Fig. 1: COVID-19 pandemic phases and relationships between soluble immune mediators and COVID-19 severity.

a Epidemic curve of study enrollment period; enrolled patients (N = 306) assigned to epidemic weeks based on date of hospitalization and colored according to World Health Organization (WHO) clinical severity classification. Right-sided y-axis reflects national SARS-CoV-2 case counts as per the WHO COVID-19 Uganda dashboard. Pandemic phases were defined based on dominant circulation of different variants and trends in national SARS-CoV-2 case counts (Varied A/B lineage phase, N = 97; A.23/A.23.1 phase, N = 141; Delta phase, N = 68). *Delta variant includes B.1.617.2 and AY.1, AY.4, AY.33, AY.39, AY.46, AY.46.4 sublineages. b Heatmap of 45 soluble immune mediator concentrations (values log₁₀-transformed, centered, and scaled) stratified by WHO clinical severity classification with rows split by k-means clustering (N = 306). Individual patient columns are ordered based on differences in mean z-score and annotated with age, self-reported sex, HIV status, and dominant SARS-CoV-2 variant at time of hospitalization. IL-3, GM-CSF, and G-CSF omitted from heatmap given large proportion of values below the lower limit of quantification. c Soluble mediator concentrations stratified by WHO clinical severity classification (N = 306). Concentrations across groups compared using Kruskal-Wallis H test followed by Dunn’s test for multiple comparisons with p values adjusted using Benjamini-Hochberg method; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. d Importance of immune mediators in gradient-boosted machine classifier for prediction of severe (N = 70) vs. non-severe (asymptomatic, mild, or moderate, N = 236) COVID-19 as per model split-gain values; top 20 variables presented in descending order of importance. e Shapley additive explanations (SHAP) values derived from gradient-boosted machine model for prediction of severe (N = 70) vs. non-severe (N = 236) COVID-19; SHAP values > 0 indicate positive impact on prediction while values < 0 indicates negative impact (e.g., high concentrations of IL-7 have a strong positive contribution to prediction of severe COVID-19). f Probabilities of COVID-19 severity stratified by HIV status (N = 302; 4 patients without definitive assessment of HIV status excluded); shading indicates 95% confidence intervals; probabilities derived from multivariable proportional odds model including WHO clinical severity as ordinal dependent variable and age, self-reported sex, and interaction term between HIV status and log₁₀-mediator concentration as independent variables; p values reflect two-sided Wald test of interaction term; PLWH persons living with HIV. Source data are provided in the Source Data file.