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Over 18 months of experience with the COVID-19 pandemic has provided some direction in terms of managing the risks for people with multiple sclerosis (MS), despite the relatively low prevalence of infection in this population. Still, uncertainties remain for people whose neurological condition and its immunomodulatory and immunosuppressive treatments may put them at increased risk for infection, with potentially more severe consequences.

"The literature shows that individuals with underlying neurological impairment are more vulnerable to infection with COVID-19, and those who are infected have been shown to have ," Nancy D. Chiaravalloti, PhD, of the Kessler Foundation in New Jersey, told 麻豆传媒. "In addition, COVID-19 is more severe in the presence of comorbidities, so it is always important for individuals with MS to be very careful. That said, the 4% rate of infection for individuals with MS is similar to that of the general population. It is not clear if this is because individuals with MS are being very cautious or if the actual infection rate is equivalent."

Indeed, recent data show significantly greater COVID severity in some people with MS. In multivariable models, "older age and higher MS-related disability are the strongest and most consistent characteristics of more severe COVID-19, independent of other factors assessed such as sex and progressive MS phenotype," Steve Simpson-Yap, PhD, MPH, of the University of Melbourne, told 麻豆传媒.

Among an of 2,340 patients with suspected (~28%) or confirmed (~72%) COVID, about one in five was hospitalized, 5.4% were admitted to the ICU, 4.1% required artificial ventilation, and 3.2% died, Simpson-Yap and co-authors reported. "Higher EDSS [Expanded Disability Status Scale] (>6) was associated with 279% higher hospitalization, 211% higher ICU admission, 281% higher ventilation, and 893% higher death frequencies," they added. Other factors implicated in COVID severity included progressive MS phenotype (associated with 68% higher risk of hospitalization), older age, and comorbidities such as cardiovascular disease, hypertension, and obesity.

Some vaccine hesitancy has been noted in the public in general. Although some people were unwilling to be vaccinated, "most of our clinic patients were very much looking forward to a vaccine," said Sarah Morrow, PhD, of the University of Western Ontario, in an interview. "The number one question we received ... was whether it was safe to get the vaccine based on the disease-modifying therapy [DMT] they were taking. Some of the disease-modifying therapies preclude the use of live vaccines. This does not apply to the mRNA vaccines and thus they are safe for all our treatments."

The second most common and "reasonable" question was whether it was safe to get the vaccine due to their MS diagnosis, Morrow noted; she added that COVID-19 vaccines are considered safe for patients with MS, and are recommended by and Canadian MS organizations.

Indeed, a preliminary analysis of a large prospective study in Italy found no increase in the short-term risk of MS relapse after vaccination with the Pfizer-BioNTech COVID-19 mRNA vaccine.

However, treatment with anti-CD20 drugs has been linked with worse illness, according to several large studies, including an analysis of shared data .

"Importantly, the finding [from our study and others] that certain disease-modifying therapies, particularly the anti-CD20 DMTs ocrelizumab [Ocrevus] and rituximab [Rituxan], were associated with more severe COVID-19 independent of demographic and clinical characteristics such as older age, progressive MS phenotype, and higher disability, suggests that the DMT associations with more severe COVID-19 are not merely a function of underlying predisposition of patients taking those medications, but are due to the DMTs themselves," Simpson-Yap noted.

"The mode by which the anti-CD20 DMTs may have an adverse impact on COVID-19 severity remains to be examined," he added, "though there are biological mechanisms potentially at play such as differential antigen presentation functions of the B lymphocytes, which are depleted by these therapies."

Given evidence that serological response to COVID immunization requires adequate circulating B-cell lymphocytes, B-cell-depleting DMTs may adversely affect the efficacy of immunization, he said. He urged medical providers to "carefully review guidance about the dose, duration of therapy, and interval since last infusion in regards to SARS-CoV-2 immunization before making any recommendations."

"The use of disease-modifying therapies continues to be guided by highly individualized considerations. ... [Use of] anti-CD20 therapies, which are among the most effective therapies available for MS ... should prioritize the optimal control of patients' MS, while minimizing individual risks associated with protracted depletion of B cells," Simpson-Yap noted.

Nancy Sicotte, MD, of Cedars-Sinai Medical Center in Los Angeles and a member of advisory committees for the National MS Society, and Julie Fiol, RN, MSCN, of the National MS Society, advised clinicians to engage with patients to determine optimal timing of the vaccination, including additional doses and boosters, vis-a-vis their anti-CD20 therapy.

"This discussion would include the patient's MS history, DMT history, current disease activity, COVID-19 risk factors, and occupational risk, among others. Emerging data support timing vaccination at least 3 months after the anti-CD20 infusion and suggest that waiting longer than 3 months could improve the antibody response. This must be balanced with the MS risk factors outlined earlier. These are individualized decisions and no one recommendation can be applied to all," they told 麻豆传媒.

The COVID-19 Vaccine Advisory Group of the National MS Society developed guidance for vaccine , as well as , Sicotte and Fiol said. "We specifically outline considerations for healthcare providers and their patients to use when making decisions for ."

People with MS look to their healthcare providers and the National MS Society for guidance on vaccines, but many want to maintain their autonomy and self-determination in healthcare decisions, they explained. A COVID-19 Vaccine Conversation has been developed by the society for a "non-judgmental, objective conversation between the healthcare provider and their patient."

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