ABSTRACT
Objectives/Aims: Disease modifying therapies (DMTs) affect immune responses to SARS-CoV-2 exposure or vaccination in patients withmultiple sclerosis(PwMS).Humoral responses were shown to be significantly compromised inPwMStreated with anti- CD20 therapies and S1P inhibitors.We evaluated the effect of DMTs(and specifically anti-CD20)on cell-mediated immune responses to 2 and 3 SARS-CoV-2 vaccinations in PwMS. Method(s): 522 PwMS and 68 healthy controls vaccinated with BNT162b2-Pfizer mRNA vaccine against SARS-CoV-2, were recruited in a nation-wide multi-center study. Blood was collected at 3 time-points: 2-16 weeks and ~6 months post 2nd vaccination and 1-16 weeks following 3rd vaccination.The cellular responseswere evaluatedby quantifying IFNgamma secretion in blood incubated with COVID-19 spike-antigen. Result(s): 75% PwMS were seropositive post 2nd or 3rd vaccination. IgG levels decreased by 82% within 6 months from vaccination (p<0.0001), but were boosted 10.3 fold by the 3rd vaccination (p<0.0001), and 1.8 fold compared to <=3m post 2nd vaccination (p=0.025). Patients treated with most DMTs were seropositive post 2nd and 3rd vaccinations,with the exception ofocrelizumaband fingolimod-treated patients(antibody positivity between38%to 56%). A time interval of >=5 months between ocrelizumab infusion and vaccination was associated with higher IgG levels (p=0.039 post-2nd vaccination;p=0.036 post-3rd vaccination), and with higher proportions of seropositive patients.Anti-spike proteinT-cell responses were detected in96% of PwMStreated with ocrelizumabpost 2nd and 3rd vaccination.The mortality rates and the proportion of patients with severe COVID-infection, were at similar levels in patients treated with ocrelizumab and those under other DMDs. Conclusion(s): PwMS treated with most DMTs developedeffectivehumoralresponses in general. In patients treated with anti-CD20 therapies, who had reduced antibodies following repeated vaccinations, strongT-cell responseswere mounted and provided a good level of protection against severe disease or death from COVID.
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.