Association of cardiometabolic microRNAs with COVID-19 severity and mortality. Issue 2 (10th November 2021)

• Record Type: Journal Article
• Authors: Gutmann, Clemens; Khamina, Kseniya; Theofilatos, Konstantinos; Diendorfer, Andreas B; Burnap, Sean A; Nabeebaccus, Adam; Fish, Matthew; McPhail, Mark J W; O'Gallagher, Kevin; Schmidt, Lukas E; Cassel, Christian; Auzinger, Georg; Napoli, Salvatore; Mujib, Salma F; Trovato, Francesca; Sanderson, Barnaby; Merrick, Blair; Roy, Roman; Edgeworth, Jonathan D; Shah, Ajay M; Hayday, Adrian C; Traby, Ludwig; Hackl, Matthias; Eichinger, Sabine; Shankar-Hari, Manu; Mayr, Manuel
• Is Part Of: Cardiovascular research. Volume 118:Issue 2(2022)
• Page Start: 461
• Page End: 474
• Publication Date: 2021-11-10
• Subjects: COVID-19 -- SARS-CoV-2 -- MicroRNAs -- RNA-Seq -- Proteomics -- Biomarkers; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvab338
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Aims: Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality. Methods and results: We performed RNA-Seq in plasma of healthy controls ( n = 11), non-severe ( n = 18), and severe ( n = 18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT–qPCR) in a separate cohort of mild ( n = 6), moderate ( n = 39), and severe ( n = 16) patients. Candidates were then measured by RT–qPCR in longitudinal samples of ICU COVID-19 patients ( n = 240 samples from n = 65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality. Conclusion: Circulating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response. Graphical Abstract: