{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:04:14Z","timestamp":1790114654522,"version":"4.0.1"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>The post\u2010acute sequelae of SARS\u2010CoV\u20102 infection pose a significant global challenge, with nearly 50% of critical COVID\u201019 survivors manifesting persistent lung abnormalities. The lack of understanding about the molecular mechanisms and effective treatments hampers their management. Here, we employed microRNA (miRNA) profiling to decipher the systemic molecular underpinnings of the persistent pulmonary complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>We conducted a longitudinal investigation including 119 critical COVID\u201019 survivors. A comprehensive pulmonary evaluation was performed in the short\u2010term (median\u2009=\u200994.0\u00a0days after hospital discharge) and long\u2010term (median\u2009=\u2009358\u2009days after hospital discharge). Plasma miRNAs were quantified at the short\u2010term evaluation using the gold\u2010standard technique, RT\u2010qPCR. The analyses combined machine learning feature selection techniques with bioinformatic investigations. Two additional datasets were incorporated for validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      In the short\u2010term, 84% of the survivors exhibited impaired lung diffusion (D\n                      <jats:sub>LCO<\/jats:sub>\n                      \u00a0&lt;\u200980% of predicted). One year post\u2010discharge, 54.4% of this patient subgroup still presented abnormal D\n                      <jats:sub>LCO<\/jats:sub>\n                      . Four feature selection methods identified two specific miRNAs, miR\u20109\u20105p and miR\u2010486\u20105p, linked to persistent lung dysfunction. The downstream experimentally validated targetome included 1473 genes, with heterogeneous enriched pathways associated with inflammation, angiogenesis and cell senescence. Validation studies using RNA\u2010sequencing and proteomic datasets emphasized the pivotal roles of cell migration and tissue repair in persistent lung dysfunction. The repositioning potential of the miRNA targets was limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Our study reveals early mechanistic pathways contributing to persistent lung dysfunction in critical COVID\u201019 survivors, offering a promising approach for the development of targeted disease\u2010modifying agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LINKED ARTICLES<\/jats:title>\n                    <jats:p>\n                      This article is part of a themed issue Non\u2010coding RNA Therapeutics. To view the other articles in this section visit\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v182.2\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v182.2\/issuetoc<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16330","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T18:29:55Z","timestamp":1708021795000},"page":"380-395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["MicroRNA\u2010guided drug discovery for mitigating persistent pulmonary complications in critical COVID\u201019 survivors: A longitudinal pilot study"],"prefix":"10.1111","volume":"182","author":[{"given":"Mar\u00eda C.","family":"Garc\u00eda\u2010Hidalgo","sequence":"first","affiliation":[{"name":"Translational Research in Respiratory 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