Long term persistence of SARS-CoV-2 humoral response in multiple sclerosis subjects

•DMTs affect SARS-COV-2 IgG titre six months after the second BNT162b2 vaccine dose;.•SARS-CoV-2 IgG levels in IFN, DMF, TERI and NAT MS subjects are comparable to HC;.•DMF-, IFN- and GA- MS patients reveal a faster decline of the humoral response;.•TERI- and NAT- MS patients show higher persistence of SARS-CoV-2 IgG levels. The persistence of the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Here, we present data regarding the decline of the SARS-CoV-2 BNT162b2 mRNA vaccine-induced humoral immune response in a monocentric cohort of MS patients. 96 MS patients undergoing eight different DMTs, all without previous SARS-CoV-2 infection, were evaluated for anti-Spike IgG levels, 21 days (T1) and 5–6 months (T2) after the second SARS-CoV-2 BNT162b2 mRNA vaccine dose. The anti-Spike IgG titre from MS subjects was compared with 21 age- and sex-matched healthy controls (HC). When compared with SARS-CoV-2 IgG levels at T2 in HC, we observed comparable levels in interferon-β 1a-, dimethyl fumarate-, teriflunomide- and natalizumab-treated MS subjects, but an impaired humoral response in MS subjects undergoing glatiramer acetate-, cladribine-, fingolimod- and ocrelizumab-treatments. Moreover, comparison between SARS-CoV-2 IgG Spike titre at T1 and T2 revealed a faster decline of the humoral response in patients undergoing dimethyl fumarate-, interferon-β 1a- and glatiramer acetate-therapies, while those receiving teriflunomide and natalizumab showed higher persistence compared to healthy controls. The prominent decline in humoral response in MS subjects undergoing dimethyl fumarate-, interferon-β 1a- and glatiramer acetate-therapies should be considered when formulating booster regimens as these subjects would benefit of early booster vaccinations.