Soluble TNF receptors predict acute kidney injury and mortality in critically ill COVID-19 patients: A prospective observational study

Elena Sancho Ferrando, Katja Hanslin, Michael Hultström, Anders Larsson, Robert Frithiof, Miklos Lipcsey, Uppsala Intensive Care COVID-19 Research Group, Elena Sancho Ferrando, Katja Hanslin, Michael Hultström, Anders Larsson, Robert Frithiof, Miklos Lipcsey, Uppsala Intensive Care COVID-19 Research Group

Abstract

Background: Although pneumonia is the hallmark of coronavirus disease 2019 (COVID-19), multiple organ failure may develop in severe disease. TNFα receptors in their soluble form (sTNFR) are involved in the immune cascade in other systemic inflammatory processes such as septic shock, and could mediate the inflammatory activation of distant organs. The aim of this study is to analyse plasma levels of sTNFR 1 and 2 in association with organ failure and outcome in critically ill patients with COVID-19.

Methods: After informed consent, we included 122 adult patients with PCR-confirmed COVID-19 at ICU admission. Demographic data, illness severity scores, organ failure and survival at 30 days were collected. Plasma sTNFR 1 and 2 levels were quantified during the first days after ICU admission. Twenty-five healthy blood donors were used as control group.

Results: Levels of sTNFR were higher in severe COVID-19 patients compared to controls (p < 0.001). Plasma levels of sTNFR were associated to illness severity scores (SAPS 3 and SOFA), inflammation biomarkers such as IL-6, ferritin and PCT as well as development of AKI during ICU stay. sTNFR 1 higher than 2.29 ng/mL and? sTNFR 2 higher than 11.7 ng/mL were identified as optimal cut-offs to discriminate survivors and non-survivors 30 days after ICU admission and had an area under the curve in receiver operating characteristic curve of 0.75 and 0.67 respectively.

Conclusion: Plasma levels of sTNFR 1 and 2 were higher in COVID-19 patients compared to controls and were strongly associated with other inflammatory biomarkers, severity of illness and acute kidney injury development during ICU stay. In addition, sTNFR 1 was an independent predictor of 30-day mortality after adjustment for age and respiratory failure.

Keywords: Acute kidney injury; Biomarkers; COVID-19; Critical care; TNF receptors.

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.

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
sTNFR 1 and 2 levels in patients with COVID-19 and healthy controls. The p-values denotes the group differences.
Fig. 2
Fig. 2
sTNFR 1 and 2 levels in groups according to the maximum AKI stage of the patients during ICU stay. The p-value denotes increase in sTNFR 1 and 2 values over AKI stages.
Fig. 3
Fig. 3
sTNFR 1 and 2 levels comparing patients who died vs. those who survived at 30 days after ICU admission. The p-values denotes the group differences.
Fig. 4
Fig. 4
ROC curves for sTNFR 1 and sTNFR 2 and 30 day mortality. Area under the curve (AUC) is shown in the graph.
Fig. 5
Fig. 5
Kaplan Meier plot depicting cumulative mortality incidence for sTNFR 1 and 2 values for cut-offs of 2.29 ng/mL and 11.7 ng/mL, respectively, during the 30 day’s follow up.
Fig. 6
Fig. 6
Multivariable analysis showing sTNFR 1 optimal cut-off as independent predictor of mortality even when adjusted by age, maximum creatinine and mechanical ventilation.

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