Soluble Angiotensin-Converting Enzyme 2 as a Prognostic Biomarker for Disease Progression in Patients Infected with SARS-CoV-2
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Abstract
Predicting disease severity in patients infected with SARS-CoV-2 is difficult. Soluble angiotensin-converting enzyme 2 (sACE2) arises from the shedding of membrane ACE2 (mACE2), which is a receptor for SARS-CoV-2 spike protein. We evaluated the predictive value of sACE2 compared with known biomarkers of inflammation and tissue damage (CRP, GDF-15, IL-6, and sFlt-1) in 850 patients with and without SARS-CoV-2 with different clinical outcomes. For univariate analyses, median differences between biomarker levels were calculated for the following patient groups (classified by clinical outcome): 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 ‘SARS-CoV-2 unexposed’ patients (Group 7). Median levels of CRP, GDF-15, IL-6, and sFlt-1 were significantly higher in hospitalized patients with SARS-CoV-2 compared with discharged patients (all p < 0.001), whereas levels of sACE2 were significantly lower (p < 0.001). ROC curve analysis of sACE2 provided cut-offs for predicting hospital admission (≤0.05 ng/mL (positive predictive value: 89.1%) and ≥0.42 ng/mL (negative predictive value: 84.0%)). These findings support further investigation of sACE2, as a single biomarker or as part of a panel, to predict hospitalization risk and disease severity in patients with SARS-CoV-2 infection.
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SciScore for 10.1101/2021.10.13.21264901: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study complied with the principles of the Declaration of Helsinki and received approval (reference: PR [AG] 577/2020) from the Research Ethics Committee for Drug Research of the Vall d’Hebron University Hospital (Barcelona
Consent: An exemption from obtaining patient informed consent was granted by the Research Ethics Committee due to the health emergency presented by the COVID-19 pandemic.Sex as a biological variable The statistical significance of the differences in demographic and biochemical variables was assessed using: Chi-squared test (male sex, chronic kidney disease, blood pressure, type 2 diabetes mellitus, dyslipidaemia, and body mass index), one way ANOVA (age and mean … SciScore for 10.1101/2021.10.13.21264901: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study complied with the principles of the Declaration of Helsinki and received approval (reference: PR [AG] 577/2020) from the Research Ethics Committee for Drug Research of the Vall d’Hebron University Hospital (Barcelona
Consent: An exemption from obtaining patient informed consent was granted by the Research Ethics Committee due to the health emergency presented by the COVID-19 pandemic.Sex as a biological variable The statistical significance of the differences in demographic and biochemical variables was assessed using: Chi-squared test (male sex, chronic kidney disease, blood pressure, type 2 diabetes mellitus, dyslipidaemia, and body mass index), one way ANOVA (age and mean arterial pressure), and Kruskal-Wallis comparison (aspartate aminotransferase, alanine aminotransferase, prothrombin time, and D-dimer). Randomization Serum samples were collected from participants in a random series from March to October 2020 and frozen until analysis. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:A limitation of this study is the single-centre design and under-representation of certain groups (i.e., patients infected with SARS-CoV-2 who were discharged and controls). In addition, the patients recruited with mild symptoms of SARS-CoV-2 infection were relatively complicated in terms of their clinical presentation, as they were recruited from the emergency department. It was not possible to obtain samples from patients with mild symptoms that did not require hospital treatment due to the public health recommendation to stay at home during the period of this study. Additionally, sACE2 measurements in this study were performed using a non-commercial kit for which the quality specifications are not as robust as those of the other markers used in clinical practice. Future validation of the present biomarker measurements in an independent cohort of patients is warranted. In particular, longitudinal studies of sACE2 levels in patients who have recovered from severe SARS-CoV-2 infection are required to confirm if sACE2 levels increase after a total recovery of symptoms or if they are permanently reduced following severe SARS-CoV-2 infection. Furthermore, characterisation of sACE2 levels is required in a younger population, in individuals with and without hypertension and chronic kidney disease, and in patients receiving treatments that may affect sACE2 activity or concentration (i.e., ACE inhibitors or angiotensin receptor blockers). In conclusion, the present findings support ...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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