COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes
Fig 1
Immune response to SARS-CoV-2 infection model schematic.
The model in Eqs. S1-S22 reduced to A) cell dynamics B) cytokine production dynamics and C) cytokine binding kinetics. Unique lines represent induced cell death (double line), recruitment (dashed line), cell type change or production (solid line), and cytokine production (square arrow). Cell and/or cytokines along joining lines denote a causal interaction. A) Virus (V) infects susceptible lung epithelial cells and creates either infected (I) or resistant (R) cells depending on the concentration of type I IFN. Infected cells then either die and produce new virus or are removed via inflammatory macrophages (MΦI) or CD8+ T cells (T) that induce apoptosis to create dead cells (D). Neutrophils (N) cause bystander damage (death) in all epithelial cells and are recruited by individually G-CSF and IL-6 concentrations. CD8+ T cells are recruited by infected cells and their population expands from IFN signalling. T cell recruitment is inhibited by IL-6 concentrations. Monocytes (M) are recruited by infected cells and GM-CSF and differentiate into inflammatory macrophages based on the individual concentrations of GM-CSF and IL-6. Tissue-resident macrophages (MΦR) also become inflammatory macrophages through interaction with dead and infected cells. Dead cells are cleared up by inflammatory macrophages and also cause their death. B) Type I IFN is produced by infected cells, inflammatory macrophages and monocytes. G-CSF is produced solely by monocytes and GM-CSF is produced by monocytes and macrophages. IL-6 is produced by monocytes, inflammatory macrophages and infected cells. C) Cytokine receptor binding, internalization and unbinding kinetics considered for each cell-cytokine interaction.