{"id":4859,"date":"2024-02-12T06:00:00","date_gmt":"2024-02-12T11:00:00","guid":{"rendered":"http:\/\/wp.cov19longhaulfoundation.org\/?p=4859"},"modified":"2024-02-04T12:30:11","modified_gmt":"2024-02-04T17:30:11","slug":"sars-cov-2-a-trigger-of-myelin-oligodendrocyte-glycoprotein-associated-disorder","status":"publish","type":"post","link":"https:\/\/cov19longhaulfoundation.org\/?p=4859","title":{"rendered":"SARS-COV-2 a trigger of myelin oligodendrocyte glycoprotein-associated disorder"},"content":{"rendered":"\n

Authors: Magnus Johnsson,Fredrik Asztely, et. al. June 2022 Annals of Clinical and Translational Neurology<\/a><\/p>\n\n\n\n

Abstract<\/h2>\n\n\n\n

SARS-COV-2 frequently cause neurological disorders and is sometimes associated with onset of autoimmune diseases affecting the nervous system. Over recent years, a rare but distinct diagnosis designated myelin oligodendrocyte glycoprotein-associated disorder (MOGAD) has been recognized in patients with attacks of optic neuritis, myelitis, or encephalomyelitis and increased levels of anti-MOG antibodies. The cause of MOGAD is unknown. However, there have been reports of single cases of MOGAD in patients with Covid-19 infection. We report a series of SARS-CoV-2 positive patients that developed MOGAD, but a homology search did not support a cross-reactive immune response to SARS-CoV-2 spike-protein and MOG.<\/p>\n\n\n\n

Introduction<\/h2>\n\n\n\n

There are several causes to neurological symptoms in coronavirus disease 2019 (Covid-19).1<\/a><\/sup> It has previously been described that MERS-CoV and HcoV-OC43 are able to initiate immunopathogenic responses in the central nervous system (CNS),2<\/a><\/sup> and reports suggest that SARS-CoV-2 can trigger host autoantibody diseases.3<\/a>–7<\/a><\/sup><\/p>\n\n\n\n

MOGAD (Myelin Oligodendrocyte Glycoprotein-Associated Disorder) is a monophasic or relapsing inflammatory demyelinating condition of the central nervous system (CNS) characterized by the presence of antibodies to MOG (Myelin Oligodendrocyte Glycoprotein).8<\/a><\/sup><\/p>\n\n\n\n

One study concluded that SARS-CoV-2 may be a trigger of MOGAD as the authors found a higher occurrence of SARS-CoV-2 IgG antibodies in patients with MOGAD, but the difference was non-significant.9<\/a><\/sup> However, another study showed that only one out of 15 patients tested positive for anti-MOG in a group of post Covid-19 acute disseminated encephalomyelitis (ADEM) or acute hemorrhagic leukoencephalitis.10<\/a><\/sup><\/p>\n\n\n\n

We report four cases with onset of MOGAD after SARS-CoV-2 infection and reviewed previously published case reports with similar associations suggesting a role of SARS-CoV-2 in the pathogenesis of MOGAD.<\/p>\n\n\n\n

Methods<\/h2>\n\n\n\n

Four patients were diagnosed with MOGAD after Covid-19 infection, three between April 2020 and April 2021 at the department of neurology, Sahlgrenska University Hospital, V\u00e4stra G\u00f6taland County, and one in May 2021 at the department of medicine, Halmstad Hospital, Halland County. We investigated the incidence of MOGAD in the county of V\u00e4stra G\u00f6taland during the observational period by searching for positive anti-MOG index results determined at the two laboratories performing MOG serology in the county (Sahlgrenska Clinical Immunology Laboratory, and Wieslab Diagnostic Services). We also searched for cases by reaching out to neurologists at neurological departments in the county, and from a recent investigation on the prevalence of MOGAD in V\u00e4stra G\u00f6taland until the year of 2020 using medical records and laboratory data, approved by the director of operations manager (unpublished). Population statistics were collected from Statistics Sweden (SCB).11<\/a><\/sup> The analysis of anti-MOG antibodies was performed with indirect immunofluorescence on MOG-transfected cells, semi-quantitatively (EU-90; Euroimmun, Lubeck, Germany), with a cutoff level at \u22651:10. Informed consent was obtained from all subjects for publication of their case.<\/p>\n\n\n\n

