Dataset Information

Association between biomarkers and COVID-19 severity and mortality: a nationwide Danish cohort study.

ABSTRACT: Objective: To evaluate the association between common biomarkers, death and intensive care unit (ICU) admission in patients with COVID-19.

Design: Retrospective cohort study. From electronic national registry data, we used Cox analysis and bootstrapping to evaluate associations between baseline levels of biomarkers and standardised absolute risks of death/ICU admission, adjusted for age and gender.

Setting: All hospitals in Denmark.

Participants: 1310 patients aged ?18 years admitted to hospital with COVID-19 from 27th of February to 1st of May 2020, with available biochemistry data.

Main outcome measures: A composite of death/ICU admission occurring within 30 days.

Results: Of the 1310 patients admitted to hospital (54.6% men; median age 73.6 years), 352 (26.9%) experienced the composite endpoint and 263 (20.1%) died. For the composite endpoint, the absolute risks for moderately and severely elevated C reactive protein (CRP) were significantly higher, 21.5% and 39.2%, respectively, compared with 5.0% for those with normal CRP. Moderately and severely elevated leucocytes were significantly higher, 34.5% and 46.6% risk, respectively, compared with 23.2% for those with normal leucocytes. Moderately and severely decreased estimated glomerular filtration rates (eGFR) were significantly higher, 41.5% and 45.9% risk, respectively, compared with 30.4% for those with normal/mildly decreased eGFR. Normal and elevated ureas were significantly higher, 22.3% and 40.6% risk, respectively, compared with 7.3% for those with low urea. Elevated D-dimer was significantly higher, 31.8% risk, compared with 17.5% for those with normal D-dimer. Moderately and severely elevated troponins were significantly higher, 27.7% and 57.3% risk, respectively, compared with 9.4% for those with normal troponin. Elevated procalcitonin was significantly higher, 52.1% risk, compared with 28.0% for those with normal procalcitonin.

Conclusion: In this nationwide study of patients admitted with COVID-19, elevated levels of CRP, leucocytes, procalcitonin, urea, troponins and D-dimer, and low levels of eGFR were associated with higher standardised absolute risk of death/ICU admission within 30 days.

SUBMITTER: Hodges G

PROVIDER: S-EPMC7712929 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Association between biomarkers and COVID-19 severity and mortality: a nationwide Danish cohort study.

Hodges Gethin G Pallisgaard Jannik J Schjerning Olsen Anne-Marie AM McGettigan Patricia P Andersen Mikkel M Krogager Maria M Kragholm Kristian K Køber Lars L Gislason Gunnar Hilmar GH Torp-Pedersen Christian C Bang Casper N CN

BMJ open 20201202 12

<h4>Objective</h4>To evaluate the association between common biomarkers, death and intensive care unit (ICU) admission in patients with COVID-19.<h4>Design</h4>Retrospective cohort study. From electronic national registry data, we used Cox analysis and bootstrapping to evaluate associations between baseline levels of biomarkers and standardised absolute risks of death/ICU admission, adjusted for age and gender.<h4>Setting</h4>All hospitals in Denmark.<h4>Participants</h4>1310 patients aged ≥18 y ...[more]

PMID: 33268425

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Project description:AimsCoronavirus 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 resultsWe 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.ConclusionCirculating 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.

Dataset Information

Association between biomarkers and COVID-19 severity and mortality: a nationwide Danish cohort study.

Publications

Association between biomarkers and COVID-19 severity and mortality: a nationwide Danish cohort study.

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