Anti-MDA5 Antibody Linking COVID-19, Type I Interferon, and Autoimmunity: A Case Report and Systematic Literature Review

Abstract

IntroductionThe SARS-CoV-2 infection has been advocated as an environmental trigger for autoimmune diseases, and a paradigmatic example comes from similarities between COVID-19 and the myositis-spectrum disease associated with antibodies against the melanoma differentiation antigen 5 (MDA5) in terms of clinical features, lung involvement, and immune mechanisms, particularly type I interferons (IFN).Case ReportWe report a case of anti-MDA5 syndrome with skin manifestations, constitutional symptoms, and cardiomyopathy following a proven SARS-CoV-2 infection.Systematic Literature ReviewWe systematically searched for publications on inflammatory myositis associated with COVID-19. We describe the main clinical, immunological, and demographic features, focusing our attention on the anti-MDA5 syndrome.DiscussionMDA5 is a pattern recognition receptor essential in the immune response against viruses and this may contribute to explain the production of anti-MDA5 antibodies in some SARS-CoV-2 infected patients. The activation of MDA5 induces the synthesis of type I IFN with an antiviral role, inversely correlated with COVID-19 severity. Conversely, elevated type I IFN levels correlate with disease activity in anti-MDA5 syndrome. While recognizing this ia broad area of uncertainty, we speculate that the strong type I IFN response observed in patients with anti-MDA5 syndrome, might harbor protective effects against viral infections, including COVID-19.

A novel intergenic variant linked to IFIH1 rs1990760 polymorphism, rs2111485, shows an association with susceptibility to coronavirus disease 2019 and influences IFIH1 protein levels.

“…Anti-MDA5 syndrome is a rare autoimmune disease that shows striking similarities to COVID-19, particularly elevated levels of pro-inflammatory cytokines (including type I IFNs) and the associated acute respiratory distress syndrome. Therefore, a common immunopathological mechanism between COVID-19 and anti-MDA5 syndrome has been proposed where MDA5 can be considered a cornerstone in this context (Giannini et al, 2020;Tonutti et al, 2022). Accordingly, understanding the mechanistic role of IFIH1 protein in the course of SARS-CoV-2 infection may have therapeutic potential and requires further studies.…”

Glucocorticoid Therapy in COVID-19

“…52 On the other hand, direct viral injury is not the only contributor in precipitating organ dysfunction in patients with COVID-19. 53 It has been postulated that factors as impaired viral clearance (due to genetic, acquired, or viral-related causes), low type I IFN signature, 54 and increased NETosis might predispose to the development of severe forms of COVID-19, which can culminate in cytokine storm. 11 However, predictors and risk factors for the occurrence of severe SARS-CoV-2 infection and cytokine storm remain largely unknown.…”

Skeletal muscle injury in COVID infection: Frequency and patterns

“…Drugs used in COVID‐19 treatment, such as steroids have also shown a detrimental effect on skeletal muscle 5 . COVID‐19 infection may also trigger idiopathic inflammatory myopathies and myasthenia gravis 6,7 …”

“…5 COVID-19 infection may also trigger idiopathic inflammatory myopathies and myasthenia gravis. 6,7 Fatigue and myalgia are common symptoms of acute COVID-19 infection. 8 Asymptomatic elevated creatine kinase (CK) levels have been reported in 16-33% of patients with acute COVID-19.…”