Anti-MDA5 DERMATOMYOSITIS FOLLOWING MILD SARS-COV-2 INFECTIONS: A SYSTEMATIC REVIEW

Simone Lattarulo¹Francesca Centrone²Maria Chironna^1,3*

• ¹Department of Interdisciplinary Medicine-Hygiene Section, University of Bari, 70124 Bari, Italy, Bari, Italy
• ²Hygiene Unit, Policlinico University Hospital, Bari, 70124 Bari, Italy, Bari, Italy
• ³University of Bari Aldo Moro, Bari, Italy

Background: Anti-MDA5 dermatomyositis (AMD) is an autoimmune disorder that targets a patient’s skin, muscle and connective tissues, followed by progression to rapid progressive-interstitial lung disease. Between 2020 and 2024, an increase in serum titres of anti-MDA5 autoantibodies (AABs) was registered among populations. Given the role of MDA5 as a viral-RNA sensor, it is considered to be a key molecule in rheumatological disorders as its activity is triggered by viral infection. Here, we conducted a systematic review of studies reporting an unambiguous association between mild Sars-CoV-2 infection and development of AMD. The aim was to clarify our understanding of this idiopathic rheumatic entity. Methods: This review meets Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The Google Scholar, PubMed, Scopus and Semantic Scholar Databases were searched using appropriate keywords to identify relevant studies published from 2020–2024. Fifteen studies of AMD in post-COVID patients, as well as molecular analyses and pharmaceutical treatments, were included. Results: Anti-MDA5 antibodies have been detected in patients with COVID-19, as well as in serum from post-COVID patients, and their presence correlates positively with disease severity. Onset of AMD increased during the COVID-19 pandemic, paralleled by an increase in the incidence of juvenile idiopathic inflammatory (JIIM). Although the literature suggests that rheumatological onset of anti-MDA5 antibodies against MDA5 epitopes occurs after vaccination, the studies and case reports reviewed herein highlight a strong correlation between anti-MDA5 antibodies and mild Sars-CoV-2 infections rather than breakthrough (i.e., post-vaccination) infections. Conclusion: This review provides evidence for an association between mild primary Sars-CoV-2 infection and emergence of AMD, driven by the virus’s inclination to trigger type-I interferonopathy in genetically predisposed individuals.