3ce4ba631964cd0aae25bad9934516c2 pmc_9031748.pdf ccbf422c6369dd242d1a125db5c31cb25a8b4170 pmc_9031748.pdf 239837b7dc690f8b0f04ed36185e8b5c0e84e4ef980545dff8406ce31ac82aa9 pmc_9031748.pdf Title: Soluble Angiotensin-Converting Enzyme 2 as a Prognostic Biomarker for Disease Progression in Patients Infected with SARS-CoV-2 Subject: 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. Keywords: disease severity; COVID-19; SARS-CoV-2; angiotensin-converting enzyme 2; SARS-CoV-2 spike protein; biomarkers; inflammation Author: Noelia Díaz-Troyano, Pablo Gabriel-Medina, Stephen Weber, Martin Klammer, Raquel Barquín-DelPino, Laura Castillo-Ribelles, Angels Esteban, Manuel Hernández-González, Roser Ferrer-Costa, Tomas Pumarola and Francisco Rodríguez-Frías Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Apr 6 14:47:36 2022 CEST ModDate: Wed Apr 6 14:57:37 2022 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2792677 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SSNIUI+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 CRPIXE+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 UKBQYD+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 ZZWLMU+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 MIJDGD+CMSY10 Type 1 Builtin yes yes no 28 0 MXTWPO+VnURWPalladioL Type 1 Custom yes yes no 32 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 40 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 44 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 48 0 BXZUUH+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 60 0 RLYTRW+CMMI10 Type 1 Builtin yes yes no 91 0 GIGFZE+CMR10 Type 1 Builtin yes yes no 95 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 102 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-05-18 03:25:23 CEST RepresentationInformation: pmc_9031748.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-05-18 02:37:47 CEST Size: 2792677 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 271 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Design and Ethical Statement Destination: subsection.2.1 Item: Title: Patients Destination: subsection.2.2 Item: Title: Sample Handling Destination: subsection.2.3 Item: Title: Assays Destination: subsection.2.4 Item: Title: Data Analysis Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Patients Destination: subsection.3.1 Item: Title: Univariate Analysis of Patients Infected with SARS-CoV-2 versus ‘SARS-CoV-2 Unexposed’ Patients Destination: subsection.3.2 Item: Title: Univariate and Bivariate Analysis of Patients Infected with SARS-CoV-2 Who Were Admitted to Hospital versus Patients Infected with SARS-CoV-2 Who Were Discharged Destination: subsection.3.3 Item: Title: Univariate Analysis of Patients Infected with SARS-CoV-2 Who Were Admitted to the ICU or Died versus Patients Infected with SARS-CoV-2 Who Were Admitted to the Ward or Discharged Destination: subsection.3.4 Item: Title: Patients Who Were RT-PCR-Confirmed Negative for SARS-CoV-2 Infection Following a Previous Positive RT-PCR Result Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.4 Info: Title: Soluble Angiotensin-Converting Enzyme 2 as a Prognostic Biomarker for Disease Progression in Patients Infected with SARS-CoV-2 Author: Noelia Díaz-Troyano, Pablo Gabriel-Medina, Stephen Weber, Martin Klammer, Raquel Barquín-DelPino, Laura Castillo-Ribelles, Angels Esteban, Manuel Hernández-González, Roser Ferrer-Costa, Tomas Pumarola and Francisco Rodríguez-Frías Subject: 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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