A single-dose strategy for immunization with live attenuated vaccines is an effective option before treatment initiation in multiple sclerosis patients

Multiple sclerosis; Infections; VaccinationEsclerosi múltiple; Infeccions; VacunacióEsclerosis múltiple; Infecciones; VacunaciónBackground: Mumps-Measles-Rubella (MMR) and Varicella zoster vaccines (VAR) are live attenuated vaccines, usually administered in a two-dose scheme at least 4 weeks apart. However, single-dose immunization schemes may also be effective and can reduce delays in immunosuppressive treatment initiation in patients with multiple sclerosis (pwMS) who need to be immunized. Objectives: To evaluate the immunogenicity of a single-dose attempt (SDA) versus the standard immunization scheme (SIS) with VAR and/or MMR in pwMS. Methods: Retrospective observational study in pwMS vaccinated against VAR and/or MMR. We compared seroprotection rates and antibody geometric mean titers (GMTs) between the two strategies. Results: Ninety-six patients were included. Thirty-one patients received VAR and 67 MMR. In the SDA group, the seroprotection rate was 66.7% (95% confidence interval (CI): 53.3–78.3) versus 97.2% (95% CI: 85.5–99.9) in the SIS (p < 0.001). For the seroprotected patients, GMTs were similar for both schemes. Conclusion: An SDA of VAR and/or MMR vaccines could be sufficient to protect almost two-thirds of patients. Testing immunogenicity after a single dose of VZ and/or MMR could be included in routine clinical practice to achieve rapid immunization.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project PI19/01606 and co-funded by the European Union and ECTRIMS clinical fellowship awarded to René Carvajal from 2021 to 2022

Vaccine Safety and Immunogenicity in Patients With Multiple Sclerosis Treated With Natalizumab

Immunogenicity; Vaccine; Multiple sclerosisImmunogenicitat; Vacuna; Esclerosi múltipleInmunogenicidad; Vacuna; Esclerosis múltipleImportance Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay. Objective To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment. Design, Setting, and Participants This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022. Eligible participants included adults with MS who completed immunization for hepatitis B virus (HBV), hepatitis A virus (HAV), and COVID-19 during natalizumab therapy. Data analysis was conducted from November 2022 to February 2023. Exposures Patients were categorized according to their time receiving natalizumab treatment at the time of vaccine administration as short-term (≤1 year) or long-term (>1 year). Main Outcomes and Measures Demographic, clinical, and radiological characteristics were collected during the year before vaccination (prevaccination period) and the year after vaccination (postvaccination period). Seroprotection rates and postvaccination immunoglobulin G titers were determined for each vaccine within both periods. Additionally, differences in annualized relapse rate (ARR), new T2 lesions (NT2L), Expanded Disability Status Scale (EDSS) scores, and John Cunningham virus (JCV) serostatus between the 2 periods were assessed. Results Sixty patients with MS (mean [SD] age, 43.2 [9.4] years; 44 female [73.3%]; 16 male [26.7%]; mean [SD] disease duration, 17.0 [8.7] years) completed HBV, HAV, and mRNA COVID-19 immunization during natalizumab treatment, with 12 patients in the short-term group and 48 patients in the long-term group. The global seroprotection rate was 93% (95% CI, 86%-98%), with individual vaccine rates of 92% for HAV (95% CI, 73%-99%), 93% for HBV (95% CI, 76%-99%), and 100% for the COVID-19 messenger RNA vaccine (95% CI, 84%-100%). Between the prevaccination and postvaccination periods there was a significant reduction in the mean (SD) ARR (0.28 [0.66] vs 0.01 [0.12]; P = .004) and median (IQR) NT2L (5.00 [2.00-10.00] vs 0.81 [0.00-0.50]; P = .01). No changes in disability accumulation were detected (median [IQR] EDSS score 3.5 [2.0-6.0] vs 3.5 [2.0-6.0]; P = .62). No differences in safety and immunogenicity were observed for all vaccines concerning the duration of natalizumab treatment. Conclusions and Relevance The findings of this cohort study suggest that immunization with inactivated vaccines during natalizumab therapy was both safe and immunogenic, regardless of the treatment duration. Natalizumab may be a valuable option for proper immunization, averting treatment delays in patients with highly active MS; however, this strategy needs to be formally evaluated.This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III (ISCIII; project PI19/01606), and cofunded by the European Union

