Diagnostic, prognostic and predictive markers of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19)

Abstract

The emergence of novel pathogens, particularly those of pandemic potential, requires large public health laboratories with expertise to lead the early development of accurate diagnostics to identify cases to enable a timely public health response. Diagnostic assays need to be designed, validated, distributed and implemented in a timely manner. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent declaration of the coronavirus disease 2019 (COVID-19) pandemic in March 2020 has seen unprecedented demands placed on healthcare systems worldwide with laboratories placed under constant pressure to expand capacity to meet rising testing demands. The primary objective of this thesis, undertaken in a large diagnostic public health laboratory, is to address knowledge gaps in diagnostics and prognostics of SARS-CoV-2 infection, and tackle new challenges posed by ongoing viral evolution with evolving public health priorities and orders in response to the COVID-19 pandemic. This thesis highlights the use and performance of different laboratory methods including nucleic acid amplification testing, virus isolation and whole genome sequencing to diagnose and characterise SARS-CoV-2 and examines their application to prognosticate, inform infectivity, detect vaccine escape, antiviral resistance and virus transmission. Manuscripts were published in real time, allowing rapid dissemination of emerging evidence; this was used to inform local, state and national policy decisions around pandemic management. With continual evolution of SARS-CoV-2, along with the introduction of novel treatments and vaccines, there is a need for refinement of currently available assays as well as the ongoing paired phenotypic and genotypic assessment of novel lineages to inform clinical management and public health responses. The COVID-19 pandemic reaffirmed the need for reliable and effective diagnostics as the cornerstone of a successful outbreak response.