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      New-Onset Rheumatic Immune-Mediated Inflammatory Diseases Following SARS-CoV-2 Vaccinations until May 2023: A Systematic Review

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          Abstract

          A comprehensive, up-to-date systematic review (SR) of the new-onset rheumatic immune-mediated inflammatory diseases (R-IMIDs) following COVID-19 vaccinations is lacking. Therefore, we investigated the demographics, management, and prognosis of new R-IMIDs in adults following SARS-CoV-2 vaccinations. A systematic literature search of Medline, Embase, Google Scholar, LitCovid, and Cochrane was conducted. We included any English-language study that reported new-onset R-IMID in adults following the post-COVID-19 vaccination. A total of 271 cases were reported from 39 countries between January 2021 and May 2023. The mean age of patients was 56 (range 18–90), and most were females (170, 62.5%). Most (153, 56.5%) received the Pfizer BioNTech COVID-19 vaccine. Nearly 50% of patients developed R-IMID after the second dose of the vaccine. Vasculitis was the most prevalent clinical presentation (86, 31.7%), followed by connective tissue disease (66, 24.3%). The mean duration between the vaccine’s ‘trigger’ dose and R-IMID was 11 days. Most (220, 81.2%) received corticosteroids; however, 42% (115) received DMARDs such as methotrexate, cyclophosphamide, tocilizumab, anakinra, IV immunoglobulins, plasma exchange, or rituximab. Complete remission was achieved in 75 patients (27.7%), and 137 (50.6%) improved following the treatment. Two patients died due to myositis. This SR highlights that SARS-CoV-2 vaccines may trigger R-IMID; however, further epidemiology studies are required.

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          The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

          The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
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            COVID-19 vaccines: modes of immune activation and future challenges

            The new vaccines against SARS-CoV-2 are novel in terms of specificity, their wide dissemination across the global population and the inclusion of newly licensed mRNA platforms. We discuss here how the approved vaccines trigger innate immunity to promote durable immunological memory and consider the future implications of protecting populations with these vaccines.
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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

                Contributors
                Journal
                VBSABP
                Vaccines
                Vaccines
                MDPI AG
                2076-393X
                October 2023
                October 08 2023
                : 11
                : 10
                : 1571
                Article
                10.3390/vaccines11101571
                37896974
                dd69b5a5-d86d-4a73-99f9-213a57f40528
                © 2023

                https://creativecommons.org/licenses/by/4.0/

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