Association of cardiometabolic microRNAs with COVID-19 severity and mortality

Clemens Gutmann, Kseniya Khamina, Konstantinos Theofilatos, Andreas B Diendorfer, Sean A Burnap, Adam Nabeebaccus, Matthew Fish, Mark J W McPhail, Kevin O'Gallagher, Lukas E Schmidt, Christian Cassel, Georg Auzinger, Salvatore Napoli, Salma F Mujib, Francesca Trovato, Barnaby Sanderson, Blair Merrick, Roman Roy, Jonathan D Edgeworth, Ajay M ShahAdrian C Hayday, Ludwig Traby, Matthias Hackl, Sabine Eichinger, Manu Shankar-Hari, Manuel Mayr

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)461-474
Number of pages14
JournalCardiovascular Research
Volume118
Issue number2
Early online date10 Nov 2021
DOIs
Publication statusPublished - 29 Jan 2022

Keywords / Materials (for Non-textual outputs)

  • Adult
  • Aged
  • Biomarkers
  • COVID-19/complications
  • Cardiometabolic Risk Factors
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intensive Care Units
  • Male
  • MicroRNAs/blood
  • Middle Aged
  • Patient Acuity
  • SARS-CoV-2

Fingerprint

Dive into the research topics of 'Association of cardiometabolic microRNAs with COVID-19 severity and mortality'. Together they form a unique fingerprint.

Cite this