Pulmonary fibrosis is a sequela of ARDS/prolonged ventilation, including severe COVID-19 (COV). There is no data on the extracellular matrix (ECM) composition of lung remodeling in COV compared to other causes of ARDS. We quantified ECM elements by IHC in lung tissues of 28 fatal COV and 27 non-COV cases and assessed the influence of sex, age, mechanical ventilation length (MVL), and PaO2/FiO2 ratio on ECM values. Lung RNA from 12 fatal COV cases divided according to MVL: <7 days (L7) (n=5) or ?7 days (H7) (n=7), and 4 controls were used for transcriptomics. Collagen(p?0.0001), fibronectin(p?0.0001), versican(p=0.044), and TGF-?(p=0.003) were increased in COV compared to the non-COV, whereas decorin was decreased in COV(p=0.033). Female COV patients had higher collagen density in the lungs than males(p=0.004). There was a positive correlation between age and decorin density(r=0.411;p=0.022), with more decorin in the older COV cases(p=0.033). TGF-? was the only protein influenced by MVL(p=0.049). COV L7 group had higher TGF-? than all groups, non-COV L7(p=0.003) and H7(p=0.001) and COV H7(p=0.043). DEG analysis revealed increased expression of genes related to collagen assembly in L7, whereas the H7 group showed increased expression of collagen types I, III, V, and several MMPs in relation to the control group. COV is characterized by increased ECM deposition when compared to non-COV, occurring in greater magnitude early after the MV onset. Within the first days of MV, genes related to collagen fibrillogenesis were overexpressed, later there was a shift of several collagens and MMPs genes upregulation, indicating a dynamic process of ECM synthesis/degradation, more pronounced in women.