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. 2021 Dec;27(14):2209-2218.
doi: 10.1177/13524585211049391. Epub 2021 Oct 1.

Humoral immune response after COVID-19 in multiple sclerosis: A nation-wide Austrian study

Gabriel Bsteh  1   2 , Sophie Dürauer  3 , Hamid Assar  4 , Harald Hegen  5 , Bettina Heschl  6 , Fritz Leutmezer  2 , Franziska Di Pauli  5 , Christiane Gradl  7 , Gerhard Traxler  8 , Gudrun Zulehner  2 , Paulus Rommer  2 , Peter Wipfler  9 , Michael Guger  8 , Romana Höftberger  3 , Christian Enzinger  6 , Thomas Berger  2
Affiliations

Humoral immune response after COVID-19 in multiple sclerosis: A nation-wide Austrian study

Gabriel Bsteh et al. Mult Scler. 2021 Dec.

Abstract

Background: Knowledge on immunity after SARS-CoV-2 infection in patients with multiple sclerosis (pwMS) and the impact of disease-modifying treatment (DMT) is limited.

Objective: To evaluate degree, duration and potential predictors of specific humoral immune response in pwMS with prior COVID-19.

Methods: Anti-SARS-CoV-2 antibody testing was performed in pwMS with PCR-confirmed diagnosis of symptomatic COVID-19 from a nation-wide registry. Predictors of seropositivity were identified by multivariate regression models.

Results: In 125 pwMS (mean age = 42.4 years (SD = 12.3 years), 70% female), anti-SARS-CoV-2 antibodies were detected in 76.0% after a median of 5.2 months from positive PCR. Seropositivity rate was significantly lower in patients on IS-DMT (61.4%, p = 0.001) than without DMT or immunomodulatory DMT (80.6%; 86.0%, respectively). In multivariate analysis, IS-DMT was associated with reduced probability of seropositivity (odds ratio (OR): 0.51; 95% confidence interval (95% CI): 0.17-0.82; p < 0.001). Predefined subgroup analyses showed marked reduction of seropositivity in pwMS on rituximab/ocrelizumab (OR 0.15; 95% CI: 0.05-0.56; p < 0.001). Rate of seropositivity did not change significantly over 6 months.

Conclusions: Humoral immunity is stable after SARS-CoV-2 infection in MS, but is reduced by immunosuppressive DMT, particularly anti-CD20 monoclonal antibodies. This provides important evidence for advising pwMS as well as for planning and prioritizing vaccination.

Keywords: COVID-19; Multiple sclerosis; SARS-CoV-2; antibody; disease-modifying treatment; humoral response; seropositivity.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: G.B. has participated in meetings sponsored by and received speaker honoraria or travel funding from Biogen, Celgene/BMS, Merck, Novartis, Roche, Sanofi-Genzyme and Teva and received honoraria for consulting Biogen, Roche and Teva. S.D. has nothing to disclose. H.A. has participated in meetings sponsored by and received honoraria (advisory boards, consultations) or travel funding from Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. H.H. has participated in meetings sponsored by and received speaker honoraria or travel funding from Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, Siemens and Teva and received honoraria for consulting Biogen, Novartis and Teva. B.H. has nothing to disclose. F.L. has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Bayer, Biogen, Celgene/BMS, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. F.D.P. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) or travel funding from Bayer, Biogen, Celgene/BMS, Merck, Novartis, Sanofi-Genzyme, Roche and Teva. C.G. has participated in meetings sponsored by and received honoraria (lectures, consultations) and/or travel funding from Biogen, D-Pharma, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. G.T. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) or travel funding from Biogen, Celgene/BMS, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. G.Z. has participated in meetings sponsored by or received travel funding from Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. P.R. has received honoraria for consultancy/speaking from AbbVie, Allmiral, Alexion, Biogen, Merck, Novartis, Roche, Sandoz and Sanofi Genzyme and has received research grants from Amicus, Biogen, Merck and Roche. P.W. has received funding for travel and honoraria (lectures, advisory boards) from Bayer, Biogen, Celgene/BMS, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. M.G. has received support and honoraria for research, consultation, lectures and education from Almirall, Bayer, Biogen, Celgene/BMS, Genzyme, MedDay, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme, Shire and Teva. R.H. has nothing to disclose. C.E. has received funding for travel and speaker honoraria from Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, Shire and Teva and has received research support from Biogen, Celgene/BMS, Merck and Teva and is serving on scientific advisory boards for Bayer, Biogen, Celgene/BMS, Merck, Novartis, Roche and Teva. T.B. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Allergan, Bayer, Biogen, Bionorica, Celgene/BMS, GSK, Janssen-Cilag, MedDay, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme and Teva. His institution has received financial support in the past 12 months by unrestricted research grants (Bayer, Biogen, Celgene/BMS, Merck, Novartis, Sanofi Aventis, Teva) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Celgene/BMS, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme and Teva.

Figures

Figure 1.
Figure 1.
Seropositivity and antibody titre levels after COVID-19 differ between DMT categories (panels a and c) and substances (panels b and d). DMT: disease modifying treatment; IM-DMT: Immunomodulating DMT: dimethyl fumarate, glatiramer acetate, interferon beta preparations, natalizumab and teriflunomide; IS-DMT: Immunosuppressive DMT: alemtuzumab, cladribine, fingolimod, ocrelizumab or rituximab; IFNb: interferon beta preparations; GLAT: glatiramer acetate; DMF: dimethyl fumarate; TERI: teriflunomide; NTZ: natalizumab; CLA: cladribine; FTY: fingolimod; OCR: ocrelizumab; RTX: rituximab; ATZ: alemtuzumab. P values calculated by Chi-square test (panel A) and Kruskal–Wallis test (panel C).
Figure 2.
Figure 2.
Seropositivity and level of anti-SARS-CoV2 antibodies. Panel (a) proportion of seropositivity according to DMT groups and time from infection to antibody testing, Panel (b) antibody levels according to DMT groups and time from infection to antibody testing, Panel (c) distribution of antibody levels in single patients according to DMT groups and time from infection to antibody testing, Panel (d) distribution of antibody levels in single patients according to DMT substances and time from infection to antibody testing after infection depend on DMT status and slightly decrease over time. BAU/ml: binding antibody units per millilitre; DMT: disease modifying treatment; IM-DMT: Immunomodulating DMT: dimethyl fumarate, glatiramer acetate, interferon beta preparations, natalizumab and teriflunomide; IS-DMT: Immunosuppressive DMT: alemtuzumab, cladribine, fingolimod, ocrelizumab or rituximab; IFNb: interferon beta preparations; GLAT: glatiramer acetate; DMF: dimethyl fumarate; TERI: teriflunomide; NTZ: natalizumab; CLA: cladribine; FTY: fingolimod; OCR: ocrelizumab; RTX: rituximab; ATZ: alemtuzumab.
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