An agent-based modeling approach for lung fibrosis in response to COVID-19

• DOI: 10.1371/journal.pcbi.1011741
• Publication Date: 2023-12-21T19:02:16Z
• Authors: Mohammad Aminul I...; Michael Getz; Paul Macklin; Ashlee N. Ford Ve...
• Keywords: Alveolar macrophage

The severity of the COVID-19 pandemic has created an emerging need to investigate long-term effects infection on patients. Many individuals are at risk suffering pulmonary fibrosis due pathogenesis lung injury and impairment in healing mechanism. Fibroblasts central mediators extracellular matrix (ECM) deposition during tissue regeneration, regulated by anti-inflammatory cytokines including transforming growth factor beta (TGF-β). TGF-β-dependent accumulation fibroblasts damaged site excess fibrillar collagen lead fibrosis. We developed open-source, multiscale simulator role TGF-β sources progression after SARS-CoV-2 exposure, intracellular viral replication, epithelial cells, host immune response. Using model, we predicted dynamics fibroblasts, TGF-β, for 15 days post-infection virtual tissue. Our results showed variation area fractions between 2% 40% depending spatial behavior (stationary or mobile), rate activation duration sources. identified M2 macrophages as primary contributors higher fraction. simulation also fibrotic outcomes even with lower fraction when spatially-localized latent were active longer times. validated our model comparing simulated fraction, macrophage cell population independent experimental data from mouse models. that partial removal changed patterns; presence persistent sources, ECM significantly increased maintenance chemotactic gradients driving fibroblast movement. computational findings consistent clinical observations not used developing model. These critical insights into activity may find applications current trials targeting resolution