About: Acute Lung injury evolution in Covid-19

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Acute Lung injury evolution in Covid-19
Creator	Cesare, Di Ravaglia, Claudia Alessandra, Dubini Antonella, Arcadu Antonio, Vizzuso Athol, Wells Carmela, Grosso Claudia, Ravaglia Claudio, Doglioni Emanuele, Russo Emiliano, Gamberini Fabbri, Elisabetta Federica, Pedica Franco, Stella Giovanni, Giovanni, Poletti Giulio, Rossi Lorenza, Pecciarini Luca Phd, Donati Lung, Network Marco, Chilosi Md, Simona Phd, Stefano Reference, European Sara, Piciucchi Silvia, Puglisi Stefano, Maitan Vanni, Agnoletti Venerino, Poletti Vincenzo, Bronte Vittorio, Sambri
source	MedRxiv
abstract	BACKGROUND Pathogenesis of Coronavirus disease 2019 (Covid-19) is poorly understood. Most histologic studies come from post-mortem analysis, with existing data indicating that histologic features of acute respiratory distress syndrome are typically present in fatal cases. However, this observation may be misleading, due to confounding factors in pre-terminal disease, including injury resulting from prolonged mechanical ventilation. Ante-mortem lung biopsy may provide major pathogenetic insights, potentially providing a basis for novel treatment approaches. AIM This comparative, multicenter, prospective, observational study was planned to identify ante-mortem histological profile and immunohistochemical features of lung tissue in patients with Covid-19 in early and late phases of the disease, including markers of inflammatory cells and major pathways involved in the cytokine storm triggering. METHODS Enrolled patients underwent lung biopsy, according to the study protocol approved by local Ethical Committee, either within 15 days of the first symptoms appearing (early phase) or after > 15 days (more advanced disease). Key exclusion criteria were excessive or uncorrectable bleeding risk and cardiovascular disease with heart failure. Lung samples were obtained by conventional trans-bronchialbiopsy, trans-bronchial lung cryobiopsy or surgical lung biopsy. RESULTS 23 patients were enrolled: 12 patients underwent lung biopsy within 15 days and 11 patients more than 15 days after the onset of symptoms. Early biopsies were characterized by spots of patchy acute lung injury (ALI) with alveolar type II cells hyperplasia and significant vascular abnormalities (disordered angiogenesis with alveolar capillary hyperplasia, luminal enlargement and thickened walls of pulmonary venules, perivascularCD4-T-cell infiltration), with no hyaline membranes. In the later stages, the alveolar architecture appeared disrupted, with areas of organizing ALI, venular congestion and capillary thromboembolic microangiopathy. Striking phenotypic features were demonstrated in hyper plastic pneumocytes and endothelial cells, including the expression of phospho-STAT3 and molecules involved in immunoinhibitory signals (PD-L1 and IDO1). Alveolar macrophages exhibited macrophage-related markers (CD68, CD11c, CD14) together with unusual markers, such as DC-Lamp/CD208, CD206, CD123/IL3AR. CONCLUSION A morphologically distinct Covid pattern was identified in the earlier stages of the disease, with prominent epithelial and endothelial cell abnormalities, that may be potentially reversible, differing strikingly from findings in classical diffuse alveolar damage. These observations may have major therapeutic implications, justifying studies of early interventions aimed at mitigating inflammatory organ injury.
has issue date	2020-08-13(xsd:dateTime)
bibo:doi	10.1101/2020.08.09.20170910
has license	medrxiv
sha1sum (hex)	068b862614556a9971ba12b044337e14875b65b7
schema:url	https://doi.org/10.1101/2020.08.09.20170910
resource representing a document's title	Acute Lung injury evolution in Covid-19
resource representing a document's body	covid:068b862614556a9971ba12b044337e14875b65b7#body_text
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