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Infection, inflammation, and intervention: mechanistic modelling of epithelial cells in COVID-19
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 (ARDS) but how this “runaway train” inflammatory response emergences and is maintained is not known. In this talk, 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, points 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.
Date:
6 November 2020, 14:00
Venue:
Mathematical Institute, Woodstock Road OX2 6GG
Venue Details:
Virtual
Speaker: Various Speakers
Organising department:
Mathematical Institute
Organiser:
Sara Jolliffe (University of Oxford)
Organiser contact email address:
sara.jolliffe@maths.ox.ac.uk
Host:
Dr Peter Minary (University of Oxford)
Part of:
Mathematical Biology and Ecology
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Sara Jolliffe
