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.

Neurological Manifestations in a Cohort of Egyptian Patients with COVID-19: A Prospective, Multicenter, Observational Study.

BACKGROUND: The COVID-19 pandemic has reached over 276 million people globally with 5.3 million deaths as of 22nd December 2021. COVID-19-associated acute and long-term neurological manifestations are well recognized. The exact profile and the timing of neurological events in relation to the onset of infection are worth exploring. The aim of the current body of work was to determine the frequency, pattern, and temporal profile of neurological manifestations in a cohort of Egyptian patients with confirmed COVID-19 infection. METHODS: This was a prospective study conducted on 582 hospitalized COVID-19 patients within the first two weeks of the diagnosis of COVID-19 to detect any specific or non-specific neurological events. RESULTS: The patients' mean (SD) age was 46.74 (17.26) years, and 340 (58.42%) patients were females. The most commonly encountered COVID-19 symptoms were fever (90.72%), cough (82.99%), and fatigue (76.98%). Neurological events (NE) detected in 283 patients (48.63%) and were significantly associated with a severe COVID-19 at the onset (OR: 3.13; 95% CI: 2.18-4.51; p < 0.0001) and with a higher mortality (OR: 2.56; 95% CI: 1.48-5.46; p = 0.019). The most frequently reported NEs were headaches (n = 167) and myalgias (n = 126). Neurological syndromes included stroke (n = 14), encephalitis (n = 12), encephalopathy (n = 11), transverse myelitis (n = 6) and Guillain-Barré syndrome (n = 4). CONCLUSIONS: Neurological involvement is common (48.63%) in COVID-19 patients within the first two weeks of the illness. This includes neurological symptoms such as anosmia, headaches, as well as a constellation of neurological syndromes such as stroke, encephalitis, transverse myelitis, and Guillain-Barré syndrome. Severity of acute COVID-19 illness and older age are the main risk factors.

The MuSC-19 study: The Egyptian cohort.

OBJECTIVE: This study aimed to report the severity of COVID-19 in a cohort of Egyptian patients with multiple sclerosis (MS) with particular attention on the impact of disease modifying drugs (DMDs). METHODS AND STUDY POPULATION: We included 119 MS patients recruited from two centers, Ain-Shams university and Cairo university with confirmed or suspected COVID-19 during the period from May to September 2020 as a part of the MuSC-19 project. Univariate logistic regression was fitted to assess risk factors for severe COVID-19 (at least one outcome among hospitalization, ICU admission and death). RESULTS: Females were 77%, mean age was 34 years, mean duration of MS was 5.28 years, median EDSS was 3, most of the patients (83%) had RRMS, while 15% and 2% had respectively SPMS and PPMS. Only eleven patients (9% of study population) had a severe outcome and 3 patients (3%) died. Headache was the only symptom significantly associated with the severity of COVID-19 (OR=10.85, P = 0.001). There was no association between any of the DMDs and severe COVID-19 outcome. CONCLUSION: This study showed an acceptable safety profile of DMDs in Egyptian MS patients who developed COVID-19, as 91% of the cohort had a favorable outcome. Headache as a symptom associated with severe outcome in Egyptian patients' needs further validation.

Could SARS-CoV-2 herald a surge of multiple sclerosis?

During the current COVID-19 pandemic, many queries are raised regarding its nature, outcome, and sequelae. This letter raises the concern of potential impact on increasing the incidence of multiple sclerosis whose pathology involves a possible viral etiology. Besides, the potential neurotropism of the acute respiratory distress syndrome corona virus-2 (SARS-CoV-2), which is still not established, may raise concerns about the use of certain disease modifying therapies namely natalizumab.

Management Strategies of Patients with Neuromyelitis Optica Spectrum Disorder During the COVID-19 Pandemic Era.

The ongoing coronavirus (COVID-19) pandemic is a global health emergency of international concern and has affected management plans of many autoimmune disorders. Immunosuppressive and immunomodulatory therapies are pivotal in the management of neuromyelitis optica spectrum disorder (NMOSD), potentially placing patients at an increased risk of contracting infections such as COVID-19. The optimal management strategy of NMOSD during the COVID-19 era remains unclear. Here, however, we examined the evidence of NMOSD disease-modifying therapies (DMTs) use during the present period and highlighted different scenarios including treatment of relapses as well as initiation and maintenance of DMTs in order to optimize care of NMOSD patients in the COVID-19 era.

Managing Disease-Modifying Therapies and Breakthrough Activity in Multiple Sclerosis Patients During the COVID-19 Pandemic: Toward an Optimized Approach.

The emergence of the novel coronavirus disease 2019 (COVID-19) pandemic has become a major public health challenge of global concern since December 2019, when the virus was recognized in Wuhan, the capital city of Hubei province in China and epicenter of the COVID-19 epidemic. Given the novelty of COVID-19 and the lack of specific anti-virus therapies, the current management is essentially supportive. There is an absence of consensus on guidelines or treatment strategies for complex disorders such as multiple sclerosis (MS), in which the risk of infections is higher than in the general population. This is due to the overall impairment of the immune system typical of autoimmune diseases, in addition to accumulation of disabilities, and the iatrogenic effect generated by corticosteroids and the recommended disease-modifying therapies (DMTs). DMTs have different modes of action, but all modulate and interfere with the patient's immune response, thereby raising concerns about adverse effects, such as an increased susceptibility to infections. In this review, we analyze the evidence for use of DMTs during the current critical period and ratify an algorithmic approach for management to optimize care between keeping DMTs, with their infection hazards, or coming off them, with the risk of disease activation. We also provide an algorithmic approach to the management of breakthrough activity during the COVID-19 pandemic.