility and extracellular trap formation (NETosis) from a drop of fresh blood, both at baseline and following in vitro stimulation, in all subjects. We will also use an established panel to characterize proinflammatory cytokines in ME/CFS, PASC, and healthy control subject blood collected at the same time as the neutrophil fingerprick samples. This will determine if proinflammatory cytokine burden will correlate with neutrophil motility and baseline NETosis across groups. An overarching aim of the proposal is to analyze neutrophil responses as a function of illness duration in both ME/CFS and PASC. Characterization of neutrophil behavior in relatively recent-onset PASC will lay the groundwork for future longitudinal studies of this condition and will help determine the mechanistic overlap with ME/CFS or lack thereof.