A percentage of COVID-19 affected patients develop post-acute sequalae of SARS-CoV-2, with evidence that SARS-CoV-2 causes ARDS leading to lung fibrosis (PASC-Fibrosis) that shares similarities with idiopathic pulmonary fibrosis (IPF). Herein, we addressed the hypothesis that fatal COVID-19, PASC, and IPF share key biomarkers of interest in lung fibrosis. Autopsy and explanted lung samples were subjected to histopathological and immunohistochemical (IHC) analysis for key biomarkers of interest in fibrosis. PASC-fibrosis-derived 2D and 3D cell cultures were treated with BRD4 inhibitors to evaluate proliferation and differentiation of fibroblasts, airway epithelial cells and lung bronchospheres. Single-cell RNA sequencing determined altered immune subpopulations. PASC-Fibrosis survivors had diffuse interstitial fibrosis, with organization into a non-specific interstitial fibrosis (NSIP) pattern. Transcriptomic analysis from fatal COVID-19 lungs showed BRD4, GDF15, IFNα2 and IL11 pathways markedly active. These findings were confirmed by IHC on PASC-fibrosis, with increased expression in myeloid cells. Altered frequencies in lung PASC-fibrosis subpopulations included loss of FABP4+ and increase of MERTK+SSP1+ macrophages and monocytes. Pharmacological inhibition of PASC-Fibrosis lung cultures and bronchospheres with BRD4 inhibitors limited outgrowth and differentiation of fibroblasts, airway epithelial cells and the formation of lung bronchospheres. In conclusion, shared profibrotic pathways among COVID-19 and chronic fibrotic ILDs provides the impetus to further explore treatment strategies to chronically ventilated COVID-19 patients.