Risk of Death in Comorbidity Subgroups of Hospitalized COVID-19 Patients Inferred by Routine Laboratory Markers of Systemic Inflammation on Admission: A Retrospective Study

Abstract

Our study objective was to construct models using 20 routine laboratory parameters on admission to predict disease severity and mortality risk in a group of 254 hospitalized COVID-19 patients. Considering the influence of confounding factors in this single-center study, we also retrospectively assessed the correlations between the risk of death and the routine laboratory parameters within individual comorbidity subgroups. In multivariate regression models and by ROC curve analysis, a model of three routine laboratory parameters (AUC 0.85; 95% CI: 0.79-0.91) and a model of six laboratory factors (AUC 0.86; 95% CI: 0.81-0.91) were able to predict severity and mortality of COVID-19, respectively, compared with any other individual parameter. Hierarchical cluster analysis showed that inflammatory laboratory markers grouped together in three distinct clusters including positive correlations: WBC with NEU, NEU with neutrophil-to-lymphocyte ratio (NLR), NEU with systemic immune-inflammation index (SII), NLR with SII and platelet-to-lymphocyte ratio (PLR) with SII. When analyzing the routine laboratory parameters in the subgroups of comorbidities, the risk of death was associated with a common set of laboratory markers of systemic inflammation. Our results have shown that a panel of several routine laboratory parameters recorded on admission could be helpful for early evaluation of the risk of disease severity and mortality in COVID-19 patients. Inflammatory markers for mortality risk were similar in the subgroups of comorbidities, suggesting the limited effect of confounding factors in predicting COVID-19 mortality at admission.

Keywords: COVID-19; comorbidity; inflammatory markers; model; severity predictors.

Figure 1

Distribution of preexisting conditions in our group of COVID-19 patients. Number of patients in the disease severity groups illustrated for all subgroups of comorbidities.

Figure 2

Characteristics of our group of COVID-19 patients. Distribution of preexisting conditions (A), age (B), and hospitalization days (C) in disease severity groups. Percentages of disease severity in female and male patients (D). Data are presented as violin plots with medians (A–C).

Figure 3

Violin plots showing distribution of laboratory parameter levels on admission. Boxplots indicate median and interquartile range. WHO severity indicates the highest disease severity of the patients during hospitalization. Mild n = 85 samples; moderate n = 98 samples; severe n = 34 samples; critical n = 37 samples. The asterisks indicate that the difference between two groups is significant (* p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001).

Figure 4

Correlogram with hierarchical clustering of COVID-19 patients. Positive and negative correlations are represented by blue and red dots. The sizes and the shades of the dots reflect the strengths of correlation between pairs of hematological parameters. Colors range from bright blue (strong positive correlation; i.e., r = 1.0) to bright red (strong negative correlation; i.e., r = −1.0). Correlations are ordered by hierarchical clustering with clusters outlined.

Figure 5

Receiver operating characteristic (ROC) curves for the individual laboratory parameters and models for prediction of disease severity. (A) The analysis of AUCs (area under the curve) for age, WBC, NEU, NLR, PLR, SII, ESR, D-dimer, CRP, AST, total bilirubin, LDH, CK, creatinine, BUN, ferritin, and models 1–3; (B) ALT, APTT, HGB, and LYM.

Figure 6

Receiver operating characteristic (ROC) curves for the individual laboratory parameters and models for prediction of mortality in COVID-19 patients. (A) The analysis of AUCs (area under the curve) for age, WBC, NEU, NLR, PLR, SII, ESR, D-dimer, CRP, AST, total bilirubin, LDH, CK, creatinine, BUN, ferritin, and models 4–8; (B) ALT, APTT, HGB, and LYM.

Figure 7

Radar plots illustrating the distribution of scaled values of the selected laboratory parameters in deceased (orange) versus discharged (green) COVID-19 patients comparing each laboratory variable with all comorbidities: Age (A), APTT (B), CRP (C), D-dimer (D), LDH (E), NEU (F), NLR (G), SII (H), and WBC (I).