Fetuin-A Deficiency but Not Pentraxin 3, FGF-21, or Irisin, Predisposes to More Serious COVID-19 Course

Abstract

Analysis of liver biopsy specimens showed that SARS-CoV-2 might have led to liver damage. This study aimed to evaluate the role of selected hepatokines and myokines in the development and progression of COVID-19. Seventy patients with laboratory-confirmed COVID-19 and 20 healthy volunteers were enrolled in the study. Irisin, pentraxin 3, fetuin-A, and FGF-21 serum concentrations and biochemical parameters were assessed using an immunoenzymatic method with commercially available enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) kits. Serum fetuin-A concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers. The serum concentration of FGF-21 was significantly increased in obese COVID-19 patients compared to overweight ones. Moreover, the FGF-21 level was higher in COVID-19 patients diagnosed with metabolic syndrome than in patients without metabolic syndrome. PTX3 concentration was higher in COVID-19 patients with higher HOMA-IR values than those with lower HOMA-IR values. COVID-19 patients with HOMA-IR ≤3 and >3 had significantly lower fetuin-A levels than the control group. Irisin concentration was significantly decreased in the HOMA-IR ≤ 3 COVID-19 subgroup when comparing with the control group. Lower levels of fetuin-A observed in COVID-19 patients despite higher HOMA-IR, CRP, and ferritin levels, pneumonia, patients requiring ICU care suggests that fetuin-A deficiency predisposes to more severe COVID-19 course. Upregulated pentraxin 3 may be used as a potential predictor of COVID-19 severity.

Chemerin as a Potential Marker of Resolution of Inflammation in COVID-19 Infection

“…Different shifts in IL-1β have also been reported in a study by Goncalves et al [ 38 ]. Moreover, we observed that, compared with non-severe COVID-19, severe infection was associated not only with significant baseline up-regulation of inflammatory biomarkers levels (TNFα, IL-1β, PTX3), which is consistent with the results of our previous study [ 39 ], but also with elevated resistin and decreased adiponectin. Resistin is reported to play a role as a pro-inflammatory cytokine, increasing the expression of IL-1, IL-6, IL-12 and TNF-α [ 40 ].…”

The Prognostic Value of Pentraxin-3 in COVID-19 Patients: A Systematic Review and Meta-Analysis of Mortality Incidence

“…Very high levels of PTX3 were found in all COVID-19 individuals with a median of 3.66 ng/mL; in addition, such levels were significantly greater in non-survivors compared to survivors ( p = 0.045) [ 31 ]. Kukla and colleagues estimated several biochemical parameters, including PTX3, using immunoenzymatic methods [ 34 ]. For this purpose, 70 confirmed COVID-19 patients (43 females and 27 males) and 20 healthy volunteers (10 females and 10 males) were enrolled in the study [ 34 ].…”

Plasma Proteomic Variables Related to COVID-19 Severity: An Untargeted nLC-MS/MS Investigation

“…It is known that Fetuin-A serum concentration indeed decreases during the acute inflammatory response via inhibition of cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and it returns to normal values after successful treatment in many systemic and non-inflammatory diseases, such as axial spondyloarthritis and inflammatory bowel disease [ 19 ], rheumatoid arthritis [ 20 ], inflammatory CNS disease [ 21 ] and also in other respiratory pathologies, i.e., chronic obstructive pulmonary disease (COPD), for which it has been considered a candidate biomarker for the prediction and evaluation of worsening conditions [ 22 ]. Kukla et al showed for the first time a significantly lower level of this hepatokine in the serum of COVID-19 patients and advanced a possible role of its deficiency in the development of cytokines storm during SARS-CoV-2 infection and in predisposing to a more severe disease course, independently from confounding factors such as sex, metabolic disorders, lipids level, BMI, respiratory symptoms, or liver injury [ 23 ]. They also observed a significant decrease in the abundance of this protein in COVID-19 patients with pneumonia and in those who required critical care, indicating that lower fetuin-A levels could influence the disease course and may be associated with a predisposition for worse prognosis.…”