One hundred and twenty MS patients were included. Baseline characteristics are summarized in Table 1. Briefly, there were 83 females (69%); MS form was relapsing–remitting (RR-) in 109 cases (91%) and secondary-progressive (SP-) in 11 cases. Most of the patients (112/120, 93%) were receiving active treatment at the time of vaccination (Table 2): a I line DMT in 29/112 cases (26%) and a II line one in the remaining 83 cases (74%).
Antibody response and DMT at vaccination
Antibody testing after a single dose was available for 19/120 cases (16%). The median titre was 202 BAU/mL (range 0–1290) and it increased at T2 (median 600 BAU/mL, range 72–2670), p < 0.001 (Fig. 1a).
Anti-S protein IgG antibody titre above the cut-off at T2 was detected in 102/120 (85%) cases; the frequency of responders was lower in MS cases treated with depletive treatments (17/34, 50%) compared to those who received non-depletive treatments (77/78, 99%), p < 0.0001. At T2, the frequency of responders was 100% in untreated patients (n = 5), and in the group of patients who were receiving a first-line treatment (injectable treatments, dimethyl-fumarate or teriflunomide) or NTZ (n = 29 and 35, respectively). Eleven/12 (92%) cases receiving FTY and 14/31 (45%) of cases receiving anti-CD20 antibodies were responders (Fig. 1b).
Details on the remaining patients treated with alemtuzumab (n = 1), autologous hematopoietic stem cell transplantation (AHSCT, n = 2), cladribine (n = 3) or cyclophosphamide (n = 2) are reported in Table 3.
In responders, a median antibody titre of 1122 BAU/mL (range 9.34–9894) was observed, and it was of median 1542 BAU/mL (range 75–9894) for patients receiving a I line DMT and of median 723 BAU/mL (range 9–7310) for patients receiving II line DMTs, p = 0.130 Amongst those receiving a II line DMT, the antibody titre was lower in patients treated with depletive treatments (27.36 BAU/mL, range 0–3800) compared to those who were not (1047 BAU/mL, range 0.44–7310), p < 0.0001, and in pwMS treated with fingolimod compared to first-line DMTs, NTZ or no treatment (p < 0.0001) (Fig. 2).
Antibody response and baseline blood cell count
Baseline blood cell count was available for 42/120 (35%) cases. Thirty-seven/42 (88%) cases were receiving DMTs at the time of vaccination. The median white blood cell count was 5300 (range 2630–8890). Median baseline white blood cell count did not differ between responders (median 5180, range 2630–8890) and non-responders (median 6070, range 3400–7900), p = 0.564 (Fig. 3a).
No significant correlations were observed between anti-S antibodies titre and baseline white blood cell counts for the 42 evaluable cases. The immunophenotyping did not differ between the two groups (Fig. 3b–e), except for the CD19+ count, which was significantly higher in the responder group (median 139, range 0–1480) than in the non-responder group (median 0, range 0–7), p < 0.0001 (Fig. 3f).
Antibody response and clinical-demographic characteristics
Analysing the whole cohort, no significant correlations were observed between antibody response at T2 and baseline clinical-demographic characteristics (age and disease duration at vaccination, EDSS).
Correlations were then explored for each DMT group. A significant correlation with age at vaccination was observed in the NTZ group (R − 0.38, p = 0.022) and patients not treated with depletive treatments (R − 0.25, p = 0.028). Antibody titre correlated inversely with the duration of treatment with anti-CD20 antibodies (R − 0.93, p < 0.0001), the number of administrations received (R − 0.59, p = 0.001) and the time interval between last dose administration and vaccination (R 0.41, p = 0.028), (data not shown).
Antibody response and type of mRNA vaccination
Seventy-eight/120 patients (65%) received vaccination with Moderna, 40/120 (33%) with Pfizer and two/120 (2%) with AstraZeneca. Antibody titre did not differ between patients who received Moderna compared to Pfizer (p = 0.846), not even within each DMT group, but the small sample size could have prevented us from finding significant differences (data not shown).
Common adverse events including injection’s site pain, fever, and asthenia were reported each by roughly one-third of the patients. Details on the frequency of each adverse event are reported in Fig. 4. Two patients experienced a clinical relapse at week 6 and 12 following the second dose, respectively. One was treated with dimethyl-fumarate for the last 4 years, while the other patient was treated with AHSCT 8 years before, and was free from therapy since then. They were both treated with high-dose IV methylprednisolone with complete recovery.
Median follow-up after the first dose of vaccine was 5 months (range 2–7). Two patients reported symptomatic COVID-19 over follow-up. One female aged 49 years old experienced fever with respiratory symptoms at month 4 following the completion of the vaccination cycle, requiring access to the emergency department and treatment with anti-SARSCov2 antibodies, followed by complete recovery without hospitalisation. At the time of vaccination, this patient was treated with rituximab (starting in 2018) and did not show any humoral response to the vaccination. The other patient is a 37 years old male treated with fingolimod since 2016, without lymphopenia at blood tests taken over the last year; 6 months following the completion of the vaccination cycle (and 1 month after having received the third dose of vaccine) he experienced fever for 3 days and mild respiratory symptoms not requiring hospitalization. Antibody response following the second dose of vaccine was positive with a low titre.