Case Report: Exacerbation of Relapses Following mRNA COVID-19 Vaccination in Multiple Sclerosis: A Case Series

Abstract

IntroductionmRNA coronavirus disease 2019 (COVID-19) vaccination has been widely used to arrest the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Rarely, autoimmune events such as relapses in patients with multiple sclerosis (MS) have been reported after vaccination. However, the possible effects of vaccination in a patient already experiencing the symptoms of a relapse represent an unusual scenario that has not been described.Patients and MethodsThis is a retrospective case series of four patients from three major tertiary referral centers that received mRNA COVID-19 vaccination after starting with symptoms of acute demyelination of the central nervous system due to non-recognized MS. A detailed description of each case, including MRI studies, serum light-neurofilament levels, and cerebrospinal fluid (CSF) cytokine profile, is provided.Case DescriptionAll patients presented exacerbation of ongoing symptoms after vaccination (range 14–112 days first dose). All patients presented MRI features suggestive of highly active MS and fulfilled McDonald 2017 criteria at the time of presentation. All patients presented high serum light-neurofilament levels and oligoclonal G bands restricted to the CSF. Higher levels of interleukin-6 in the CSF were present in the more severe cases.DiscussionWe describe exacerbation of relapses after mRNA COVID-19 vaccination. We hypothesize RNA sensors such as Toll-like receptor 7 may be activated and contribute to amplify the inflammatory response during a relapse.ConclusionPatients should seek medical attention if experiencing acute neurological symptoms, especially before vaccination. Fast diagnostic procedures and prompt treatment should be performed in these patients. Pharmacovigilance and further study are warranted to confirm causality.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) following COVID-19 vaccines: A systematic review

“…Each vaccine triggers a different set of signaling pathways. Regarding innate immunity, vector-based vaccines elicit Toll-like receptor (TLR) 9, the major dsDNA sensor, and mRNA vaccines elicit TLR7 and MDA5, the major RNA sensor [ 54 ]. In microglia, macrophages, plasmacytoid dendritic cells, monocytes, and B lymphocytes, TLR 7 (upregulated in experimental autoimmune encephalomyelitis (EAE)) can detect single-stranded RNA.…”

“…In microglia, macrophages, plasmacytoid dendritic cells, monocytes, and B lymphocytes, TLR 7 (upregulated in experimental autoimmune encephalomyelitis (EAE)) can detect single-stranded RNA. By triggering TLR7, naive T cells are induced to secrete IL-1, IL-6, and IL-12 and differentiate into Th1 and Th17 cells, which may release IL-17 and IFN-gamma [ [54] , [55] ]. Vector-based vaccines activate TLR9 to cause the production of IFN-B, which modulates IL-17 production and suppresses T-cell activity.…”

“…Therefore, the vaccination may have exacerbated a relapse in these patients. Due to this contrast with TLR9 signaling by vector-based vaccines, this vaccine is characterized by a relatively low occurrence of severe relapses [ [54] , [56] ].…”

“…Also, these vaccines lead to the triggering of innate immunity which stimulates IFN-B and inflammatory cytokines production. Relapse and triggering of MS are the possible consequences of systemic side effects and possibly the modulation of ongoing inflammation [ 54 ]. During MS, immune cells identify vaccine-related antigens, activating other immune cells, including T cells, plasma cells, neutrophils, and macrophages.…”

Neurological Complications Following COVID-19 Vaccination

“…Quintanilla-Bordás et al reported a case series of four patients that received mRNA COVID-19 vaccination while already suffering from symptoms related to CNS demyelination due to yet undiagnosed MS [ 66 •]. All of these patients presented with exacerbation of ongoing symptoms after vaccination with MRI features suggestive of highly active MS, fulfilling McDonald 2017 criteria; high serum light-neurofilament levels and oligoclonal bands restricted to the CSF.…”