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.

Objectives Respiratory failure is the major cause of death in coronavirus disease 2019 (COVID-19). Autopsy-based reports describe diffuse alveolar damage (DAD), organizing pneumonia, and fibrotic change, but data on early pathologic changes and during progression of the disease are rare. Methods We prospectively enrolled three patients with COVID-19 and performed full clinical evaluation, including high-resolution computed tomography. We took transbronchial biopsy (TBB) specimens at different time points and autopsy tissue samples for histopathologic and ultrastructural evaluation after the patients’ death. Results Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed by reverse transcription polymerase chain reaction and/or fluorescence in situ hybridization in all TBBs. Lung histology showed reactive pneumocytes and capillary congestion in one patient who died shortly after hospital admission with detectable virus in one of two lung autopsy samples. SARS-CoV-2 was detected in two of two autopsy samples from another patient with a fulminant course and very short latency between biopsy and autopsy, showing widespread organizing DAD. In a third patient with a prolonged course, autopsy samples showed extensive fibrosis without detectable virus. Conclusions We report the course of COVID-19 in paired biopsy specimens and autopsies, illustrating vascular, organizing, and fibrotic patterns of COVID-19–induced lung injury. Our results suggest an early spread of SARS-CoV-2 from the upper airways to the lung periphery with diminishing viral load during disease.

BackgroundAcute respiratory distress syndrome (ARDS) is the major cause of death in coronavirus disease 2019 (COVID-19). Multiple autopsy-based reports of COVID-19 lung pathology describe diffuse alveolar damage (DAD), organizing pneumonia (OP) and fibrotic change, but data on early pathological changes as well as during progression of the disease are rare.Research questionComparison of histopathological and ultrastructural findings in paired transbronchial biopsies (TBBs) and autopsy material from three patients with confirmed SARS-CoV-2-infection.MethodsWe prospectively enrolled 3 patients with confirmed SARS-CoV-2 infection. Full clinical evaluation was performed including high-resolution computed tomography (HR-CT). We took TBBs at different time points during the disease and autopsy tissue samples after the patients’ death.ResultsSARS-CoV-2 was detected by RT-PCR and/or FISH in all TBBs. Lung histology revealed pneumocyte hyperplasia and capillary congestion in one patient who died short after hospital admission with detectable virus in 1/2 autopsy samples from the lung. SARS-CoV-2 was detected in 2/2 autopsy samples from a patient with a fulminant course of the disease and very short latency between biopsy and autopsy, both showing widespread DAD. In a third patient with a prolonged course, i.e. five weeks of ICU treatment with ECMO, autopsy samples showed extensive interstitial fibrosis without detectable virus by RT-PCR and/or FISH.InterpretationWe report the course of COVID-19 in paired TBB and autopsy samples from three patients at an early stage, in rapidly progressive and in a prolonged disease course. Our findings illustrate vascular, organizing and fibrotic patterns of COVID-19-induced lung injury and suggest an early spread of SARS-CoV-2 from the upper airways to the lung periphery with diminishing viral load during disease.

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