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

尿液半胱氨酰白三烯作为 COVID-19 患者严重程度生物标志物和推定治疗靶点的评估

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作者:Marta Reina-Couto #, Mariana Roboredo-Madeira #, Patrícia Pereira-Terra, Carolina Silva-Pereira, Sandra Martins, Luísa Teixeira-Santos, Dora Pinho, Andreia Dias, Gonçalo Cordeiro, Cláudia Camila Dias, António Sarmento, Margarida Tavares, João T Guimarães, Roberto Roncon-Albuquerque, José-Artur Paiva

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.

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.

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.

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