biostudies-literatureGutmann CCancer Research UKFrancis Crick InstituteVersus ArthritisNHS Foundation TrustInnovative Medicines Initiative 2 Joint UndertakingNational Institute of Academic AnaesthesiaNational Institute for Health Research Clinician Scientist AwardAustrian Ministry for Digital and Economic AffairsEuropean Union’s Horizon 2020National Institute for Health Research (NIHR)Leducq FoundationUK Medical Research Council Clinical Research Training FellowshipNIHR Academic Clinical Fellowship in Combined Infection TrainingAustrian Research Promotion Agency FFGCentre for Promoting Vascular Health in the Ageing CommunityBritish Heart FoundationJohn Black Charitable FoundationThe NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation TrustRosetrees TrustLower Green FoundationBiomedical Research CentreBiomedical Research Centre at Guy’s and St ThomasMedical Research CouncilMedizinisch-Wissenschaftlicher Fonds des Buergermeisters der Bundeshauptstadt WienAustrian Ministry for Transport, Innovation and TechnologyWellcome TrustBHF Centre for Vascular Regeneration with Edinburgh461-474https://www.ebi.ac.uk/biostudies/studies/S-EPMC8689968biostudies-literatureUnknown118(2)<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.Cardiovascular researchAssociation of cardiometabolic microRNAs with COVID-19 severity and mortality.PMC8689968FC001093ACF-2019-17-014M943COVID041FS/18/60/34181BRE/18/2/34213RM/17/3/33381FS/18/60/3418182128387156218CVD02PG/17/48/32956CH/16/3/32406SP/17/10/33219CH/1999001/11735CS-2016-16-011MR/R017751/1RG/16/14/32397Khamina KBurnap SACassel CNapoli SMcPhail MJWMerrick BEichinger SMayr MShankar-Hari MMujib SFShah AMTheofilatos KHackl MFish MRoy RGutmann CSchmidt LETraby LNabeebaccus AAuzinger GTrovato FDiendorfer ABO'Gallagher KHayday ACEdgeworth JDSanderson BfalseAssociation of cardiometabolic microRNAs with COVID-19 severity and mortality.<h4>Aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.2022-01-01T00:00:00Z2022 Jan2024-10-16T05:24:17.567Z2022-02-11T15:41:50.412ZS-EPMC86899683475584210.1093/cvr/cvab338