Clinical Performance of Paraoxonase-1-Related Variables and Novel Markers of Inflammation in Coronavirus Disease-19. A Machine Learning Approach.

Elisabet Rodríguez-Tomàs,Simona Iftimie,Gerard Baiges-Gaya,Anna Hernández-Aguilera,Jordi Camps,Antoni Castro,Jorge Joven,Helena Castañé,María González-Viñas

doi:10.3390/antiox10060991

Elisabet Rodríguez-Tomàs, Simona Iftimie + Show 7 more

Open Access

https://doi.org/10.3390/antiox10060991

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Abstract

SARS-CoV-2 infection produces a response of the innate immune system causing oxidative stress and a strong inflammatory reaction termed ‘cytokine storm’ that is one of the leading causes of death. Paraoxonase-1 (PON1) protects against oxidative stress by hydrolyzing lipoperoxides. Alterations in PON1 activity have been associated with pro-inflammatory mediators such as the chemokine (C-C motif) ligand 2 (CCL2), and the glycoprotein galectin-3. We aimed to investigate the alterations in the circulating levels of PON1, CCL2, and galectin-3 in 126 patients with COVID-19 and their interactions with clinical variables and analytical parameters. A machine learning approach was used to identify predictive markers of the disease. For comparisons, we recruited 45 COVID-19 negative patients and 50 healthy individuals. Our approach identified a synergy between oxidative stress, inflammation, and fibrogenesis in positive patients that is not observed in negative patients. PON1 activity was the parameter with the greatest power to discriminate between patients who were either positive or negative for COVID-19, while their levels of CCL2 and galectin-3 were similar. We suggest that the measurement of serum PON1 activity may be a useful marker for the diagnosis of COVID-19.

Highlights

Manipulation of host cell function by viral pathogens is vital for successful infection and the creation of a habitat favoring viral replication
The present study found a marked decrease in PON1 activity and an increase in PON1, CCl2, and galectin-3 concentrations in COVID-19 positive hospitalized patients, compared to healthy individuals
When comparing COVID-19 positive with COVID-19 negative patients, we found higher PON1 concentrations in the former, but no significant differences were observed with respect to CCL2, and galectin-3 concentrations were lower

Summary

Introduction

Manipulation of host cell function by viral pathogens is vital for successful infection and the creation of a habitat favoring viral replication. Most viruses manipulate the host cell’s metabolism in order to optimize the biosynthetic needs of the virus through proviral metabolic changes [1]. On the other hand, have developed metabolic strategies to inhibit viral replication through antiviral metabolic changes [2]. Among the mechanisms of innate immunity is the mitochondrial production of mediators that stimulate the transcription of inflammatory cytokines and chemokines, or their maturation by inflammasomes [3,4,5]. Oxidative stress produced by infectious processes may cause mitochondrial dysfunction and this alteration may, in turn, produce a further increase in the production of free radicals [6,7]

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