A prospective study of cellular immune response to booster COVID-19 vaccination in multiple sclerosis patients treated with a broad spectrum of disease-modifying therapies.

BACKGROUND: Most people with Multiple Sclerosis (pwMS) are subjected to immunomodulatory disease-modifying treatments (DMTs). As a result, immune responses to COVID-19 vaccinations could be compromised. There are few data on cellular immune responses to the use of COVID-19 vaccine boosters in pwMS under a broad spectrum of DMTs. METHODS: In this prospective study, we analysed cellular immune responses to SARS-CoV-2 mRNA booster vaccinations in 159 pwMS with DMT, including: ocrelizumab, rituximab, fingolimod, alemtuzumab, dimethyl fumarate, glatiramer acetate, teriflunomide, natalizumab and cladribine. RESULTS: DMTs, and particularly fingolimod, interact with cellular responses to COVID-19 vaccination. One booster dose does not increase cellular immunity any more than two doses, except in the cases of natalizumab and cladribine. SARS-CoV-2 infection combined with two doses of vaccine resulted in a greater cellular immune response, but this was not observed after supplementary booster jabs. Ocrelizumab-treated pwMS who had previously received fingolimod did not develop cellular immunity, even after receiving a booster. The time after MS diagnosis and disability status negatively correlated with cellular immunity in ocrelizumab-treated pwMS in a booster dose cohort. CONCLUSIONS: After two doses of SARS-CoV-2 vaccination, a high response yield was achieved, except in patients who had received fingolimod. The effects of fingolimod on cellular immunity persisted for more than 2 years after a change to ocrelizumab (which, in contrast, conserved cellular immunity). Our results confirmed the need to find alternative protective measures for fingolimod-treated people and to consider the possible failure to provide protection against SARS-CoV-2 when switching from fingolimod to ocrelizumab.

Seroprevalence of SARS-CoV-2 in a Cohort of Patients with Multiple Sclerosis under Disease-Modifying Therapies.

BACKGROUND: Disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS) alter the immune system and therefore increase the risk of infection. There is growing concern about the impact of COVID-19 on patients with MS (pwMS), especially those treated with DMTs. METHODS: This is a single-center prospective observational study based on data from the Esclerosis Múltiple y COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data and SARS-CoV-2 serology, and symptoms of COVID-19 in pwMS treated with any DTM were extracted. The relationship among demographics, MS status, DMT, and COVID-19 was evaluated. RESULTS: A total of 259 pwMS were included. The administration of interferon was significantly associated with the presence of SARS-CoV-2 antibodies (26.4% vs. 10.7%, p = 0.006). Although patients taking interferon were significantly older (49.1 vs. 43.5, p = 0.003), the association of interferon with the presence of SARS-CoV-2 antibodies was still significant in the multivariate analysis (OR 2.99 (1.38; 6.36), p = 0.006). CONCLUSIONS: According to our data, pwMS present a higher risk of COVID-19 infection compared with results obtained from the general population. There is no evidence of a worse COVID-19 outcome in pwMS. DMTs did not significantly change the frequency of COVID-19, except for interferon; however, these findings must be interpreted with caution given the small sample of pwMS taking each DMT.

Guillain-Barré syndrome associated with leptomeningeal enhancement following SARS-CoV-2 infection.

INTRODUCTION: Patients with coronavirus disease 2019 (COVID-19) typically present with respiratory symptoms, but little is known about the disease's potential neurological complications.We report a case of Guillain-Barré syndrome (GBS) following a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, in association with leptomeningeal enhancement. CASE PRESENTATION: A 56-year-old woman presented with recent unsteadiness and paraesthesia in both hands. Fifteen days earlier, she complained of fever, dry cough and shortness of breath. Her chest X-ray showed a lobar consolidation and PCR was positive for SARS-CoV-2; she was admitted due to mild COVID-19 pneumonia.In the first 48 hours of hospitalisation, she started to experience lumbar pain and weakness of the proximal lower extremities, progressing to bilateral facial nerve palsy, oropharyngeal weakness and severe proximal tetraparesis with cervical flexion 2/5 on the MRC scale. Full spine magnetic resonance imaging (MRI) showed a brainstem and cervical leptomeningeal enhancement. Analysis of cerebrospinal fluid (CSF) revealed albumin-cytological dissociation. Microbiological studies on CSF, including SARS-CoV-2, were negative. Nerve conduction studies were consistent with demyelinating neuropathy. She was treated with intravenous immunoglobulin, with significant neurological improvement noted over the next 2 weeks. CONCLUSION: Leptomeningeal enhancement is an atypical feature in GBS, but could be a marker of its association with SARS-CoV-2 infection.