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BACKGROUND AND PURPOSE: An enhanced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen could improve humoral vaccine response in patients with multiple sclerosis (MS) treated by anti-CD20. The aim was to evaluate the serological response and the neutralizing activity after BNT162b2 primary and booster vaccination in MS patients, including patients on anti-CD20 receiving a primary vaccine regimen enhanced with three injections. METHODS: In this prospective longitudinal cohort study of 90 patients (47 on anti-CD20, 10 on fingolimod, 33 on natalizumab, dimethylfumarate or teriflunomide), anti-SARS-CoV-2 receptor binding domain (RBD) immunoglobulin G antibodies were quantified and their neutralization capacity was evaluated by enzyme-linked immunosorbent assay (GenScript) and a virus neutralization test against B.1 historical strain, Delta and Omicron variants, before and after three to four BNT162b2 injections. RESULTS: After the primary vaccination scheme, the anti-RBD positivity rate was strongly decreased in patients on anti-CD20 (28% [15%; 44%] after two shots, 45% [29%; 62%] after three shots) and fingolimod (50% [16%; 84%]) compared to other treatments (100% [90%; 100%]). Neutralization activity was also decreased in patients on anti-CD20 and fingolimod, and notably low for the Omicron variant in all patients (0%-22%). Delayed booster vaccination was performed in 54 patients, leading to a mild increase of anti-RBD seropositivity in patients on anti-CD20 although it was still lower compared to other treatments (65% [43%; 84%] vs. 100% [87%; 100%] respectively). After a booster, Omicron neutralization activity remained low on anti-CD20 and fingolimod treated patients but was strongly increased in patients on other treatments (91% [72%; 99%]). DISCUSSION: In MS patients on anti-CD20, an enhanced primary vaccination scheme moderately increased anti-RBD seropositivity and anti-RBD antibody titre, but neutralization activity remained modest even after a fourth booster injection. TRIAL REGISTRATION INFORMATION: COVIVAC-ID, NCT04844489, first patient included on 20 April 2021.
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Introduction Les traitements anti-CD20 augmentent le risque de formes sévères de COVID-19 chez les patients SEP, mais on ignore si ce surrisque varie selon le type de SEP (rémittentes ou progressives). Objectifs Évaluer l'impact des thérapies anti-CD20 sur la sévérité de la COVID-19 chez les patients atteints de SEP rémittentes (SEP-R) et progressive (SEP-P), au sein de la cohorte COVISEP. Méthodes Les critères d'inclusion étaient : SEP ;COVID-19 ;traitement de fond de haute efficacité (fingolimod-natalizumab-rituximab-ocrélizumab) pour les SEP-R ;âge < 70 ans et score EDSS≤8 pour les SEP-P. L'impact des anti-CD20 sur la sévérité de la COVID-19 (≥ hospitalisation avec oxygénothérapie) a été évalué séparément chez SEP-R et SEP-P par régression logistique pondérée par score de propension. Des analyses de sous-groupes ont été réalisées selon le statut vaccinal, le sexe, le score EDSS et l'âge. Résultats Au total, 971 patients SEP-R (43,0 % sous anti-CD20) et 429 SEP-P (52,7 % sous anti-CD20) ont été analysés. Chez les SEP-R, les anti-CD20 étaient associés à un surrisque de COVID-19 sévère (OR 5,29 IC95 %[2,81 ;9,95]), persistant chez les patients vaccinés (8,74 [1,12 ;68,23]). Chez les SEP-P, les anti-CD20 n'était pas associés au COVID-19 sévère (1,28 [0,76 ;2,15]), le surrisque était uniquement retrouvé chez les SEP-P avec EDSS < 6 (3,89 [1,39 ;10,9]) et < 54 ans (3,00 [1,14 ;7,94]). (Tableau 1 et 2). Discussion Les anti-CD20 augmentent le risque de COVID-19 sévère chez les SEP-R, y compris chez les patients vaccinés. En revanche, ces traitements ne sont pas associés à un surrisque de COVID-19 sévère chez les patients SEP-P. Le handicap neurologique et l'âge interagissent négativement avec l'exposition aux anti-CD20 sur le risque de COVID-19 sévère chez les SEP-P. Conclusion Cette étude met en évidence un impact différent des anti-CD20 sur la sévérité de la COVID-19 chez les patients SEP-R et SEP-P.
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INTRODUCTION: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. CASE SERIES: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. DISCUSSION: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.