Two studies—one in the Annals of Neurology, the other in Neurology Neuroimmunology and Neuroinflammation—examined Covid-19 vaccine response and reactions in people with multiple sclerosis (MS).

Compared with MS patients on no disease-modifying therapy, patients using the anti-CD20 monoclonal antibodies ocrelizumab, rituximab, and ofatumumab had lower seroconversion following dose two of vaccination (OR 0.03, 95% CI 0.01-0.06, P<0.001), reported Ruth Dobson, PhD, of Queen Mary University London in England, and co-authors. MS patients using fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, also had lower seroconversion (OR 0.04, 95% CI 0.01-0.12, P<0.001), they wrote in Annals of Neurology.

A separate study, from Farren Basil Shaw Briggs, PhD, of Case Western Reserve University, in Cleveland, Ohio, and co-authors in Neurology Neuroimmunology and Neuroinflammation, showed that reactions to Covid-19 vaccination within 24 hours of the first shot were reported by 64% of MS patients, and profiles were similar to those of the general population.

Covid-19 Vaccine Response

While anti-CD20 drugs and fingolimod showed lower odds of seroconversion after SARS-CoV-2 vaccination, all other tested drugs did not differ significantly from the untreated cohort, Dobson and co-authors noted.

“Our overall finding of a differential humoral response according to vaccine type replicates data in healthy control cohorts, but was not replicated in people on anti-CD20 disease modifying therapy,” the researchers wrote. “Whereas this provides no current rationale for recommending one vaccine type over another in those at risk of an attenuated response, this is deserving of further study given potential limitations of power.”

“Both time since last anti-CD20 treatment and total time on treatment were significantly associated with the response to the vaccination,” they added. “The vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications.”

The observational study reported on 473 MS patients seen at MS clinics in the U.K. who were recruited between November 2020 and June 2021. Covid-19 infection, vaccination, and medical history were assessed along with dried blood spot testing for antibodies to SARS-CoV-2. The researchers determined odds of seroconversion by therapy and considered vaccine timing, treatment duration, age, vaccine type, and lymphocyte count in the analysis.

Vaccine type was available in 85.4% participants: 180 people had the BNT162b2 vaccine and 224 had an adenoviral vector vaccine (223 participants had ChAdOx1 nCoV-19, and one received Ad26.CoV2.S).

People with MS who were not receiving MS therapy were used as the reference group. The overall rate of seroconversion after dose two of a vaccine in this group was 92% (OR 1.0 by definition), with 93% seroconversion after the ChAdOx1 nCoV-19 vaccine and 100% seroconversion for the BNT162b2 vaccine. The OR for seroconversion after the BNT162b2 versus ChAdOx1 nCoV-19 vaccine was 2.65 (95% CI 1.27-5.52, P<0.01).

“Delaying commencement of fingolimod or anti-CD20 disease modifying therapy should be considered in new starters, to allow time for vaccination,” Dobson and co-authors recommended. While the study did not show a relationship between delaying established anti-CD20 infusions and improving seroconversion, this analysis is likely to have been underpowered, the researchers observed.

“The proportion of individuals who seroconverted increased between vaccine 1 and 2, in keeping with studies in the healthy control population, supporting the use of a booster vaccination, particularly for those who may have had an attenuated response to the initial vaccination,” they noted.

Though it is not yet routine to test anti-SARS-CoV-2 antibodies in clinical practice, knowledge of seronegative status in people with MS may allow more vigilant infection control precautions, for example, continuing to socially distance and ensuring that household contacts are vaccinated, the researchers suggested. Seronegative patients may also benefit from monoclonal antibodies to SARS-CoV- 2, they added.

Vaccine Reactogenicity

In a separate study, Briggs and colleagues looked at retrospective data from 719 MS patients in iConquerMS, an online patient-response research network. Most participants (84.6%) were women, and 94.2% were White.

Between March and June 2021, participants reported experiences within 24 hours of vaccination as none, mild, moderate, or severe for local symptoms (itch, pain, redness, swelling, or warmth at injection site) and systemic symptoms (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other).

“SARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of people with MS appear similar to those reported in the general population,” Briggs and co-authors wrote. “People with MS on specific disease-modifying therapies were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.”

MS patients on an S1P modulator or fumarate were significantly less likely to report a reaction, the researchers noted. “Furthermore, there were no associations between vaccine reactogenicity and MS subtype or disease duration, but people with MS with a higher PDDS [Patient-Determined Disease Steps, a measure of disability] may experience a slight increase in severe reactions after the first but not the second vaccination—reasons for this observation are unclear,” they wrote.

Overall, 64% of participants reported any reaction after the first vaccination shot, with 17% reported as severe. Younger age, being female, and prior SARS-CoV-2 infection were associated with experiencing a reaction after the first vaccine dose. Higher odds of reaction were also seen with more physical impairment, while lower odds of reactions were seen for patients treated with an alpha4-integrin blocker (ofatumumab) or S1P inhibitor (fingolimod, siponimod, ozanimod).

The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Any reaction after a second vaccination shot were reported by 74% of the 442 patients with second vaccination; 22% reported a severe reaction.

The iConquerMS system may have introduced selection bias in their cohort, Briggs and colleagues noted.


Biogen, Merck, Novartis, Roche, Sanofi/Genzyme, and Teva manufacture MS drugs used in the vaccine seroconversion study, or which could be affected by the study, the researchers noted. Dobbs and co-authors had relationships with these companies.

The Covid-19 vaccination reactogenicity study was supported by the National Multiple Sclerosis Society (NMMS). Briggs has received research grants from the NMSS, the Michael J. Fox Foundation, and the National Institute for Health.



Paul Smyth, MD, Contributing Writer, BreakingMED™

Kaiser Health News

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.