Case presentations of MOGAD following COVID-19<\/h2>\n\n\n\n

See also Table 1<\/a>, section 1.<\/p>\n\n\n\n

Case of acute disseminated encephalomyelitis<\/h3>\n\n\n\n

A 25-year-old woman with fever and headache tested positive for PCR SARS-CoV-2. Two weeks after Covid-19 infection her condition deteriorated rapidly with severe paraparesis, hypesthesia below Th 5, urinary retention, and decreased consciousness. MRI of the brain and spinal cord revealed multiple non-enhancing cerebral parenchymal and spinal cervicothoracic T2 high intensity lesions. Cerebrospinal fluid (CSF) showed 295\u2009\u00d7\u2009106<\/sup>\/L lymphocytes, 229\u2009\u00d7\u2009106<\/sup>\/L neutrophils, 103\u2009\u00d7\u2009106<\/sup>\/L monocytes, and two oligoclonal IgG bands. She was diagnosed with ADEM and started treatment with iv methylprednisolone 1\u2009g for 5\u2009days. Infectious diagnostics workup was negative, including CSF SARS-CoV-2 PCR. Serum IgG AQP4-antibodies was negative, but serum anti-MOG IgG proved positive (1:1000). MRI 2\u2009weeks later showed new non-contrast enhancing high signal lesions on T2\/FLAIR in pons, corpus callosum, mesencephalon, and progress of intramedullary lesions in the cervical and thoracic spinal cord including contrast enhancement from Th6-Th9 (Fig.\u20091A-C<\/a>). The patient had a new course of intravenous steroids followed by a 5-day regimen of plasmapheresis, and then methotrexate and slow tapering of oral prednisolone. Four weeks later she had a relapse of optic neuritis with optic disc edema at ophthalmologic examination and confirmed by optical coherence tomography (OCT). MRI revealed a new lesion in the cerebellar peduncle. After e new course of high dose steroids iv, she made a quick recovery and at 4 months follow-up after MOGAD onset MRI revealed virtually complete radiological resolution of the cerebral and spinal lesions. The patient had slight lower extremity dysesthesia and moderate bladder dysfunction, and continued prednisolone 10\u2009mg daily and methotrexate 15\u2009mg weekly.<\/p>\n\n\n\n

\"Details<\/a>
Figure 1<\/strong>Open in figure viewer<\/a>PowerPoint<\/a>(A-C) MRI brain and spinal cord. Depicted axial cerebral (A) T2-weighted images show high signal lesions bilaterally in pons and left dorsal hippocampus, and (B) sagittal T2-weighted images of the spinal medulla show medullary high signal lesions most pronounced at C4-C6 levels. There was slight patchy contrast enhancement at Th6-Th9 levels in T1 contrast images. (C) Axial T2-weighted image at C4 level.<\/figcaption><\/figure>\n\n\n\n

Case of bilateral optic neuritis and myelitis<\/h3>\n\n\n\n

A 20-year-old man with a history of personality disorder and polysubstance abuse had SARS-CoV-2 PCR positive Covid-19 infection with minor respiratory symptoms. Eight weeks post infection he presented with gradual onset of headache, photo-and phonophobia, left sided hemianesthesia, severe paraparesis, urinary retention, back pain, and reduced vision. A neuro-ophthalmologic examination including OCT showed bilateral optic disc edema, reduced visual acuity, and color vision consistent with optic neuritis. MRI of the spinal cord revealed pronounced medullary T2 lesions from Th9 to conus medullaris, small focal lesions at Th7 and C6 levels, and slight contrast enhancement at Th9-Th11. A lumbar puncture showed 159\u2009\u00d7\u2009106<\/sup>\/L lymphocytes, 39\u2009\u00d7\u2009106<\/sup>\/L monocytes, 33\u2009\u00d7\u2009106<\/sup>\/L neutrophils, normal IgG index, normal kappa index, and no oligoclonal IgG bands in the CSF. Serum MOG-antibody test was positive at a 1:100 titer. Anti-AQP4 antibody test was negative. Diagnostic workup regarding infectious or rheumatological disease was negative. He was treated with plasmapheresis on five consecutive days followed by iv methylprednisolone 1\u2009g daily for 3\u2009days and then oral prednisolone tapered to 10\u2009mg daily and 15\u2009mg methotrexate weekly. At follow-up after 6 months he displayed residual symptoms of moderate paraparesis.<\/p>\n\n\n\n

