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COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes
Fig 9
Virtual cohort of SARS-CoV-2 infected patients.
200 virtual patients were generated by sampling parameters related to macrophage, IL-6, and IFN production (
, pL,MΦ, pF,I, pM,I, ηF,MΦ, ϵF,I, and pF,M) from normal distributions with mean equal to their original values and standard deviation inferred from clinical observations (Fig 8). Each virtual patient had a distinct parameter set optimized to that patient’s dynamics in response to SARS-CoV-2 infection which corresponded to physiological intervals reported in the literature (see Materials and methods). A) Infection and immune response metrics (blue) in individual patients were compared to inflammatory variable Ψ (green). Each point represents an individual patient, ordered according to Ψ. The correlation coefficient (R) and p-value are indicated for each, with α<0.05 denoting significant correlations. B) The effect of exposure dose V0 on maximum IL-6 (a), maximum neutrophil counts (b) and inflammation marker Ψ (c) for V0 = 0.1, 1, 4.5 and 8 log10(copies/ml). In a and b, rows are coloured according to each virtual patient’s inflammation marker value; virtual patients were ordered by the value of Ψ from the baseline scenario in A (V0 = 4.5 log10(copies/ml)). C) Correlations between maximal IFN, IL-6, and T cell concentrations for each patient (circles). Circle colours correspond to the maximal T cell concentration of each patient. D) Parameters most correlated to the IFN peak time were the rates of macrophage production via a) IL-6 (
) and the b) IFN production by infected cells (pF,I). Individual patient values for these parameters are plotted as circles coloured by the patient’s corresponding day of IFN peak (see color bar). Patients were ordered by their inflammation marker Ψ.
doi: https://doi.org/10.1371/journal.ppat.1009753.g009