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.