A recent study published in eBioMedicine has highlighted a concerning correlation between SARS-CoV-2 infection and an autoimmune condition known as melanoma differentiation-associated protein-5 (MDA5) autoimmunity. This research explores the shared immunopathology between these distinct conditions and emphasizes the significance of understanding the factors contributing to MDA5-related diseases, particularly against the backdrop of the COVID-19 pandemic.
Dermatomyositis (DM), an autoimmune disorder characterized by inflammation in the skin and muscles often accompanied by interstitial lung disease (ILD) leading to pulmonary fibrosis, has been associated with MDA5, a protein encoded by the IFIH1 gene. Interestingly, individuals with MDA5 autoimmunity may display ILD without the typical skin rash associated with DM, presenting instead with skin symptoms such as tender palmar papules and ulceration.
The study investigated the epidemiological factors driving MDA5-related diseases, particularly MDA5 autoimmunity with interstitial pneumonitis concurrent with the COVID-19 pandemic (MIP-C). Transcriptomic data analysis was utilized to uncover shared mechanisms between MDA5-associated diseases, COVID-19, and other lung conditions such as idiopathic pulmonary fibrosis (IPF). The research identified a model linking severe anti-viral cytokine responses with IFIH1 stimulation, potentially underpinning the unique immunophenotype associated with progressive ILD in MDA5-associated diseases.
This retrospective observational study examined the surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between January 2018 and December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcomes, as well as regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to understand the genesis of the observed MDA5+ – DM outbreak.
The results of the study showed that sixty new anti-MDA5+ cases surged between 2020 and 2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021), and 1.7% (2022). While a few cases had a prior history of confirmed COVID-19, peak rates coincided with regional SARS-CoV-2 community positivity rates in 2021, and a significant portion had received anti-SARS-CoV-2 vaccines. A subset of cases developed ILD, which rapidly progressed with fatal outcomes. Transcriptomic studies revealed robust IFIH1 induction in COVID-19 and autoimmune-ILD, but not IPF, suggesting a distinct immunological signature associated with progressive ILD.
The study highlights the importance of understanding the relationship between SARS-CoV-2, MDA5 autoimmunity, and ILD. This exploration could potentially lead to advancements in diagnostics and treatments for individuals affected by these conditions. Multicenter validation of these findings across diverse populations is crucial for a comprehensive understanding of this emerging phenomenon.
Reference
David P, Sinha S, Iqbal K, Marco GD, Taheri S, McLaren E, et al. MDA5-autoimmunity and interstitial pneumonitis contemporaneous with the COVID-19 pandemic (MIP-C). eBioMedicine [Internet]. 2024 Jun 1 [cited 2024 May 16];104.