OBJECTIVE: The impact of SARS-CoV-2 infection on brain and spinal cord pathology in patients with multiple sclerosis (pwMS) remains unclear. We aimed to describe changes in brain lesion activity and brain and spinal cord volumes following SARS-CoV-2 infection. METHODS: We included 177 pwMS (570 MRI scans) diagnosed with and tested positive for SARS-CoV-2 infection between August 2020 and May 2021. All patients were free of clinical disease activity, disease-modifying therapy changes, and corticosteroids during the study. MRI scans were performed using a standardized protocol on a 3-Tesla scanner. We analyzed the effect of SARS-CoV-2 on brain lesion load accrual and brain and spinal cord volume measures using adjusted mixed-effect models. RESULTS: During SARS-CoV-2 infection, patients had a median disease duration of 14.2 years, a median age of 44.9 years, and a median Expanded Disability Status Scale of 2.0. SARS-CoV-2 infection did not lead to any changes in the number or volume of T1 or T2 lesions in the brain. However, SARS-CoV-2 was associated with an increased whole brain (B = -0.17; SE = 0.08; p = 0.028), grey matter (B = -0.25; SE = 0.12; p = 0.040), and cortical grey matter volume loss (B = -0.32; SE = 0.13; p = 0.014). Greater ventricular enlargement following SARS-CoV-2 infection was evident only in individuals over the age of 40 (interaction of age vs. ventricular enlargement: B = 0.17; SE = 0.05; p = 0.0003). Only patients with more severe SARS-CoV-2 infection showed a reduction in mean upper cervical cord area (MUCCA) (B = 1.14; SE = 0.52; p = 0.030). INTERPRETATION: SARS-CoV-2 infection in clinically stable pwMS was linked to increased neuronal tissue loss.

• Keywords
• COVID‐19, MRI, SARS‐CoV‐2, brain atrophy, brain lesion, multiple sclerosis,
• Publication type
• Journal Article MeSH

AIMS: Multiple sclerosis treatment strategies are changing in the Czech Republic. According to data from 2013-2021, the proportion of patients starting high-efficacy disease-modifying therapies is increasing. In this survey, we describe the actual data trends in multiple sclerosis (MS) patients beginning their first disease‑modifying therapies (DMTs) from 2013 to 2021. The secondary objective was to present the history, data collection, and scientific potential of the Czech National MS registry (ReMuS). METHODS: First, using descriptive statistics, we analysed the data for patients starting their first DMTs, either platform (including dimethyl fumarate) or high-efficacy DMTs (HE-DMTs), for each successive year. Second, a detailed description of the history, data collection, completeness, quality optimising procedures, and legal policies of ReMuS is provided. RESULTS: Based on the dataset from December 31, 2021, the total number of monitored patients with MS in ReMuS increased from 9,019 in 2013 (referred from 7 of 15 MS centres) to 12,940 in 2016 (referred from all 15 Czech MS centres) to 17,478 in 2021. In these years, the percentage of patients treated with DMTs in the registry ranged from 76 to 83%, but the proportion of patients treated with HE-DMTs changed from 16.2% in 2013 to 37.1% in 2021. During the follow-up period, a total of 8,491 treatment-naive patients received DMTs. The proportion of patients (all MS phenotypes) starting HE-DMTs increased from 2.1% in 2013 to 18.5% in 2021. CONCLUSION: Patient registries, including ReMuS, provide an essential quality data source, especially in light of the increasing percentage of patients on HE-DMTs. Although early initiation of HE-DMT can provide considerable benefits, it also carries greater potential risks. Consistent long-term follow-up of patients in real‑world clinical practice, which only registries allow, is therefore crucial to evaluate the efficacy and safety of therapeutic strategies, for epidemiological research and to assist decision making by healthcare providers and regulatory bodies.

• Keywords
• disease-modifying therapy, epidemiology, high-efficacy therapy, multiple sclerosis, platform therapy, real-world data, registry, treatment initiation,
• MeSH
• Adult MeSH
• Immunologic Factors therapeutic use   MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Humans MeSH
• Registries * MeSH
• Multiple Sclerosis * drug therapy   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Immunologic Factors MeSH
• Immunosuppressive Agents MeSH

