Host immune responses to SARS-CoV-2

COVID-19 is a heterogeneous disease causing a range of presentations and disease severities. While scientific advances including the development of effective vaccines and antivirals have allowed a relaxation of public health measures despite the ongoing circulation of SARS-CoV-2, significant research gaps remain. Firstly, vaccine or infection mediated protection wanes over time, and we lack diagnostic tests to determine if protection against infection or severe disease has been lost. Secondly, only a minority of individuals will progress to more severe disease, and the immune changes which precede deterioration remain poorly understood, limiting our ability to identify those who might benefit most from targeted immunotherapy. Thirdly, millions of individuals have experienced long term effects of COVID-19 or ‘long COVID’ but these remain poorly characterised and no effective treatments are available. This thesis addresses these three questions. We describe an antibody threshold which predicts robust immunity against wild type and variant SARS-CoV-2, characterise inflammatory profiles in early COVID-19, demonstrating unique profiles at greatest risk of severe disease, and finally we outline clinical phenotypes of long COVID, and the impact of variants of concern and vaccination on these phenotypes.