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

by Mohammad Aminul Islam, Michael Getz, Paul Macklin, Ashlee N. Ford Versypt The severity of the COVID-19 pandemic has created an emerging need to investigate the long-term effects of infection on patients. Many individuals are at risk of suffering pulmonary fibrosis due to the pathogenesis of lung injury and impairment in the healing mechanism. Fibroblasts are the central mediators of extracellular matrix (ECM) deposition during tissue regeneration, regulated by anti-inflammatory cytokines including transforming growth factor beta (TGF- β). The TGF-β-dependent accumulation of fibroblasts at the damaged site and excess fibrillar collagen deposition lead to fibrosis. We developed an open-source, multiscale tissue simulator to investigate the role of TGF-β sources in the progression of lung fibrosis after SARS-CoV-2 exposure, intra cellular viral replication, infection of epithelial cells, and host immune response. Using the model, we predicted the dynamics of fibroblasts, TGF-β, and collagen deposition for 15 days post-infection in virtual lung tissue. Our results showed variation in collagen area fractions between 2% and 40 % depending on the spatial behavior of the sources (stationary or mobile), the rate of activation of TGF-β, and the duration of TGF-β sources. We identified M2 macrophages as primary contributors to higher collagen area fraction. Our simulation results also predicted fibrotic outcomes even with lo wer collagen area fraction when spatially-localized ...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research