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.

BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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.