ABSTRACT
Introduction: Knowledge regarding the development of protective immunity after COVID-19 vaccines is needed to guide medical, political and public health measures against the current and future pandemics. Objectives and Aims: To characterise and compare the safety, immunogenicity and efficacy of mRNA-COVID-19 vaccines in people with multiple sclerosis (pwMS) and healthy controls (HCs). Method(s): All pwMS vaccinated against COVID-19 in Norway were invited to participate in an ongoing observational cohort study (NevroVAX) from March 2021. Demographic-, immunisation-and disease-specific data were acquired from patient journals, web-questionnaires, the Norwegian Immunization Registry and Surveillance System for Communicable Diseases. Antibodies to full length spike protein and the receptor-binding domain (RBD) from SARS-CoV-2 were measured using a bead-based flow cytometric assay, while cellular immunity was investigated using high dimensional multiparameter analyses. Results and Conclusion(s): To date, 5545 pwMS were included with results available regarding humoral responses in 3021 (mean follow-up time 257 days), cellular responses in 140, and clinical efficacy in 900 pwMS. Those treated with anti-CD20 therapy or sphingosine-1-phosphate receptor modulators (S1PM) had weak humoral immune responses after two doses of mRNA-COVID-19 vaccines (80% and 91% <200 BAU/ml, respectively). Additional vaccine doses were safe and associated with a modest increase of anti-SARS-CoV-2 spike RBD IgG antibodies (72% and 83% <200 BAU/ml after three, 74% and 89% <200 BAU/ml after four doses). Humoral responses were weaker after all vaccine doses in pwMS (also in those without treatment) compared to HCs. Cellular responses were significantly attenuated in pwMS treated with S1PM. An elevated rate of non-omicron breakthrough infections was observed in the anti-CD20 (19%), S1PM (18%), and HSCT (14%) group, compared to pwMS on other high-or low-efficacy DMTs or without treatment (13%, 10%, and 7%, respectively). Among 900 pwMS treated at the same hospital, 12 (1%) were hospitalized due to COVID-19, one requiring intensive care. Our results show that antibody responses correlated with the rate of breakthrough infections but is not necessarily indicative of a failed cellular or clinical response to vaccination, and that pwMS have weaker humoral responses than HCs regardless of treatment status. Updated, real-world data from NevroVAX will be presented at ECTRIMS 2022.
ABSTRACT
Background and goals: The goal of this study was to assess the rate of self-reported side effects, need for medical assistance and hospitalizations after a third COVID-19 vaccination in people with multiple sclerosis (pwMS) with or without disease-modifying treatments. We also wanted to investigate if SARS-CoV2 antibody levels correlate with side effects. Method(s): Participants enrolled in the vaccination trial Nevrovax were invited to complete a questionnaire on side effects after the third dose of SARS-CoV-2 vaccination. SARS-CoV2 antibodies were measured in BAU/mL after 3 weeks or longer after vaccination. The results were linked to data from the Norwegian Immunization Registry. Statistical analyses were performed using SPSS Stastistics version 26. Group comparisons were analyzed using independent samples t-tests and chi-square tests with a significance level of 0.05. Result(s): In total 606 pwMS (77.4% female, mean age 48.3 years) were included in this study. At the time of immunization, 61.7% of all pwMS were treated with anti-CD20 monoclonal antibodies and 19%with sphingosine 1-phosphate receptor modulators. Mean time to follow up from third dose to answering the questionnaire was 29.9 days.586 patients received an mRNAvaccine (257 BNT162b2 and 344 mRNA1273 as dose 3) while 20 received a viral vector vaccine-AZD1222 (One as dose 3). Data on vaccine type of dose 3 was missing in 4 patients. Side effects were reported by 66.2% of all pwMS. Mean age of patients with and without side effects were 47.0and 50.7 years, respectively (p < 0.01). We found a higher rate of side effects among women (68.8%) than men (59.1%) (p=0.047), and a higher rate among those using anti-CD20 therapy (73.3%) (p<0.05). Blood samples of SARS-CoV2 antibodies were obtained in 547 patients. There were no significant difference in antibody levels in patients with side effects (mean 1185 BAU/ mL) and patients without side effects (mean 1174 BAU/mL), p= 0.66. 16 pwMS (2.6%) sought medical help after vaccination. No pwMS needed hospitalization. Conclusion(s): Our results demonstrate that a third dose of SARSCov2 vaccines are safe in pwMS using different DMTs. Rate and severity of side effects vary with both treatment and demographic factors. SARS-CoV2 IgG levels did not correlate with side effects. There were no hospitalizations after vaccination with a 3rd dose.
ABSTRACT
Introduction: Expert organizations worldwide recommend that all patients with multiple sclerosis (MS) should be vaccinated against acute respiratory syndrome coronavirus 2 disease of 2019 (COVID- 19). However, the effect of disease-modifying therapies (DMTs) on the efficacy to mount an appropriate immune response is unknown. There is increasing evidence of altered protective humoral immunity after mRNA-COVID-19 vaccines among patients treated with fingolimod, rituximab and ocrelizumab. However, the role of cellular immunity is still unknown. Appropriate knowledge regarding the development of protective immunity is of paramount importance in respect to medical, political and public health measures to aid the fight against the COVID-19 pandemic. Objectives and Aims: We aimed to characterize humoral and cellular immunity after mRNA-COVID-19 vaccines in patients with MS treated with high-efficacy DMTs (NEVROVAX). Methods: All patients treated with alemtuzumab, natalizumab, fingolimod, rituximab or cladribine, and vaccinated with BNT162b2- or mRNA-1273-COVID-19 vaccine were invited. We assessed protective humoral immunity by measuring acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG response using anti-spike protein-based serology in all included patients before, and 3-6 weeks after full vaccination (NEVROVAX-HUMORAL). Cellular immunity was investigated using high dimensionality multiparameter analyses in 50 pre-selected individuals (10 patients in each treatment group;NEVROVAX-CELLULAR) and in all patients not developing protective humoral immunity in the former group (NEVROVAX-EXTENSION). Results and Conclusions: Over 900 patients were invited and, to date, more than 300 patients have been included in our study. Preliminary results show altered protective humoral immunity in MS patients treated with rituximab and fingolimod. Continuous analysis of cellular immunity is conducted in these patients. The percentage of vaccinated inhabitants in Norway is still under 10%. We expect to complete all analyses by September 2021 and will present our results during ECTRIMS 2021.