Characterisation of biochemical and haematological mechanisms associated with SARS-CoV-2 and COVID-19

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dc.check.date2028-12-31
dc.check.infoControlled Access
dc.contributor.advisorMcCarthy, Justin V.
dc.contributor.advisorO'Connor, Rosemary
dc.contributor.advisorexternalColeman-Vaughan, Caroline
dc.contributor.authorHarte, James V.en
dc.contributor.funderEli Lilly and Company
dc.date.accessioned2025-10-16T15:25:53Z
dc.date.available2025-10-16T15:25:53Z
dc.date.issued2025en
dc.date.submitted2025
dc.description.abstractThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to a significant burden on global health. Despite extensive research worldwide, the pathomechanisms remain unclear. Therefore, in this thesis, we aimed to investigate biochemical and haematological mechanisms underlying the pathophysiology of SARS-CoV-2 and COVID-19. Firstly, we investigated the processing of the SARS-CoV-2 spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor by host proteases. Using whole-cell assays, we identify host metalloproteases as novel activators of both virus–cell fusion and cell–cell fusion. We also demonstrate that SARS-CoV-2 spike protein-induced fusion results in calcium-activated phospholipid scrambling, leading to the functionalisation of tissue factor and enhanced procoagulant activity. Sequential cleavage of the SARS-CoV-2 spike protein and the ACE2 receptor by host proteases was also found to potentially affect physiological and pathological processes, suggesting that host proteases may serve as viable targets for indirect antivirals. Finally, we demonstrated that patients with COVID-19 present with distinct haemocytometric characteristics and identify a monocyte subpopulation with altered morphology and enhanced procoagulant activity. Correlative analyses linked the haemocytometric changes to clinical markers of coagulopathy, supporting a mechanistic role for monocyte‐dependent immunothrombosis in patients with COVID-19. Collectively, the findings described in this thesis contribute to the ongoing characterisation of both the biochemical and haematological mechanisms associated with COVID-19. As SARS-CoV-2 transitions towards endemicity, this thesis provides informative groundwork for future research — as well as clinical strategies — aimed at improving outcomes for patients with SARS-CoV-2-associated COVID-19.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHarte, J. V. 2025. Characterisation of biochemical and haematological mechanisms associated with SARS-CoV-2 and COVID-19. PhD Thesis, University College Cork.
dc.identifier.endpage391
dc.identifier.urihttps://hdl.handle.net/10468/18057
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::IMI2-RIA/777389/EU/conect4children (COllaborative Network for European Clinical Trials For Children)/c4c
dc.rights© 2025, James V. Harte.
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCoagulationen
dc.subjectCOVID-19en
dc.subjectHaematologyen
dc.subjectSARS-CoV-2en
dc.titleCharacterisation of biochemical and haematological mechanisms associated with SARS-CoV-2 and COVID-19en
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
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