Humoral immune response to COVID-19 mRNA (BNT162b2-Pfizer) vaccine in patients with multiple sclerosis

ABSTRACT

Introduction and Objective: Whether therapies for Multiple Sclerosis (MS) might reduce the efficiency of the immune response to COVID19 disease or vaccination is a major concern. The rapid COVID19 vaccination program in Israel provides a unique opportunity to assess the anti-COVID19 IgG response in MS patients. Methods: This multi-center study coordinated by the Israeli Neuroimmunology Research Group included 331 MS patients and 53 healthy controls, vaccinated against SARS-CoV-2 (BNT162b2- Pfizer) (n=361) or recovered from COVID19. IgG against the spike receptor-binding domain of SARS-CoV-2 (Abbott) was measured in sera collected 2-23 weeks after the 2nd vaccination or after COVID19 diagnosis. Serum positivity was defined at > 50 AU/ml. Results: IgG levels were comparable in vaccinated MS patients (in general) and healthy controls, but were significantly lower in treated compared to untreated MS patients, and in COVID19- recovered compared to vaccinated patients. All patients treated with Interferon-β preparations, Dimethyl Fumarate, Alemtuzumab, Glatiramer Acetate, Natalizumab, Ofatumumab, Ponesimod, Siponimod or Teriflunomide were positive for IgG anti-spike antibodies, following vaccination or COVID19 disease. 90% of Cladribine-, 31% of Ocrelizumab- and 51% of Fingolimod-treated patients were IgG positive after vaccination, and 50%, 63% and 68%, respectively, after recovery from COVID19. No significant correlation was found between IgG-levels and the interval from last treatment of Ocrelizumab or Cladribine, or the lymphocyte counts in Fingolimod-treated patients. IgG-levels negatively correlated with time from 2nd vaccination, whereas no correlation was found with time since COVID19 disease. There were no significant gender differences or associations with smoking or BMI. Aging was associated with lower titers of IgGs after vaccination, but not after COVID19 disease. Conclusions: Most DMTs did not interfere with elicitation of a sufficient humoral immune response to vaccination or disease, but ≥50% of MS patients treated with Fingolimod or Ocrelizumab did not develop anti- spike antibodies. Following vaccination, IgG levels declined over time, while appeared to be stable (though lower) after COVID19 disease. Testing of cellular responses in IgG-negative patients and an update of COVID19 vaccination guidelines for MS according to therapy and patient's characteristics, seem to be warranted.