ABSTRACT
Disease-modifying therapies (DMTs) can affect vaccine responses in individuals with multiple sclerosis (MS). We assessed the humoral and T-cell responses following SARS-CoV-2 mRNA vaccination in MS patients receiving various DMTs. We prospectively enrolled 243 participants, including 113 healthy control subjects and 130 MS patients. Blood samples for detecting SARS-CoV-2 antibodies were collected at three time points: T0, before the first vaccine dose; T1, before the second dose; and T2, one month after the second dose. In a subgroup of 51 patients and 20 controls, samples were collected at T0 and T2 to assess the T-cell immune response to the Spike antigen of SARS-CoV-2 using ELISPOT-IFNγ. The IgG levels in patients treated with fingolimod and ocrelizumab (159.1 AU/ml and 467.1 AU/ml, respectively) were significantly lower than those in healthy controls and patients on other DMTs (P â< â0.0001). The mean Ig titers were higher in patients with an absolute lymphocyte count ≥1000 âcells/mm3 compared to those with a count between 500 and 1000 and with a count <500 (mean â± âSD:7205.6 â± â7339.2, 2413.1 â± â4515.4 and 165.9 â± â152.2, respectively; p â= â0.008). We found correlations between antibody levels and age (r â= â0.233, p â= â0.008). A positive Spike-specific T-cell response was detectable in 100 â% of vaccinated healthy controls and patients treated with teriflunomide, dimethyl-fumarate, and natalizumab, in 90.5 â% of fingolimod patients, and in 63.8 â% of ocrelizumab patients. There is a correlation between IgG-specific titer after SARS-CoV-2 vaccination and clinical variables (age, lymphocyte count). Notably, a T-cell-specific response to SARS-CoV-2 developed in patients treated with fingolimod and ocrelizumab, even with lower rates of humoral response.
Subject(s)
COVID-19 , Multiple Sclerosis , Humans , COVID-19 Vaccines/therapeutic use , SARS-CoV-2 , Multiple Sclerosis/drug therapy , mRNA Vaccines , Fingolimod Hydrochloride/therapeutic use , COVID-19/prevention & control , T-Lymphocytes , Immunoglobulin G , VaccinationABSTRACT
BACKGROUND: Many patients treated with Natalizumab experience wearing-off symptoms (WoS) towards the end of the administration cycle. During the pandemic we advised and asked patients undergoing treatment with Natalizumab if they wanted to be shifted from a standard interval dosing (StID of 4 weeks) to an extended interval dosing (ExID of 5-6 weeks), regardless of their JCV index. Our main objective was to study prevalence and incidence of WoS when ExID was adopted. METHODS: We enrolled 86 patients, from May 2020 to January 2021, evaluated at baseline and during a 6 months follow-up with a survey focused on WoS, Fatigue Severity Scale (FSS), Expanded Disability Status Scale (EDSS) and MRI. RESULTS: Among the 86 patients, 32 (37.2%) reported WoS. Most common one was fatigue (93.7%). Mean EDSS was higher in the group reporting WoS (3.8 WoS vs 3.1 non-WoS, p < 0.05). Sphincterial function was the EDSS item that significantly differed between the WoS group and the non-WoS group (1.4 WoS vs 0.6 non-WoS, p < 0.001). WoS correlate with the FSS scale (p < 0.001). CONCLUSION: Adopting an extended interval dosing does not result in significantly different occurrence of WoS between the ExID and the StID populations, in our cohort of patients. Interestingly, there is a strong correlation between WoS and a higher EDSS and FSS. Safety and efficacy of Natalizumab with ExID are relatively preserved in our study.