Case of bilateral optic neuritis<\/h3>\n\n\n\n

A 29-year-old man had subacute onset of bilateral visual impairment and frontal headache. No significant antecedent health issue was identified apart from a Covid-19 infection 15\u2009days earlier. An ophthalmologist established a diagnosis of papillitis compatible with optic neuritis. OCT showed bilateral optic disc edema. The patient was admitted to the neurology department, but no other neurological deficits were detected. An MRI of the brain showed normal results, and lumbar puncture revealed normal opening pressure, normal levels of CSF white blood cells and protein, and oligoclonal IgG bands were negative. Methylprednisolone iv 1\u2009g treatment daily for 3\u2009days was commenced, followed by oral prednisolone tapered to 10\u2009mg daily. No serum AQP4-antibodies were detected, but anti-MOG IgG was positive at a 1:100 titer. Vision returned to normal within 1 month. Anti-MOG serum titer was 1:10 at 6\u2009weeks and negative at 4 months after optic neuritis.<\/p>\n\n\n\n

Case of unilateral optic neuritis<\/h3>\n\n\n\n

A 60-year-old woman, originating from China, presented with Covid-19 with fever, cough, myalgia, and dyspnea. She tested positive for PCR SARS-CoV-2. She was admitted to the intensive care unit due to respiratory insufficiency and received oxygen and oral betamethasone and rivaroxaban. She improved and was discharged from the hospital, but 54\u2009days after the Covid-19 onset she developed a right sided eye pain and an ophthalmologist diagnosed a unilateral optic neuritis with papillitis and reduced visual acuity to 20\/100. MRI showed swelling and contrast enhancement in the right optic nerve, but there was no significant pathology in the cerebral parenchyma or the spinal cord. CSF analysis revealed normal cell count, albumin, neurofilament light chain (NfL), and no oligoclonal IgG bands. She was treated with methylprednisolone 1\u2009g daily for 3\u2009days followed by prednisolone with slow tapering. Serology testing for anti-AQP4 was negative but MOG-antibodies were positive with a 1:1000 titer.<\/p>\n\n\n\n

Incidence of MOGAD in the county of V\u00e4stra G\u00f6taland<\/h2>\n\n\n\n

We identified a total of eight adult new incident MOGAD patients in the county of V\u00e4stra G\u00f6taland (population 1 365 245 in 202011<\/a><\/sup>) with a clinical onset between April 2020 and April 2021, corresponding to a MOGAD incidence of 0.59:100 000. These included the three post Covid-19 cases of this report, and none of the other five cases were preceded by a Covid-19 infection. Between April 2019 and April 2020, the year prior the observational period, there was five incident adult cases of MOGAD corresponding to an incidence of 0.37:100 000. An estimation of the incidence of PCR confirmed SARS-CoV-2 infection and MOGAD in the V\u00e4stra G\u00f6taland County between April 2020 and April 2021 was 1.94\/100.000 (154 388 cases12<\/a><\/sup>). However, the Covid-19 incidence is probably an underestimation since only few patients with suspected Covid-19 had a confirmatory PCR test during the early phase of the pandemic.<\/p>\n\n\n\n

Search for published cases in the literature<\/h2>\n\n\n\n

A search for previously published cases of MOGAD following a previous PCR confirmed SARS-CoV-2 infection was performed in September 2021 in PubMed and Google Scholar using the keywords COVID OR SARS-CoV-2 AND MOG OR Myelin Oligodendrocyte Glycoprotein OR Neuromyelitis Optica. We found 16 previously published case reports of possible Covid-19 related MOGAD.13<\/a>–28<\/a><\/sup> (Table\u20091<\/a>; section 2).Table 1. Case 1\u20134 clinical data (section 1) and previously published case reports (section 2) with Covid-19 and MOGAD association. All had positive serum anti-MOG.<\/p>\n\n\n\n

