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.
【저자키워드】 COVID-19, Cytokine storm, inhaled corticosteroids, hyperinflammation, 【초록키워드】 Corticosteroids, SARS-COV-2 infection, lung, Intervention, Asymptomatic carrier, virus, Simulation, Patient, pathway, Inhaled, Mild, sensitivity analysis, trajectory, moderate, severe COVID-19 disease, acute respiratory distress, Evidence, Inflammatory response, hyperinflammatory state, severe disease, Clinical deterioration, physiological, anti-inflammatory agent, biochemical, individual, syndrome, COVID-19 illness, respiratory compromise, therapeutic intervention, blockade, while, Hyperinflammatory, FIVE, Prevent, pathological mechanism, current, develop, involved, supported, increasingly, mathematical, acting, pro-inflammatory mediator, 【제목키워드】 Inflammation, epithelial cell,