key: cord-282053-ftjx29lw
authors: Luis García de GuadianaRomualdo; Mulero, María Dolores Rodríguez; Olivo, Marta Hernández; Rojas, Carlos Rodríguez; Arenas, Verónica Ramos; Morales, Mercedes González; Abellán, Ana Blazquez; Zamora, Pablo Conesa; García, Josefina; Hernández, Andrés Conesa; Morell-García, Daniel; Otón, María Dolores Albaladejo; Consuegra-Sánchez, Luciano
title: Circulating levels of GDF-15 and calprotectin for prediction of in-hospital mortality in COVID-19 patients: a case series
date: 2020-08-12
journal: J Infect
DOI: 10.1016/j.jinf.2020.08.010
sha: 
doc_id: 282053
cord_uid: ftjx29lw

nan

We read the recent articles by Li and colleagues and Lin and colleagues about the role of two inflammatory biomarkers, serum amyloid A 1 and ferritin 2 , in the evaluation of severity in coronavirus disease 2019 (COVID-19) patients. We fully agree with authors that early identification of patients with a higher risk for severity remains crucial to define an optimal strategy for the management of COVID-19 patients.

In severe cases, the interaction of SARS-CoV-2 with the immune system contributes to a dysfunctional immune response, which triggers a cytokine storm that mediates widespread inflammation and multi-organ damage, major cause of disease severity and death in infected patients 3, 4 . Higher blood levels of inflammatory biomarkers in blood, such as C-reactive protein (CRP), ferritin and D-dimer, have been reported as predictors of a poor outcome in COVID-19 patients 5 . The role of biomarkers associated to inflammation other than those above mentioned, such as calprotectin or growth differentiation factor 15 (GDF-15), is less known.

The association of inflammation and calprotectin and GDF-15 has been previously reported [6] [7] [8] . During the inflammatory response, neutrophils and monocytes quickly arrive to the site of inflammation. The heterodimeric protein S100A8/A9, named as calprotectin, is an alarmin mainly derived by both cell types which play a critical role in inflammatory response, exerting its functions by binding to two patterns recognition receptors: Toll-like receptor and Receptor of Advanced Glycation Endproducts and activating pro-inflammatory signaling pathways leading to further recruitment and activation of immune cells 6 .

Infection-induced inflammation is one of the main triggers that leads to calprotectin liberation 8 . In a recent study, calprotectin levels were significantly higher in COVID-19 patients who required mechanical ventilation, similarly to CRP 9 . GDF-15 is a member of the Tumor Growth Factor-beta (TGF-) family, primarily expressed under conditions of inflammation and oxidative stress.

Recently, an experimental study showed a novel function of GDF-15 in the promotion of lung human rhinovirus and virus-associated inflammation, contributing to the severity of respiratory viral infection 10 .

In the present observational study, we aimed to explore a potential role of In our cohort, the mortality rate was 12.1% (8/66). Median time from symptoms onset to ED admission was 7 (5-10) days. Table 1 shows the differences in demographics and comorbidities between survivors and non-survivors. Table 2 ), as assessed by the analysis of the AUC of ROC curve for in-hospital mortality, similar to both D-dimer and CRP but numerically higher than ferritin ( Figure 1 and Table 2 ). Table 2 shows the unadjusted odds ratio to each of the studied biomarkers stratified by a cut off obtained by means of the Youden Index for the prediction of in-hospital mortality.

We have shown that circulating levels of two emerging inflammatory biomarkers, calprotectin and GDF-15, are significantly higher in COVID-19 patients who died, suggesting a potential role in the evaluation of prognosis in these patients. Our study is the first, to our knowledge, exploring a potential prognostic value of both in COVID-19 patients.

This early report has some limitations, namely the small sample size. Hence, we did not perform multivariable analysis, due to the small number of included patients and outcomes. However, the IPW method allowed us to adjust for the SOFA score, that was shown to be a powerful predictor of mortality. The aim was not to generate a predictive model, but rather to explore the potential role of these novel biomarkers.

Our findings suggest that calprotectin and GDF-15 might have a potential role in the assessment of prognosis in COVID-19 patients.

The authors declare no competing interests Note: Data are expressed as frequency (percentage) or mean (standard deviation). Weighted by inverse probability of dying during admission (obtained from a propensity score model using SOFA sca 95% CI: 0.919-1) 2 For the calculation the Youden index derived cutoffs for each of the biomarkers were used.

Serum Amyloid A is a biomarker of severe Coronavirus Disease and poor prognosis

Serum ferritin as an independent risk factor for severity in COVID-19 patients

Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages

The trinity of COVID-19: immunity, inflammation and intervention

Molecular, serological, and biochemical diagnosis and monitoring of COVID-19: IFCC taskforce evaluation of the latest evidence

S100A8/A9: From basic science to clinical application

Growth Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint

S100A8/A9 in Inflammation

Neutrophil calprotectin identifies severe pulmonary disease in COVID-19

Overproduction of growth differentiation factor 15 promotes human rhinovirus infection and virus-induced inflammation in the lung