Case author<\/th>Syndrome<\/th>Covid-19; MOGAD interval(days)<\/th>Age (y)<\/th>Sex<\/th>Covid-19 symptoms<\/th>SARS-CoV-2 test<\/th>CSF<\/th><\/tr><\/thead>
Case nr 1\u20134 in this report:<\/td><\/tr>
<\/td>ADEM<\/td>14<\/td>25<\/td>Female<\/td>Fever, headache<\/td>NP PCR+<\/td>Lymphocytes 295\/qL<\/td><\/tr>
ON and myelitis<\/td>56<\/td>20<\/td>Male<\/td>Minor resp. symptoms<\/td>NP PCR+<\/td>Lymphocytes 159\/qL<\/td><\/tr>
Bilateral ON<\/td>14<\/td>29<\/td>Male<\/td>Minor resp. symptoms<\/td>NP PCR+<\/td>Normal<\/td><\/tr>
Unilateral ON<\/td>29<\/td>60<\/td>Female<\/td>Fever, dyspnea<\/td>NP PCR+<\/td>Normal<\/td><\/tr>
Previously published case reports (N\u2009=\u200916):<\/td><\/tr>
Zhou et al, 2020 13<\/a><\/sup><\/td>Bilateral ON<\/td>\u201ca few days\u201d<\/td>26<\/td>Male<\/td>Cough.<\/td>NP PCR+*<\/em><\/a><\/td>WBC 55\/qL<\/td><\/tr>
Sawalha et al, 202014<\/a><\/sup><\/td>Bilateral ON<\/td>14<\/td>44<\/td>Male<\/td>Dyspnea, cough.<\/td>NP PCR+*<\/em><\/a><\/td>WBC 3\/qL<\/td><\/tr>
Zoghi et al, 202015<\/a><\/sup><\/td>Encephalomyelitis<\/td>14<\/td>21<\/td>Male<\/td>Fever, dyspnea, cough.<\/td>IgG positive<\/td>Lymphocytes 90\/qL<\/td><\/tr>
Woodhall et al, 202016<\/a><\/sup><\/td>MOGAD relapse; ON<\/td>6<\/td>39<\/td>Female<\/td>Malaise, coryzal symptoms.<\/td>NP PCR+ *<\/em><\/a><\/td>NA<\/td><\/tr>
Jumah et al, 202117<\/a><\/sup><\/td>Myelitis (HHV6+)<\/td>No interval<\/td>61<\/td>Male<\/td>Fever, arthralgia. Hospitalized<\/td>NP PCR+*<\/em><\/a><\/td>WBC 279\/qL<\/td><\/tr>
Khan et al, 202118<\/a><\/sup><\/td>Bilateral ON<\/td>14<\/td>11<\/td>Male<\/td>Brief febrile illness.<\/td>NP PCR+*<\/em><\/a><\/td>Lymphocytes 55\/qL<\/td><\/tr>
Pinto et al, 202019<\/a><\/sup><\/td>CNS vasculopathy<\/td>7<\/td>44<\/td>Female<\/td>Minor resp. symptoms.<\/td>NP PCR+*<\/em><\/a><\/td>WBC 13\/qL<\/td><\/tr>
Kogure et al, 202120<\/a><\/sup><\/td>Bilateral ON<\/td>NA<\/td>47<\/td>Male<\/td>None<\/td>NP PCR+*<\/em><\/a><\/td>Normal<\/td><\/tr>
\u017dori\u0107 et al, 202121<\/a><\/sup><\/td>ON<\/td>28<\/td>63<\/td>Male<\/td>Pneumonia. Hospitalized<\/td>IgG positive<\/td>NA<\/td><\/tr>
Peters et al, 202122<\/a><\/sup><\/td>Encephalitis<\/td>35<\/td>23<\/td>Male<\/td>Headache.<\/td>NP PCR+<\/td>WBC 57\/qL<\/td><\/tr>
Vraka et al, 202123<\/a><\/sup><\/td>Encephalitis<\/td>10<\/td>1<\/td>Female<\/td>Fever<\/td>NP PCR+*<\/em><\/a><\/td>WBC 10\/qL<\/td><\/tr>
Sinha et al, 202124<\/a><\/sup><\/td>Encephalomyelitis<\/td>10<\/td>11<\/td>Female<\/td>Fever, cough<\/td>NP PCR+*<\/em><\/a><\/td>NA<\/td><\/tr>
Athanasopoulos et al, 202125<\/a><\/sup><\/td>Encephalitis<\/td>No interval<\/td>1<\/td>Female<\/td>Fever<\/td>NP PCR+*<\/em><\/a><\/td>Normal<\/td><\/tr>
Rojas-Correa et al, 202126<\/a><\/sup><\/td>Bilateral ON<\/td>45<\/td>69<\/td>Male<\/td>Fever, mild cough<\/td>IgG positive<\/td>Normal<\/td><\/tr>
Cay-Martinez et al, 202127<\/a><\/sup><\/td>Encephalomyelitis<\/td>NA<\/td>7<\/td>Female<\/td>None<\/td>IgG positive<\/td>WBC 551\/qL<\/td><\/tr>
Ruijter et al, 202028<\/a><\/sup><\/td>Bilateral ON<\/td>Weeks<\/td>15<\/td>Male<\/td>Fever, cough<\/td>NA<\/td>Normal<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n