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Short report
SARS-CoV-2 omicron breakthrough infections in patients with multiple sclerosis
  1. Zoé L E van Kempen1,
  2. Eileen W Stalman1,
  3. Maurice Steenhuis2,3,
  4. Laura Y L Kummer1,2,
  5. Koos P J van Dam1,
  6. Maarten F Wilbrink1,
  7. Anja ten Brinke2,4,
  8. S Marieke van Ham2,5,
  9. Taco Kuijpers6,
  10. Theo Rispens2,
  11. Filip Eftimov1,
  12. Luuk Wieske1,7,
  13. Joep Killestein1
  14. on behalf of the T2B! immunity against SARS-CoV-2 study group
    1. 1 Neurology, Amsterdam Neuroscience, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
    2. 2 Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, location VUMC, Amsterdam, The Netherlands
    3. 3 Biologics Laboratory, Sanquin Diagnostic Services, Amsterdam, the Netherlands
    4. 4 Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands
    5. 5 Swammerdam Insitute for Life Sciences, Amsterdam UMC, Amsterdam, The Netherlands
    6. 6 Pediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
    7. 7 Clinical Neurophysiology, St. Antonius Hospital, Nieuwegein, the Netherlands
    1. Correspondence to Dr Zoé L E van Kempen, Neurology, Amsterdam UMC - Locatie VUMC, Amsterdam 1081 HV, The Netherlands; Z.vankempen{at}


    Background It is unclear which patients with multiple sclerosis (MS) are most susceptible for omicron breakthrough infections.

    Methods We assessed omicron breakthrough infections in vaccinated patients with MS with and without disease-modifying therapies enrolled in an ongoing large prospective study. We longitudinally studied humoral responses after primary and booster vaccinations and breakthrough infections.

    Results Omicron breakthrough infections were reported in 110/312 (36%) patients with MS, and in 105/110 (96%) infections were mild. Omicron breakthrough infections occurred more frequently in patients treated with anti-CD20 therapies and sphingosine-1 phosphate receptor (S1PR) modulators, patients with impaired humoral responses after primary immunisation (regardless of treatment) and patients without prior SARS-CoV-2 infections. After infection, antibody titres increased in patients on S1PR modulator treatment while anti-CD20 treated patients did not show an increase.

    Conclusions SARS-COV-2 omicron breakthrough infections are more prevalent in patients with MS on anti-CD20 therapies and S1PR modulators compared with other patients with MS, which correlated with decreased humoral responses after vaccination. Humoral responses after infection were higher in S1PR modulator-treated patients in comparison to patients on anti-CD20 therapies, suggesting that immunological protection from contracting infection or repeated exposures may differ between these therapies.

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    • LW and JK contributed equally.

    • Collaborators T2B! immunity against SARS-CoV-2 study group: AJ vd Kooi, (Amsterdam UMC, location AMC), J Raaphorst, (Amsterdam UMC, location AMC), AH Koos Zwinderman, (University of Amsterdam), M Löwenberg, (Amsterdam UMC, location AMC), AG Volkers, (Amsterdam UMC, location AMC), G.R.A.M. D'Haens, (Amsterdam UMC, location AMC), RB Takkenberg, (Amsterdam UMC, location AMC), SW Tas, (Amsterdam UMC, location AMC), PI Spuls, (Amsterdam UMC, location AMC), MW Bekkenk, (Amsterdam UMC, location AMC), AH Musters, (Amsterdam UMC, location AMC), NF Post, (Amsterdam UMC, location AMC), AL Bosma, (Amsterdam UMC, location AMC), ML Hilhorst, (Amsterdam UMC, location AMC), Y Vegting, (Amsterdam UMC, location AMC), FJ Bemelman, (Amsterdam UMC, location AMC), N.J.M. Verstegen, (Sanquin Research and Landsteiner Laboratory), L Fernandez, (Sanquin Research and Landsteiner Laboratory), S Keijzer, (Sanquin Research and Landsteiner Laboratory), J.B.D. Keijser, (Sanquin Research and Landsteiner Laboratory), O Cristianawati, (Sanquin Research and Landsteiner Laboratory), AE Voskuyl, (Amsterdam UMC, location VUMC), B Broens, (Amsterdam UMC, location VUMC), AP Sanchez, (Amsterdam UMC, location VUMC), S Nejentsev, (Amsterdam UMC, location VUMC), ES Mirfazeli, (Amsterdam UMC, location VUMC), GJ Wolbink, (Amsterdam Rheumatology and Immunology Center, location Reade), L Boekel, (Amsterdam Rheumatology and Immunology Center, location Reade), BA Rutgers, (University Medical Center Groningen), K de Leeuw, (University Medical Center Groningen), B Horváth, (University Medical Center Groningen), J.J.G.M. Verschuuren, (Leiden University Medical Center), A.M. Ruiter, (Leiden University Medical Center), L van Ouwerkerk, (Leiden University Medical Center), D van der Woude, (Leiden University Medical Center), RCF Allaart, (Leiden University Medical Center), YKO Teng, (Leiden University Medical Center), PA. Pieter van Paassen, (Maastricht University Medical Center), MH Busch, (Maastricht University Medical Center), E Brusse, (Erasmus MC University Medical Center), PA van Doorn, (Erasmus MC University Medical Center), MAE Baars, (Erasmus MC University Medical Center), DJ Hijnen, (Erasmus MC University Medical Center), CRG Schreurs, (Erasmus MC University Medical Center), WL van der Pol, (Brain Center UMC Utrecht), HS Goedee, (Brain Center UMC Utrecht), C.A.C.M. van Els, (National Institute for Public Health and the Environment (RIVM)), J de Wit, (National Institute for Public Health and the Environment (RIVM)).

    • Contributors TK, ATB, MSMvH, TR, FE and JK contributed to the conception and design of the study. ZLEvK, EWS, MS, LYLK, KPJvD, MFW and LW contributed to the acquisition and analysis of the data. LW performed the statistical analyses. ZLEvK, LW and JK drafted a significant portion of the manuscript or figures. All authors revised the manuscript critically for intellectual content.

    • Funding We are grateful for ZonMw (The Netherlands Organization for Health Research and Development) for funding this study (grant number 10,430,072,010,007). The sponsor had no role in the design, analyses or reporting of the study.

    • Competing interests JK reported speaking and consulting relationships with Biogen, Genzyme, Merck, Novartis, Roche, Sanofi and TEVA. Amsterdam UMC, location VUmc, MS Center Amsterdam has received financial support for research activities from Biogen, Celgene, Genzyme, Merck, Novartis, Roche, Sanofi and TEVA. TR reports consulting fees from Novartis. No other disclosures were reported.

    • Provenance and peer review Not commissioned; externally peer reviewed.