Infection, inflammation and intervention: mechanistic modelling of epithelial cells in COVID-19

Fadai, Nabil T.; Sachak-Patwa, Rahil; Byrne, Helen M.; Maini, Philip K.; Bafadhel, Mona; Nicolau, Dan V.

Abstract

While the pathological mechanisms in COVID-19 illness are still poorly understood, it is increasingly clear that high levels of pro-inflammatory mediators play a major role in clinical deterioration in patients with severe disease. Current evidence points to a hyperinflammatory state as the driver of respiratory compromise in severe COVID-19 disease, with a clinical trajectory resembling acute respiratory distress syndrome, but how this ‘runaway train’ inflammatory response emerges and is maintained is not known. Here, we present the first mathematical model of lung hyperinflammation due to SARS-CoV-2 infection. This model is based on a network of purported mechanistic and physiological pathways linking together five distinct biochemical species involved in the inflammatory response. Simulations of our model give rise to distinct qualitative classes of COVID-19 patients: (i) individuals who naturally clear the virus, (ii) asymptomatic carriers and (iii–v) individuals who develop a case of mild, moderate, or severe illness. These findings, supported by a comprehensive sensitivity analysis, point to potential therapeutic interventions to prevent the emergence of hyperinflammation. Specifically, we suggest that early intervention with a locally acting anti-inflammatory agent (such as inhaled corticosteroids) may effectively blockade the pathological hyperinflammatory reaction as it emerges.

Citation

Fadai, N. T., Sachak-Patwa, R., Byrne, H. M., Maini, P. K., Bafadhel, M., & Nicolau, D. V. (2021). Infection, inflammation and intervention: mechanistic modelling of epithelial cells in COVID-19. Journal of the Royal Society, Interface, 18(175), Article 20200950. https://doi.org/10.1098/rsif.2020.0950

• Journal Article Type: Article
• Acceptance Date: Jan 26, 2021
• Online Publication Date: Feb 17, 2021
• Publication Date: 2021-02
• Deposit Date: Feb 22, 2021
• Publicly Available Date: Mar 4, 2021
• Journal: Journal of The Royal Society Interface
• Print ISSN: 1742-5689
• Electronic ISSN: 1742-5662
• Publisher: The Royal Society
• Peer Reviewed: Peer Reviewed
• Volume: 18
• Issue: 175
• Article Number: 20200950
• DOI: https://doi.org/10.1098/rsif.2020.0950
• Keywords: Biotechnology; Biophysics; Biochemistry; Bioengineering; Biomaterials; Biomedical Engineering
• Public URL: https://nottingham-repository.worktribe.com/output/5336229
• Publisher URL: https://royalsocietypublishing.org/doi/full/10.1098/rsif.2020.0950