Plasma Proteomics Identifies a Microtesla Magnetic Therapy Response Signature in Long COVID

Abstract

Cognitive impairment is a disabling feature of Long COVID with no established disease-modifying therapy, and little is known about the biological changes accompanying clinical improvement. Microtesla Magnetic Therapy (MMT) is a low amplitude radiofrequency electromagnetic field intervention delivered to the whole brain. In a randomized, sham-controlled feasibility trial, at home MMT was feasible, safe, and well tolerated, with evidence of clinical improvement among treated participants. We explored molecular changes associated with response using SomaScan 11K plasma proteomics on paired baseline and week 4 samples. Participants were classified post hoc within each treatment arm using a clinician-selected response phenotype integrating cognitive and symptom domains. These groups were used for proteomic, pathway, and OrganAge analyses. MMT response was associated with selective proteome remodeling and an exploratory 17 protein response pattern in which Hedgehog interacting protein (HHIP), a Hedgehog signaling antagonist, was most strongly associated with response. Directional pathway analysis identified patterns consistent with lower inflammatory and injury biology and higher repair and adaptive remodeling. OrganAge analysis showed trends toward lower Brain and Organismal OrganAge with MMT. These findings prioritize HHIP and the exploratory 17 protein response pattern for prospective validation and support evaluation of plasma proteomics for monitoring treatment response.