PMC10129030_01
CT images at admission and before transplantation at admission: axial (a) and coronal (b) chest CT shows ground-glass and reticular opacities in the dependent lung with bronchiectasis (arrow). Before transplantation: axial (c) and coronal (d) chest CT shows extensive bilateral ground-glass opacities, reticulation, and bronchiectasis consistent with ARDS pattern. ARDS, acute respiratory distress syndrome.
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F1
A chest CT scan performed at admission revealed bilateral, diffuse ground-glass opacities, bronchiectasis and subpleural reticular changes consistent with pulmonary fibrosis predominantly in the middle and lower lobes (Fig. 1a, b). Imaging demonstrated a rapid decline of his condition with an acute respiratory distress syndrome pattern, upon which the patient was intubated (Fig. 1c, d). Fig. 1).
Gross findings of lung explant. Dense parenchyma with areas of brownish yellowish carnification and diffuse calcification (yellow arrows).
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F2
The lungs were heavy, firm, with brownish yellowish carnification of the parenchyma, and showed signs of diffuse calcification (Fig. 2), as evidenced by a video demonstration of the macroscopic examination (see online suppl.
Major histological findings of the lung explant. a Extensive interstitial pulmonary fibrosis with dendriform ossification with the formation of lamellar bone and fatty bone marrow (asterisk). b Higher magnification reveals bronchiolocentric, diffuse interstitial fibrosis with bronchiolar/mucinous and transitional cell metaplasia (yellow arrow) and mucostasis (black asterisk) as well as intra-alveolar and intrabronchiolar desquamation of macrophages (yellow asterisk) and occasional multinucleated giant cells (black arrow). c Accumulation of CD206+ (M2-polarized) macrophages in alveolar spaces and the interstitium. d Overexpression of phosphorylated ERK in macrophages but not in alveolar pneumocytes (upper half of the figure). e Increased density of CD105+ vessels indicative of neoangiogenesis. Lymphocyte characterization shows a predominance of Tbet+ TH1 cells (f) over GATA3+ TH2 cells (g). h Positivity for N-protein of SARS-CoV-2 in the endothelial lining of an arteriole.
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F3
As a correlate to the calcification, histology revealed extensive, diffuse interstitial dendriform ossification, comprising of lamellar bone with fatty marrow with focal hematopoiesis (Fig. 3a). Diffuse interstitial fibrosis with bronchiolar, mucinous and transitional cell metaplasia of the alveolar epithelium (Fig. 3b); traction bronchiectasis; bronchiolar mucostasis; fibrinous pleuritic; and multifocal alveolar hemorrhages were evident throughout the parenchyma. There were various signs of pulmonary remodeling, as evidenced by an increase of interstitial collagen and a disarray of elastic fibers, proliferative diffuse alveolar damage (DAD) and an interstitial accumulation of M2-polarized CD163+ and CD206+ macrophages (Fig. 3c) with an increased expression of phospho-ERK (Fig. 3d) and increased neoangiogenesis (CD105+ vessels) (Fig. 3e). PD1 positivity). Cytotoxic T cells (CD8+) and T-helper 1 subsets (Tbet+ TH1) were more frequent than T-helper 2 subsets (GATA3+ TH2) (Fig. 3f, g). T-regulatory cells (FoxP3+ Treg) and gammadelta T cells (gammadelta+) comprised 2-3% of lymphocytes. Plasma cells were polytypic; there was no plasmablast excess (no Immunohistochemistry for SARS-CoV-2 nucleocapsid (N)-antigen showed focal endothelial deposition in arterioles (Fig. 3h).