Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies

Abstract

Background and Aims: The National Multiple Sclerosis Society and other expert organizations recommended that all patients with multiple sclerosis (MS) should be vaccinated against COVID-19. However, the effect of disease-modifying therapies (DMTs) on the efficacy to mount an appropriate immune response is unknown. We aimed to characterize humoral immunity in mRNA-COVID-19 MS vaccinees treated with high-efficacy DMTs. Methods: We measured SARS-CoV-2 IgG response using anti-spike protein-based serology (EUROIMMUN) in 125 MS patients vaccinated with BNT162b2-COVID-19 vaccine 1 month after the second dose. Patients were either untreated or under treatment with fingolimod, cladribine, or ocrelizumab. A group of healthy subjects similarly vaccinated served as control. The percent of subjects that developed protective antibodies, the titer, and the time from the last dosing were evaluated. Results: Protective humoral immunity of 97.9%, 100%, 100%, 22.7%, and 3.8%, was observed in COVID-19 vaccinated healthy subjects ( N = 47), untreated MS patients ( N = 32), and MS patients treated with cladribine ( N = 23), ocrelizumab ( N = 44), and fingolimod ( N = 26), respectively. SARS-CoV-2 IgG antibody titer was high in healthy subjects, untreated MS patients, and MS patients under cladribine treatment, within 29.5–55 days after the second vaccine dose. Only 22.7% of patients treated with ocrelizumab developed humoral IgG response irrespective to normal absolute lymphocyte count. Most fingolimod-treated MS patients had very low lymphocyte count and failed to develop SARS-COV-2 antibodies. Age, disease duration, and time from the last dosing did not affect humoral response to COVID-19 vaccination. Conclusions: Cladribine treatment does not impair humoral response to COVID-19 vaccination. We recommend postponing ocrelizumab treatment in MS patients willing to be vaccinated as a protective humoral response can be expected only in some. We do not recommend vaccinating MS patients treated with fingolimod as a protective humoral response is not expected.

Humoral response to SARS-CoV-2 COVID-19 vaccines in patients with multiple sclerosis treated with immune reconstitution therapies

“…Until now, only one study investigated humoral immune response to COVID-19 vaccine in PwMS treated with high efficacy DMTs (Achiron et al, 2021). Patients were vaccinated exclusively with Pfizer-BioNTech vaccine.…”

T-cell responses to SARS-CoV-2 in multiple sclerosis patients treated with ocrelizumab healed from COVID-19 with absent or low anti-spike antibody titers

“…Little is known about cell-mediated responses in patients receiving B-cell depleting therapies after SARS-CoV-2 natural infection or vaccination (Asplund Högelin et al, 2021), while several case reports have demonstrated the absence of detectable anti-SARS-CoV-2 antibodies (Ab) (Iannetta et al, 2020;Khayat-Khoei et al, 2021;Smets et al, 2021;Thornton and Harel, 2020). Recently, Achiron et al showed poor seroconversion rates after SARS-CoV-2 vaccination in MS patients receiving B-cell depleting treatments (Achiron et al, 2021). The role of T-cell responses in terms of protection against SARS-CoV-2 infection and re-infection needs to be further elucidated.…”

B cell numbers predict humoral and cellular response upon SARS-CoV-2 vaccination among patients treated with rituximab

“…Protection through immunization is achieved by an orchestrated immune response between different cellular subsets of innate (APCs) and adaptive immunity, such as B and T cells. Anti-B cell therapies like anti-CD20 antibodies (rituximab, obinutuzumab and ocrelizumab) and BTK inhibitors are associated with poor humoral SARS-CoV-2 vaccination responses, in patients with AIIRD[17][18][19][20] , multiple sclerosis26…”