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Anti-CD20 therapies increase while mRNA vaccines decrease the risk of COVID-19 in multiple sclerosis and neuromyelitis optica patients.

During the COVID-19 pandemic, concerns were raised for vulnerable patients suffering from neuroinflammatory diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MS patients showed a higher hospitalization rate with COVID-19 than the general population. 

A retrospective study in the Journal of Clinical Medicine examined the impact of disease-modifying treatment, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, and vaccination on COVID-19 risk in MS and NMOSD patients.

Study Population

A total of 352 patients were included. The median age was 48.5 years, and 68.2% were female. Out of these, 315 were vaccinated for SARS-CoV-2 with mRNA vaccines. Vaccinated patients were significantly older than non-vaccinated patients. Overall, 134 patients had experienced COVID-19 by data collection time. Of the 315 vaccinated patients, 206 never experienced COVID-19, 82 experienced breakthrough COVID-19 after vaccination, and 27 were vaccinated after a previous SARS-CoV-2 infection.

Vaccination Lowers the Risk of COVID-19 in MS and NMOSD

Univariate logistic regression analysis showed that greater age, higher expanded disability status scale (EDSS) score, and being vaccinated were significantly associated with lower risk of COVID-19. Of these variables, only vaccination status remained significant (odds ratio (OR): 0.10, 95% confidence interval (CI): 0.05-0.20, p < 0.001) after multivariate analysis, while age and EDSS associations were attenuated.

Anti-CD-20 Treatment Increases the Risk of COVID-19 in MS and NMOSD

Treatment with anti-CD20 was associated with a higher risk of COVID-19 (OR: 2.26, 95% CI: 1.284.00, p = 0.005) using the multivariate model. Within the group of vaccinated patients, age was inversely associated, while anti-CD20 treatment was positively associated with the risk of COVID-19 using the multivariate model.

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Differing Variables in Mild and Severe Cases of COVID-19

Of the 144 patients with COVID-19 infection, 129 had mild disease, and 15 had a severe course requiring hospitalization. Patients with severe COVID-19 were older and had higher EDSS scores compared to those with mild disease. Of 15 severe cases, 13 occurred during treatment with anti-CD20 antibodies, one in a patient treated with natalizumab, and one under no treatment. Only 26.7% of severe cases occurred in those vaccinated before infection, compared to 66.7% of mild cases. The most frequent variant among severe cases was Alpha (73.3%), while the most frequent among mild cases was Omicron (69.8%).

Anti-CD-20 Treatment and Omicron Variant
Univariate analysis showed that higher EDSS and anti-CD-20 treatment at the time of infection were positively associated with severe COVID-19. Meanwhile, being vaccinated and infection with the Omicron variant were associated with a lower risk of severe COVID-19. In multivariate analysis, only anti-CD-20 treatment (OR: 27.41, 95% CI: 3.68204.25, p = 0.001) and the Omicron variant (OR: 0.03, 95% CI: 0.010.35, p = 0.006) remained significant.


Eisler, J. J., Disanto, G., Sacco, R., Zecca, C., & Gobbi, C. (2023). Influence of Disease modifying Treatment, Severe Acute Respiratory Syndrome Coronavirus 2 variants and vaccination on coronavirus Disease 2019 Risk and Outcome in multiple sclerosis and neuromyelitis Optica. Journal of Clinical Medicine, 12(17), 5551. https://doi.org/10.3390/jcm12175551