Dr. Cliona Ni Cheallaigh

Summary

Funding Agency

SFI

Summary

Funding Agency

HRB

Programme

Applied Partnership Award

Summary

A key issue during the ongoing SARS-CoV2 pandemic is to determine the proportion of the population possessing effective antibodies for virus clearance and long-term immunity. Screening post-infection immunity will identify key/frontline healthcare workers that can work without risk of re-infection. This assay will also be crucial to monitor the true scale of the pandemic as many infections will be mild/ asymptomatic without testing. Furthermore, with ongoing plasmapheresis trials using anti-SARS-CoV2 antibody-containing sera for critical COVID-19 patients, identifying donors with high levels of anti-viral antibody will be a valuable factor to assess. RNA-based qPCR diagnostic tests currently used in Ireland to detect SARS-COV2 viral RNA in a nose/throat swabs can sensitively detect active infection at an early stage of infection but cannot detect immunity to the virus after clearance. This can only be achieved using Immunoglobulin(Ig)-based tests for antibodies against key SARS-COV2 antigens (predominantly virion 'Spike' or S protein). While serological tests are in development for SARS-COV2 antibodies, few are approved for use and will likely be expensive with substantial delays in global distribution. A recent pre-print (Amanat et al., published 18 March 2020) described a novel assay for SARS-COV2 antibodies. The aim of this project is to establish this assay in Ireland, screen SARS-COV2 positive serum samples from Irish patients and determine its accuracy using a larger cohort of SARS-COV2 positive sera. If the method can be replicated, a non-accredited test could be developed to screen the Irish population for post-infection immunity in a rapid and cost-effective manner.

Funding Agency

SFI

Programme

COVID 19 Rapid Response

Summary

In this study, a comprehensive assessment of how past exposure to viruses impacts risk of COVID-19 in older people will be carried out and how it is linked to inflammageing and anti-viral immunity. A well-established longitudinal ageing cohort, TILDA, which has the detailed demographic, clinical and biomarker information - rich phenotyping data will be combined with a state-of-the-art approach, VirScanTM, to determine a person's complete viral exposure history.

Funding Agency

SFI

Programme

COVID-19 Rapid Response

Summary

Novel coronavirus (COVID-19) pneumonia is associated with significant mortalitypredominantly attributable to a progressive bilateral pneumonia, that ultimately progresses to acute respiratory distress syndrome (ARDS) which is refractory to standard therapies. Previous multivariate regression analysis studies performed in Wuhan have shown that elevated plasma levels of fibrin degradation D-dimers constitute a key independent biomarker of poor prognosis in COVID-19. Interestinglyhowever, despite this prognostic increase in D-dimers, COVID-19 patients do not typically develop systemic disseminated intravascular coagulation (DIC). Nonetheless, post-mortem studies in COVID-19 infected patients have highlighted marked pathological changes restricted to within the lung microvasculature. These include disseminated micro-thrombi and haemorraghic necrosis. Cumulatively, these findings suggest that the refractory ARDS phenotype observed in COVID-19 is due in part to a novel pulmonary-specific vasculopathy. Critically however, pathobiological mechanisms underpinning this unique vasculopathy remain completely undefined.Although D-dimer levels are being used globally as prognostic marker in patients with COVID-19, no studies have sought to investigate why coagulation D-dimers areelevated, nor why D-dimer levels and coagulation activation correlate so strongly with clinical outcomes. In this cross-disciplinary IrishCOVID-19VasculopathyStudy (iCVS), we will systematically investigate the biological pathways that ultimately lead to elevated plasma D-dimer levels. These include (i) EC activation (ii) procoagulant cascade activation (iii) down-regulation of normal anticoagulant pathways (iv) fibrinolytic pathways (v) platelet activation respectively. The plan of investigation will define novel vascular biomarkers beyond crude D-dimers that can be used to betterdefine prognosis for COVID-19 patients and thereby prioritise ICU resources. In addition, elucidating the biology underlying the unique pulmonary vasculopathy involved in severe COVID-19 sepsis will identify subsets of patients likely to benefitfrom specific anti-inflammatory, anticoagulant and/or antiplatelet therapies respectively. Consequently, the proposed studies are not only of scientific interest,but directly address an important clinical unmet need.

Funding Agency

HRB

Programme

COVID 19