Evaluation of urinary cysteinyl leukotrienes as biomarkers of severity and putative therapeutic targets in COVID-19 patients

Abstract

Introduction: Despite the likely involvement of cysteinyl leukotrienes (CysLTs) in progressing COVID-19, they remain scarcely explored in this context. We aimed to evaluate urinary CysLT (U-CysLTs) as severity biomarkers and putative therapeutic targets in hospitalized COVID-19 patients. The impact of hypertension and veno-venous extracorporeal membrane oxygenation (VV-ECMO) on U-CysLTs was also assessed. Patients and methods: Blood and spot urine were collected in "severe" (n=27), "critically ill" (n=17) and "criticallly ill on VV-ECMO" (n=17) patients with COVID-19 at days 1-2 (admission), 3-4, 5-8 and weekly thereafter, and in controls (blood donors, n=23) at a single time point. U-CysLT were measured by ELISA. Prognostic scores and outcomes were also evaluated. Results: Although there were no differences on U-CysLTs between groups at admission, they were markedly increased at days 3-4 and 5-8 in "critically ill on VV-ECMO" patients compared to severe patients (p<0.010). Among "critically ill on VV-ECMO" patients, those who were hypertensive had higher U-CysLT values (p<0.05 vs normotensives, at days 5-8). Along hospitalization, U-CysLTs significantly increased in critical groups, but not in "severe" patients. U-CysLTs values during the first hospitalization week were positively correlated with ICU and total hospital length of stay among all critically ill patients, being also significantly higher in non-survivors than in survivors when comparing all patient groups. Conclusions: Critical COVID-19 is associated with increased U-CysLTs during hospitalization, especially in hypertensive patients on VV-ECMO. The positive association of U-CysLTs with severe outcomes underlines their usefulness as biomarkers for risk stratification and prognostication and also as therapeutic targets.