Disease-Modifying Therapies, Outcomes, Risk Factors and Severity of COVID-19 in Multiple Sclerosis: A MENACTRIMS Registry Based Study

BACKGROUND: Multiple sclerosis (MS) patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, there is little data in our Middle East and North Africa region (MENA) identifying clinical characteristics of MS associated with worse COVID-19 outcomes. MATERIAL(S) AND METHOD(S): This a nationwide, multicenter, retrospective cohort study conducted between March 2020 and February 2021 and included MS patients with a suspected or confirmed COVID-19. Using data collected from the MENACTRIMS registry and local COVID-19 registries, the association of patient demographics, MS disease characteristics, and use of disease-modifying therapies with outcomes and severity of COVID-19 illness were evaluated by multivariate logistic models. RESULTS: A total of 600 MS patients with suspected (n=58) or confirmed (n=542) COVID-19 (mean age: 36.4 ± 10.16 years; 414 (69%) females; mean disease duration: 8.3± 6.6 years) were analyzed. Seventy-three patients (12.2%) had a COVID-19 severity score of 3 or more, and 15 patients (2.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 559 patients (93.2%) were receiving disease-modifying therapy (DMT). There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients treated with DMTs relative to untreated patients (82.9% vs 17.1%; P < .001), from whom the majority (n=117; 19.7%) were maintained on anti-CD20 therapies such as ocrelizumab and rituximab. Comorbidities mainly hypertension and cardiovascular diseases, progressive MS, disease duration, and EDSS were associated with severe or worse COVID-19 disease outcome. Multivariate logistic regression analysis showed that older age (odds ratio per 10 years, 1.5 [95%CI, 1.1-2.0]), male gender (OR, 2.1 [95%CI. 1.2-3.8]), obesity (OR, 2.8 [95%CI, 1.3-5.8]), and treatment ocrelizumab/rituximab (OR for ocrelizumab, 4.6 [95%CI. 1.2-17.7], OR for rituximab, 14.1 [95%CI, 4.8-41.3]) or off-label immunosuppressive medications such as azathioprine or mycophenolate mofetil (OR, 8.8 [95%CI. 1.7-44.0]) were risk factors for moderate to severe COVID-19 requiring hospitalization. Surprisingly, smoking and diabetes were not identified as risk factors for severe COVID-19 disease in our cohort. CONCLUSION: In this registry-based cohort study of patients with MS, age, sex, EDSS, obesity, progressive MS were independent risk factors for severe COVID-19. Moreover, there was an association found between exposure to anti-CD20 DMTs and COVID-19 severity. Knowledge of these risk factors may help improve the clinical management of MS patients with COVID-19 infection.