BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19) which can lead to acute respiratory distress syndrome (ARDS) and evolve to pulmonary fibrosis. Computed tomography (CT) is used to study disease progression and describe radiological patterns in COVID-19 patients. This study aimed to assess disease progression regarding lung volume and density over time on follow-up in vivo chest CT and give a unique look at parenchymal and morphological airway changes in "end-stage" COVID-19 lungs using ex vivo microCT. METHODS: Volumes and densities of the lung/lobes of three COVID-19 patients were assessed using follow-up in vivo CT and ex vivo whole lung microCT scans. Airways were quantified by airway segmentations on whole lung microCT and small-partition microCT. As controls, three discarded healthy donor lungs were used. Histology was performed in differently affected regions in the COVID-19 lungs. RESULTS: In vivo, COVID-19 lung volumes decreased while density increased over time, mainly in lower lobes as previously shown. Ex vivo COVID-19 lung volumes decreased by 60% and all lobes were smaller compared to controls. Airways were more visible on ex vivo microCT in COVID-19, probably due to fibrosis and increased airway diameter. In addition, small-partition microCT showed more deformation of (small) airway morphology and fibrotic organization in severely affected regions with heterogeneous distributions within the same lung which was confirmed by histology. CONCLUSIONS: COVID-19-ARDS and subsequent pulmonary fibrosis alters lung architecture and airway morphology which is described using in vivo CT, ex vivo microCT, and histology.

Department of Imaging and Pathology KU Leuven Leuven Belgium

Department of Physics and Astronomy Centre for 10 Ray Tomography Radiation Physics Ghent University Gent Belgium

Department of Pneumology Cliniques Universitaires Saint Luc Institute of Experimental and Clinical Research Université Catholique de Louvain Brussels Belgium

Division of Anesthesiology and Algology Department of Cardiovascular Sciences KU Leuven Leuven Belgium

Laboratory of Respiratory Diseases and Thoracic Surgery BREATHE Department of Chrometa KU Leuven Leuven Belgium

Prague Lung Transplant Program Department of Pneumology Motol University Hospital 2nd Faculty of Medicine Charles University Prague Prague Czech Republic

Section of Pulmonary Critical Care and Sleep Medicine Yale University School of Medicine New Haven CT USA

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