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mRNA COVID-19 Vaccination Does Not Exacerbate Symptoms or Trigger Neural Antibody Responses in Multiple Sclerosis
Yolanda Blanco1, Domingo Escudero1, Cinta Lleixà1
1From the Neuroimmunology and Multiple Sclerosis Unit (Y.B., D.E., S.L., R.R.G., M.A., S.A., J.M.C.-M., M.G., A.H., E.M.-H., M.S., T.A., J.D., A.S.), Hospital Clinic de Barcelona, and Universitat de Barcelona; Neurommunology Program, Fundació de Recerca Clinic Barcelona-IDIBAPS (Y.B., S.L., R.R.G., M.A., E.A., M.A., E.C., J.M.C.-M., E.F., M.G., E.M.-H., G.O.-C., M.R., L.S., M.S., E.S., T.A., J.D., A.S.), Barcelona; Neuromuscular Diseases Unit, Neurology Department (C.L., L.M.-A., C.T.-I., N.V.-F., L.Q.), Hospital de Sant Pau, Barcelona; Centro para la Investigación en Red en Enfermedades Raras (CIBERER) (C.L., M.G., C.T.-I., J.D., L.Q.), Madrid; Department of Immunology (N.E., R.R.G.), Hospital Clinic de Barcelona; Department of Preventive Medicine and Epidemiology (M.A., A.V.), Hospital Clinic de Barcelona, Spain; Department of Neurology (E.F.), School of Medicine, Pontificia Universidad Católica de Chile, Santiago de Chile; Pediatric Neurology Unit (G.O.-C.), Hospital Parc Taulí de Sabadell, Barcelona; Infectious Diseases Unit, Department of Internal Medicine, (J.L.-C., A.R.) Hospital de Sant Pau, Universitat Autónoma de Barcelona, Barcelona; Immunology Department (L.M.-M.), Sant Pau, Institut de Recerca del Hospital de Sant Pau, Universitat Autónoma de Barcelona, Barcelona; Department of Pediatrics, and Infectious Diseases Department (C.F.), Institut de Recerca Pediàtrica Hospital de Sant Joan de Déu, Esplugues de Llobregat, Barcelona; Pediatric Neuroimmunology Unit, Department of Neurology (S.J.D.), Sant Joan de Déu Children´s Hospital (T.A), University of Barcelona, Spain; Department of Neurology, (J.D.) Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Catalan Institute for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
Background And Objective:
In people with multiple sclerosis (pwMS), concern for potential disease exacerbation or triggering of other autoimmune disorders contributes to vaccine hesitancy. We assessed the humoral and T-cell responses to SARS-CoV-2 after mRNA vaccination, changes in disease activity, and development of antibodies against central or peripheral nervous system antigens.
Methods:
This was a prospective 1-year longitudinal observational study of pwMS and a control group of patients with other inflammatory neurologic disorders (OIND) who received an mRNA vaccine. Blood samples were obtained before the first dose (T1), 1 month after the first dose (T2), 1 month after the second dose (T3), and 6 (T4), 9 (T5), and 12 (T6) months after the first dose. Patients were assessed for the immune-specific response, annualized relapse rate (ARR), and antibodies to onconeuronal, neural surface, glial, ganglioside, and nodo-paranodal antigens.
Results:
Among 454 patients studied, 390 had MS (22 adolescents) and 64 OIND; the mean (SD) age was 44 (14) years; 315 (69%) were female; and 392 (87%) were on disease-modifying therapies. Antibodies to the receptor-binding domain were detected in 367 (86%) patients at T3 and 276 (83%) at T4. After a third dose, only 13 (22%) of 60 seronegative patients seroconverted, and 255 (92%) remained seropositive at T6. Cellular responses were present in 381 (93%) patients at T3 and in 235 (91%) patients at T6 including all those receiving anti-CD20 therapies and in 79% of patients receiving fingolimod. At T3 (429 patients) or T6 (395 patients), none of the patients had developed CNS autoantibodies. Seven patients had neural antibodies that were already present before immunization (3 adult patients with MS had MOG-IgG, 2 with MG and 1 with MS had neuronal cell surface antibodies [unknown antigen], and 1 with MS had myelin antibody reactivity [unknown antigen]. Similarly, no antibodies against PNS antigens were identified at T3 (427 patients). ARR was lower in MS and not significantly different in patients with OIND. Although 182 (40%) patients developed SARS-CoV-2 infection, no cases of severe COVID-19 or serious adverse events occurred.
Discussion:
In this study, mRNA COVID-19 vaccination was safe and did not exacerbate the autoimmune disease nor triggered neural autoantibodies or immune-mediated neurologic disorders. The outcome of patients who developed SARS-CoV-2 infection was favorable.
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