Longitudinal humoral and cellular immune responses to COVID-19 vaccination in persons with multiple sclerosis across...

Humoral responses to COVID-19 vaccination are attenuated in some people with multiple sclerosis (PwMS), particularly those receiving B-cell-depleting therapies or sphingosine-1-phosphate receptor modulators (S1PR). Less is known about how disease-modifying therapies (DMTs) shape cellular responses over time.

Evaluate longitudinal SARS-CoV-2 Spike IgG and antigen-specific T-cell responses in vaccinated PwMS across DMT classes in a decentralized study.

COVER-MS participants underwent decentralized biospecimen collection through Quest Diagnostics Patient Service Centers or mobile phlebotomy, paired with electronic surveys through iConquerMS. The study included 183 participants at Visit 1, 161 at Visit 2, and 141 at Visit 3. Spike IgG was categorized into ordered levels, and SARS-CoV-2-specific T-cell responses were measured using QuantiFERON Ag1, Ag2, and Ag3 interferon-gamma release assays. Participant-level mixed-effects models evaluated associations for DMTs, visit, and DMT × visit interactions.

Longitudinal immune-response patterns differed across DMTs for Spike IgG (omnibus DMT × visit p=0.003) and Ag1 (p=0.025). B-cell depleters were associated with lower Spike IgG responses, with further attenuation by Visit 3, while Ag1-Ag3 responses were preserved. S1PR modulators were consistently associated with lower Spike IgG and Ag1-Ag3 responses. Fumarate-treated PwMS had lower cellular responses at later visits, with a significantly more negative Visit 1 to Visit 2 change in Ag1. Prior SARS-CoV-2 infection was associated with higher humoral and cellular responses, and mRNA-1273 vaccination was associated with higher Spike IgG.

DMT class was associated with distinct humoral and cellular SARS-CoV-2 immune-response profiles in vaccinated PwMS, supporting multidimensional immune assessment and decentralized longitudinal biospecimen collection in MS research.