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. 2021 May:141:155455.
doi: 10.1016/j.cyto.2021.155455. Epub 2021 Jan 28.

Prognostic bioindicators in severe COVID-19 patients

L Bergantini  1 , E Bargagli  2 , M d'Alessandro  2 , R M Refini  2 , P Cameli  2 , L Galasso  3 , C Scapellato  3 , F Montagnani  4 , S Scolletta  5 , F Franchi  5 , S Valente  6 , D Bennett  2 , G Sebastiani  7 , B Frediani  8 , F Dotta  7
Affiliations

Prognostic bioindicators in severe COVID-19 patients

L Bergantini et al. Cytokine. 2021 May.

Abstract

Background: Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity.

Materials and methods: Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups.

Results: In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95.

Conclusions: Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients.

Keywords: Biomarkers; COVID-19; IL-6; KL-6.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
. (a) Linearity of IL-6 in the Lumipulse G600II system. (b) Method comparison of the two technology. (c) Assay validation Bland-Altman plots. Dotted lined indicates 95% limits of agreement.
Fig. 2
Fig. 2
. (a) comparison analysis of IL-6 between Healthy controls (HC), Mild-to-moderate and Severe Covid-19 Patients. (b–c) comparison analysis of KL-6 and CRP between Mild-to-moderate and Severe Covid-19 Patients. *p < 0.05, **p < 0.01, ***p < 0.001, *** p < 0.0001.
Fig. 3
Fig. 3
. (a) ROC curve analysis of CRP (blue), KL-6 (Red) and IL-6 (black) between mild to moderate and severe Covid-19 patients. (b) Combination model of KL-6, IL-6 and CRP.
See this image and copyright information in PMC

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