Involvement of the chemerin-ChemR23 system in severe COVID-19 patients

Abstract

Background: ChemR23 knock-out mice displays aggravated viral pneumonia, with similar features as observed in severe COVID-19 patients.

Aims and objectives: We evaluated the involvement of the chemerin-ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic role.

Methods: Blood 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).

Results: 21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. The concentration of chemerin in plasma was significantly higher in ICU patients vs HC at any time-point (p<.0001) and also when comparing deceased patients vs survivors (p=.02). In line with that, chemerin levels correlated with inflammatory biomarkers such as C-reactive protein, interleukin-6 and tumour necrosis factor α. Plasmacytoid dendritic cells and natural killers (NK) cells were strongly decreased in hospitalized and ICU COVID 19 patients. On NK cells of all COVID 19 patients, the expression of ChemR23 was reduced regardless its severity. Moreover, IHC analysis showed a strong expression of ChemR23 on smooth muscle cells and chemerin on myofibroblasts during the organizing phase of acute respiratory distress syndrome (ARDS).

Conclusions: Chemerin is an early marker of severity in COVID-19 patients and could be involved in lung fibrosis post-ARDS.