Identification of circulating microRNA profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS
Creators: name: García-Hidalgo, María C.
name: González, Jessica
name: Benítez, Iván D.
name: Carmona, Paola
name: Santisteve, Sally
name: Pérez-Pons, Manel
name: Moncusí-Moix, Anna
name: Gort-Paniello, Clara
name: Rodríguez-Jara, Fátima
name: Molinero, Marta
name: Belmonte, Thalia
name: Torres, Gerard
name: Labarca, Gonzalo
name: Nova-Lamperti, Estefania
name: Caballero, Jesús
name: Bermejo-Martin, Jesús F.
name: Ceccato, Adrián
name: Fernández-Barat, Laia
name: Ferrer, Ricard
name: Garcia-Gasulla, Dario
name: Menéndez, Rosario
name: Motos, Ana
name: Peñuelas, Oscar
name: Riera, Jordi
name: Torres, Antoni
name: Barbé, Ferran
name: de Gonzalo-Calvo, David
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Biophysics
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Physiology
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer
subject: Mental Health

description: There is a limited understanding of the pathophysiology of postacute pulmonary sequelae in severe COVID-19. The aim of current study was to define the circulating microRNA (miRNA) profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS. The study included patients who developed ARDS secondary to SARS-CoV-2 infection (n=167) and a group of infected patients who did not develop ARDS (n=33). Patients were evaluated 3 months after hospital discharge. The follow-up included a complete pulmonary evaluation and chest computed tomography. Plasma miRNA profiling was performed using RT-qPCR. Random forest was used to construct miRNA signatures associated with lung diffusing capacity for carbon monoxide (D<sub>LCO</sub>) and total severity score (TSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted. D<sub>LCO</sub>&lt;80% predicted was observed in 81.8% of the patients. TSS showed a median [P<sub>25</sub>;P<sub>75</sub>] of 5 [2;8]. The miRNA model associated with D<sub>LCO</sub> comprised miR-17-5p, miR-27a-3p, miR-126-3p, miR-146a-5p and miR-495-3p. Concerning radiologic features, a miRNA signature composed by miR-9-5p, miR-21-5p, miR-24-3p and miR-221-3p correlated with TSS values. These associations were not observed in the non-ARDS group. KEGG pathway and GO enrichment analyses provided evidence of molecular mechanisms related not only to profibrotic or anti-inflammatory states but also to cell death, immune response, hypoxia, vascularization, coagulation and viral infection. In conclusion, diffusing capacity and radiological features in survivors from SARS-CoV-2-induced ARDS are associated with specific miRNA profiles. These findings provide novel insights into the possible molecular pathways underlying the pathogenesis of pulmonary sequelae. <b>Trial registration:</b>ClinicalTrials.gov identifier: NCT04457505.. <b>Trial registration:</b>ISRCTN.org identifier: ISRCTN16865246..