Study Finds Some Disease-Modifying Therapies Reduce COVID-19 Protective Immunity in Patients With MS

Some immunosuppressive medications, particularly anti-CD20 monoclonal antibodies, were found to reduce antibodies designed to protect against SARS-CoV-2 infection in patients with multiple sclerosis (MS) who have recovered from COVID-19, investigators concluded.

Immunosuppressive medications for the treatment of multiple sclerosis (MS) were found to cut the levels of SARS-CoV-2 antibodies by half in patients who have recovered from symptomatic COVID-19, according to a recent study.

The nationwide, multicenter, prospective study from Austria, published in the Multiple Sclerosis Journal, provided important evidence that can serve as an advisement for patients with MS for the planning and prioritization of vaccinations against COVID-19 and raised prominent concerns over the impact that DMTs, particularly anti-CD20 monoclonal antibodies, can have on prolonged immunity against SARS-CoV-2 infection.

After recovering from COVID-19, the immune response of the general population is high and stable for at least 6 to 9 months. However, some investigators have raised concerns over whether immunomodulatory or immunosuppressive disease-modifying therapies (DMTs) may change the immune response to antibodies for SARS-CoV-2, the virus that causes COVID-19, in patients with MS.

“The global struggle for returning to life once termed ‘normal’ and dealing with the tremendous social and economic consequences of the pandemic hinders to a large part on developing protective immunity both as societies and individuals,” wrote the study authors.

Anti-CD20 monoclonal antibodies are typically used to treat B-cell proliferative disorders, including non-Hodgkin lymphoma and chronic lymphocytic leukemia. Examples of anti-CD20 monoclonal antibodies include rituximab (Rituxan), ofatumumab (Kesimpta), and ocrelizumab (Ocrevus).

Current literature suggested that DMTs do not significantly impact the clinical course or severity of COVID-19. However, the degree or duration of protective immunity against future infections of SARS-CoV-2 may be impaired. Also, data on SARS-CoV-2 antibodies in patients with MS are lacking.

The investigators invited all the patients from the Austrian MS-COVID-19 registry who had a clinical diagnosis of MS and a history of symptomatic COVID-19 to participate. The recruitment period ended on May 31, 2021. Of the 183 patients in the registry, 125 were available for antibody testing and were included in the analysis, of whom 87 (69.9%) were women and the mean (SD) age was 42.4 (12.3) years.

After a median of 5.2 months after receiving a positive polymerase chain reaction to antibody test confirming the presence of COVID-19, anti–SARS-CoV-2 antibodies were detected among 76.0% (n = 95) of patients. Seropositivity rates were observed to be lower in patients receiving an immunosuppressive DMT (61.4%; P = .001) compared with patients who were not receiving a DMT (80.6%) or who were receiving an immunomodulatory DMT (86.0%).

Rates of seropositivity were found to be the lowest in patients who were treated with ocrelizumab (50.0%), alemtuzumab (50.0%), rituximab (60.0%), fingolimod (68.8%), and cladribine (75.0%). Seropositivity rates were at or above 80% for patients that were receiving dimethyl fumarate (80.0%), teriflunomide (83.0%), interferon beta (88.9%), glatiramer acetate (88.9%), and natalizumab (90.9%).

During a multivariate analysis, immunosuppressive DMTs were found to be associated with a reduced probability of seropositivity, demonstrating an odds ratio (OR) of 0.51 (95% CI, 0.17-0.82; P < .001). Additionally, predefined subgroup analyses showed marked reduction of seropositivity in those who were being administered rituximab or ocrelizumab (OR, 0.15; 95% CI, 0.05-0.56; P < .001). The rate of seropositivity was not significantly altered during the first 6 months after receiving a positive test for COVID-19 and was not impacted by age, sex, or COVID-19 severity.

Limitations of the study included that the investigators did not conduct serial antibody testing, that they did not perform any significance tests on single DMT levels, and that confounders influencing seropositivity in patients with MS may have been unaccounted for during the analyses.


Bsteh G, Dürauer S, Assar H, et al. Humoral immune response after COVID-19 in multiple sclerosis: a nation-wide Austrian study. Mult Scler J. Published online October 1, 2021. Accessed October 6, 2021. doi:10.1177/13524585211049391