Humoral immune response after COVID-19 in multiple sclerosis: A nation-wide Austrian study

Abstract

Background: Knowledge on immunity after SARS-CoV-2 infection in patients with multiple sclerosis (pwMS) and the impact of disease-modifying treatment (DMT) is limited. Objective: To evaluate degree, duration and potential predictors of specific humoral immune response in pwMS with prior COVID-19. Methods: Anti-SARS-CoV-2 antibody testing was performed in pwMS with PCR-confirmed diagnosis of symptomatic COVID-19 from a nation-wide registry. Predictors of seropositivity were identified by multivariate regression models. Results: In 125 pwMS (mean age = 42.4 years (SD = 12.3 years), 70% female), anti-SARS-CoV-2 antibodies were detected in 76.0% after a median of 5.2 months from positive PCR. Seropositivity rate was significantly lower in patients on IS-DMT (61.4%, p = 0.001) than without DMT or immunomodulatory DMT (80.6%; 86.0%, respectively). In multivariate analysis, IS-DMT was associated with reduced probability of seropositivity (odds ratio (OR): 0.51; 95% confidence interval (95% CI): 0.17–0.82; p < 0.001). Predefined subgroup analyses showed marked reduction of seropositivity in pwMS on rituximab/ocrelizumab (OR 0.15; 95% CI: 0.05–0.56; p < 0.001). Rate of seropositivity did not change significantly over 6 months. Conclusions: Humoral immunity is stable after SARS-CoV-2 infection in MS, but is reduced by immunosuppressive DMT, particularly anti-CD20 monoclonal antibodies. This provides important evidence for advising pwMS as well as for planning and prioritizing vaccination.

SARS-CoV-2 mRNA vaccination fails to elicit humoral and cellular immune responses in multiple sclerosis patients receiving fingolimod

“…SARS-CoV-2 vaccines mitigate symptom severity of COVID-19 by inducing specific T cell and B cell memory 30,31 but how B and T cells individually act to prevent severe COVID-19 is so far unclear. The higher incidence of severe COVID-19 disease in aCD20-BCD-treated MS patients suggests that a lack of specific antibodies and B cells can severely impair COVID-19 immunity 32,6 . However, antibody responses to SARS-CoV-2 appear to be short-lived even in healthy individuals without known immunodeficiency, thus shifting the focus to memory B and T cellular immune memory to provide long-term protection from severe disease.…”

Vaccination and immunotherapies in neuroimmunological diseases

“…Early data suggest that treatment with monoclonal antibodies that deplete B cells carries an increased risk of serious illness 99 , 100 , 104 – 109 . Patients with MS or NMOSD who are receiving anti-CD20 therapy have lower antibody responses after SARS-CoV-2 infection than patients receiving other DMTs or no DMT 110 – 113 . However, in a Swedish cohort of patients with MS, rituximab treatment did not increase the risk of hospitalization above that with other DMTs and neither the timing of rituximab infusion nor the cumulative lifetime dose influenced COVID-19 severity 114 .…”

Cellular and Humoral Immunity to SARS‐CoV‐2 Infection in Multiple Sclerosis Patients on Ocrelizumab and Other Disease‐Modifying Therapies: A Multi‐Ethnic Observational Study

“…Multiple sclerosis (MS) is treated with disease‐modifying therapies (DMTs), some of which may impair immune responses to the pandemic severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection. The commonly used anti‐CD20 therapies (aCD20) are associated with reduced antibody titers following SARS‐CoV‐2 infection and vaccination, 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 likely due to depletion of peripheral B cells that would otherwise be available for recruitment into germinal centers for antigen‐mediated activation and clonal expansion. The T‐cell compartment is relatively unaffected by aCD20 as only a small subset of CD20‐bearing CD3+ lymphocytes are removed by aCD20.…”