Studies have suggested that patients with MS have a greater susceptibility to COVID-19 infection as a result of the disease and/or the use of disease-modifying therapies (DMTs).

For a study published in the Journal of Neurology, Eduardo Agüera, MD, PhD, and colleagues sought to examine available data about how COVID-19 affects people with MS. “The massive publication of articles on the predisposition to COVID-19 in patients with autoimmune diseases and in patients with treatments that alter some immune mechanisms can lead to confusing conclusions, with very different opinions and results,” the researchers wrote. “With this review article, we intended to update the status of said predisposition, ordering and homogenizing the data. The initial publications with results based on limited population samples have resulted in conclusions that are not as valid as the current ones. The most recent publications seem to yield more homogeneous results that lead to conclusions that are more faithful to reality.”

Dr. Agüera and colleagues conducted a literature review using two databases for articles published between 2020 and 2021 with the terms COVID-19, SARS-CoV-2, and MS. Of 257 articles that were identified, 142 were included in the analysis.

An estimated 70% of patients with MS take DMTs that are classified as either immunomodulators or immunosuppressants, according to the study results. Safety concerns have been raised that suggest patients with MS on these treatments may be more susceptible to SARSCoV-2 infection.

First-Line Treatments

First-line DMTs such as interferon β (IFN-β), glatiramer acetate, teriflunomide, and dimethyl fumarate (DMF) have been associated with a lower risk for SARS-CoV-2 infection. IFN-β, for example, has powerful anti-viral effects in vivo. Some studies have shown that IFN-β could be protective in the early stages of infection, but caution that it could become harmful in the stages of hyperinflammation. IFN-β and glatiramer acetate are both being tested as possible treatments for SARS-CoV-2 infection, according to the study results.

Teriflunomide may have a role as a potential treatment for SARS-CoV-2 infections. One small study found that COVID-19 was mild in patients treated with teriflunomide, while others have demonstrated potential beneficial effects against COVID-19.

DMF was suggested as a treatment for COVID-19. It can, however, lead to severe prolonged lymphopenia in a small number of patients with MS. The activity of DMF has led to suggestions that it may be protective against SARS-CoV-2, though existing data are not robust enough to make definitive conclusions.

Second-Line Treatments

Second-line DMTs such as natalizumab, fingolimod, alemtuzumab, cladribine and anti-CD20 treatment, rituximab, ocrelizumab, and ofatumumab were also reviewed.

Studies examining natalizumab and fingolimod have included some deaths among patients on these treatments who became infected with COVID-19. However, the percentages were very low, and another study observed no deaths in similar subjects. Dr. Agüera and colleagues wrote that these DMTs could be considered safe and a good choice for individuals with active disease during the pandemic.

Patients taking alemtuzumab and cladribine have shown no increased risk for severe COVID-19 compared with the general population. Moreover, no fatalities have been reported among patients with COVID-19 who are taking alemtuzumab and cladribine.

Anti-CD20 treatments have been associated with a greater risk for SARS-CoV-2 infection and increased severity. Researchers have raised concerns about the use of ocrelizumab, a humanized anti-CD20 antibody, and a greater risk for severe COVID-19, though studies show that delaying the drug’s use may mitigate risk.

There is conflicting evidence regarding the safety of rituximab and its use during the pandemic. Investigators from one study team suggested that it be used with caution, though it has not been shown to increase morbidity and mortality.

“At the beginning of the pandemic, it was thought that patients with MS had a higher risk for SARSCoV-2 infection than the general population. After several waves of the pandemic, the descriptions in the medical literature have led us to consider that it is not the disease itself or its treatment that increases the susceptibility or incidence of the disease, but the morbidity within the patient (Figure),” the researchers wrote. “To date, anti-CD20 agents are the only treatments related to greater COVID-19 susceptibility, but only time and new publications will be able to clarify this association. Physicians should not delay MS treatments during the pandemic, and these DMTs should not be aconcern, although the predisposition with antiCD20 is pending elucidation.”