5b255ade15985d770be15b2dfc9e9ad2 302125.pdf e5069f0a4aa1f16985082471eedb72f8f07909ba 302125.pdf 266f0d7153c028fe4cf74b1da7c5b9dc1dea0e03605ecdc9359241b8e1ede0ee 302125.pdf Title: Altered Plasma microRNA Signature in Hospitalized COVID-19 Patients Requiring Oxygen Support Subject: To discover potential micro(mi)RNA biomarkers of SARS-CoV-2 infection and disease progression, large-scale deep-sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for SARS-CoV-2 infection (median 13.50 [IQR 9–24] days since symptoms initiation) and 21 healthy noninfected individuals. A total of 1218 different miRNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2-infected patients showed significantly (fold change [FC] > 1.2 and adjusted p [padj] < 0.05) altered expression of 190 miRNAs. The top-10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 10-32 to 2.21 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin, and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found, when patients on high- and low-flow oxygen therapy were compared. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Specific miRNA profiles are associated with COVID-19 prognosis in patients requiring oxygen flow. Keywords: SARS-CoV-2; miRNA; biomarker; COVID-19 prognosis; disease severity Author: Sandra Franco, Lourdes Mateu, Raquel Pluvinet, Jose Francisco Sanchez-Herrero, Ruth Toledo, Lauro Sumoy, Marta Massanella and Miguel Angel Martinez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Thu Feb 22 03:18:51 2024 CET ModDate: Thu Feb 22 03:23:44 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1148089 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YWQWLZ+VnURWPalladioL Type 1 Custom yes yes yes 10 0 JREUDH+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 MZMHQZ+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 WDWUTH+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 SOSCBV+CMSY10 Type 1 Builtin yes yes yes 32 0 SIXRFS+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 48 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 68 0 AYXMDM+EURM10 Type 1 Builtin yes yes yes 76 0 OQRGBG+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 88 0 DABIDC+PalatinoLinotype-Italic TrueType WinAnsi yes yes yes 96 0 ETTYRA+PalatinoLinotype-Bold TrueType WinAnsi yes yes yes 100 0 JTCCJQ+PalatinoLinotype-Roman TrueType WinAnsi yes yes yes 104 0 OQRGBG+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 116 0 DABIDC+PalatinoLinotype-Italic TrueType WinAnsi yes yes yes 124 0 ETTYRA+PalatinoLinotype-Bold TrueType WinAnsi yes yes yes 128 0 JTCCJQ+PalatinoLinotype-Roman TrueType WinAnsi yes yes yes 132 0 OQRGBG+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 147 0 DABIDC+PalatinoLinotype-Italic TrueType WinAnsi yes yes yes 155 0 ETTYRA+PalatinoLinotype-Bold TrueType WinAnsi yes yes yes 159 0 JTCCJQ+PalatinoLinotype-Roman TrueType WinAnsi yes yes yes 163 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-11-07 02:43:53 CET RepresentationInformation: 302125.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-11-06 14:05:02 CET Size: 1148089 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 329 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 Cohort Destination: subsection.2.1 Item: Title: RNA Extraction Destination: subsection.2.2 Item: Title: Small RNA Library Generation and Sequencing Destination: subsection.2.3 Item: Title: miRNA Sequence Analysis Destination: subsection.2.4 Item: Title: Statistical Analysis Destination: subsection.2.5 Item: Title: Results Destination: section.3 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: appendix.A. Info: Title: Altered Plasma microRNA Signature in Hospitalized COVID-19 Patients Requiring Oxygen Support Author: Sandra Franco, Lourdes Mateu, Raquel Pluvinet, Jose Francisco Sanchez-Herrero, Ruth Toledo, Lauro Sumoy, Marta Massanella and Miguel Angel Martinez Subject: To discover potential micro(mi)RNA biomarkers of SARS-CoV-2 infection and disease progression, large-scale deep-sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for SARS-CoV-2 infection (median 13.50 [IQR 9 24] days since symptoms initiation) and 21 healthy noninfected individuals. A total of 1218 different miRNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2-infected patients showed significantly (fold change [FC] > 1.2 and adjusted p [padj] < 0.05) altered expression of 190 miRNAs. The top-10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 10-32 to 2.21 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin, and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found, when patients on high- and low-flow oxygen therapy were compared. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Specific miRNA profiles are associated with COVID-19 prognosis in patients requiring oxygen flow. 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