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S C I E N T I F I C H I G H L I G H T S

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3D X-ray imaging reveals lung scarring mechanism in Long-COVID syndrome

X-ray-based hierarchical phase-contrast tomography has revealed how lung scarring occurs in Long- COVID and pulmonary fibrosis. Innovative blood biomarkers of the scarring were also identified. The data contribute to knowledge of the pathophysiology of severe COVID-19, and thus its treatment.

Long-COVID syndrome, or the origin of the long-term consequences of SARS-CoV-2 infection, is still not fully understood, more than two years after the onset of the pandemic. In particular, the long-term changes in lung tissue following severe COVID-19 disease pose significant limitations for many patients. Some of these patients continue to develop post-COVID pulmonary fibrosis, which covers a variety of different lung diseases in which persistent inflammation leads to progressive scarring of the lung tissue. Although these serious diseases can be mitigated with medication, they are still incurable and usually have a higher mortality rate than many cancers. For many of those affected, lung transplantation is the only remaining, life-saving alternative. Epidemiological data from patients with severe COVID-19 suggest that approximately 20% of hospitalised patients develop

Fig. 1: Microvascular alterations in COVID-19 lungs. a) Volume rendering of a representative hierarchical phase-contrast tomography (HiP-CT) slice demonstrates the spatial involvement of microischemia and fibrotic remodelling of airways. Regular-shaped airways: blue; hot spots of condensation and fibrotic remodelling: yellow. b) Micro-CT-based 3D reconstruction of pulmonary arteries (red) and airways (blue) demonstrates (sub-)total occlusion of the arteries in COVID-19 lungs of early and late hospitalised patients as compared to uninfected controls (scale bar 200 µm). c) Three-dimensional evaluation of microvascular corrosion casts by micro-CT, illustrating the altered and increased alveolar vascularity in COVID-19 lungs.