ABSTRACT
Introduction: Some multiple sclerosis (MS) disease-modifying therapies (DMTs) are associated with blunted humoral vaccination responses, but relevance for SARS-CoV-2 infection is unclear. Objective(s): To determine SARS-CoV-2 exposure rates and formation of antibody memory among participants of the COMparison Between All immunoTherapies for MS (COMBAT-MS;NCT03193866) and the Immunomodulation and MS Epidemiology (IMSE) studies. Aim(s): To determine SARS-CoV2 serological response of people living with MS (pwMS). Method(s): Using a multiplex bead-based assay we determined SARS-CoV-2 spike and nucleocapsid antibody levels in 3,723 pwMS in paired serum samples (n=7,157) donated prior (<January 31st 2020) and during the pandemic (July-October 2020);16.6% had natalizumab, 6.4% fingolimod, 9.7% dimethyl fumarate, 1.9% interferon beta, 50.4% rituximab, 1.4% cladribine, 7.6% other DMTs, and 6.1% were untreated. Median fluorescent intensity (MFI) and bead-count were determined for spike and nucleocapsid antibodies, and samples were regarded as positive only when reactive to both viral antigens. Hazard ratios, from multivariable Cox regression models, were derived to assess association between antibody levels above cut-off for each antigen, comparing exposure to rituximab or fingolimod at time of sampling vs. other reference DMTs. All models were adjusted for age, sex, treatment center, time since reported infection, MS severity, disease duration, and number of previous DMTs. Result(s): Specificity and sensitivity of the assay for SARS-CoV-2 was 100% and 99.7%, respectively. The proportion of positive samples for SARS-CoV-2 differed moderately across DMTs with the highest values among cladribine-treated (7.4%) and the lowest number among rituximab-treated pwMS (3.9%). Similarly, the proportion of positive cases not reported in the Swedish MS registry varied from 100% for cladribine to 33.3% among untreated pwMS. Comparing levels of antibodies titers showed that levels were lower among those treated with rituximab or fingolimod vs interferon treated pwMS. Point estimates indicated a similar trend comparing rituximab or fingolimod vs untreated pwMS. Conclusion(s): Overall rates of SARS-CoV-2 antibody positivity after the first COVID-19 wave differed only moderately across DMTs, while antibody levels were lower with rituximab or fingolimod compared to interferon-treated pwMS. This indicates quantitative rather than qualitative differences in the humoral response to infection.