Multiple sclerosis (MS) patients who received anti-CD20 treatment (ocrelizumab) prior to receiving both doses of SARS-CoV-2 vaccines had a significantly reduced response to the vaccinations, according to a recent study published in Multiple Sclerosis and Related Disorders. After 2 vaccine doses, just 36.7% of the patients in the study had detectable levels of SARS-CoV-2-specific immunoglobulin-G antibodies.

For the patients with detectable antibodies, 5 (8.3%) had antibodies levels >264 binding antibody units (BAU)/mL, 12 (20%) had levels between 54 BAU/mL and 264 BAU/mL, and 5 (8.3%) had levels <54 BAU/mL. According to the authors, antibody levels of 264 BAU/mL and 54 BAU/mL provide 80% and 50% protection against COVID-19 infection, respectively.

“Patients with low to intermediate levels of [antibodies] may have decreased protection against COVID-19, which is important knowledge since these patients also tend to have more severe disease course,” the authors said. “Patients with untreated MS respond to vaccination similar to healthy controls, indicating that the reduced [antibody] response is related to the treatment with ocrelizumab.”

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The study also showed an effect of serial vaccination, with the number of seropositive patients increasing between the first (13.5%) and second doses (an additional 21.6%) of the vaccine. Patients who were seropositive after the first dose also showed increased levels of antibodies after the second dose.

“Given these findings, our findings of an effect of the second dose, suggest that a 3rd vaccine might potentially convert additional B-cell depleted patients to seropositive status, and increase [antibody] levels in already [antibody]-positive patients, to achieve higher protection from COVID-19,” the authors said.

However, the study did not observe a relationship between time since anti-CD20 treatment and vaccine response, with the time interval ranging from 1.9 to 36.7 weeks in the seronegative group and 4.6 to 43.0 weeks in the seropositive group.

Age and vaccine response did not appear to be related in the participants, with nonsignificant differences being observed between groups, according to the study. The median age was 47 years in the undetectable antibody group and 44 years in the detectable group.

A total of 60 MS patients were recruited for the study from 3 clinical sites in Denmark (n=37) and 1 site in the US (n=23). Fifty-nine patients received the BNT162b2 vaccine (Pfizer-BioNTech) while 1 patient received mRNA-1273 (Moderna). Blood samples were collected from all patients 0 to 7 days prior to their first vaccine and 2 to 4 weeks after their second vaccine. The Danish patients also provided blood samples 0 to 7 days prior to their second vaccine.


Novak F, Nilsson AC, Nielsen C, et al. Humoral immune response following SARS-CoV-2 mRNA vaccination concomitant to anti-CD20 therapy in multiple sclerosis. Mult Scler Relat Disord. 2021;56(103251). doi:10.1016/j.msard.2021.103251.