COVID-19 vaccination in patients with multiple sclerosis: Safety and humoral efficacy of the third booster dose

Abstract

Background As immunity against SARS-COV-2 wanes following first and second doses of vaccination, a third dose is administered in several countries around the world. Similarly to the first doses, risks related to vaccination and humoral immune response in patients with multiple sclerosis (MS) need to be assessed. Objective Characterize safety and humoral immune response following the third dose of COVID-19 vaccination in a large cohort of MS patients. Methods We assessed the safety of the third dose of the BNT162b2-COVID-19 mRNA vaccination in adult MS patients and evaluated SARS-CoV-2 IgG response. Results Two hundred and eleven adult MS patients received a third dose of BNT162b2 COVID-19 vaccination. Median follow up time was 66 days from vaccine administration (IQR 54–84). The frequency of any adverse event was 54.5%, with the most common reported adverse events being fatigue, local pain at the injection site, fever and muscle or joint pain. Transient increase in MS symptoms was reported in 3.8% of patients, none of them requiring treatment. The rate of acute relapses treated with IV steroids was 3.3%. In a sub-group of 55 patients, 20 untreated and 35 treated with vaccination-safe disease-modifying treatments, SARS-CoV-2 IgG levels increased 21-fold (median ± SD 21.6 ± 53.05). Conclusions The third dose of COVID-19-BNT162b2 vaccine proved safe for MS patients, with no increased risk of relapse activity. Untreated patients and patients treated with vaccination-safe disease-modifying treatments show significant increase in SARS-CoV-2 IgG levels following the third dose of vaccination.

Humoral response after the booster dose of anti-SARS-CoV-2 vaccine in multiple sclerosis patients treated with high-efficacy therapies

“…However, they efficiently eliminate the infection probably due to a preserved functionality of innate and T cells response ( Giovannoni et al., 2021 ). Overall, the results reported in this study confirmed that cladribine treatment does not compromise the development of a specific humoral response, as previously observed ( Achiron et al., 2021b ; Dreyer-Alster et al., 2022 ); for ocrelizumab and fingolimod, a significant Ab response can be achieved with further vaccinations. Studies in larger cohorts, together with B and T cell-mediated responses profiling, will be needed to better clarify the effect of vaccination booster in pwMS in relation to their DMT and for any future vaccination campaign.…”

“…Despite the low Ab response following vaccination, discontinuation of highly effective DMTs has not been recommended due to the high risk of relapse ( Giovannoni et al., 2021 ) and a booster dose was recommended. To date, data on booster have shown an adequate safety profile with a comparable adverse event incidence between the first vaccination cycle and booster ( Dreyer-Alster et al., 2022 ). IgG levels increase after booster in untreated and treated patients ( Dreyer-Alster et al., 2022 ), but data on B-depleting therapies and S1P modulators are not currently available.…”

“…To date, data on booster have shown an adequate safety profile with a comparable adverse event incidence between the first vaccination cycle and booster ( Dreyer-Alster et al., 2022 ). IgG levels increase after booster in untreated and treated patients ( Dreyer-Alster et al., 2022 ), but data on B-depleting therapies and S1P modulators are not currently available. Here, we evaluated the effects of the booster in pwMS under high-efficacy treatments by measuring anti-receptor-binding domain (RBD) IgG titers, that can be considered as neutralizing Abs (nAb).…”

Neuro-Ophthalmic Implications of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Related Infection and Vaccination

“…In individuals with MS, a relapse can be triggered by SARS-CoV-2 infection and vaccination 27,28 . In a cohort of 211 individuals with MS, the third dose of the BNT162b2 mRNA vaccine was associated with a transient increase of MS symptoms in 3.8% and a relapse in 3.3% 29 . Increased mortality and reduced efficacy of vaccination in MS are related to anti-CD20 therapies that reduce the B -cell count and can cause hypogammaglobulinemia 26,29 .…”

“…27,28 In a cohort of 211 individuals with MS, the third dose of the BNT162b2 mRNA vaccine was associated with a transient increase of MS symptoms in 3.8% and a relapse in 3.3%. 29 Increased mortality and reduced efficacy of vaccination in MS are related to anti-CD20 therapies that reduce the B-cell count and can cause hypogammaglobulinemia. 26,29 The IRR for an acute demyelinating event is higher in the 28 days following 2 1.…”