Key mechanisms discovered in the persistence of pulmonary sequelae in critically ill COVID-19 patients

Two recent studies led from Lleida have shed light on the mechanisms associated with the persistence of pulmonary sequelae in critically ill COVID-19 patients. The research, which has been published in the scientific journals “Molecular Therapy – Nucleic Acids“ and “British Journal of Pharmacology”, have been coordinated by the researcher of the Translational Research in Respiratory Medicine group of the Biomedical Research Institute of Lleida (IRBLleida), David de Gonzalo, who is also part of Ferran Barbé’s group in the CIBER area of Respiratory Diseases (CIBERES).  

With the increase in the number of people surviving severe cases of COVID-19, there is growing concern about chronic sequelae, particularly those related to the respiratory system, and their social and economic impact on the lives of patients, their families and healthcare systems. In this context, it is essential to identify early those patients with compromised pulmonary recovery and to explore effective therapeutic strategies.

The first study, whose first author is the trainee researcher at the University of Lleida and IRBLleida in the Translational Research in Respiratory Medicine group, Manel Pérez Pons, was based on the evaluation of microRNAs (miRNAs) as prognostic and therapeutic tools in survivors of critical COVID-19. Using patient samples collected during the acute phase of the disease, miRNAs associated with pulmonary sequelae following hospital discharge were identified, which has allowed the establishment of possible therapeutic targets to address these sequelae.

The second study, with researcher María Coronada Gracía Hidalgo as first author, described possible altered biological pathways three months after hospital discharge, associated with the persistence of sequelae even up to one year after follow-up. This research combined the quantification of circulating miRNAs in samples from survivors of critical COVID-19 with machine learning techniques, which allowed the identification of two miRNAs linked to the persistence of sequelae and the genes regulated by these miRNAs. This approach has allowed us to define several molecular mechanisms related to the long-term persistence of respiratory sequelae of severe COVID-19.

“The findings of both studies have a potential impact both on the lives of patients and on healthcare systems, as they could contribute to improving the recovery of lung function in those who have overcome critical clinical pictures of COVID-19,” says David de Gonzalo, highlighting the relevance of these advances in the understanding and treatment of the pulmonary sequelae of the critically ill patient.

This research is part of the multicenter CIBERESUCICOVID project of the Instituto de Salud Carlos III, led by the Translational Research in Respiratory Medicine IRBLleida (Lleida) research group. This group is led by the territorial clinical director of chronic respiratory diseases of the Arnau de Vilanova University Hospital of Lleida (HUAV), Ferran Barbé. The research has been carried out in collaboration with researchers from the Hannover Medical School, the University of La Rioja and the University of Concepción (Chile).

Article reference:

MicroRNA-centered theranostics for pulmoprotection in critical COVID-19. Perez-Pons M, Molinero M, Benítez ID, García-Hidalgo MC, Chatterjee S, Bär C, González J, Torres A, Barbé F, de Gonzalo-Calvo D; CIBERESUCICOVID Project (COV20/00110, ISCIII). Mol Ther Nucleic Acids. 2024 Jan 10;35(1):102118. doi: 10.1016/j.omtn.2024.102118. eCollection 2024 Mar 12. PMID: 38314095. https://pubmed.ncbi.nlm.nih.gov/38314095/

MicroRNA-guided drug discovery for mitigating persistent pulmonary complications in critical COVID-19 survivors: A longitudinal pilot study. García-Hidalgo MC, Benítez ID, Perez-Pons M, Molinero M, Belmonte T, Rodríguez-Muñoz C, Aguilà M, Santisteve S, Torres G, Moncusí-Moix A, Gort-Paniello C, Peláez R, Larráyoz IM, Caballero J, Barberà C, Nova-Lamperti E, Torres A, González J, Barbé F, de Gonzalo-Calvo D. Br J Pharmacol. 2024 Feb 15. doi: 10.1111/bph.16330. PMID: 38359818. https://pubmed.ncbi.nlm.nih.gov/38359818/