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Alteration of circulating ACE2 regulating microRNAs profiles in patients with COVID-19

Z. Wicik1, C. Eyileten1, J. Jarosz-Popek1, D. Jakubik1, A. Nowak1, M. Wolska2, A. Shahzadi3, D. Martins-Jr4, S. Simões5, J. Siller-Matula6, M. Postula1

1Medical University of Warsaw, Warsaw, Mazowieckie, Poland, 2Medical University of Warsaw, warsaw, Mazowieckie, Poland, 3Istanbul Cerrahpasa University, Istanbul, Istanbul, Turkey, 4Federal University of ABC, Sao Paulo, Sao Paulo, Brazil, 5Federal Institute of Espírito Santo, Sao Paulo, Sao Paulo, Brazil, 6medical university of vienna, vienna, Wien, Austria

Abstract Number: VPB0611

Meeting: ISTH 2022 Congress

Theme: COVID and Coagulation » COVID and Coagulation, Basic Science

Background: SARS-CoV-2 tropism for the ACE2 receptor, along with the multifaceted inflammatory reaction, is likely to drive the generalized hypercoagulable state seen in patients with COVID-19.

Aims: According to our previously published bioinformatics analysis, we aimed to analyze the diagnostic and predictive utility of miRNAs regulating ACE2 network (miR-26b-5p, miR-10b-5p, miR-302c-5p, hsa-miR-200b-3p, hsa-miR-124-3p) in patients with COVID-19

Methods: We determined the expressions of ACE2-related-miRNAs in 79 hospitalized COVID-19 patients and 32 healthy volunteers by PCR and monitored miRNAs patterns during the acute phase of COVID-19, as well as the prognostic potential of these miRNAs as biomarkers.

Results: The expression levels of miR-26b-5p in COVID-19 patients were found lower at the baseline, 7 and 21-days after admission. compared to the healthy controls (p < 0.0001 for all time points). Similarly, miR-10b-5p expression levels were lower at the baseline and 21-days post admission in COVID-19 patients when compared to the healthy individuals (p=0.001 in both time points). Moreover, expression levels of this miRNA were higher 7-days post-admission when compared to the baseline (p=0.003). According to the ROC curve analysis, low miR-200b-3p expression presents predictive utility in assessment of the hospital length of stay and/or death (AUC:0.730, p=0.002). According to the multivariable logistic regression model, low delta miR-200p expression, together with diabetes mellitus (DM), are independent predictors of increased hospital length of stay and/or death (OR: 5.775; 95% CI, 1.572-21.214; p=0.008 and OR: 4.888; 95% CI, 1.001-23.858; p=0.050, respectively).

Conclusion(s): This study enabled us to better characterize changes in gene expression and signaling pathways related to COVID-19 thrombosis. In this study we identified, characterized and validated miRNAs which could serve as novel, thrombosis-related biomarkers of the COVID-19, can be used for early stratification of patients and prediction of severity of infection development in an individual.

Image

Comparison of circulating miRNAs expression between the groups. a- miR-26b-5p; b- miR-124-3p; c- miR-10b-5p; d- miR-200b-3p; e-miR-302c-5p. Mann-Whitney U test and Wilcoxon test were used appropriately. Kruskal-Wallis test shows the difference among the four groups. Abbreviations: COVID-19, coronavirus disease 2019; miR, microRNA; p, p value. MiRNAs expression data is presented after logarithmic transformation correction.

image

Delta of miR-200b-3p -7-days post admission changing to the day of admission- expression box-plots and receiver operating characteristic -ROC- curves A- Delta of miR-200b-3p box-plots for increased hospital length of stay and/or death comparison; B- Delta of miR-200b-3p for prediction of hospital length of stay and/or death. Abbreviations: AUC, Area under the ROC Curve; COVID-19, coronavirus disease 2019; miR, microRNA.

To cite this abstract in AMA style:

Wicik Z, Eyileten C, Jarosz-Popek J, Jakubik D, Nowak A, Wolska M, Shahzadi A, Martins-Jr D, Simões S, Siller-Matula J, Postula M. Alteration of circulating ACE2 regulating microRNAs profiles in patients with COVID-19 [abstract]. https://abstracts.isth.org/abstract/alteration-of-circulating-ace2-regulating-micrornas-profiles-in-patients-with-covid-19/. Accessed September 29, 2023.

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