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. 2022 Oct 20;12(10):2554.
doi: 10.3390/diagnostics12102554.

Calprotectin Levels and Neutrophil Count Are Prognostic Markers of Mortality in COVID-19 Patients

Giovanna Cardiero  1   2 , Daniela Palma  1   2 , Martina Vano  1 , Claudia Anastasio  1 , Biagio Pinchera  3 , Martina Ferrandino  1 , Carlo Gianfico  1 , Luca Gentile  1 , Marcella Savoia  1 , Ivan Gentile  3 , Maria Donata Di Taranto  1   2 , Giuliana Fortunato  1   2
Affiliations

Calprotectin Levels and Neutrophil Count Are Prognostic Markers of Mortality in COVID-19 Patients

Giovanna Cardiero et al. Diagnostics (Basel). .

Abstract

Inflammation plays a crucial role in worsening coronavirus disease (COVID-19). Calprotectin is a pro-inflammatory molecule produced by monocytes and neutrophilic granulocytes. The aim of the study was to evaluate both the prognostic role of circulating calprotectin levels and neutrophil count toward fatal outcome in COVID-19 patients. We retrospectively collected and analyzed data on 195 COVID-19 adult patients, 156 hospitalized in the infectious disease unit and 39 in the intensive care unit (ICU). Calprotectin levels and neutrophil counts measured at the first hospitalization day were higher in the patients with a fatal outcome than in surviving ones. The association of high calprotectin levels and neutrophil count to patient death remain significant by logistic regression, independent of patient age. ROC curves analysis for calprotectin levels and neutrophil count revealed a good discriminatory power toward survival (area under the curve of 0.759 and 0.843, respectively) and identified the best cut-off (1.66 mg/L and 16.39 × 103/µL, respectively). Kaplan-Meier analysis confirmed the prognostic role of high calprotectin levels and neutrophil count in death prediction. In conclusion, this study highlights that calprotectin levels together with neutrophil count should be considered as biomarkers of mortality in COVID-19 patients.

Keywords: COVID-19; S100A8/S100A9; biomarker; calprotectin; inflammation; neutrophil; prognosis; survival.

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Conflict of interest statement

I.G. acted as a consultant for Gilead, MSD, Abbvie, Pfizer, Nordic, Angelini, Correvio. All of the other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
ROC curves of calprotectin levels and neutrophil count in relation to survival. The ROC curve is indicated by a bold line and full circles represent the different criterion points. The open circle indicates the best cut-off point. The dotted line indicates the bisector. AUC = area under the curve. (A). ROC curve of calprotectin levels. (B). ROC curve of neutrophil count.
Figure 2
Figure 2
ROC curve of age, calprotectin levels and neutrophil count combined together. The weight of each parameter was obtained by logistic regression. The ROC curve is indicated by a bold line and full circles represent the different criterion points. The open circle indicates the best cut-off point. The dotted line indicates the bisector. AUC = area under the curve.
Figure 3
Figure 3
Kaplan–Meier survival curves of patients in relation to calprotectin levels or neutrophil count. (A) Patients were divided based on calprotectin levels higher or lower than 1.66 mg/L at the first measurement. (B) Patients were divided based on neutrophil count higher or lower than 16.39 × 103/µL at the first measurement. Each vertical drop of the curve represents a single event. Plus signs indicate censored cases.
Figure 4
Figure 4
Kaplan–Meier survival curves of patients in relation to both calprotectin levels and neutrophil count. Patients were divided based on levels over the cut-off for both calprotectin and neutrophil count, levels over the cut-off for only one of the parameters or levels below the cut-off for both parameters. Calprotectin cut-off at the first measurement: 1.66 mg/L. Neutrophil count cut-off at the first measurement: 16.39 × 103/µL. Each vertical drop of the curve represents a single event. Plus signs indicate censored cases.
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