Background and Objectives Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Methods We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. Results Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 vs. 10%; p = 0.002) and occurrence of severe complications (75 vs. 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils. Conclusions We are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.
【저자키워드】 SARS-CoV-2, Autoimmunity, Coronavirus disease 2019, autoantibodies, connective tissue disease, 【초록키워드】 COVID-19, coronavirus disease, ARDS, Respiratory failure, severe COVID-19, Pneumonia, SARS-COV-2 infection, detection, Interstitial lung disease, Histopathology, Laboratory testing, Computed tomography, Clinical course, pathophysiology, Patient, Therapeutic strategies, understanding, Autoimmune, collagen, immunofluorescence, serological, disease, predict, mechanism, COVID-19 patients, acute respiratory distress, Analysis, similarity, COVID-19 patient, High-resolution, autoantibody, interstitial thickening, overlapping, Activation, acute exacerbation, intensive care treatment, syndrome, heterogeneous, positive, fibroblast, connective tissue, immunoblot, objective, FIVE, feature, Occurrence, Result, enrolled, died, significantly, investigated, the disease, was performed, tissue sample, determine, severe complication, ENA, exacerbating, histopathological finding, 【제목키워드】 COVID-19, clinical, Exacerbation,