COVID‐19 Vaccine Response in People with Multiple Sclerosis

Abstract

Objective The purpose of this study was to investigate the effect of disease modifying therapies on immune response to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccines in people with multiple sclerosis (MS). Methods Four hundred seventy‐three people with MS provided one or more dried blood spot samples. Information about coronavirus disease 2019 (COVID‐19) and vaccine history, medical, and drug history were extracted from questionnaires and medical records. Dried blood spots were eluted and tested for antibodies to SARS‐CoV‐2. Antibody titers were partitioned into tertiles with 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 the SARS‐CoV‐2 vaccine according to disease modifying therapy. We used regression modeling to explore the effect of 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 [CI] = 0.01–0.06, p < 0.001) and fingolimod (odds ratio = 0.04; 95% CI = 0.01–0.12) were associated with lower seroconversion following the SARS‐CoV‐2 vaccine. All other drugs did not differ significantly from the untreated cohort. Both time since last anti‐CD20 treatment and total time on treatment were significantly associated with the response to the vaccination. The vaccine type significantly predicted seroconversion, but not in those on anti‐CD20 medications. Preliminary data on cellular T‐cell immunity showed 40% of seronegative subjects had measurable anti‐SARS‐CoV‐2 T cell responses. Interpretation Some disease modifying therapies convey risk of attenuated serological response to SARS‐CoV‐2 vaccination in people with MS. We provide recommendations for the practical management of this patient group. ANN NEUROL 2021

CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis

“…However, maximising the chance of an effective response to vaccination in immunosuppressed people should be a priority, if it is safe to do so. It is evident that CD19 B cells recover rapidly following cladribine and alemtuzumab ( Gibiansky et al, 2021 , Baker et al, 2017 ) and this is probably consistent with a robust COVID-vaccine response in most people if vaccination in undertaken once immune-reconstitution occurs ( Achiron et al, 2021 , Sormani et al, 2021 , Tallantyre et al, 2021 ). However based on the B cell repopulation kinetics and poor vaccine response, one could argue that delaying treatment for a short period to facilitate the most-effective booster programme possible may be a justifiable risk, based on this uncontrolled trial data, which suggested comparable annualised relapse rate and disease breakthrough during the treatment-delayed period to that seen in other studies during continuous treatment ( Baker et al, 2020 ), and notably the experience with treatment delays during the COVID-19 pandemic ( Maarouf et al, 2020 , Rolfes et al, 2021 , van Lierop et al, 2021 , Baker et al, 2021 ).…”

“…This is further complicated as SARS-CoV-2 variants appear that have increased infectivity and immune-escape features requiring more antibody to neutralize infection, compared to the initial SAR-CoV-2 strain ( Uriu et al, 2021 ). As CD20-treated individuals often produce lower titre antibody responses than untreated controls ( Achiron et al, 2021 , Sormani et al, 2021 , Tallantyre et al, 2021 ), they are potentially in particular need of effective booster (third cycle) vaccinations to limit infection. However, it is clear that the majority of CD20-depleted individuals, even in those with low antibody titres, generate robust CD4 and CD8 anti-viral T cell responses following the initial vaccination that can provide protective immunity following infection ( Madelon et al, 2021 , Apostolidis et al, 2021 , Gadani et al, 2021 , Brill et al, 2021 ).…”

“…Given the blunted antibody response to other vaccines ( Baker et al, 2020 ) it is not surprising that CD20-depleting antibodies, notably rituximab and ocrelizumab, repeatedly and consistently appear to induce poor seroconversion following natural infection with SARS-CoV-2 ( Louapre et al, 2020 , Sormani et al, 2021 ). Furthermore seroconversion in CD20-depleted, COVID-19 vaccinated individuals is universally poor ( Achiron et al, 2021 , Sormani et al, 2021 , Tallantyre et al, 2021 ). In contrast many people treated with cladribine tablets and alemtuzumab after therapy show seroconversion following COVID-19 vaccination ( Achiron et al, 2021 , Sormani et al, 2021 , Tallantyre et al, 2021 ).…”

“…Furthermore seroconversion in CD20-depleted, COVID-19 vaccinated individuals is universally poor ( Achiron et al, 2021 , Sormani et al, 2021 , Tallantyre et al, 2021 ). In contrast many people treated with cladribine tablets and alemtuzumab after therapy show seroconversion following COVID-19 vaccination ( Achiron et al, 2021 , Sormani et al, 2021 , Tallantyre et al, 2021 ).…”

Fingolimod impairs inactivated vaccine (CoronaVac)-induced antibody response to SARS-CoV-2 spike protein in persons with multiple sclerosis

“…Nevertheless, little known about the impact of DMTs on the efficacy of inactivated SARS-CoV-2 vaccines. In this context, fingolimod is a particular concern due to previous observations regarding humoral and T-cell-specific immune response dampening actions of this DMT in MS ( Achiron et al, 2021 ; Guerrieri et al, 2021 ; Kurtuncu et al, 2019 ; Tallantyre et al, 2022 ).…”