Work

Resolvin E1-Chemerin receptor 1 axis is dysregulated in critical COVID-19 patients

Year: 2025

Type: article

Abstract: Resolvin E1 (RvE1) and Resolvin D1 (RvD1) are key resolvins implicated in inflammation resolution of respiratory and infectious diseases. In contrast to cytokines, they have been scarcely explored in COVID-19 and their ability for discriminating COVID-19 severity and patient outcomes has not been compared with that of cytokines. Therefore, among a panel comprising cytokines (interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor alpha, interferon gamma and granulocyte-macrophage colony-stimulating factor), RvD1 and RvE1 and their respective receptors (FPR2, Chemerin 1 ), we evaluated which mediators better distinguished COVID-19 severity, the need of mechanical ventilation and patient mortality. Blood was collected from 61 patients with “severe” ( n = 27), “critical” ( n = 17) and “critical on veno-venous extracorporeal membrane oxygenation (VV-ECMO)” (n = 17) COVID-19 at admission, days 3–4 and days 5–8, and from controls ( n = 23) at a single time point. We measured cytokines by multiplex immunoassays, resolvins by enzyme-linked immunosorbent assays, and FPR2 and Chemerin 1 mRNA by real-time quantitative polymerase chain reaction. We obtained principal component analysis (PCA)/partial least squares discriminant analysis (PLS-DA) models significantly differentiating ( P < 0.001): controls from each patient group; “severe” from all critical patients; patients without or with mechanical ventilation, and survivors from non-survivors. RvE1 consistently showed a variable importance in projection (VIP) score > 2.5 and a p(corr) >0.8, being the most relevant discriminating variable. Univariate and repeated measures multivariate analyses showed higher RvE1 in “critical on VV-ECMO”, mechanically ventilated patients and non-survivors, while Chemerin 1 exhibited an opposite profile. RvE1 positively correlated with inflammation and partial pressure of CO 2 , whereas Chemerin 1 correlated with lower inflammation, better respiratory function and lower hospital length of stay. We conclude that RvE1 was the mediator best distinguishing COVID-19 severity and that RvE1-Chemerin 1 axis is dysregulated in this disease. • Serum RvE1 distinguishes COVID-19 severity better than proinflammatory cytokines. • Critical on VV-ECMO COVID-19 patients have higher serum RvE1 and lower Chemerin 1 mRNA. • Mechanically ventilated patients have higher serum RvE1 and lower Chemerin 1 mRNA. • COVID-19 mortality is associated with higher serum RvE1 and lower Chemerin 1 mRNA. • Serum RvE1 and Chemerin 1 mRNA correlate with lung function in COVID-19 patients.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2025.115669