ABSTRACT
Introduction: People with multiple sclerosis (PwMS) treated with anti-CD20 therapies and fingolimod are less likely to successfully produce a humoral response to COVID-19 vaccines 1 and 2. Objective(s): To measure the humoral and/or cellular response to COVID-19 booster vaccinations in a cohort of PwMS who were previously seronegative after their initial COVID vaccine course. Aim(s): To determine whether there is a benefit of COVID-19 booster vaccinations for people with MS who are known to have had an attenuated response to initial vaccines. Method(s): We studied a cohort of PwMS all of whom were seronegative for anti-SARS-CoV-2 spike protein IgG after the 1st and 2nd COVID-19 vaccines, including PwMS treated with ocrelizumab (n=53), fingolimod (n=15), other DMTs (n=9) and no DMT (n=2). Dried blood spot +/- whole blood samples were obtained from participants at 2-8 weeks after their 3rd (n=79) and 4th (n=40) COVID-19 vaccines. Samples were used to measure anti-SARS-CoV-2 spike protein IgG (ELISA) and T-cell response (IFN-g release assay measured on whole blood). Result(s): Overall 27/79 (34%) who were seronegative after COVID vaccine 2 seroconverted after vaccine 3. Seroconversion rates were 17% for PwMS treated with ocrelizumab, 47% for fingolimod and 100% for other DMTs. A further 2/30 (7%) of those who remained seronegative after vaccine 3 seroconverted after vaccine 4. Anti-SARS-CoV-2 T-cell responses were measurable in 26/40 (65%) after vaccine 3 and 13/19 (68%) after vaccine 4 but were conspicuously absent in people treated with fingolimod. Overall, 75% of participants showed either humoral or cellular response after receiving 4 COVID vaccinations. PwMS with laboratory evidence of prior COVID-19 infection had higher measurable T-cell responses. Conclusion(s): Booster vaccinations for COVID-19 are associated with incremental benefits in measurable immunity in those with attenuated responses to the initial vaccine course. Overall, three quarters of those who were seronegative after COVID vaccines 1 & 2 had a measurable immune response after COVID vaccine 4. This data supports the use of booster vaccinations in pwMS at risk of attenuated vaccine response.
ABSTRACT
Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available.