Dual-positive anti-aminoacyl-tRNA synthetase and anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease in a patient with severe coronavirus disease 2019 complicated by probable pulmonary aspergillosis and pneumothorax: a case report

Occasionally, severe coronavirus disease 2019 (COVID-19) can lead to rapidly progressive interstitial lung disease (RP-ILD) by triggering or unmasking various myositis-specific autoantibodies (MSAs). Although dual positivity for anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma differentiation-associated gene 5 (MDA5) antibodies is extremely rare, its management is exceptionally complex when complicated by secondary infections. Identifying a specific anti-ARS subtype is often difficult, but clinical features such as amyopathic phenotypes and refractory lung involvement often confirm a non-Jo-1 antibody subtype, which carries a poor prognosis. A 77-year-old female patient was admitted with COVID-19. Despite standard treatment, her respiratory condition progressively deteriorated. Initial laboratory findings revealed bicytopenia, suggesting underlying immune dysregulation. Further evaluation demonstrated dual positivity for anti-ARS and anti-MDA5 antibodies, leading to a diagnosis of RP-ILD, for which tacrolimus was initiated. During the clinical course, she developed probable COVID-19-associated pulmonary aspergillosis (CAPA). Despite multimodal therapy, including careful management of drug–drug interactions between antifungal and immunosuppressive agents, the patient experienced recurrent pneumothorax and died on day 29. This case illustrates an extreme therapeutic challenge of managing the quadruple burden of advanced age, dual MSA positivity, severe COVID-19, and opportunistic fungal infection. Clinicians should recognize that initial bicytopenia and refractory RP-ILD in patients with severe COVID-19 may be early clinical indicators of an underlying, subclinical autoimmune state. The early identification of these features is essential for balancing intensive immunosuppression and infection control in complex cases.