Importance: Management of long-term consequences after acute COVID-19 in people with multiple sclerosis and related disorders (pwMSRD) is challenging due to overlapping clinical presentations. There have been limited investigations of post-COVID sequelae in pwMSRD. Objective: We assessed whether pwMSRD were more susceptible to post-COVID sequelae when compared to controls. Design: This cross-sectional study leveraged a multi-center cohort of pwMSRD and controls. Setting: A one-time web-based survey was conducted between August and December 2022. Participants: Out of the 2,156 participants who consented, the analysis included 1,972 after excluding 184 due to missing data. Main Exposure: Diagnosis of MSRD. Main Outcomes and Measures: We surveyed 71 symptoms that emerged at least 1 month after the initial acute COVID-19 and were either new onset or worsening from the pre-COVID baseline. We assessed whether each participant experienced (1) ≥1 new symptom, (2) ≥1 worsening symptom from baseline. Results: The study included 969 pwMSRD (799 [82.5%] women, mean age 51.8 [SD 12.1] years) and 1,003 controls (796 [79.4%] women, mean age 45.2 [SD 10.3] years). 613 pwMSRD (63.5%) and 614 controls (61.2%) experienced acute COVID-19. Compared to controls, pwMSRD had higher odds of developing a new symptom (OR=1.55; 95%CI=1.22-1.98; p<.01) and experiencing a worsening symptom from baseline (OR=3.39; 95%CI=2.64-4.36; p<.01). PwMSRD were more likely to develop new symptoms involving the pulmonary as well as head, eyes, ears, nose, and throat systems, and have worsening systemic, musculoskeletal, and neuropsychiatric symptoms from baseline. Acute COVID-19 severity mediated >20% of the association between MSRD diagnosis and post-COVID sequelae. In the subgroup of pwMS, having post-COVID sequelae was associated with worse functional disability. Conclusions and Relevance: Compared to controls, pwMSRD experienced an increased risk of post-COVID sequelae involving multiple organ systems. Post-COVID sequelae was associated with greater disability in pwMS. The findings highlighted the importance of recognizing and managing long-term symptoms following acute COVID-19 in this vulnerable population.

The authors have declared no competing interest.

The study is supported in part by NINDS R01NS098023 and NINDS R01NS124882

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