Fig. 5: A stimulation signature based on LPS and R848 stimulated cytokine responses at baseline associated with peak severity.

a Combined LPS and R848 stimulated cytokine variables at baseline. Each column represents a patient, each row represents a stimulus-cytokine variable. Columns are grouped by future peak severity, rows are grouped by inclusion/exclusion in the LPS + R848 model. Hierarchical clustering by Euclidean distance as dissimilarity metric was preformed within groups/splits (dendrogram only shown for rows). The top annotations represent (up-down): “Sev”: future peak severity, “Pred.Sev”: predicted severity in current cohort based on the LPS + R848 LASSO regression model, “Sex”: sex at birth, “Age”: age at time of inclusion in study, “Imm.Sup”: whether an immunosuppressive pre-condition was present, “Centroid”: the row mean value. Row annotations represent (left-right): “Model”: Inclusion/exclusion of variable in the LPS + R848 model, “Stimuli”: the stimulus for each cytokine variable. Data used for visualization were log-transformed and standardized. Data from the variables excluded from the LPS + R848 model have been blurred. b Correlation between all LPS and R848 stimulated cytokine variables by Pearson. All data were log-transformed cytokine concentrations. Row annotation represent inclusion/exclusion of a variable in the LPS + R848 model. c Projection of LPS + R848 data at baseline using isomap revealing a severity gradient in the data structure. LPS lipopolysaccharide, R848 resiquimod, L O2 liters/minute of oxygen supply, ICU intensive care unit.