scholarly journals Soluble angiotensin-converting enzyme 2 as a prognostic biomarker for disease progression in patients infected with SARS-CoV-2

Author(s):  
Noelia Diaz Troyano ◽  
Pablo Gabriel Medina ◽  
Stephen Weber ◽  
Martin Klammer ◽  
Raquel Barquin-DelPino ◽  
...  

Background: There is a need for better prediction of disease severity in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble angiotensin-converting enzyme 2 (sACE2) arises from shedding of membrane ACE2 (mACE2) that is known to be a receptor for the spike protein of SARS-CoV-2; however, its value as a biomarker for disease severity is unknown. This study evaluated the predictive value of sACE2 in the context of other known biomarkers of inflammation and tissue damage (C-reactive protein [CRP], growth/differentiation factor-15 [GDF-15], interleukin-6 [IL-6], and soluble fms-like tyrosine kinase-1 [sFlt-1]) in patients with and without SARS-CoV-2 with different clinical outcomes. Methods: For univariate analyses, median differences between biomarker levels were calculated for the following patient groups classified according to clinical outcome: reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 positive (Groups 1 – 4); RT-PCR-confirmed SARS-CoV-2 negative following previous SARS-CoV-2 infection (Groups 5 and 6); and RT-PCR-confirmed SARS-CoV-2 negative controls (Group 7). Results: Median levels of CRP, GDF-15, IL-6, and sFlt-1 were significantly higher in patients with SARS-CoV-2 who were admitted to hospital compared with patients who were discharged (all p<0.001), whereas levels of sACE2 were significantly lower (p<0.001). Receiver operating characteristic curve analysis of sACE2 provided cut-offs for the prediction of hospital admission of ≤0.05 ng/mL (positive predictive value: 89.1%) and ≥0.42 ng/mL (negative predictive value: 84.0%). Conclusion: These findings support further investigation of sACE2, either as a single biomarker or as part of a panel, to predict hospitalisation risk and disease severity in patients infected with SARS-CoV-2.

Author(s):  
Aliye Çelikkol ◽  
Eda Çelik Güzel ◽  
Mustafa Doğan ◽  
Berna Erdal ◽  
Ahsen Yilmaz

Abstract Objectives As a result of developed generalized inflammation, the main prognostic factor determining morbidity and mortality in coronavirus disease 2019 (COVID-19) patients is acute respiratory distress syndrome. The purpose of our study was to define (1) the laboratory tests that will contribute to the diagnosis and follow-up of COVID-19 patients, (2) the differences between the laboratory-confirmed (LC), unconfirmed (LUC), and control (C) groups, and (3) the variation between groups of acute-phase reactants and biomarkers that can be used as an indicator of disease severity and inflammation. Materials and Methods A total of 102 patients undergoing treatment with COVID-19 interim guidelines were evaluated. Reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive in 56 (LC), classified as mild or severe, and negative in 46 (LUC) patients. In addition, 30 healthy subjects (C) with negative RT-PCR tests were also evaluated.All statistical analyses were performed with the SPSS 22.0 program and the p-values for significant findings were less than 0.05. Parametric/nonparametric distribution was determined by performing the Kolmogorov–Smirnov test for all groups. Student's t-test was used for variables with parametric distribution and the Mann–Whitney U-test for variables with the nonparametric distribution. A cut-off level for biomarkers was determined using the ROC (receiver operator characteristic) curve. Results In the LC group, platelet, platecrit, mean platelet volume, platelet diameter width, white blood cell, lymphocyte, eosinophil, neutrophil, immature granulocyte, immature lymphocyte, immature monocyte, large immune cell, and atypical lymphocyte counts among the complete blood count parameters of mature and immature cell counts showed a significant difference according to the C and LUC groups. C-reactive protein, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and C-reactive protein-to-albumin ratio (CAR) indices were significantly elevated in LC patients and were significantly higher in patients classified as severe compared to mild. When CAR optimal cutoff was determined as 0.475, area under the curve was 0.934, sensitivity was 90.91%, specificity was 86.21%, positive predictive value was 92.59%, and negative predictive value was 83.33%. The diagnostic accuracy for CAR was 89.29%. Conclusion The CAR index with the highest diagnostic value and the highest predictability could be the most useful biomarker in the diagnosis and evaluation of disease severity in COVID-19 patients.


2020 ◽  
Vol 130 ◽  
pp. 161-162 ◽  
Author(s):  
Ying Xuan Gue ◽  
Rahim Kanji ◽  
Vias Markides ◽  
Diana Adrienne Gorog

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>


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