ABSTRACT
Introduction: Booster vaccination against SARS-CoV-2 is recommended for patients with multiple sclerosis (pwMS), usually six months after the last vaccination. Objectives and aims: To investigate humoral response after SARS-CoV-2 booster vaccination in pwMS compared to healthy controls (HC), as well as the role of the third vaccination in the primarily seronegative and therefore more vulnerable group of treated pwMS (S1PMs, anti-CD20 mAbs). Method(s): In this prospective multicenter study on 292 pwMS and 46 HC, who had all received two vaccinations, SARS-CoV-2 IgG response was measured in the month before and 2-4 months after booster vaccination. PwMS were categorized as follows: untreated (N-DMT, n=32), receiving disease-modifying therapy (DMT) with expected humoral response (er-DMT: interferon-beta preparations, glatiramer acetate, dimethyl fumarate, teriflunomide, natalizumab, cladribine, alemtuzumab;n=120) or no expected humoral response (nr-DMT: S1PMs, CD20mAb;n=140). Result(s): PwMS on nr-DMT had significantly lower median antibody levels before (12.1 U/ml [0.4-2500]) and after booster vaccination (305 U/ml [0.4-2500]) in comparison to other groups (p<0.001). We did not find differences in antibody levels after homologous (n=281;2500 [0.4-2500]) and heterologous (n=57;2500 [0.4-2500]) vaccination regime regardless of the DMT group. The DMT group (= -0.16;95% CI -34.88, -5.08;p=0.009) were associated with antibody levels after booster vaccination, while time to revaccination(6 months [1-13]) was not. After booster vaccination, seropositivity was reached in 75.8% and 82.2% of pwMS on anti-CD20 mAbs and S1PMs, respectively. Complete B-cell depletion significantly decreased the probability of seroconversion even after the third vaccination (OR 0.14;p=0.021), whereas time interval to last DMT intake and time to revaccination did not. Twenty-three patients reported a SARSCoV- 2 infection (3 N-DMT, 10 er-DMT, 10 nr-DMT), one being asymptomatic and the rest having a mild course. Conclusion(s): Humoral response to SARS-CoV-2 booster vaccination in pwMS is excellent. While reduced by S1PMs and CD20mAb, protective response is still expected in the majority of patients.
ABSTRACT
Background and aims: Booster vaccination against SARSCoV- 2 is recommended for everyone approximately six months after the last vaccination, including for patients with multiple sclerosis (pwMS). Methods: In this prospective single-center study on 171 pwMS and 38 healthy controls (HC), who had all received two vaccinations, SARS-CoV-2 IgG response was measured in the month before and 2-4 months after booster vaccination. PwMS were categorized as follows: untreated (N-DMT, n=17), receiving DMT with expected humoral response (er-DMT: all but S1PM and CD20mAB;n=65) or no expected humoral response (nr-DMT: S1PM, CD20mAb;n=89). Results: Absolute antibody levels (median 253.5 U/ml [range 0.4-2500]) before booster vaccination were similar between HC (516 [49.5-2500]), N-DMT (648 [0.4-2345]) and er-DMT (858.5 [25.6-2500]), while nr-DMT had significantly lower antibody levels (32.8 [0.4-2500];p<0.001). After booster vaccination, the absolute antibody levels were as follows: HC (2500 [2190-2500]), N-DMT (2500 [32.2-2500]), er-DMT (2500 [1951-2500]), and nr-DMT (548 [0.4-2500];p<0.001). We did not find differences in antibody levels after homologous (n=96;2500 [0.4-2500]) and heterologous (n=53;2500 [0.4- 2500]) booster vaccination. Time to revaccination (6 months [1-10] was not associated with antibody level. Four of 13 (30.8%, all CD20mAb) seronegative pwMS remained seronegative after booster vaccination. Seven patients reported a SARS-CoV-2 infection (1 N-DMT, 6 nr-DMT). Efficacy rate for preventing hospitalization or death was 100% in all groups. Conclusion: Humoral response to SARS-CoV-2 booster vaccination in pwMS is excellent. While reduced by immunosuppressive DMT, protective humoral response is still expected in the majority of patients.