Post-COVID-19 syndrome (PCS) is a significant long-term complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, yet its prevalence and risk factors in people with multiple sclerosis (pwMS) under disease-modifying therapies (DMTs) remain underexplored.

This study aimed to characterize the clinical course of coronavirus disease 2019 (COVID-19) and identify predictors of PCS in pwMS, focusing on vaccination status, infection severity and frequency, and DMT categories.

In this cross-sectional study, 107 pwMS from two centers completed a survey assessing COVID-19 history, persistent symptoms, immunotherapy, and vaccination status. PCS was defined as symptoms persisting >12 weeks after infection. Participants were stratified by DMT categories, infection number, and vaccination status.

Of 107 participants, 7 (6.5 %) reported PCS. The most frequent symptoms were fatigue (71.4 %), pain (57.1 %), and headache (42.9 %). Patients with PCS had a higher mean number of SARS-CoV-2 infections (2.1, 95 % CI: 1.3–3.0) compared to those without (1.3, 95 % CI: 1.2–1.4; p = 0.004). A significant association was found with DMT category: 71.4 % (5/7) of affected individuals were on category I therapies (Interferon/Glatiramer acetate, Dimethyl fumarate, Teriflunomide) compared to 17 % of pwMS without PCS (p < 0.001). No significant effect was observed for COVID-19 severity or vaccination status.

PCS prevalence in this MS cohort was lower than in the general population, but category I DMTs and repeated infections were key risk factors. Findings suggest the need for individualized risk assessment, indicating that higher efficacy DMTs do not appear to pose an increased risk of PCS in pwMS.

Post-COVID-19 Syndrome

Multiple Sclerosis

Disease-modifying therapies

Vaccination

Long COVID

SARS-CoV-2

Fatigue

© 2025 The Author(s). Published by Elsevier B.V.