Novel serological biomarkers for inflammation in predicting disease severity in patients with COVID-19

Abstract

Background: Patients with severe coronavirus disease 2019 (COVID-19) develop acute respiratory distress and multi-system organ failure and are associated with poor prognosis and high mortality. Thus, there is an urgent need to identify early diagnostic and prognostic biomarkers to determine the risk of developing serious illness.

Methods: We retrospectively analyzed 114 patients with COVID-19 at the Jinyintan Hospital, Wuhan based on their clinical and laboratory data. Patients were categorized into severe and mild to moderate disease groups. We analyzed the potential of serological inflammation indicators in predicting the severity of COVID-19 in patients using univariate and multivariate logistic regression, receiver operating characteristic curves, and nomogram analysis. The Spearman method was used to understand the correlation between the serological biomarkers and duration of hospital stay.

Results: Patients with severe disease had reduced neutrophils and lymphocytes; severe coagulation dysfunction; altered content of biochemical factors (such as urea, lactate dehydrogenase); elevated high sensitivity C-reactive protein levels, neutrophil-lymphocyte, platelet-lymphocyte, and derived neutrophil-lymphocyte ratios, high sensitivity C-reactive protein-prealbumin ratio (HsCPAR), systemic immune-inflammation index, and high sensitivity C-reactive protein-albumin ratio (HsCAR); and low lymphocyte-monocyte ratio, prognostic nutritional index (PNI), and albumin-to-fibrinogen ratio. PNI, HsCAR, and HsCPAR correlated with the risk of severe disease. The nomogram combining the three parameters showed good discrimination with a C-index of 0.873 and reliable calibration. Moreover, HsCAR and HsCPAR correlated with duration of hospital stay.

Conclusion: Taken together, PNI, HsCAR, and HsCPAR may serve as accurate biomarkers for the prediction of disease severity in patients with COVID-19 upon admission/hospitalization.

Keywords: COVID-19; High sensitivity C-reactive protein-albumin ratio; High sensitivity C-reactive protein-prealbumin ratio; Nomogram; Prognostic nutritional index; Severity.

Fig. 1

Novel serological indicators in COVID-19 patients. Patients with severe form of COVID-19 had higher levels of NLR (a), PLR (b), HsCAR (d), dNLR (e), SII (g), and HsCPAR (i), and lower levels of LMR (c), PNI (f), and AFR (h) when compared to those in mild to moderate patients. Statistical significance was determined using the Mann-Whitney U test. Abbreviations: NLR, neutrophil–lymphocyte ratio; PLR, platelet-lymphocyte ratio; LMR, lymphocyte-monocyte ratio; dNLR, derived neutrophil–lymphocyte ratio; HsCAR, high sensitivity C-reactive protein-albumin ratio; AFR, albumin-to-fibrinogen ratio; PNI, prognostic nutritional index; SII, systemic immune-inflammation index; HsCPAR, high sensitivity C-reactive protein-prealbumin ratio.

Fig. 2

Forest plot for the age and gender-adjusted serological indicators based on logistic regression analysis.

Fig. 3

ROC curves for HsCAR, HsCPAR, PNI, and a combination of the three indices for predicting the severity of COVID-19. HsCAR^AUC = 0.81 (95% CI, 0.73–0.88), p < 0.0001. HsCPAR^AUC = 0.80 (95% CI, 0.72–0.87), p < 0.0001. PNI^AUC = 0.76 (95% CI, 0.67–0.84), p < 0.0001. Combination ^AUC = 0.827 (95% CI, 0.81–0.93), P < 0.0001. Abbreviations: ROC, receiver operating characteristic curves; AUC, area under ROC curve; HsCAR, high sensitivity C-reactive protein-albumin ratio; PNI, prognostic nutritional index; HsCPAR, high sensitivity C-reactive protein-prealbumin ratio.

Fig. 4

Nomogram for the risk of severe illness. (a) The HsCAR, HsCPAR, and PNI combination nomogram. (b) Calibration curves of nomograms to show the correlation between the predicted probability and actual diagnostic results. (c) Decision curve analysis of the nomogram to predict severe illness. Abbreviations: HsCAR, high sensitivity C-reactive protein-albumin ratio; PNI, prognostic nutritional index; HsCPAR, high sensitivity C-reactive protein-prealbumin ratio.

Fig. 5

The correlation between duration of hospital stay for COVID-19 patients and novel serological markers. Abbreviations: NLR, neutrophil–lymphocyte ratio; LMR, lymphocyte-monocyte ratio; HsCAR, high sensitivity C-reactive protein-albumin ratio; PNI, prognostic nutritional index; AFR, albumin-to-fibrinogen ratio; HsCPAR, high sensitivity C-reactive protein-prealbumin ratio.