Response to COVID-19 booster vaccinations in seronegative people with MS. (preprint)

Importance: Uncertainties remain about the benefit of a 3rd COVID-19 vaccine for people with attenuated response to earlier vaccines. This is of particular relevance for people with multiple sclerosis (pwMS) treated with anti-CD20 therapies and fingolimod, who have substantially reduced antibody responses to initial vaccine course. Objective: To report humoral and T-cell responses following COVID-19 vaccine 3 in pwMS who were seronegative after COVID-19 vaccines 1&2. Design, setting and participants: PwMS taking part in a seroprevalence study without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Data on demographics, MS treatment, and COVID-19 infection/vaccine dates were derived from the medical notes. Methods: Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. The relationship between evidence of prior COVID-19 infection and immune response to COVID-19 vaccine 3 was evaluated using Fishers exact test. Results: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There no association between laboratory evidence of prior COVID-19 infection and anti-spike seroconversion following COVID-19 vaccine 3. Conclusions: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.

COVID-19 vaccine response in people with multiple sclerosis (preprint)

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.