Pulmonary fibrosis (PF) is a chronic disease characterised by inappropriate fibroblast proliferation in the interstitial space of the lungs, causing the lungs to stiffen, leading ultimately to respiratory failure and death. Whilst PF has been found to have many aetiologies, post-viral PF is an emerging disease manifestation. In particular, post-COVID-19 PF (PC19PF) and other historical viruses including SARS, MERS and severe H1N1 influenza have all been shown to cause post-viral PF. Crucially, current treatments for PC19PF have been found to have no effect on disease progression. This project aims to develop a novel human in vitro platform to better understand the underlying mechanisms of PC19PF and identify novel therapeutic interventions. Our approach uses directed differentiation of human induced pluripotent stem cells (iPSCs) to create the alveolar cells implicated in disease. Initially, we sought to coculture iPSC-derived type II alveolar epithelial cells (iAT2s) and lung mesenchymal cells (iLM) in an air-liquid interface. Through optimising cell seeding densities and media composition, we found the cocultures could be successfully maintained for 11 days with both cell types maintaining their cellular identity. However, further optimisation will be necessary to pursue longer timepoints without cytotoxicity. Next, we established tri-cultures by including iPSC-derived macrophages (iMacs) to the cocultures previously set-up, prior to infection with SARS-CoV-2. Interestingly, the tri-cultures did not clear the infection, with waves of continuous viral shedding over 2-3 weeks. Gene expression analyses revealed key fibrotic cytokine, TGF-β, was upregulated in tri-cultures post-infection, whilst interferon-stimulated gene (ISG), MX-1 was expressed in waves by cells in a similar pattern to viral shedding. Future work will focus on quantifying fibrosis post-SARS-CoV-2 infection and extending our tri-culture work to other fibrosis-inducing agents (eg, bleomycin). In conclusion, we have established the first iPSC-derived model that incorporates the three major cell types implicated in PF to investigate PC19PF.