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Multicenter Study
. 2022 Sep:65:104009.
doi: 10.1016/j.msard.2022.104009. Epub 2022 Jul 2.

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

Nik Krajnc  1 , Harald Hegen  2 , Gerhard Traxler  3 , Fritz Leutmezer  1 , Franziska Di Pauli  2 , Barbara Kornek  1 , Paulus Rommer  1 , Gudrun Zulehner  1 , Katharina Riedl  1 , Sophie Dürauer  4 , Angelika Bauer  2 , Sarah Kratzwald  4 , Sigrid Klotz  4 , Michael Winklehner  4 , Florian Deisenhammer  2 , Michael Guger  5 , Romana Höftberger  4 , Thomas Berger  1 , Gabriel Bsteh  6
Affiliations
Multicenter Study

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

Nik Krajnc et al. Mult Scler Relat Disord. 2022 Sep.

Abstract

Background: Third vaccination against SARS-CoV-2 is recommended for patients with multiple sclerosis (pwMS), usually six months after the last vaccination.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: Disease-modifying therapy; Multiple sclerosis; SARS-CoV-2; Third; Vaccination.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

Figures

Fig 1
Fig. 1
Seroconversion rates after first two vaccinations were lower in patients on sphingosine-1-phosphate receptor modulators (S1PMs) and anti-CD20 monoclonal antibodies (a, b). After third vaccination, all patients were positive for anti-SARS-CoV-2 antibodies apart from patients on S1PM and anti-CD20 monoclonal antibodies (c, d). ATZ: alemtuzumab, CLA: cladribine, DMT: dimethyl fumarate, GLAT: glatiramer acetate, HC: healthy controls, IFN: interferon, NTZ: natalizumab, TFN: teriflunomide.
Fig 2
Fig. 2
Patients on nr-DMT had significantly lower SARS-CoV-2 antibody levels before and after third vaccination compared to other pwMS and HC (a). No differences in antibody levels between homologous and heterologous vaccination regime were found (b). Antibody levels in patients on S1PMs and anti-CD20 mAbs increased significantly after third vaccination. However, median antibody levels after first immunization and third vaccination did not differ in either of the groups (c, d). Data are presented as median values with range (minimum, maximum).
Fig 3
Fig. 3
Complete B-cell depletion was the only predictor of no seroconversion in patients on anti-CD20 mAbs.
See this image and copyright information in PMC

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