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

Abstract

Background Cysteinyl leukotrienes (CysLT) are potent inflammation-promoting mediators, but remain scarcely explored in COVID-19. We evaluated urinary CysLT (U-CysLT) relationship with disease severity and their usefulness for prognostication in hospitalized COVID-19 patients. The impact on U-CysLT of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and of comorbidities such as hypertension and obesity was also assessed. Methods Blood and spot urine were collected in “severe” (n = 26), “critically ill” (n = 17) and “critically 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 (n = 23) at a single time point. U-CysLT were measured by ELISA. Routine markers, prognostic scores and outcomes were also evaluated. Results U-CysLT did not differ between groups at admission, but significantly increased along hospitalization only in critical groups, being markedly higher in VV-ECMO patients, especially in hypertensives. U-CysLT values during the first week were positively associated with ICU and total hospital length of stay in critical groups and showed acceptable area under curve (AUC) for prediction of 30-day mortality (AUC: 0.734, p = 0.001) among all patients. Conclusions U-CysLT increase during hospitalization in critical COVID-19 patients, especially in hypertensives on VV-ECMO. U-CysLT association with severe outcomes suggests their usefulness for prognostication and as therapeutic targets.

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

“…Relatively few reports have focused on eicosanoids, less abundant oxylipins that act locally, but are nonetheless powerful modulators of the immune response 4 . Elevated levels of eicosanoids have been reported in plasma, 21 tracheal aspirate, 22 urine 23 and in stimulated peripheral blood monocytes 24 of patients with severe COVID‐19. Snider et al 25 .…”

“…[11][12][13][14][15][16][17][18][19][20] Relatively few reports have focused on eicosanoids, less abundant oxylipins that act locally, but are nonetheless powerful modulators of the immune response. 4 Elevated levels of eicosanoids have been reported in plasma, 21 tracheal aspirate, 22 urine 23 and in stimulated peripheral blood monocytes 24 of patients with severe COVID-19. Snider et al 25 proposed the eicosanoid generating enzyme, group IIA secretory (s) phospholipase (PL)A 2 , as a marker of disease severity in COVID-19.…”

Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis

“…Relatively few reports have focused on eicosanoids, less abundant oxylipins that act locally, but are nonetheless powerful modulators of the immune response (4). Elevated levels of eicosanoids have been reported in plasma (21), tracheal aspirate (22), urine (23) and in stimulated peripheral blood monocytes (24) of patients with severe COVID-19. Snider et al (25) proposed the eicosanoid generating enzyme, group IIA secretory (s) phospholipase (PL)A2, as a marker of disease severity in COVID-19.…”