Usefulness of the Measurement of Serum Paraoxonase-1 Arylesterase Activity in the Diagnoses of COVID-19

Abstract

The development of inexpensive, fast, and reliable screening tests for COVID-19 is, as yet, an unmet need. The present study was aimed at evaluating the usefulness of serum arylesterase activity of paraoxonase-1 (PON1) measurement as a screening test in patients with different severity levels of COVID-19 infection. We included 615 COVID-19-positive patients who were classified as asymptomatic, mildly symptomatic, severely symptomatic, or fatally symptomatic. Results were compared with 50 healthy volunteers, 330 patients with cancer, and 343 with morbid obesity. Results showed PON1 activity greatly decreased in COVID-19 compared to healthy volunteers; a receiver operating characteristics plot showed a high diagnostic accuracy. The degree of COVID-19 severity did not influence PON1 levels. Our results indicated that PON1 determination was efficient for disease diagnosis, but not for prognosis. Furthermore, patients with obesity or cancer presented alterations similar to those of COVID-19 patients. As such, elevated levels of PON1 indicate the absence of COVID-19, but low levels may be present in various other chronic diseases. The assay is fast and inexpensive. We suggest that PON1 measurement could be used as an initial, high cut-off point screening method, while lower values should be confirmed with the more expensive nucleic acid amplification test.

Plasma Proteomics Elucidated a Protein Signature in COVID-19 Patients with Comorbidities and Early-Diagnosis Biomarkers

“…Previous LC-MS/MS proteomics studies determined an increase in PON1 levels along the first month of infection, as well as a decrease in severity [30,37]. While our study and previous proteomics analysis measured the total PON1 protein abundance, another study showed that PON1 enzymatic activity is reduced in COVID-19, cancer, and obesity compared to healthy controls [51]. In contrast, GPX3 was decreased in COVID-19 patients with comorbidities-consistent with previous reports-which revealed lower glutathione peroxidase activity due to the SARS-CoV-2 infection [52] as well as Epstein-Barr virus infection in diabetic patients [53].…”

Modulatory Effect of Lifestyle-Related, Environmental and Genetic Factors on Paraoxonase-1 Activity: A Review

“…A study by Cho [80] provided similar results, as HDLs isolated from severe COVID-19 patients were deprived of their protective effect on endothelial cells and displayed a great loss in anti-inflammatory and antioxidant activity. Preliminary data obtained from a small, hospitalized group by Rodríguez-Tomàs et al [81], confirmed later by a larger study involving over 1300 subjects divided into study and control groups [82], have shown that serum PON1 AREase activity in COVID-19 patients drops to about half the value characteristic for healthy individuals. The concurrent increase in PON1 concentration is in all likelihood related to the upregulation of its synthesis in order to balance its insufficient enzymatic activity.…”

Serum oxidant, antioxidant, and paraoxonase levels in COVID-19 patients

“…PON1 is a lipoperoxide hydrolase that breaks down lipoperoxides in lipoproteins and cells, participating in the individual's innate immune system and defense against oxidative stress 26,27 . Decreased PON1 activity has been reported in bacterial infections [28][29][30] and viral infections such as COVID-19 25 . When routine laboratory findings of COVID-19 are examined, an increase in inflammatory biomarkers such as CRP, procalcitonin, ferritin, and LDH, lymphocytopenia in complete blood count, leukocytopenia and thrombocytosis are observed 31,32 .…”

“…The Paraoxonase enzyme family includes three antioxidant isoenzymes, PON-1, PON-2, and PON-3. In recent studies, it has been reported that PON1 concentration decreases in diseases associated with increased oxidative stress, including COVID-19 24,25 .…”