ArticlePLoS computational biology2023
An agent-based modeling approach for lung fibrosis in response to COVID-19.
Article in PLoS computational biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Metabolic control of macrophages in coronavirus disease 2019.Virulence · 2026Review
- An agent-based model suggests how senescent cell behavior and matrix mechanics drive pulmonary fibrosis in aged mice.bioRxiv : the preprint server for biology · 2026Article
- PTPN1 Regulation via YBX1-PTBP1 Interaction Promotes Fibroblast Activation and Fibrotic Remodeling in the Lung.International journal of biological sciences · 2026Article
- Spatially structured models of viral dynamics: a scoping review.Microbiology and molecular biology reviews : MMBR · 2025Article
- Article
- Cytoimmunological Profile of Lower Airways in Post-COVID-19 Syndrome (PCS): Predictive Value of Bronchoalveolar Lavage.Journal of clinical medicine · 2025Article
- Mathematical modeling of impacts of patient differences on renin-angiotensin system and applications to COVID-19 lung fibrosis outcomes.Computers in biology and medicine · 2025Article
- Smart biomaterials: as active immune modulators to shape pro-regenerative microenvironments.Frontiers in cell and developmental biology · 2025Review
- SIRT3/6/7: promising therapeutic targets for pulmonary fibrosis.Frontiers in cell and developmental biology · 2025Review
- Multiscale computational model predicts how environmental changes and treatments affect microvascular remodeling in fibrotic disease.PNAS nexus · 2025Article
- A multiscale model of immune surveillance in micrometastases gives insights on cancer patient digital twins.NPJ systems biology and applications · 2024Article
- The role and regulation of SIRT1 in pulmonary fibrosis.Molecular biology reports · 2024Review
- A mathematical model of glomerular fibrosis in diabetic kidney disease to predict therapeutic efficacy.Frontiers in pharmacology · 2024Article
- An in silico modeling approach to understanding the dynamics of the post-burn immune response.Frontiers in immunology · 2024Article
- Mmp2 Deficiency Leads to Defective Parturition and High Dystocia Rates in Mice.International journal of molecular sciences · 2023Article
- Digitize your Biology! Modeling multicellular systems through interpretable cell behavior.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
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, intracellular 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 lower collagen area fraction when spatially-localized latent TGF-β sources were active for longer times. We validated our model by comparing simulated dynamics for TGF-β, collagen area fraction, and macrophage cell population with independent experimental data from mouse models. Our results showed that partial removal of TGF-β sources changed the fibrotic patterns; in the presence of persistent TGF-β sources, partial removal of TGF-β from the ECM significantly increased collagen area fraction due to maintenance of chemotactic gradients driving fibroblast movement. The computational findings are consistent with independent experimental and clinical observations of collagen area fractions and cell population dynamics not used in developing the model. These critical insights into the activity of TGF-β sources may find applications in the current clinical trials targeting TGF-β for the resolution of lung fibrosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.