COVID-19 vaccine response in people with multiple sclerosis

Objective: To investigate the effect of disease modifying therapies on serological response to SARS-CoV2 vaccines in people with multiple sclerosis Methods: 473 people with multiple sclerosis from 5 centres provided one or more dried blood spot samples and a questionnaire about COVID-19 and vaccine history. Information about disease and drug history was extracted from their medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV2 receptor binding domain. Seropositivity was expressed according to validated cut-off indices. Antibody titers were partitioned into tertiles using data from people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (Univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following SARS-CoV2 vaccine according to disease modifying therapy. We used regression modelling to explore the effect of factors including vaccine timing, treatment duration, age, vaccine type and lymphocyte count on vaccine response. Results: Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio 0.03; 95% confidence interval 0.01-0.06, p<0.001) and fingolimod (odds ratio 0.41; 95% confidence interval 0.01-0.12) were associated with lower seroconversion following SARS-CoV2 vaccine. All other drug groups did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly related with serological response to vaccination. Vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Interpretation: Some disease modifying therapies carry a risk of attenuated response to SARS-CoV2 vaccination in people with MS. We provide recommendations for the practical management of this patient group.