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Thus, new therapeutic alternatives are needed. Some in silico analyses, including the role of microRNAs, have shown promising results, but they are based on computational simulations and predictions, so their consistency with real-world results may vary. This study investigated the potential of three miRNAs (miR-196a-5p, miR-98-5p, and miR-27a-3p) obtained from published bioinformatics results as promising biomarkers for different aspects of COVID-19 (susceptibility, severity, and therapeutic possibilities). The current study found that, serum levels of these miRNAs were significantly elevated in COVID-19 patients compared to healthy controls, particularly during the third wave patients which is contrast to that reported in In silico study regarding miR-98-5p. Additionally, serum levels of inflammatory markers such as interleukin \u2212\u20096 (IL-6) and hypoxia inducible factor- 1 \u03b1 (HIF-1\u03b1) were higher in patients compared to healthy control. miR-196a-5p exhibited high sensitivity and specificity for COVID-19 diagnosis. Finally, we highlight the necessity of validating microRNAs in patient serum, as our findings show that their differential expression is robust and independent of the initial predictive model. This study effectively translates a bioinformatics hypothesis into a verifiable biomarker through experimental validation regardless of the contradictory findings between hypothesis and the actual results.<\/jats:p>","DOI":"10.1007\/s10238-025-02028-9","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T09:04:26Z","timestamp":1768986266000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Translational MicroRNA research in COVID-19: bridging in Silico prediction with clinical biomarker potential"],"prefix":"10.1007","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5745-8296","authenticated-orcid":false,"given":"Fathia Z.","family":"El Sharkawi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa A.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3539-5703","authenticated-orcid":false,"given":"Karim","family":"Montasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4527-7532","authenticated-orcid":false,"given":"Mamdouh M.","family":"Mahdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8593-9137","authenticated-orcid":false,"given":"Hanaa B.","family":"Atya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"2028_CR1","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/inm.12726","volume":"29","author":"K Usher","year":"2020","unstructured":"Usher K, Durkin J, Bhullar N. 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