PB0160 - Circulating EV and platelet releasate proteomes mirror the hyperactive, pro-inflammatory state of COVID-19 patients and may be adjunctive markers of COVID-19 severity

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

PS

Paulina Szklanna

Post-doctoral Research Scientist
UCD Conway SPHERE Research Group, Conway Institute, University College Dublin, Ireland
Dublin, Dublin, Ireland

Presenting Author(s)

Luisa Weiss, BSc, MSc, PhD

Post-doctoral Scientist
UCD Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland
Dublin, Dublin, Ireland

Co-Author(s)

SC

Shane Comer

Post-doctoral Research Scientist
UCD Conway SPHERE Research Group, Conway Institute, University College Dublin, Ireland
Dublin, Dublin, Ireland
LB

Lara Boehm

Undergraduate Student
UCD Conway SPHERE Research Group, Conway Institute, University College Dublin, Ireland
Dublin, Dublin, Ireland
SC

Sarah Cullivan

MD student
UCD Conway SPHERE Research Group, Conway Institute, University College Dublin, Ireland
Dublin, Dublin, Ireland
SK

Sarah Kelliher

PhD candidate
UCD Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland
Dublin, Dublin, Ireland
KW

Kieran Wynne

Mass spectrometry technician
Systems Biology Ireland, University College Dublin, Dublin, Ireland
Dublin, Dublin, Ireland
CS

Caitriona Scaife

Mass Spectrometry Core Facility Technician
Mass Spectrometry Core Facility, Conway Institute, University College Dublin, Ireland
Dublin, Dublin, Ireland
FN

Fionnuala Ní Áinle

Consultant Haematologist
Department for Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
Dublin, Dublin, Ireland
Barry Kevane, MB PhD

Consultant Haematologist
UCD Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland
Dublin, Dublin, Ireland
Patricia B. Maguire, PhD

Full Professor
School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
Dublin, Dublin, Ireland

Background: COVID-19 infection can present with a heightened inflammatory state and platelet hyperactivation, however the roles of circulating extracellular vesicles (cEVs; pro-coagulant and pro-inflammatory mediators of intercellular communication) and the platelet releasate (PR; cargo released from activated platelets) remain uncharacterised. We hypothesised that the cEVs and PR proteomic signatures are altered in COVID-19 patients.

Aims: To characterise and contrast paired cEVs and PR proteomes from COVID-19 patients and controls.

Methods: Ethical approval for this study was granted by the Mater Misericordiae University Hospital, Ireland. PR and platelet poor plasma (PPP) samples from COVID-19 patients requiring intensive care (severe, n=6) or hospital care (non-severe, n=6), and appropriate controls (n=6 healthy controls and n=5 COVID-negative hospitalised patients) were obtained with informed consent. cEVs were enriched from PPP by ultrafiltration. Samples were analysed by mass spectrometry and immunoassays.

Results: Comparative statistical analysis revealed substantial overlap in the proteomic signatures of the cEVs and PR across COVID-19 patients and controls. Profound increases in circulating levels of pro-inflammatory proteins correlated with severity of infection, alongside significant dysregulation of proteins involved in blood coagulation including von Willebrand factor and fibrinogen. We also found evidence of ‘spent’ platelets in COVID-19 patients, with reduced platelet factor 4 (PF4) levels in the PR and concomitant increase of PF4 in plasma. Strikingly, several platelet-released proteins exhibited strong correlation with routinely obtained haematological parameters and together clearly differentiated between a severe and non-severe hospitalised COVID-19 patients.

Conclusion(s): These preliminary data suggest that severe COVID-19 patients have a distinct cEV and PR profile and that proteomic signatures may be a useful tool in assessing the severity of COVID-19 when characterized in larger sample sizes. Our findings may lay the foundations to provide healthcare professionals with an adjunctive and minimally invasive tool towards assessing COVID-19 severity.