COVID-19 Vaccination in Multiple Sclerosis and Inflammatory Diseases: Effects from Disease-Modifying Therapy, Long-Term Seroprevalence and Breakthrough Infections

Abstract

Background: To determine the effect of disease-modifying therapies (DMT) on humoral postvaccine seroconversion, long-term humoral response, and breakthrough COVID-19 infections in persons with multiple sclerosis (PwMS) and other neuroinflammatory disorders. Methods: A total of 757 PwMS and other neuroinflammatory disorders were recruited in two MS centers and vaccinated with one of the FDA-approved vaccines (BNT162b2, mRNA-1273, Ad26.COV2.S). The primary outcomes are the rate of humoral postvaccine seroconversion and anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) immunoglobulin G (IgG) differences between patients on different DMTs. Secondary measures include breakthrough infections and humoral response after six months. Other outcomes include differences in vaccine response between SARS-CoV-2 vaccines and the effects of age and comorbidities on the vaccine response. Results: A total of 465 (68.4%) PwMS and 55 (74.3%) patients with neuroinflammatory diseases were seropositive at 4–12 weeks after vaccination. A significant difference in seroconversion based on the DMT used at the time of vaccination (p < 0.001) was observed, with the lowest rates seen in patients treated with anti-CD20 antibodies (23.2%) and sphingosine-1-phosphate modulators (S1P) (30.8%). In seropositive patients, there was a significant decrease in anti-SARS IgG from mean 20.0 to 4.7 at six months (p = 0.004). Thirty-nine patients had breakthrough infection, but only two seronegative patients required hospitalization. mRNA vaccines resulted in significantly greater seroconversion compared to Ad26.COV2.S (p < 0.001). Older age and presence of cardiovascular comorbidities were associated with lower anti-SARS IgG (p = 0.021 and p = 0.003, respectively) Conclusions: PwMS and neuroinflammatory disorders treated with anti-CD20 and S1P medications have lower humoral response after anti-SARS-CoV-2 vaccination, even after booster dose. Waning of the humoral response puts vaccinated PwMS at a greater risk of COVID-19 breakthrough.

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

“…Indeed, in our study, pwMS belonging to the depleting/sequestering-out subgroup (including alemtuzumab-, cladribine-, fingolimod- and ocrelizumab-treated) showed a significantly lower humoral response to vaccination when compared to HD and to the enriching-in subgroup (natalizumab-treated). This is in agreement with several published studies in which a pattern of low humoral response to SARS-CoV-2 vaccination, with respect to healthy subjects, has been previously reported, mainly for patients receiving B-cell depleting drugs ( 35 – 37 ) and fingolimod ( 32 , 38 ). Even though the depleting/sequestering-out subgroup displayed lower anti-Spike antibody titers, most patients had near-normal total anti-Spike IgG levels, while only few did not seroconvert.…”

Longitudinal adaptive immune responses following sequential SARS-CoV-2 vaccinations in MS patients on anti-CD20 therapies and sphingosine-1-phosphate receptor modulators

“…Previous studies have demonstrated that antibody responses in anti-CD20 mAb and S1P-treated patients are significantly blunted following two doses of SARS-CoV-2 vaccination 2 , 3 . Several recent prospective studies demonstrated a higher risk of breakthrough COVID-19 in vaccinated patients on these DMT classes, which was correlated with reduced spike-specific-antibody levels 4 , 5 . It is therefore imperative to determine if additional vaccinations may improve immune responses.…”

“…We and others have previously demonstrated that two classes of certain MS disease modifying therapies (DMTs), in particular anti-CD20 monoclonal antibodies (mAb) and sphingosine-1-phosphate (S1P) receptor modulators, significantly reduce spike antibody responses following the first two doses of SARS-CoV-2 vaccination 2 , 3 . The impaired responses to initial vaccination appear to result in increased risk of breakthrough COVID-19 in vaccinated MS patients on ocrelizumab, rituximab, and fingolimod 4 , 5 .…”

Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian multiple sclerosis patients, a follow-up study

“…Based on these results, it has been suggested that the immune response after SARS-CoV-2 vaccination can be improved through additional booster shots ( 7 , 8 ) and by optimally adjusting vaccination timing based on the timing of immune cell repopulation after the last administration of specific immunosuppressive DMTs ( 9 ). Specifically, in contrast to the initial international recommendation for timing DMTs (msfi.org) of a 3-month waiting time after the last dose of immune-suppressive therapies, we and others have observed that a 6-month waiting time would be optimal ( 2 , 10 ).…”