Slowly Progressive Melanoma Differentiation-Associated Gene 5 (MDA-5) Interstitial Lung Disease Following COVID-19 Infections: A Pulmonary Puzzle

Our plain-English summary of Slowly Progressive Melanoma Differentiation-Associated Gene 5 (MDA-5) Interstitial Lung Disease Following COVID-19 Infections: A Pulmonary Puzzle, by S.A. Armstrong, D. Sese, A. Menon (Curēus, 2025).

The study

• Authors: S.A. Armstrong, D. Sese, A. Menon
• Journal: Curēus
• Published: 2025;17(4):e81584
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Melanoma differentiation-associated gene 5 (MDA-5) autoimmunity has been increasingly recognized in association with interstitial lung disease (ILD), particularly in the context of viral infections. While MDA-5 ILD is typically rapidly progressive with high mortality, emerging evidence suggests that COVID-19 may induce a distinct, more indolent phenotype. We report two cases of MDA-5 ILD following COVID-19 infection with a slowly progressive course. In Case 1, an 87-year-old woman with a history of breast cancer, chronic obstructive pulmonary disease (COPD), and a prior COVID-19 infection developed progressive dyspnea. Imaging revealed new-onset ILD with subpleural reticulations and traction bronchiectasis. A myositis antibody panel was positive for MDA-5 autoantibodies. She was diagnosed with MDA-5 ILD and initiated on corticosteroids, later transitioned to mycophenolate. She has since remained clinically stable over the past two years. In Case 2, an 84-year-old man with a history of smoking and asbestos exposure developed severe dyspnea and hypoxia after a mild COVID-19 infection. CT imaging revealed diffuse ground-glass opacities and interlobular septal thickening. He was diagnosed with MDA-5 ILD and Group 1 and 3 pulmonary hypertension. He was treated with mycophenolate and pulmonary vasodilators, leading to symptom stabilization. These cases illustrate a possible post-COVID-19 endotype of MDA-5 ILD that follows a slower disease trajectory, distinct from the classical rapidly progressive phenotype. The association between viral infections and MDA-5 autoimmunity is supported by prior studies demonstrating viral-induced interferon signaling and MDA-5 gene activation. Given the indolent nature of disease progression in our patients, a tailored immunosuppressive approach was pursued, resulting in the stabilization of symptoms and pulmonary function. These cases contribute to the growing recognition of post-COVID-19 MDA-5 ILD as a unique clinical entity. Further research is needed to elucidate the precise mechanisms underlying virus-induced autoimmunity and to guide treatment strategies for this emerging ILD subtype.

Copyright © 2025, Armstrong et al.

In plain English

This article is a case report by authors at the Medical University of South Carolina. It describes two patients diagnosed with MDA-5 interstitial lung disease (ILD), a lung disease linked to MDA-5 autoantibodies, after a COVID-19 infection. The first was an 87-year-old woman with COPD and past breast cancer who had no notable occupational exposures. The second was an 84-year-old man who had worked in the Navy as a welder, with exposures to asbestos and fiberglass installation. Both tested positive for MDA-5 antibodies. The article does not examine asbestos as a cause of either patient's disease. The man was also diagnosed with Group 1 and 3 pulmonary hypertension. Both were treated with mycophenolate, and the man also received tadalafil and inhaled treprostinil. At one-year follow-up, CT scans showed mild progression in both. The woman's walking distance fell by 320 feet, while her diffusion capacity rose from 32% to 41% predicted. The man's lung function stayed stable, but his resting oxygen need rose from 4 L to 6 L. The authors concluded that these cases show a more slowly progressive form of the disease. They added that case reports alone cannot establish that COVID-19 caused it.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (two cases; the authors call it an observational case series)
• Who was studied: Two patients seen at a pulmonary clinic: an 87-year-old woman with breast cancer, COPD and a prior mild COVID-19 infection, and an 84-year-old man with a 90-pack-year smoking history whose symptoms began after hospitalization for mild COVID-19. Both were diagnosed with MDA-5 ILD after COVID-19 infection.
• Exposure: The condition was studied as following COVID-19 infection. The man (Case 2) had worked in the Navy as a welder with exposures to asbestos and fiberglass installation. No fiber type is named, and the article does not analyze asbestos as a cause. The woman (Case 1) had no notable environmental or occupational exposures.
• Main results:
  • Case 1 (woman): MDA-5 antibodies were 32 (normal below 20). CT showed new ILD; CT from two years earlier showed emphysema but no pre-existing ILD.
  • Case 1 (woman): eight months after diagnosis, diffusion capacity was 41% predicted, up from 32%.
  • Case 1 (woman): imaging after one year showed mild progression of ILD, and six-minute walk distance fell by 320 feet (1020 ft to 700 ft).
  • Case 2 (man): MDA-5 antibodies were 27 (normal below 20).
  • Case 2 (man): on mycophenolate sodium, pulmonary function tests remained stable (diffusion capacity 18% to 19% predicted), but follow-up imaging showed mild progression of ILD.
  • Case 2 (man): he required 6 L oxygen at rest, compared with 4 L when he first presented.
  • Case 2 (man): estimated right ventricular systolic pressure was 86 mmHg at presentation and decreased to 54 mmHg on repeat echocardiogram after tadalafil and treprostinil were started.
• The authors' conclusion: The authors concluded that the two cases highlight a subset of MDA-5 ILD with a more indolent, slowly progressive course, in contrast to the traditionally aggressive, high-mortality presentation. They suggested a possible link with COVID-19.
• Limitations the authors state:
  • As an observational case series, the findings have limited generalizability.
  • A definitive causal link between COVID-19 and MDA-5 autoimmunity cannot be established from case reports alone.
  • The second patient had no prior imaging to show that ILD was absent before COVID-19.

Topics

Medical terms in this study, explained in our Lexicon: Interstitial Lung Disease, COPD, Dyspnea, Asbestos Exposure, Hypoxia, Pulmonary Hypertension, Disease Progression.

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