Acute Lung Injury Biomarkers in the Prediction of COVID-19 Severity: Total Thiol, Ferritin and Lactate Dehydrogenase.

Alvaro Martinez Mesa,Pilar Martinez Lopez,Maria Garcia-Fernandez,Yanina Romero-Zerbo,Esther Sanchez Alvarez,Eva Cabrera César,Elisa Martín-Montañez,Jose Luis Velasco Garrido

doi:10.3390/antiox10081221

Abstract

SARS-CoV-2 (COVID-19) patients who develop acute respiratory distress syndrome (ARDS) can suffer acute lung injury, or even death. Early identification of severe disease is essential in order to control COVID-19 and improve prognosis. Oxidative stress (OS) appears to play an important role in COVID-19 pathogenesis; we therefore conceived a study of the potential discriminative ability of serum biomarkers in patients with ARDS and those with mild to moderate disease (non-ARDS). 60 subjects were enrolled in a single-centre, prospective cohort study of consecutively admitted patients: 29 ARDS/31 non-ARDS. Blood samples were drawn and marker levels analysed by spectrophotometry and immunoassay techniques. C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin were significantly higher in ARDS versus non-ARDS cases at hospital admission. Leukocytes, LDH, ferritin, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were also significantly elevated in ARDS compared to non-ARDS patients during the hospital stay. Total thiol (TT) was found to be significantly lower in ARDS. Conversely, D-dimer, matrix metalloproteinase-9 (MMP-9) and advanced glycosylated end products (AGE) were elevated. Leukocytes, LDH, CRP, ferritin and IL-6 were found to be significantly higher in non-survivors. However, lymphocyte, tumour necrosis factor beta (TGF-β), and TT were lower. In summary, our results support the potential value of TT, ferritin and LDH as prognostic biomarkers for ARDS development in COVID-19 patients, distinguishing non-ARDS from ARDS (AUCs = 0.92; 0.91; 0.89) in a fast and cost-effective manner. These oxidative/inflammatory parameters appear to play an important role in COVID-19 monitoring and can be used in the clinical management of patients.

Highlights

Previous studies have shown the relation between haematologic, inflammatory and coagulation parameters with the severity of the disease [20,21,22,23,24], only a limited number of studies examine the effect of pro-fibrotic and Oxidative stress (OS) markers on the severe clinical course of COVID-19 patients
In this study we analysed, for the first time, the potential value of haematologic, inflammatory and coagulation parameters, together with profibrotic and OS markers as prognostic biomarkers for acute respiratory distress syndrome (ARDS) development in COVID-19 patients. We selected these biomarkers from the existing literature [25], and new ones in relation to the role that OS appears to play in the pathogenesis of COVID-19
Our results provide support for the potential use of Total thiol (TT), ferritin, lactate dehydrogenase (LDH), interleukin 6 (IL-6) and

Summary

Introduction

Coronaviruses (CoVs) have been the cause of respiratory tract infections for over. Previous epidemic CoV outbreaks include severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV [1]. The new coronavirus disease produced by SARS-CoV-2 (COVID-19), causing a wide range of effects from nonsymptomatic, mild to moderate disease, to severe infection resulting in fatal disease, has been a threat to public health since the end of 2019. While many patients experience only a mild form, severe illness develops in 14% of cases, and critical illness in 5%, with acute respiratory distress syndrome (ARDS), multiple organ failure, and even death [2,3]

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