Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPCOSTA, Natalia de Souza XavierRIBEIRO JUNIOR, GabrielNASCIMENTO, Ellen Caroline Toledo doBRITO, Jose Mara deANTONANGELO, LeilaFARIA, Caroline SilverioMONTEIRO, Jhonatas SirinoSETUBAL, Joao CarlosPINHO, Joao Renato RebelloPEREIRA, Roberta VercianoSEELAENDER, MariliaCASTRO, Gabriela Salim deLIMA, Joanna D. C. C.MONTEIRO, Renata Aparecida de AlmeidaDUARTE-NETO, Amaro NunesSALDIVA, Paulo Hilario NascimentoSILVA, Luiz Fernando Ferraz daDOLHNIKOFF, MarisaMAUAD, Thais2023-12-152023-12-152023RESPIRATORY RESEARCH, v.24, n.1, article ID 281, 11p, 2023https://observatorio.fm.usp.br/handle/OPI/57525BackgroundLung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS.MethodsWe have quantified different ECM elements and TGF-beta expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile.ResultsWe observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-beta, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-beta was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course.ConclusionsFatal COVID-19 is associated with an early TGF-beta expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.engopenAccessCOVID-19Lung fibrosisExtracellular matrixAutopsyrespiratory-distress-syndromeversicandecorinarticleCopyright BMC10.1186/s12931-023-02555-7Respiratory System1465-993X