Longitudinal quantification of neutralising antibodies after two doses of SARS-CoV-2 mRNA vaccine in MS, NMOSD and other neuroimmunological diseases

ABSTRACT

Introduction: Several studies have reported attenuated humoral responses following SARS-CoV-2 mRNA vaccination in Multiple Sclerosis (MS) patients on anti-CD20 therapies and fingolimod. However, neutralising antibodies (NAbs) against the receptorbinding domain of the SARS-CoV-2 spike protein were quantified in only a few reports and there is limited data in neuromyelitis optica spectrum disorder (NMOSD) patients. Objectives and Aims: To measure serum NAbs levels prior to, and, at several time points after the first (V1) and second (V2) SARS-CoV-2 mRNA vaccination in patients with neuroimmunological conditions on various immunotherapies, and, to identify the factors associated with poor humoral responses. Method(s) This was a prospective observational study performed at the National Neuroscience Institute, Singapore. Patients with MS (n=77), NMOSD (n=33), myelin oligodendrocyte glycoprotein- antibody associated disease (n=6), autoimmune encephalitis (n=3), other CNS inflammatory diseases (n=5), myasthenia gravis (n=9) and healthy controls (HCs, n=42) were recruited. No subjects had COVID-19 infection prior to V1, V2 and the sampling time points. NAbs were measured using the Genscript cPassTM surrogate virus neutralisation test. Result(s) No patients or HCs had detectable NAbs prior to V1. Two to 4 weeks after V1, patients on anti-CD20 therapies had lower NAbs levels (p=0.010) compared to HCs and untreated patients. Two to 6 weeks post V2, patients on disease-modifying anti-rheumatic drugs (DMARDs) (p=0.010), fingolimod (p<0.0001) and anti-CD20 therapies (p<0.0001) showed decreased NAbs levels compared to HCs and untreated patients. This was also observed 8 to 16 weeks post V2 - DMARDs (p=0.046), fingolimod (p<0.0001) and anti-CD20 therapies (p<0.0001). NAbs levels decreased in both HCs and patients with increasing time interval following V2. There was no correlation between NAbs levels and the time interval from last anti-CD20 treatment to V1 (p=0.508). A multivariable logistic regression model adjusted for age, expanded disability status scale, gender, mRNA vaccine type, ethnicity and body mass index, revealed that fingolimod (p=0.026) and anti-CD20 therapies (p=0.003) were independent predictors of undetectable NAbs following V2. Conclusion(s) Fingolimod and anti-CD20 therapies are associated with attenuated NAbs levels post-vaccination. Future studies are needed to determine whether this translates to an increased risk of COVID-19 infection.