Abstract
This thesis details the investigation by mass spectrometry and ‘omics-based data science of the impact on human hosts of CoronaVirus Disease 2019 (COVID-19), an illness that has levied a heavy cost across the globe in terms of both health and life. The work described herein, which was produced through the pandemic stages of the illness, analyses the impact of COVID-19 on a set of biofluids obtained from hospitalised participants recruited with the assistance of the NHS Frimley Health Foundation Trust in the UK.
The results of the work undertaken are presented in this thesis as four published journal articles. The first of these presents a pilot study for the potential for diagnosis of COVID-19 by skin swabs, using mass spectrometry to differentiate the sebum lipidomes of infected individuals from controls. This approach was initially seen as promising but as of today has been overtaken by the rapid rollout of other testing regimes. The second article presents a systematic review and meta-analysis of the overall progress of the scientific community in finding new diagnostic methods for COVID-19 by mass spectrometry. At the time of publication, proteomic analysis by mass spectrometry offered the most promise, with sensitivity and specificity approaching target product specifications for diagnostic tests. In the UK, however, as of the time of writing of this thesis, no mass spectrometry based technique has met clinical requirements for diagnosis or prognosis. The third article presents an interrogation of the relationships between saliva, sebum and serum metabolites and lipids in infected individuals, to identify correlations between them. In this part of the work, sebum lipids showed relationships with certain serum lipids and immune-system related metabolites, illustrating the whole-body nature of COVID-19 infection. The fourth article provides an integrated analysis of the proteomic and metabolomic mechanism of action of glucocorticoids such as dexamethasone on those infected with severe COVID-19. Whilst the benefits of glucocorticoid treatment are well-described in severely affected patients, the pleiotropic effects of the drug are suggestive that in mild cases there may be no overall benefit to treatment, or even a cost.