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      Autoimmune myasthenia gravis after COVID-19 in a triple vaccinated patient

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          ABSTRACT

          Despite a well characterized mechanism, myasthenia gravis (MG) remains a dilemma in terms of etiology. Several case reports and series of cases suggest a potential cause-effect relation between SARS-CoV-2 infection or vaccination and MG. We present the case of an autoimmune MG occurring post Covid-19 in an elderly male, vaccinated with three doses of the BNT162b2/Pfizer-BioNTech vaccine. The 78-year-old male was admitted in the Neurology Clinic in early November 2021 with double vision, bilateral ptosis, dysphonia and dysphagia, 16 days after receiving a third dose of the BNT162b2/Pfizer-BioNTech SARS-CoV-2 vaccine and 12 days after testing positive for SARS-CoV-2 infection. The symptoms began to emerge at 9 days after COVID-19 diagnosis. Clinical neurological examination included ice-pack test and intramuscular neostigmine, both with positive results. Myasthenia gravis positive diagnosis was confirmed by slow repetitive nerve stimulation and abnormally increased serum levels of antibodies against acetylcholine receptors. Due to patient's refusal of further hospitalization, he was discharged with therapy recommendations. Under treatment with oral pyridostigmine, but no oral corticosteroid due to therapeutic noncompliance, the patient was readmitted two months later with aggravated symptoms. The myasthenic crisis was successfully treated with intravenous immunoglobulins, corticosteroid therapy and oral pyridostigmine. The novelty of the current case resides in the fact that, to the best of our knowledge, appears to be the first case of MG clinically manifested after COVID-19 infection in a fully vaccinated patient.

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          Toll-Like Receptor Signaling Pathways

          Toll-like receptors (TLRs) play crucial roles in the innate immune system by recognizing pathogen-associated molecular patterns derived from various microbes. TLRs signal through the recruitment of specific adaptor molecules, leading to activation of the transcription factors NF-κB and IRFs, which dictate the outcome of innate immune responses. During the past decade, the precise mechanisms underlying TLR signaling have been clarified by various approaches involving genetic, biochemical, structural, cell biological, and bioinformatics studies. TLR signaling appears to be divergent and to play important roles in many aspects of the innate immune responses to given pathogens. In this review, we describe recent progress in our understanding of TLR signaling regulation and its contributions to host defense.
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            Miller Fisher Syndrome and polyneuritis cranialis in COVID-19

            To report two patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) who acutely presented with Miller Fisher syndrome and polyneuritis cranialis, respectively. Patient data were obtained from medical records from the University Hospital “Príncipe de Asturias”, Alcalá de Henares, Madrid, Spain and from the University Hospital “12 de Octubre”, Madrid, Spain. The first patient was a 50-year-old man who presented with anosmia, ageusia, right internuclear ophthalmoparesis, right fascicular oculomotor palsy, ataxia, areflexia, albuminocytologic dissociation and positive testing for GD1b-IgG antibodies. Five days before, he had developed a cough, malaise, headache, low back pain, and a fever. The second patient was a 39-year-old man who presented with ageusia, bilateral abducens palsy, areflexia and albuminocytologic dissociation. Three days before, he had developed diarrhea, a low-grade fever, and a poor general condition. The oropharyngeal swab test for coronavirus disease 2019 (COVID-19) by qualitative real-time reverse-transcriptase–polymerase-chain-reaction assay was positive in both patients and negative in the cerebrospinal fluid. The first patient was treated with intravenous immunoglobulin and the second, with acetaminophen. Two weeks later, both patients made a complete neurological recovery, except for residual anosmia and ageusia in the first case. Our two cases highlight the rare occurrence of Miller Fisher syndrome and polyneuritis cranialis during the COVID-2 pandemic. Neurological manifestations may occur because of an aberrant immune response to COVID-19. The full clinical spectrum of neurological symptoms in patients with COVID-19 remains to be characterized.
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              Immune-Mediated Disease Flares or New-Onset Disease in 27 Subjects Following mRNA/DNA SARS-CoV-2 Vaccination

              Background: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. Methods: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. Findings: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis ( n = 2), neurosarcoidosis with small fiber neuropathy ( n = 1), demyelination ( n = 1), and myasthenia gravis ( n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. Interpretation: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. Funding: none.
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                Author and article information

                Journal
                Arch Clin Cases
                Arch Clin Cases
                ACC
                Archive of Clinical Cases
                UMF “Gr. T. Popa” Iasi Publishing House (Iași, Romania )
                2360-6975
                2022
                26 September 2022
                : 9
                : 3
                : 104-107
                Affiliations
                [1 ]I Neurology Clinic, Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iaşi, Romania.
                [2 ]Department Medical III - Neurology, Grigore T. Popa University of Medicine and Pharmacy, Iaşi, Romania.
                [3 ]Department Morpho-Functional Sciences I - Histology, Grigore T. Popa University of Medicine and Pharmacy, Iaşi, Romania.
                [4 ]Department of Immunology, Grigore T. Popa University of Medicine and Pharmacy, Iaşi, Romania.
                Author notes
                [* ] Correspondence: Petru Cianga, Department of Immunology, Grigore T. Popa University of Medicine and Pharmacy, Iaşi, 16 Universitatii Str. Iasi 700115, Romania. Email: petru.cianga@ 123456umfiasi.ro

                How to cite this article: Croitoru C-G, Cuciureanu DI, Prutianu I, et al. Autoimmune myasthenia gravis after COVID-19 in a triple vaccinated patient. Arch Clin Cases. 2022; 9(3):104-107. doi: 10.22551/2022.36.0903.10212

                Article
                10.22551/2022.36.0903.10212
                9512128
                36176496
                211e3955-c9d2-4b95-99bd-a600e05d772c

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : July 2022
                : September 2022
                Categories
                Case Report

                post-infectious autoimmune myasthenia gravis,covid-19,sars-cov-2 vaccination,cause-effect relationship

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