A multicenter, prospective cohort study on the anti-SARS-CoV-2 vaccination response in patients with multiple sclerosis in Germany

Achim Berthele¹Clemens Gödel²Boris-Alexander Kallmann³Markus Christian Kowarik⁴Klaus Lehmann-Horn⁵Martin Marziniak⁶Sebastian Rauer⁷Veit Rothhammer⁸Florian Then Bergh²Mathias Wahl⁹Brigitte Wildemann¹⁰Ksenija Schirduan^11*

• ¹Department of Neurology, Technische Universitat Munchen School of Medicine and Health, Munich, Germany
• ²Leipzig University, Department of Neurology, Leipzig, Germany
• ³MS Center Bamberg (mszb), Bamberg, Germany
• ⁴Department of Neurology and Stroke, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
• ⁵Neuropraxis München Süd, Unterhaching, Germany
• ⁶kbo-Isar-Amper-Klinikum München-Ost, Department of Neurology, Haar, Germany
• ⁷Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Department of Neurology and Neuroscience, Freiburg, Germany
• ⁸University Hospital Erlangen, Department of Neurology, Erlangen, Germany
• ⁹DKD Helios Klinik Wiesbaden, Department of Neurology, Wiesbaden, Germany
• ¹⁰University Hospital Heidelberg, Department of Neurology, Molecular Neuroimmunology Group, Heidelberg, Germany
• ¹¹Biogen GmbH, Ismaning, Germany

Background: This epidemiologic cohort study documented clinical and serological data in MS patients over several vaccination cycles against SARS-CoV-2 in a real-world setting. Methods: Adult patients with MS were included during a period of 26 months from July 2021 if SARS-CoV-2 vaccination was planned, or first dose was given, or vaccination was completed within the last 6 weeks, or vaccination was completed >6 weeks ago and a booster dose was planned within the next 90 days. Humoral immune response to authorized SARS-CoV-2 vaccines was investigated during each vaccination cycle at baseline and approx. 1 month and 6 months after vaccination. Immune response was defined as an anti-SARS-CoV-2 spike protein IgG titer >100 BAU/mL above pre-vaccination level and, separately, by the presence of SARS-CoV-2 neutralizing antibodies (NAb) approx. 1 month after the last vaccination. Results: Of 159 patients enrolled, 140 (88.1%) were being treated with a DMT. Most patients (67.9%, n=108) entered the study after complete initial SARS-CoV-2 vaccination (up to 2 doses) and before the 1st booster dose. Approx. 1 month after the 1st booster vaccination, response was seen in 68.1% of the patients (n=79/116) based on anti-S1-IgG increase and in 72.1% (n=88/122) based on NAb seropositivity. Persisting immune response approximately 6 months after vaccination was observed in 71.8% (n=51/71) and in 93.7% (n=74/79) of the responders, respectively. Adequate humoral immune response and persistence of response was less frequent in patients on anti-CD20 antibodies or sphingosine-1-phosphate receptor (S1PR) modulators compared to patients on other DMTs or DMT-untreated patients. Breakthrough infections with the SARS-CoV-2 virus were reported in 58 patients (36.5%). Seven patients (4.4%) experienced an MS relapse during the study period. Conclusions: With the exception of anti-CD20 antibodies and S1PR modulators, DMTs did not impair humoral response to any of the authorized SARS-CoV-2 vaccines. Persistence of humoral immune response was seen over a period of at least 3 months in the majority of initial responders but was decreased in the anti-CD20 antibodies/S1PR modulator subgroup. Clinical Trial Registration: This epidemiological study is registered in the German Clinical Trials Register (DRKS00025893).