Covid-19 vaccination can induce multiple sclerosis via cross-reactive CD4+ T cells recognizing SARS-CoV-2 spike protein and myelin peptides

Introduction: Infection with the SARS-CoV-2 coronavirus can lead to a wide range of acute and also chronic disease manifestations. The rapidly developed vaccinations are highly effective in preventing severe disease courses and have been proven safe. Both natural infection and, to a much lower extent, the mRNAbased vaccinations can be accompanied by transient autoimmune phenomena or onset of autoimmune diseases. Objective(s): We report here two cases of multiple sclerosis (MS) with clinical and new radiological signs beginning in close temporal relation to spike (S) protein mRNA-based vaccinations. Aim(s): To establish that the onset of MS in these two cases is very likely caused by CD4+ T cell clones that cross-recognize SARSCoV- 2 S protein-derived peptides and peptides derived from myelin proteins, which have previously been implicated in MS. Method(s): Spike specific CD4+ T cells from peripheral blood and CD4+ T cells from CSF sample were isolated and expanded for autoantigen screening test. A list of well-known MS-related autoantigens including immunodominant peptides and isoforms from MBP, MOG, PLP, RASGRP2, TSTA3 peptides were included to assess T cell reactivity. CD4+ CFSElow fraction were sorted after stimulate with positive autoantigen pools or SARSCov- 2 Spike protein, followed by expansion and testing with autoantigen peptides and Spike protein. Supernatant from cell culture were further analyzed for IFN-gamma secretion. Result(s): Self-reactive T cells were detected from Spike specific T cell population in both patients. CD4+ T from CSF also showed reactivity to MBP, MOG, PLP peptide pools. Finally, we found proinflammatory T cell clones that recognize both Spike protein and immunodominant MBP peptides and MOG peptides, which have previously been implicated in MS. Conclusion(s): Detailed studies of both peripheral blood- and CSFderived CD4+ T cells show that the onset of MS in these two cases is very likely caused by CD4+ T cell clones that cross-recognize SARS-CoV-2 S protein-derived peptides and peptides derived from myelin proteins, which have previously been implicated in MS.

A systematic review of neurological manifestations of SARS-CoV-2 infection: the devil is hidden in the details.

BACKGROUND AND PURPOSE: We systematically reviewed available evidence for reports of neurological signs and symptoms in patients with COVID-19 to identify cases with severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection or immune-mediated reaction in the nervous system. METHODS: We followed PRISMA guidelines and used the MEDLINE, EMBASE, Google Scholar, MedRxiv and ChinaXiv databases to search for articles on COVID-19 and nervous system involvement that were published from 1 January to 24 April 2020. Data on design, sample size, neurological assessment and related work-up were extracted. Biases were assessed with the Newcastle-Ottawa scale. RESULTS: We analysed 27 publications on potential neuroinvasive or parainfectious neurological complications of COVID-19. The reports focused on smell and taste (n = 5) and evaluation of neurological symptoms and signs in cohorts (n = 5). There were cases of Guillain-Barré syndrome/Miller-Fisher syndrome/cranial neuropathy (seven cases), meningitis/encephalitis (nine cases) and various other conditions (five cases). The number of patients with examination of cerebrospinal fluid and, in particular, SARS-CoV-2 polymerase chain reaction was negligible. Two had a positive SARS-CoV-2 polymerase chain reaction examination of cerebrospinal fluid specimen. Study of potential parenchymal involvement with magnetic resonance imaging was rare. Only four reports received a rating of the highest quality standards. CONCLUSIONS: This systematic review failed to establish comprehensive insights into nervous system manifestations of COVID-19 beyond immune-mediated complications in the aftermath of respiratory symptoms. The authors therefore provide guidance for more careful clinical, diagnostic and epidemiological studies to characterize the manifestations and burden of neurological disease caused by SARS-CoV-2 on behalf of the Infectious Disease Panel of the European Academy of Neurology.