2026 American Academy of Neurology Abstract Website

Objective:

To examine differential DNA methylation in Neurological Post Acute Sequelae of SARS-CoV2 Infection (Neuro-PASC), Multiple Sclerosis (MS), and Neuromyelitis Optica (NMO).

Background:

PASC (also known as long COVID) is associated with neurological signs and symptoms in a subset of patients, but its pathogenesis and possible associations with autoimmune processes are poorly understood. MS and NMO are neurological autoimmune conditions with well-established effects on the central nervous system.

Design/Methods:

Following informed consent, peripheral blood samples were collected from MS (n=70), Neuro-PASC (n=24), NMO (n=10), and control donors with non-inflammatory neurological conditions (n=42) at the University of Illinois Chicago Neurology Clinic. Genomic DNA was isolated from whole blood samples and characterized using Infinium MethylationEPIC bead arrays. Data analysis was performed in R software using the Minfi, MissMethyl, and DMRcate packages, as done in previous DNA methylation analysis pipelines in our research group.

Results:

The top 20,000 most significant differentially methylated probe loci (DMPs) from MS (p<1.3e-13, ANOVA), Neuro-PASC (p<4.1e-9), and NMO (p<2.0e-4) were analyzed. A total of 47,919 unique DMPs were identified. Approximately 22% (n=10,560) of the DMPs were common between MS and Neuro-PASC but only about 2% between Neuro-PASC and NMO (n=908). The number of DMPs unique to each disease state was 18% (n=8,827) for MS, 19% (n=9,178) for Neuro-PASC, and 39% (n=18,479) for NMO. Analysis of differentially methylated regions (DMRs) demonstrated CTSZ and ARID5B as common markers between MS and Neuro-PASC. Unique associations included CLU, SPI1, and TNF superfamily members for MS, CD19 and IER3 for NMO, and NLRC4 for Neuro-PASC. KEGG pathway analysis showed associations of T cell receptor and chemokine signaling in MS and Neuro-PASC, and unexpected associations of methylation signatures of solid tumors with NMO.

Conclusions:

Shared DNA methylation signatures between Neuro-PASC and MS, but not NMO, suggest involvement of common inflammatory pathways in the pathogenesis of the two conditions.