New Blood RNA Markers Help Advance Precision Medicine for Respiratory Patients

Risk stratification in hospitalized respiratory disease, particularly among older adults with COVID-19, remains challenging despite rich clinical datasets. Blood-based non-coding RNA biomarkers are promising, yet patient heterogeneity and measurement variability can undermine their reliability. Clinical laboratories also need robust endogenous controls to standardize RNA quantification across studies. Researchers now present new findings describing a prognostic microRNA signal in elderly COVID-19 subphenotypes and a candidate long non-coding RNA reference gene for blood assays.

At the Biomedical Research Institute of Lleida (IRBLleida) and the University of Lleida, the Clinical and Molecular Phenotyping group conducted two complementary investigations focused on blood-derived non-coding RNA biomarkers. One study evaluated circulating microRNAs as prognostic indicators for hospitalized patients with COVID-19 aged over 65 years. A companion study assessed long non-coding RNAs as stable internal controls to strengthen quantification workflows in blood-based assays.

Image: The researchers Manel Pérez Pons y Carlos Rodriguez Muñoz at the IRBLleida laboratory (Photo courtesy of IRBLleida)

The prognostic approach integrated the circulating microRNA profile (miRNome) with routine clinical information to delineate biologically meaningful patient subphenotypes and refine mortality prediction. Analysis of hospitalized older adults identified three clinical subtypes and highlighted miR-106b-3p as a candidate marker for forecasting 90-day mortality within the subgroup burdened by multiple comorbidities. 

Incorporating this microRNA marker into clinical models improved predictive performance compared with models using clinical variables alone. In parallel, the methodological study measured the expression of dozens of long non-coding RNAs (lncRNAs) in blood from 182 individuals to identify a reliable endogenous reference; the results point to TUG1 as a stable control gene for lncRNA quantification.

The prognostic microRNA study, encompassing samples and clinical data from 763 patients older than 65 years hospitalized with COVID-19, was published in iScience on August 10, 2026. The internal-control study is published in Biomarker Research (December 30, 2025). Collaborations included the Translational Research in Respiratory Medicine group; healthcare professionals and researchers at Arnau de Vilanova and Santa Maria University Hospitals in Lleida; and the Biomedical Research Institute of Salamanca (IBSAL).

Together, the findings support the utility of non-coding RNA readouts to enhance risk stratification in vulnerable respiratory cohorts and to standardize RNA measurements across laboratories. The authors note that one line of work advances prognostic biomarker discovery while the other provides a methodological foundation to improve reproducibility and comparability in future blood-based RNA studies.

“These findings reinforce the idea that molecular biomarkers can complement traditional clinical information and contribute to more accurate risk stratification in particularly vulnerable populations,” explained Manel Pérez Pons, first author of the article and researcher at IRBLleida.

“Having a robust reference is essential to ensure that detected biomarkers reflect genuine biological changes rather than technical variations in laboratory procedures,” said Carlos Rodríguez Muñoz, first author of the article and researcher at IRBLleida.

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