{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:45:25Z","timestamp":1784133925831,"version":"3.55.0"},"reference-count":15,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007615","name":"Imam Abdulrahman Bin Faisal University","doi-asserted-by":"publisher","award":["Rawabi Scientific Chair for Regenerative and Precision Medicine"],"award-info":[{"award-number":["Rawabi Scientific Chair for Regenerative and Precision Medicine"]}],"id":[{"id":"10.13039\/501100007615","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Although circular RNAs are increasingly implicated in host responses, their longitudinal behaviors to predict outcomes in severe COVID-19 remain unclear. The purpose of this study is to distinguish the circRNA signature associated with COVID-19 outcome. Method: Public total RNA-seq data from GEO (GSE273149) were used to assess circRNA differences among COVID-19 non-survivors, COVID-19 survivors, and patients with acute respiratory distress syndrome (ARDS) serving as severity-matched disease controls at two timepoints: Early (Day 3) and Late (Days 7 to 10). Differential expression was assessed after quality filtering, with the results reported as significant (FDR &lt; 0.05) or suggestive (0.05\u20130.10); |log2FC| \u2265 1 was used as a guide for interpretation. Early and Late effects were combined using a two-timepoint, precision-weighted approach to prioritize time-consistent signals. Results: A distinction between non-survivors and survivors was observed, with nine significant and four suggestive candidates identified in the combined analysis; in addition, some candidates indicated a difference between survivors and ARDS controls. Early and Late effects primarily occurred in the same direction, and several circRNAs that were borderline at one timepoint became significant when the two timepoints were combined. Conclusion: This time-resolved, precision-weighted analysis of public RNA-seq data reveals stable circRNA differences between key clinical groups (patients with severe COVID-19 and those with ARDS), improving detection and interpretability relative to single-timepoint tests and yielding a concise set of candidates suitable for mechanistic follow-up and potential biomarker development.<\/jats:p>","DOI":"10.3390\/genes17010034","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:05:01Z","timestamp":1767193501000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["circRNA Signatures Distinguishing COVID-19 Outcomes and Acute Respiratory Distress Syndrome: A Longitudinal, Two-Timepoint, Precision-Weighted Analysis of a Public RNA-Seq Cohort"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5384-8764","authenticated-orcid":false,"given":"Alawi","family":"Habara","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41579-023-00878-2","article-title":"The evolution of SARS-CoV-2","volume":"21","author":"Markov","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chung, Y.-S., Lam, C.-Y., Tan, P.-H., Tsang, H.-F., and Wong, S.-C.C. (2024). Comprehensive review of COVID-19: Epidemiology, pathogenesis, advancement in diagnostic and detection techniques, and post-pandemic treatment strategies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158155"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2762582","DOI":"10.1155\/2022\/2762582","article-title":"Hsa_circ_0000479\/Hsa-miR-149-5p\/RIG-I, IL-6 Axis: A potential novel pathway to regulate immune response against COVID-19","volume":"2022","author":"Firoozi","year":"2022","journal-title":"Can. J. Infect. Dis. Med. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"198205","DOI":"10.1016\/j.virusres.2020.198205","article-title":"The role of circular RNAs in viral infection and related diseases","volume":"291","author":"Xie","year":"2021","journal-title":"Virus Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00018-021-04119-8","article-title":"Competing endogenous RNA network mediated by circ_3205 in SARS-CoV-2 infected cells","volume":"79","author":"Barbagallo","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7991","DOI":"10.1038\/s41598-021-86134-0","article-title":"A study of differential circRNA and lncRNA expressions in COVID-19-infected peripheral blood","volume":"11","author":"Wu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s13059-023-03120-7","article-title":"A time-resolved meta-analysis of consensus gene expression profiles during human T-cell activation","volume":"24","author":"Rade","year":"2023","journal-title":"Genome Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1038\/s41467-021-25805-y","article-title":"Differentially expressed genes reflect disease-induced rather than disease-causing changes in the transcriptome","volume":"12","author":"Porcu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1089\/gtmb.2024.0337","article-title":"Immune Regulatory Circular RNAs, circRasGEF1B and circHIPK3, Are Upregulated in Peripheral Blood Mononuclear Cells of COVID-19 Patients","volume":"28","author":"Mirzaei","year":"2024","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e24666","DOI":"10.1002\/jcla.24666","article-title":"Upregulation of hsa_circ_0004812 promotes COVID-19 cytokine storm via hsa-miR-1287-5p\/IL6R, RIG-I axis","volume":"36","author":"Mohammadisoleimani","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/s41392-023-01669-0","article-title":"Non-coding RNAs expression in SARS-CoV-2 infection: Pathogenesis, clinical significance and therapeutic targets","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ayaz, H., Aslam, N., Awan, F.M., Basri, R., Rauff, B., Alzahrani, B., Arif, M., Ikram, A., Obaid, A., and Naz, A. (2023). Mapping CircRNA\u2013miRNA\u2013mRNA regulatory axis identifies hsa_circ_0080942 and hsa_circ_0080135 as a potential theranostic agents for SARS-CoV-2 infection. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0283589"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"D52","DOI":"10.1093\/nar\/gkad770","article-title":"circAtlas 3.0: A gateway to 3 million curated vertebrate circular RNAs based on a standardized nomenclature scheme","volume":"52","author":"Wu","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Eltobgy, M., Johns, F., Farkas, D., Leuenberger, L., Cohen, S.P., Ho, K., Karow, S., Swoope, G., Pannu, S., and Horowitz, J.C. (2024). Longitudinal transcriptomic analysis reveals persistent enrichment of iron homeostasis and erythrocyte function pathways in severe COVID-19 ARDS. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1397629"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"W319","DOI":"10.1093\/nar\/gkad392","article-title":"miEAA 2023: Updates, new functional microRNA sets and improved enrichment visualizations","volume":"51","author":"Hirsch","year":"2023","journal-title":"Nucleic Acids Res."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/1\/34\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T05:10:29Z","timestamp":1767503429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/1\/34"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,30]]},"references-count":15,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["genes17010034"],"URL":"https:\/\/doi.org\/10.3390\/genes17010034","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,30]]}}}