Chemerin plasma levels are increased in COVID-19 patients and are an independent risk factor of mortality

Abstract

BackgroundChemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value.MethodsBlood samples from confirmed COVID-19 patients were collected at day 1, 5 and 14 from admission to Erasme Hospital (Brussels – Belgium). Chemerin concentrations and inflammatory biomarkers were analyzed in the plasma. Blood cells subtypes and their expression of ChemR23 were determined by flow cytometry. The expression of chemerin and ChemR23 was evaluated on lung tissue from autopsied COVID-19 patients by immunohistochemistry (IHC).Results21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. Plasma chemerin concentration were significantly higher in ICU patients than in HC at all time-points analyzed (p<0.0001). Moreover, they were higher in deceased patients compared to survivors (p<0.05). Logistic univariate regression and multivariate analysis demonstrated that chemerin level at day 14 of admission was an independent risk factor for death. Accordingly, chemerin levels correlated with inflammatory biomarkers such as C-reactive protein and tumor necrosis factor α. Finally, IHC analysis revealed a strong expression of ChemR23 on smooth muscle cells and chemerin on myofibroblasts in advanced acute respiratory distress syndrome (ARDS).DiscussionIncreased plasma chemerin levels are a marker of severity and may predict death of COVID-19 patients. However, multicentric studies are needed, before chemerin can be considered as a biomarker of severity and death used in daily clinical practice. Further studies are also necessary to identify the precise mechanisms of the chemerin/ChemR23 system in ARDS secondary to viral pneumonia.

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

“…Furthermore, we did not assess the isoforms of chemerin, and the changes in chemerin isoforms may be relevant in different clinical conditions. Finally, there was a difference between chemerin concentration measured using multiplex immunofluorescence assay in the present study in comparison to the previous studies [ 14 , 17 ], which determined chemerin by conventional enzyme-linked immunosorbent assay (ELISA). On the other hand, the differences between the cytokine measurements performed by multiplex methods and ELISA have been previously reported, but with high concordance correlations between the methods [ 45 ].…”

“…There is a paucity of data regarding the kinetics of biomarkers during acute COVID-19 infection, including adipokines. The results of the existing studies are often inconsistent, with some studies reporting higher levels of chemerin [ 14 ], resistin [ 15 ], adiponectin [ 16 ], while others show lower levels of chemerin [ 17 ], and similar concentrations of adiponectin in COVID-19 patients as compared with non-COVID-19 patients [ 18 ].…”

Adipokines as Diagnostic and Prognostic Markers for the Severity of COVID-19

“…Plasma chemerin concentrations correlated with the amount of inflammatory markers CRP and tumour necrosis factor (TNF). Plasma chemerin levels on Day 1 did not differ between patients when classified into non-hospitalized, hospitalized in conventional care unit or hospitalized in intensive care unit [62]. This changed on Day 14 with hospitalized patients displaying higher chemerin levels compared to patients with mild disease.…”

Crucial Regulatory Role of Organokines in Relation to Metabolic Changes in Non-Diabetic Obesity

“…These and other investigations suggested a mechanistic influence of chemerin over blood pressure and hypertension [ 26 ]. In addition, in COVID-19 patients, elevated plasma chemerin was found to be a marker of disease severity and suggested to be an independent risk factor for the mortality [ 27 ]. Therefore, determination of serum chemerin could be an excellent disease marker in the daily clinical practice both in diseases with low-grade inflammation and in acute illnesses.…”