MicroRNA-guided drug discovery for mitigating persistent pulmonary complications in critical COVID-19 survivors: A longitudinal pilot study.

Autor: García-Hidalgo MC; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain., Benítez ID; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain., Perez-Pons M; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain., Molinero M; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain., Belmonte T; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain., Rodríguez-Muñoz C; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain., Aguilà M; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain., Santisteve S; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain., Torres G; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain.; Group of Precision Medicine in Chronic Diseases, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain., Moncusí-Moix A; Group of Precision Medicine in Chronic Diseases, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain., Gort-Paniello C; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain., Peláez R; Biomarkers and Molecular Signaling Group, Neurodegenerative Diseases Area Center for Biomedical Research of La Rioja, CIBIR, Logroño, Spain., Larráyoz IM; Biomarkers and Molecular Signaling Group, Neurodegenerative Diseases Area Center for Biomedical Research of La Rioja, CIBIR, Logroño, Spain.; BIAS, Department of Nursing, University of La Rioja, Logroño, Spain., Caballero J; Grup de Recerca Medicina Intensiva, Intensive Care Department Hospital Universitari Arnau de Vilanova, Lleida, Spain., Barberà C; Intensive Care Department, University Hospital Santa María, IRBLleida, Lleida, Spain., Nova-Lamperti E; Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, Universidad de Concepcion, Concepcion, Chile., Torres A; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain.; Pneumology Department, Clinic Institute of Thorax (ICT), Hospital Clinic of Barcelona, Insitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), ICREA, University of Barcelona (UB), Barcelona, Spain., González J; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain., Barbé F; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain., de Gonzalo-Calvo D; Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2025 Jan; Vol. 182 (2), pp. 380-395. Date of Electronic Publication: 2024 Feb 15.
DOI: 10.1111/bph.16330
Abstrakt: Background and Purpose: The post-acute sequelae of SARS-CoV-2 infection pose a significant global challenge, with nearly 50% of critical COVID-19 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.
Experimental Approach: We conducted a longitudinal investigation including 119 critical COVID-19 survivors. A comprehensive pulmonary evaluation was performed in the short-term (median = 94.0 days after hospital discharge) and long-term (median = 358 days after hospital discharge). Plasma miRNAs were quantified at the short-term evaluation using the gold-standard technique, RT-qPCR. The analyses combined machine learning feature selection techniques with bioinformatic investigations. Two additional datasets were incorporated for validation.
Key Results: In the short-term, 84% of the survivors exhibited impaired lung diffusion (D LCO  < 80% of predicted). One year post-discharge, 54.4% of this patient subgroup still presented abnormal D LCO . Four feature selection methods identified two specific miRNAs, miR-9-5p and miR-486-5p, 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-sequencing 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.
Conclusion and Implications: Our study reveals early mechanistic pathways contributing to persistent lung dysfunction in critical COVID-19 survivors, offering a promising approach for the development of targeted disease-modifying agents.
Linked Articles: This article is part of a themed issue Non-coding RNA Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.2/issuetoc.
(© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
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