PB0601 - Differential expression of platelet microRNAs in hospitalized patients with severe COVID-19

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

MP

Marianna Pócsi

PhD-student
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Debrecen, Hajdu-Bihar, Hungary
Zsolt Fejes, PhD

research fellow
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Debrecen, Hajdu-Bihar, Hungary
HG

Harriet Ghansah

PhD-student
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Debrecen, Hajdu-Bihar, Hungary
RS

Renáta Sütő

medical doctor
Gyula Kenézy Campus, Intensive Care Unit, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Debrecen, Hajdu-Bihar, Hungary
ZS

Zsolt Szabó

medical doctor
Gyula Kenézy Campus, Intensive Care Unit, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Debrecen, Hajdu-Bihar, Hungary
SP

Szilárd Póliska

Research fellow
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Debrecen, Hajdu-Bihar, Hungary
�G

Ágnes Gyetvai

Research fellow
Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Debrecen, Hajdu-Bihar, Hungary
ZS

Zoltán Szentkereszty

medical doctor
Gyula Kenézy Campus, Intensive Care Unit, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Debrecen, Hajdu-Bihar, Hungary
JK

János Kappelmayer

professor
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Debrecen, Hajdu-Bihar, Hungary

Presenting Author(s)

BN

Béla Nagy Jr., Jr., MD, PhD

associate professor
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Debrecen, Hajdu-Bihar, Hungary

Background: Coronavirus disease 2019 (COVID-19) is often associated with enhanced platelet activation and thrombotic complications which may be reflected by altered microRNA (miRNA) levels in blood cells.

Aims: We here investigated the expression of miRNAs in the background of platelet reactivity in severe COVID-19 and evaluated them for the prediction of disease mortality.

Methods: Platelet miRNAs were isolated from leukocyte-depleted platelets and profiled in COVID-19 survivors and non-survivors vs healthy controls using TaqMan Open Array. Candidate miRNAs showing at least 2-fold alteration between two groups were validated by RT-qPCR in 10 individuals from each group, and these data were correlated with clinical outcome in COVID-19. Differentially regulated miRNAs were bioinformatically analyzed to identify their mRNA targets and Cytoscape ClueGO was used for functional enrichment analysis. Platelet reactivity was evaluated via quantification of P-selectin expression, platelet-leukocyte aggregates and platelet-derived microparticles (PMPs) by flow cytometry.

Results: Increased platelet activation was detected via elevated level of P-selectin positivity (6.5 vs 1.1%, P< 0.0001), platelet-monocyte aggregates (40 vs 17 %, P=0.0315) and PMPs (22 vs 18 PMPs/10^5 platelets, P=0.3789) in severe COVID-19 vs controls. Out of 340 detected platelet miRNAs, there were 127 attenuated (e.g. miR-221) and 8 upregulated (e.g. miR-320b) miRNAs in abnormal COVID-19 platelets compared to normal samples. Furthermore, non-survivors showing 28-day mortality demonstrated a different profile of miRNAs vs survivors including 66 downregulated (e.g. miR-126) and 4 upregulated (e.g. miR-27b) miRNAs. Network analysis revealed the association of altered miRNAs with 241 genes involved in several mechanisms, such as regulation of cell activation, response to cytokines, and cell surface receptor signalling pathway involved in cell-cell signalling. Among downregulated miRNAs, CD40LG was regulated by miR-146a, miR-30b targeted SERPINE1, while miR-29b modulated the expression of CDC42.

Conclusion(s): Altered platelet miRNAs regulate the development of platelet reactivity in severe COVID-19 and may serve as possible biomarkers to predict disease mortality.