Immunité cellulaire et humorale anti-SARS-CoV-2 chez les patients SEP traités par anti-CD20

Introduction Les patients SEP sous anti-CD20 présentent un surrisque de forme sévère de COVID-19 et une réponse humorale anti-SARS-CoV-2 altérée. Peu de données existent sur la réponse cellulaire chez ces patients. Objectifs Caractériser les réponses immunitaires humorales et cellulaires spécifiques après au moins 2 vaccinations anti-SARS-CoV-2 chez des patients atteints de SEP traités par anti-CD20. Méthodes Étude observationnelle prospective monocentrique à l'hôpital neurologique de Lyon, France, de novembre 2021 à février 2022 chez 61 patients SEP traités par anti-CD20 et 10 volontaires sains comme contrôles, ayant bénéficié d'au moins 2 doses de vaccin anti-SARS-CoV-2. La réponse cellulaire anti-SARS-CoV-2 était évaluée par la prolifération des lymphocytes T spécifiques après stimulation antigénique par des peptides du SARS-CoV-2. La sérologie SARS-CoV-2 et l'immunophénotypage lymphocytaire étaient également analysés. Résultats Dix-huit pour cent (11/61) des patients présentaient une réponse humorale contre 100 % des contrôles (p < 0,0001). Soixante-dix pour cent (43/61) des patients présentaient une réponse cellulaire contre 100 % (10/10) des contrôles (p = 0,056). Les patients sous anti-CD20 développant des réponses humorales et cellulaires présentaient des délais plus courts depuis la dernière vaccination (45 j versus 152 j, p = 0,0089) et un nombre de lymphocytes B CD20+/μL plus élevé (8 contre 0, p < 0,0001), par rapport aux patients sans aucune réponse. Discussion Après vaccination anti-SARS-CoV-2, la plupart des patients SEP sous anti-CD20 développent une réponse cellulaire spécifique malgré l'absence de réponse humorale. Un délai plus court après le dernier rappel vaccinal et la réplétion lymphocytaire B étaient associés à une meilleure réponse immunitaire cellulaire et humorale. L'impact clinique des réponses cellulaires et/ou humorales reste à évaluer. Conclusion Ces résultats suggèrent que les rappels vaccinaux devraient être répétés chez les patients SEP sous anti-CD20 avec un délai personnalisé, basé sur la réplétion des lymphocytes B.

Is there a correlation between MOG-associated disorder and SARS-CoV-2 infection?

BACKGROUND AND PURPOSE: Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) distinguish a group of inflammatory disorders which can be preceded by specific or non-specific infections. A few single cases have been reported in association with SARS-CoV-2 infection, but a specific study on the correlation between COVID-19 and myelin oligodendrocyte glycoprotein (MOG)-associated disorder (MOGAD) has not yet been performed. The aim of this study was to determine the impact of the pandemic on this condition. METHODS: We analysed SARS-CoV-2 serology in patients newly diagnosed with MOGAD (1 August 2020 to 31 May 2021). MOG-Ab-seronegative age- and time-matched subjects were used as controls. SARS-CoV-2 immunoglobulin G (IgG) levels were analysed using an anti-SARS-CoV-2 US Food and Drug Administration-approved ELISA assay and confirmed with a trimeric anti-SARS-CoV-2 S1/S2 IgG immunochemiluminescent test, concomitantly assaying the anti-receptor binding domain (RBD) of spike protein IgG and anti-RBD total Ig. We actually compared the number of cases referred in each of the last 3 years. RESULTS: Presence of SARS-CoV-2 IgG antibodies was more common (12/30, 40%) in MOGAD patients than in controls (6/30, 20%), although the difference was not significant (p = 0.16; odds ratio 2.67, 95% confidence interval 0.85-9.17). The most common clinical presentations of MOGAD SARS-CoV-2-seropositive patients included optic neuritis (n = 6) and myelitis (n = 3). The number of diagnosed cases increased over the last 3 years, in particular, when including cases referred to us before the COVID-19 pandemic, in the initial phase of the first wave and in the late phase of the second wave (n = 9, rate 10.6% in 2019; n = 13, rate 12.3% in 2020; n = 15, rate 14.7% in 2021). CONCLUSION: Our findings provide preliminary data on SARS-CoV-2 as a potential trigger of MOGAD.

Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders.

BACKGROUND: Outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown. METHODS: We conducted a multicenter, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between 1 March 2020 and 30 June 2020. Main outcome was COVID-19 severity score assessed on a seven-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death). RESULTS: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower expanded disability severity score (EDSS) score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]). CONCLUSIONS: COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19; however, we recommend personal protective measures to reduce risk of SARS-CoV-2 infection in this immunocompromised population.