Características clínicas, radiológicas, análise liquórica e desfecho em pacientes com encefalite infectados pelo Sars-Cov-2 admitidos em hospitais da Rede D'Or São Luiz

A infecção pelo SARS-CoV-2 é responsável por uma doença com acometimento prioritário das vias respiratórias, porém de envolvimento multissistêmico. Sua alta transmissibilidade e virulência culminaram em uma pandemia, desafiando a produção de conhecimento científico e capacidade assistencial de todo o planeta. Apesar de uma relevante incidência de sintomas neurológicos, a patogênese desses sintomas não está bem definida. Entre eles, alguns pacientes evoluíram com síndromes neurológicas classificadas como encefalites, seja no período peri infeccioso ou no período pós infeccioso. Dessa forma, temos o objetivo de descrever os achados clínicos, radiológicos e de análise liquórica nos casos de encefalite em pacientes infectados pelo SARS-CoV-2. Trata-se de um estudo observacional retrospectivo, em que foram selecionados pacientes com coleta de líquor e diagnóstico recente de infecção pelo SARS-CoV-2, através de análise de prontuário. Descrevemos seus achados clínicos, radiológicos, liquóricos e de eletroencefalograma. Analisamos o desfecho desses pacientes através de um questionário de auto avaliação. Entre os 135 pacientes analisados, 11 pacientes foram selecionados. A maior parte desses pacientes foi admitido por seus sintomas neurológicos (73%), e em 63% dos casos os sintomas neurológicos ocorreram nos primeiros sete dias de sintomas sistêmicos. Três pacientes apresentaram mais de 25% de acometimento pulmonar avaliado na tomografia de tórax. Na análise liquórica, o achado mais relevante foi a hiperproteinorraquia, enquanto o vírus foi identificado em apenas um dos pacientes. Apenas três pacientes (33%) apresentam ressonância magnética alterada, sem achados similares entre eles. Na análise de desfecho, realizada em média 377 dias depois da alta, apenas dois pacientes se sentiam completamente recuperados. A maior parte (77%) reportou dificuldades na marcha e 66% reportaram dificuldades de memória e concentração. Portanto, a encefalite associada à infecção por SARS-CoV-2 é uma complicação que apesar de rara, traz consequências aos pacientes, mesmo após um ano da enfermidade. No entanto, a fisiopatologia parece estar associada tanto ao processo imunomediado quanto a alguns casos de invasão pelo próprio vírusSARS-CoV-2 infection is responsible for a disease mainly involving the airways, but with multisystem implications. Its high transmissibility and virulence culminated in a pandemic, challenging the production of scientific knowledge and care capacity across the planet. Despite a relevant incidence of neurological symptoms, the pathogenesis of these symptoms is not well defined. Among them, some patients developed neurological syndromes classified as encephalitis, either in the peri-infectious or post-infectious period. Thus, we aim to describe the clinical, radiological and cerebrospinal fluid (CSF) analysis findings in cases of encephalitis in patients infected with SARS-CoV-2. This is a retrospective observational study, in which patients with CSF collection and recent diagnosis of SARS-CoV-2 infection were selected, through analysis of medical records. We describe its clinical, radiological, cerebrospinal fluid and electroencephalogram findings. We analyzed the outcome of these patients through a self-assessment questionnaire. Among the 135 patients analyzed, 11 patients were selected. Most of these patients were admitted for their neurological symptoms (73%), and in 63% of cases, neurological symptoms occurred within the first seven days of systemic symptoms. Three patients had more than 25% of pulmonary involvement assessed on chest tomography. In the cerebrospinal fluid analysis, the most relevant finding was hyperproteinorraquia, while the virus was identified in only one of the patients. Only three patients (33%) had altered MRI, with no similar findings among them. In the outcome analysis, performed an average of 377 days after discharge, only two patients felt completely recovered. Most patients (77%) reported gait difficulties and 66% reported memory and concentration difficulties. Therefore, encephalitis associated with SARS-CoV-2 infection is a complication that, despite being rare, has consequences for patients, even after one year of illness. However, the pathophysiology seems to be associated with both the immune-mediated process and some cases of invasion by the virus itself38 f