TY - JOUR
T1 - Association of cardiometabolic microRNAs with COVID-19 severity and mortality
AU - Gutmann, Clemens
AU - Khamina, Kseniya
AU - Theofilatos, Konstantinos
AU - Diendorfer, Andreas B
AU - Burnap, Sean A
AU - Nabeebaccus, Adam
AU - Fish, Matthew
AU - McPhail, Mark J W
AU - O'Gallagher, Kevin
AU - Schmidt, Lukas E
AU - Cassel, Christian
AU - Auzinger, Georg
AU - Napoli, Salvatore
AU - Mujib, Salma F
AU - Trovato, Francesca
AU - Sanderson, Barnaby
AU - Merrick, Blair
AU - Roy, Roman
AU - Edgeworth, Jonathan D
AU - Shah, Ajay M
AU - Hayday, Adrian C
AU - Traby, Ludwig
AU - Hackl, Matthias
AU - Eichinger, Sabine
AU - Shankar-Hari, Manu
AU - Mayr, Manuel
N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2022/1/29
Y1 - 2022/1/29
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Biomarkers
KW - COVID-19/complications
KW - Cardiometabolic Risk Factors
KW - Female
KW - High-Throughput Nucleotide Sequencing
KW - Humans
KW - Intensive Care Units
KW - Male
KW - MicroRNAs/blood
KW - Middle Aged
KW - Patient Acuity
KW - SARS-CoV-2
U2 - 10.1093/cvr/cvab338
DO - 10.1093/cvr/cvab338
M3 - Article
C2 - 34755842
SN - 0008-6363
VL - 118
SP - 461
EP - 474
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 2
ER -