Alterations in genetic transcription related to respiratory sequelae derived from severe COVID identified

Months after the infection is overcome, patients with respiratory sequelae derived from severe COVID present a specific profile of alterations in genetic transcription. This is demonstrated by a study led by researchers from the Respiratory Diseases area of the CIBER (CIBERES), the Biomedical Research Institute of Lleida (IRBLleida), the Biomedical Research Center of La Rioja (CIBIR) and the University of La Rioja, which publishes the Biomedicine & Pharmacotherapy journal . This panel of genes could constitute a catalog of early biomarkers for the clinical management of these sequelae and contribute to the development of personalized therapies for patients with these manifestations associated with persistent COVID.

In the current post-pandemic context, there is a large number of people suffering from sequelae derived from COVID-19, including respiratory sequelae. In the clinical setting, there is no consensus regarding the management of these sequelae and no specific therapeutic strategies have been described for these patients. For this reason, it is urgent to advance in the understanding of the mechanisms associated with these effects in order to address potential treatments.

In this new study, which is part of the CIBERESUCICOVID project of the Carlos III Health Institute (ISCIII), the CIBERES researchers and the Translational Research in Respiratory Medicine research groups of the IRBLleida (Lleida), Biomarkers and Molecular Signaling of the CIBIR (Logroño) and GRUPAC from the University of La Rioja, focused on the search for new molecular information associated with the respiratory consequences of severe COVID-19 symptoms that progressed to acute respiratory distress syndrome (ARDS).

"Up to 80% of patients who survive acute respiratory distress syndrome secondary to SARS-CoV-2 infection have persistent lung function abnormalities after hospital discharge. Obtaining a better understanding of the molecular foundations that mediate persistent pulmonary dysfunction could help in the development of therapies and biomarkers for post-COVID sequelae", explains David de Gonzalo, researcher at CIBERES and IRBLleida and one of the coordinators of this study.

With this objective, this team of researchers focused on identifying, by means of complete genome sequencing, those genes that are differentially expressed in these patients. "Genome-wide transcriptional profiling is a powerful tool for analyzing gene expression with enormous potential to identify new drug targets, improve current therapies, and discover biomarkers. Currently, RNA sequencing (RNA-seq) is considered the gold standard among transcriptome profiling tools and makes it possible to decipher pathological processes underlying multiple diseases, including respiratory ones", points out Ignacio M. Larráyoz, researcher at CIBIR and the University of La Rioja and another of the main authors of the research.

Specifically, the research carried out the study of the transcriptional profile of the entire genome from blood samples from a selection of 50 patients who were admitted to the Arnau de Vilanova-Santa María University Hospital (Lleida) with severe COVID-19 symptoms , and those who underwent an evaluation three months after hospital discharge.

The results obtained in this genetic study show that, three months after discharge, there is a profile of alterations in gene transcription that is specific to patients who suffer from the most severe respiratory sequelae. "Specifically, using machine learning techniques, we identified a panel of 14 genes that allows us to accurately classify patients according to their pulmonary results one quarter after infection," says David de Gonzalo.

The research determined that the genes BAG2, ETV7, SERPINB6, TMEM161B and TUBB4A were more expressed in patients with the most severe pulmonary outcomes, while decreased expression of BCL2L11, GAS2, GRK2, PPP1R10 and TBC1D10B was observed. "This is a gene profile mainly related to biological pathways associated with cell survival", adds the researcher. As Ignacio M. Larráyoz points out, "this transcriptomic signature points to different mechanisms that mediate lung damage and recovery and that would be potentially involved in the respiratory sequelae of persistent COVID."

"From the point of view of clinical practice, this panel of genes can be useful as early biomarkers for the management of these sequelae, as well as a source of useful and innovative information for the development of personalized therapies", they conclude.

This study is part of the multicenter project Risk factors and prognosis of COVID-infected patients and one-year follow-up of patients admitted to Spanish ICUs (CIBERESUCICOVID), of the Carlos III Health Institute (ISCIII), developed by CIBER researchers of Respiratory Diseases (CIBERES).

This research has had the support of the Carlos III Health Institute, co-financed by the European Regional Development Fund (ERDF) "A way to make Europe"; and with the support of Fundación Francisco Soria Melguizo, UNESPA, and Fundació La Marató de TV3.

Reference article:

María C. García-Hidalgo, Rafael Peláez, Jessica González, Sally Santisteve, Iván D. Benítez, Marta Molinero, Manel Perez-Pons, Thalía Belmonte, Gerard Torres, Anna Moncusí-Moix, Clara Gort-Paniello, Maria Aguilà, Faty Seck , Paola Carmona, Jesús Caballero, Carme Barberà, Adrián Ceccato, Laia Fernández-Barat, Ricard Ferrer, Dario Garcia-Gasulla, Jose Ángel Lorente-Balanza, Rosario Menéndez, Ana Motos, Oscar Peñuelas, Jordi Riera, Jesús F. Bermejo-Martin , Antoni Torres, Ferran Barbé, David de Gonzalo-Calvo, Ignacio M. Larráyoz, Genome-wide transcriptional profiling of pulmonary functional sequelae in ARDS- secondary to SARS-CoV-2 infection, Biomedicine & Pharmacotherapy, Volume 154, 2022, 113617, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2022.113617

About CIBERES

The Network Biomedical Research Center (CIBER) is a consortium dependent on the Carlos III Health Institute (Ministry of Science and Innovation) and co-financed with FEDER funds. The purpose of the CIBER for Respiratory Diseases (CIBERES) is to promote and facilitate research into respiratory diseases through excellent research and its rapid and safe translation into clinical practice. Created in 2007, CIBERES currently brings together nearly 400 researchers from 9 autonomous communities who work together in 3 Scientific Programs, which integrate the following lines of research: lung cancer, sleep apnea, pulmonary fibrosis, pulmonary hypertension , asthma, acute pulmonary disease, tuberculosis, pneumonia, Chronic Obstructive Pulmonary Disease (COPD) and new therapeutic targets.

About the ISCIII COVID Fund

The CIBERESUCICOVID study is possible thanks to the aid that the CIBER received from the COVID-19 Fund and that was granted by the Carlos III Health Institute (ISCIII) to support research projects that will improve the clinical approach to COVID-19. These grants are aimed at promoting proposals "that allow immediate implementation and start-up in the National Health System, with concrete, early and applicable results to the current emergency situation generated by the impact of this pandemic", according to the call of the ISCIII.