Soluble Urokinase Receptor as a Promising Marker for Early Prediction of Outcome in COVID-19 Hospitalized Patients

Napolitano, Filomena; Spigna, Gaetano Di; Vargas, Maria; Iacovazzo, Carmine; Pinchera, Biagio; Cernia, Daniela Spalletti; Ricciardone, Margherita; Covelli, Bianca; Servillo, Giuseppe; Gentile, Ivan; Postiglione, Loredana; Montuori, Nunzia

doi:10.3390/jcm10214914

Cited by 16 publications

(21 citation statements)

References 45 publications

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“…Our data corroborated with findings by Napolitano F et al wherein the authors suggest CKD as a significant risk factor for severity and mortality among ICU COVID-19 Patients [26]. Earlier studies have evaluated the role of suPAR in chronic dis-eases conditions, coronary artery disease severity [27], cardiovascular disease in chronic kidney disease [28] and others like diabetes, cancer and liver disease [22]. Azamet et al, 2020 suggested suPAR may be associated with pathophysiology of AKI in COVID-19 patients [29].…”

Section: Discussionsupporting

confidence: 92%

A comparative analysis of serial measurements of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) and C-reactive protein in patients with moderate COVID-19: a single center study from India

Kakar

Mahapatra

Batra

et al. 2022

Preprint

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Soluble urokinase plasminogen-activator receptor (suPAR) is a secreted protein associated with inflammation and proven its usefulness in triage/risk stratifications. This prospective study aimed to evaluate the utility of suPAR in comparison to C-reactive protein (CRP) in hospitalized moderate COVID-19 patients.This is a prospective comparative study during second pandemic wave. Serum suPAR level and CRP were measured serially in 31 confirmed COVID-19 hospitalized patients (20 males, 11 females) on day-1 (24-hours of admission), day-3 and day-5 using suPARnostic AUTO flex ELISA and Nephelometry (ThermoFischer) respectively. Schapiro Wilk test verified the data distribution; Wilcoxon signed rank test compared CRP and suPAR between deceased/alive subject and identified link between co-morbidity and COVID-19 severity.In our study, the mean age was 61.8 ranging from 28-82 with 9.7% (n=3/31) mortality rate. Deceased patients showed significant higher suPAR levels correlating with increasing severity from day 1 to 5 (p<0.016-0.006) than CRP (p=0.717). Patients with pre-existing co-morbidities showed significantly elevated suPAR levels on days 1-5, especially those with hypertension (HTN;p<0.03) and chronic kidney disease (CKD;p<0.001).In conclusion, levels of suPAR were higher in deceased patients with severe symptoms of COVID-19 during hospitalization and in patients with pre-existing co-morbid conditions, HTN and CKD. This preliminary study provides evidence suggesting that circulating suPAR can be a potential biomarker to assess the severity of COVID 19 compared to CRP.

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Section: Discussionsupporting

confidence: 92%

A comparative analysis of serial measurements of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) and C-reactive protein in patients with moderate COVID-19: a single center study from India

Kakar

Mahapatra

Batra

et al. 2022

Preprint

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“… 9 Research so far has shown that the early identification of COVID‐19 individuals at low or high risk of serious illness may improve patient stratification, but, currently, admission blood biomarkers have only moderate predictive value for COVID‐19 outcome and decision making in the clinical setting. 10 suPAR seems extremely promising as a COVID‐19 prognostic marker and may assist in the early selection of patients who can be discharged and continue self‐isolation at home or must be admitted to the hospital and/or intensive care unit. 10 , 11 , 12 , 13 In order to investigate the prognostic ability of suPAR in COVID‐19, we designed the SPARCOL study to assess whether suPAR measured at hospital admission is associated with illness severity in adult patients hospitalized primarily for COVID‐19.…”

Section: Introductionmentioning

confidence: 99%

“… 10 suPAR seems extremely promising as a COVID‐19 prognostic marker and may assist in the early selection of patients who can be discharged and continue self‐isolation at home or must be admitted to the hospital and/or intensive care unit. 10 , 11 , 12 , 13 In order to investigate the prognostic ability of suPAR in COVID‐19, we designed the SPARCOL study to assess whether suPAR measured at hospital admission is associated with illness severity in adult patients hospitalized primarily for COVID‐19.…”

