Humoral immune response to SARS-CoV-2 third vaccination in patients with multiple sclerosis and healthy controls: A prospective multicenter study

• Published in: Multiple sclerosis and related disorders Vol. 65; p. 104009
• Main Authors: Krajnc, Nik, Hegen, Harald, Traxler, Gerhard, Leutmezer, Fritz, Di Pauli, Franziska, Kornek, Barbara, Rommer, Paulus, Zulehner, Gudrun, Riedl, Katharina, Dürauer, Sophie, Bauer, Angelika, Kratzwald, Sarah, Klotz, Sigrid, Winklehner, Michael, Deisenhammer, Florian, Guger, Michael, Höftberger, Romana, Berger, Thomas, Bsteh, Gabriel
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2022; The Author(s). Published by Elsevier B.V
• Subjects: Disease-modifying therapy; Multiple sclerosis; SARS-CoV-2; Third; Vaccination; RRMS; Multiple sclerosis; PPMS; SPMS; Vaccination; DMT; N-DMT; Disease-modifying therapy; SARS-CoV-2; nr-DMT; Third; pwMS; HC; S1PM; er-DMT; EDSS
• ISSN: 2211-0348; 2211-0356
• DOI: 10.1016/j.msard.2022.104009

•Treatment with S1PMs and anti-CD20 monoclonal antibodies is associated with lower seroconversion rates and antibody levels after booster vaccination.•Time to revaccination and vaccination regime (homologous vs. heterologous) do not seem to play a role in humoral immune response.•After booster vaccination, seropositivity is reached in 75.8% and 82.2% of patients on anti-CD20 monoclonal antibodies and S1PMs, respectively.•Complete B-cell depletion is a predictor of no seroconversion in patients treated with anti-CD20 monoclonal antibodies. Third vaccination against SARS-CoV-2 is recommended for patients with multiple sclerosis (pwMS), usually six months after the last vaccination. In this prospective multicenter study on 292 pwMS and 46 healthy controls (HC), who had all received two vaccinations prior to study enrollment, SARS-CoV-2 IgG response was measured in the month before and 2–4 months after third 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). PwMS on nr-DMT had significantly lower median antibody levels before (12.1 U/ml [0.4–2500]) and after third 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 (β= –0.60; 95% CI –1195.73, –799.10; p<0.001) was associated with antibody levels after third vaccination, while time to revaccination (6 months [1–13]) was not. After third 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-two patients reported a SARS-CoV-2 infection (3 N-DMT, 9 er-DMT, 10 nr-DMT), one being asymptomatic and the rest having a mild course. Humoral response to SARS-CoV-2 third vaccination in pwMS is excellent. While reduced by S1PMs and CD20mAb, protective response is still expected in the majority of patients