BACKGROUND: Rituximab (RTX) and ocrelizumab (OCR), B cell-depleting therapy targeting CD20 molecules, affect the humoral immune response after vaccination. How these therapies influence T-cell-mediated immune response against SARS-CoV-2 after immunization remains unclear. We aimed to evaluate the humoral and cellular immune response to the COVID-19 vaccine in a cohort of patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG). METHODS: Patients with MS (83), NMOSD (19), or MG (7) undergoing RTX (n=47) or OCR (n=62) treatment were vaccinated twice with the mRNA BNT162b2 vaccine. Antibodies were quantified using the SARS-CoV-2 IgG chemiluminescence immunoassay, targeting the spike protein. SARS-CoV-2-specific T cell responses were quantified by interferon γ release assays (IGRA). The responses were evaluated at two different time points (4-8 weeks and 16-20 weeks following the 2nd dose of the vaccine). Immunocompetent vaccinated individuals (n=41) were included as controls. RESULTS: Almost all immunocompetent controls developed antibodies against the SARS-CoV-2 trimeric spike protein, but only 34.09% of the patients, without a COVID-19 history and undergoing anti-CD20 treatment (via RTX or OCR), seroconverted. This antibody response was higher in patients with intervals of longer than 3 weeks between vaccinations. The duration of therapy was significantly shorter in seroconverted patients (median 24 months), than in the non-seroconverted group. There was no correlation between circulating B cells and the levels of antibodies. Even patients with a low proportion of circulating CD19+ B cells (<1%, 71 patients) had detectable SARS-CoV-2 specific antibody responses. SARS-CoV-2 specific T cell response measured by released interferon γ was detected in 94.39% of the patients, independently of a humoral immune response. CONCLUSION: The majority of MS, MG, and NMOSD patients developed a SARS-CoV-2-specific T cell response. The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in a portion of anti-CD20 treated patients. The seroconversion rate was higher in OCR-treated patients compared to those on RTX. The response represented by levels of antibodies was better in individuals, with intervals of longer than 3 weeks between vaccinations.

• Keywords
• IFN gamma release assay, SARS-CoV-2, SARS-CoV-2 mRNA vaccine, humoral immune response, multiple sclerosis, myasthenia gravis, neuromyelitis optica spectrum disorder,
• MeSH
• Autoimmune Diseases of the Nervous System * MeSH
• COVID-19 * MeSH
• Spike Glycoprotein, Coronavirus MeSH
• Antibodies, Monoclonal, Humanized therapeutic use   MeSH
• Humans MeSH
• Myasthenia Gravis * MeSH
• Antibodies, Viral MeSH
• Rituximab therapeutic use   MeSH
• Multiple Sclerosis * drug therapy   MeSH
• SARS-CoV-2 MeSH
• BNT162 Vaccine MeSH
• Vaccination MeSH
• COVID-19 Vaccines MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Spike Glycoprotein, Coronavirus MeSH
• Antibodies, Monoclonal, Humanized MeSH
• ocrelizumab MeSH Browser
• Antibodies, Viral MeSH
• Rituximab MeSH
• spike protein, SARS-CoV-2 MeSH Browser
• BNT162 Vaccine MeSH
• COVID-19 Vaccines MeSH

BACKGROUND: COVID-19 vaccination and infection are speculated to increase the activity of immune-mediated diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to evaluate a short-term risk of relapse after COVID-19 vaccination and COVID-19 infection in patients with these demyelinating disorders of the central nervous system and to determine disease exacerbation risk factors. METHODS: Data in this retrospective, observational cohort study was collected via the Czech nationwide registry ReMuS from March 1, 2020, to October 30, 2021. We compared the proportion of patients with at least one clinical relapse in the 90 days following vaccination or infection to the 90-day intervals during the year before. For the evaluation of the risk factors of relapse, a comparison between groups with and without relapses after COVID-19 vaccination or infection was made. RESULTS: We identified 1661 vaccinated (90.11% BNT162b2) patients with MS without a history of COVID-19 and 495 unvaccinated patients with MS who experienced COVID-19. A mild increase in the proportion of patients with at least one clinical relapse (-360 to -270 days: 4.46%; -270 to -180: 4.27%; -180 to -90: 3.85%; -90 to 0: 3.79% vs. 0 to +90 days: 5.30%) after vaccination in patients with MS was observed, as well as a rise in the proportion of patients with at least one clinical relapse after COVID-19. Lower age was associated with MS relapse after vaccination or infection. Although there were only 17 vaccinated and eight post-COVID-19 patients with NMOSD, the results were broadly consistent with those of patients with MS. CONCLUSION: There is a mild increase in the relapse incidence after the COVID-19 vaccination. The risks, however, need to be balanced against the risks of COVID-19 itself, also leading to the rise in relapse rate and particularly to morbidity and mortality.

• Keywords
• Acute relapse, COVID-19, Multiple sclerosis, Neuromyelitis optica, Vaccination,
• MeSH
• COVID-19 * prevention & control   MeSH
• Humans MeSH
• Neuromyelitis Optica * complications   MeSH
• Recurrence MeSH
• Retrospective Studies MeSH
• Multiple Sclerosis * complications   MeSH
• BNT162 Vaccine MeSH
• Vaccination adverse effects   MeSH
• COVID-19 Vaccines * adverse effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• BNT162 Vaccine MeSH
• COVID-19 Vaccines * MeSH

• MeSH
• COVID-19 * MeSH
• Humans MeSH
• Myasthenia Gravis * complications   MeSH
• SARS-CoV-2 MeSH
• Thymectomy MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH
• Comment MeSH