Section: Introductionmentioning

confidence: 99%

“…COVID‐19 is recognized as a hyperinflammatory syndrome with aberrant immune activation which may lead to cytokine storm and organ damage 9 . Research so far has shown that the early identification of COVID‐19 individuals at low or high risk of serious illness may improve patient stratification, but, currently, admission blood biomarkers have only moderate predictive value for COVID‐19 outcome and decision making in the clinical setting 10 10‐13 .…”

Section: Introductionmentioning

confidence: 99%

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Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

Papagiannakis

Tourlakopoulos

Pagonis

et al. 2022

Eur J Clin Investigation

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Background COVID‐19 disease progression is characterized by hyperinflammation and risk stratification may aid in early aggressive treatment and advanced planning. The aim of this study was to assess whether suPAR and other markers measured at hospital admission can predict the severity of COVID‐19. Methods The primary outcome measure in this international, multi‐centre, prospective, observational study with adult patients hospitalized primarily for COVID‐19 was the association of WHO Clinical Progression Scale (WHO‐CPS) with suPAR, ferritin, CRP, albumin, LDH, eGFR, age, procalcitonin, and interleukin‐6. Admission plasma suPAR levels were determined using the suPARnostic ® ELISA and suPARnostic ® Turbilatex assays. Results Seven hundred and sixty‐seven patients, 440 (57.4%) males and 327 (42.6%) females, were included with a median age of 64 years. Log‐suPAR levels significantly correlated with WHO‐CPS score, with each doubling of suPAR increasing the score by one point ( p < .001). All the other markers were also correlated with WHO‐CPS score. Admission suPAR levels were significantly lower in survivors (7.10 vs. 9.63, 95% CI 1.47–3.59, p < .001). A linear model (SALGA) including suPAR, serum albumin, serum lactate dehydrogenase, eGFR, and age can best estimate the WHO‐CPS score and survival. Combining all five parameters in the SALGA model can improve the accuracy of discrimination with an AUC of 0.80 (95% CI: 0.759–0.836). Conclusions suPAR levels significantly correlated with WHO‐CPS score, with each doubling of suPAR increasing the score by one point. The SALGA model may serve as a quick tool for predicting disease severity and survival at admission.

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“…Both full-length and cleaved forms of uPAR can be subjected to the cleavage of the GPI anchor. This further cut generates soluble forms of uPAR that circulate in the blood at a very low level, but its circulatory level is elevated in cancer and in diverse inflammatory conditions [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Plasminogen Activation System in Platelet Pathophysiology: Emerging Concepts for Translational Applications

Napolitano

Montuori

2022

IJMS

Self Cite

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Traditionally, platelets have been exclusively considered for their procoagulant and antifibrinolytic effects during normal activation of hemostasis. Effectively, activated platelets secrete coagulation factors, expose phosphatidylserine, and promote thrombin and fibrin production. In addition to procoagulant activities, platelets confer resistance of thrombi to fibrinolysis by inducing clot retraction of the fibrin network and release of huge amounts of plasminogen activator inhibitor-1, which is the major physiologic inhibitor of the fibrinolytic cascade. However, the discovery of multiple relations with the fibrinolytic system, also termed Plasminogen Activation System (PAS), has introduced new perspectives on the platelet role in fibrinolysis. Indeed, the activated membrane surface of platelets provides binding sites on which fibrinolytic enzymes can be activated. This review discusses the evidence of the profibrinolytic properties of platelets through the description of PAS components and related proteins that are contained in or bind to platelets. Our analyses of literature data lead to the conclusion that in the initial phase of the hemostatic process, antifibrinolytic effects prevail over profibrinolytic activity, but at later stages, platelets might enhance fibrinolysis through the engagement of PAS components. A better understanding of spatial and temporal characteristics of platelet-mediated fibrinolysis during normal hemostasis could improve therapeutic options for bleeding and thrombotic disorders.

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Soluble Urokinase Receptor as a Promising Marker for Early Prediction of Outcome in COVID-19 Hospitalized Patients

Cited by 16 publications

References 45 publications

A comparative analysis of serial measurements of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) and C-reactive protein in patients with moderate COVID-19: a single center study from India

A comparative analysis of serial measurements of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) and C-reactive protein in patients with moderate COVID-19: a single center study from India

Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

Role of Plasminogen Activation System in Platelet Pathophysiology: Emerging Concepts for Translational Applications

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