MOG antibody-associated disease after vaccination with ChAdOx1 nCoV-19

Abstract

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a rare condition, with an estimated incidence of up to 3·4 per million per year (as measured in Oxfordshire, UK).1O'Connell K Hamilton-Shield A Woodhall M et al.Prevalence and incidence of neuromyelitis optica spectrum disorder, aquaporin-4 antibody-positive NMOSD and MOG antibody-positive disease in Oxfordshire, UK.J Neurol Neurosurg Psychiatry. 2020; 91: 1126-1128Google Scholar It is most frequently associated with optic neuritis in adults and acute disseminated encephalomyelitis in children, which often encompasses longitudinally extensive transverse myelitis and brainstem encephalitis.2Jurynczyk M Messina S Woodhall MR et al.Clinical presentation and prognosis in MOG-antibody disease: a UK study.Brain. 2017; 140: 3128-3138Google Scholar Here, we describe four adults who developed clinical features of MOGAD along with serum MOG-IgG1 antibodies3Waters P Woodhall M O'Connor KC et al.MOG cell-based assay detects non-MS patients with inflammatory neurologic disease.Neurol Neuroimmunol Neuroinflamm. 2015; 2: e89Google Scholar within 21 days of receiving the first dose of the ChAdOx1 nCoV-19 vaccine (Oxford–AstraZeneca) against SARS-CoV-2 (appendix p 1). These patients were reviewed by the specialised neuromyelitis optica service at the John Radcliffe Hospital (Oxford, UK) between April and September, 2021. A 58-year-old man (patient 1) developed lower limb sensory impairment and right-sided spastic hemiplegia 14 days after vaccination. MRI showed multiple brain and short spinal cord lesions. He was treated for 3 days with 1 g intravenous methylprednisolone per day followed by a 12-month tapering course of oral prednisolone, starting at 15 mg daily. 83 days after symptom onset, he had recovered almost completely. A 28-year-old woman (patient 2) developed lower limb weakness and sensory disturbance with faecal incontinence and urinary retention 14 days after vaccination. MRI showed longitudinally extensive transverse myelitis from C2 to the conus and an occipital white matter lesion (figure). She received five cycles of plasma exchange and 1 g intravenous methylprednisolone daily for 5 days followed by 60 mg oral prednisolone daily, reduced in 10 mg increments each month. She was discharged with a urinary catheter in situ. 135 days after symptom onset, she had ongoing urinary incontinence. Repeat MRI at 3 months showed resolution of the left occipital lesion but persistent spinal cord lesions. A 32-year-old man (patient 3) developed urinary retention and spastic paraplegia 21 days after vaccination. MRI revealed diffuse spinal cord lesions. He was treated with 1 g intravenous methylprednisolone daily for 5 days followed by 40 mg oral prednisolone daily, reducing gradually over 12 months. By 135 days after symptom onset he had recovered almost completely. A 38-year-old woman (patient 4) developed altered sensation in the left upper limb 7 days after vaccination. Over the next 4 days, she developed pyrexia, confusion, headache, paraplegia, and urinary retention. MRI revealed multiple spinal cord and infratentorial lesions (figure). She received 1 g intravenous methylprednisolone daily for 3 days followed by 2 g/kg intravenous immunoglobulin daily for 5 days and 60 mg oral prednisolone per day, tapered in 10 mg increments each month. 118 days after symptom onset, she had ongoing sensory impairment in the lower limbs. Patients 1, 3, and 4 had additional serum samples taken and tested for MOG antibodies between 2 and 12 weeks after the initial assay. Despite receiving steroids, these patients remained strongly MOG-antibody positive (appendix p 1). Longer-term follow-up will determine whether or not these patients will be at risk of relapse. These cases highlight some of the typical features of MOGAD. For example, all patients made good recoveries from a mobility point of view, but all presented with bladder dysfunction that persisted long into the recovery phase. However, atypical for adult MOGAD,2Jurynczyk M Messina S Woodhall MR et al.Clinical presentation and prognosis in MOG-antibody disease: a UK study.Brain. 2017; 140: 3128-3138Google Scholar none of the patients presented with optic neuritis, all had myelitis, and three had cerebral or brainstem involvement. The close temporal association between vaccination with ChAdOx1 nCoV-19 and MOGAD onset meets WHO causality criteria for possible causation.4The Uppsala Monitoring CentreThe use of the WHO-UMC system for standardised case causality assessment.https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdfDate accessed: January 21, 2022Google Scholar Another feature that supports causality between vaccination and these symptoms is the atypical presentation: instead of presenting with optic neuritis, the patients presented with disease that resembles acute disseminated encephalomyelitis with frequent brainstem involvement, which is more often seen in children with MOGAD after infection or vaccination.5Hennes E-M Baumann M Schanda K et al.Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome.Neurology. 2017; 89: 900-908Google Scholar Taken together, these features suggest the vaccine could be inducing MOGAD with a predilection for the brain and spinal cord. However, we do not know the incidence of MOGAD after other vaccinations and the annual incidence of MOGAD is low, making it difficult to be certain of a causal relationship between this vaccine and MOGAD. Two other diseases have been reported as rare side-effects of both the ChAdOx1 nCoV-19 and Ad26.COV2.S (Johnson & Johnson) vaccines: vaccine-induced thrombocytopaenia and thrombosis, which is associated with autoantibodies against platelet factor 4,6Greinacher A Thiele T Warkentin TE Weisser K Kyrle PA Eichinger S Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination.N Engl J Med. 2021; 384: 2092-2101Google Scholar and Guillain-Barré syndrome, which is associated with autoantibodies against gangliosides.7Maramattom BV Krishnan P Paul R et al.Guillain-Barré syndrome following ChAdOx1-S/nCoV-19 vaccine.Ann Neurol. 2021; 90: 312-314Google Scholar Regulatory warnings regarding the rare occurrence of these adverse effects are now included in the summary of product characteristics for these vaccines.8UK GovernmentInformation for UK recipients on COVID-19 vaccine AstraZeneca (regulation 174).https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazeneca/information-for-uk-recipients-on-covid-19-vaccine-astrazenecaDate accessed: November 24, 2021Google Scholar Together, these observations suggest that adenoviral-vectored COVID-19 vaccines might rarely trigger serious autoimmune disease but the pathophysiology underlying a potential association is uncertain. Possible mechanisms include that the adenovirus vector or the SARS-CoV-2 spike protein might activate pre-existing autoantibody-producing B lymphocytes. Alternatively, simultaneous binding of vaccine component and self-antigen by B cells could lead to autoantibody synthesis,9Prüss H Autoantibodies in neurological disease.Nat Rev Immunol. 2021; 21: 798-813Google Scholar particularly if inflammation caused by the vaccine impairs the integrity of the blood–brain barrier, allowing antigen-presenting cells and B cells to interact with MOG epitopes. Finally, sequence homology between an element of the ChAdOx1 nCoV-19 vaccine and MOG protein could trigger autoreactive B cell expansion and activation (molecular mimicry). Further study is essential to help understand development of MOGAD irrespective of vaccine status. JP has received grants or contracts from Merck-Serono, Roche, and MedImmune; has served on advisory panels for UCB, Mitsubishi, Amplo Roche, Alexion, Chugai, and Merck-Serono; has received payment or honoraria for academic work from Alexion, Roche, MedImmune, and Chugail; serves on the steering committee of MAGNIMS; is on the board of the European Charcot Foundation; is the co-lead of International Women in MS; and has stock or stock options in AstraZeneca. AF and LF declare no competing interests. Download .pdf (.06 MB) Help with pdf files Supplementary appendix