Pandemic genomic surveillance: SARS-CoV-2 real-time genomic epidemiology to identify and track variants in South Africa and Africa.

Abstract

The SARS-CoV-2 pandemic has both been one of the largest public health emergencies of modern times and an unprecedented opportunity to track the epidemic progression of an evolving virus. Globally, more than 13 million genomic sequences have been generated, over 140,000 of which was from surveillance in African countries. The work presented in this thesis employs methods of real-time genomic surveillance and epidemiology, genome assembly, phylogenetic analysis and phylodynamic modelling to characterise the evolution of SARS-CoV-2 in South Africa and Africa with immediate public health impact globally. Chapter 2 describes the setting up and results of genomic surveillance in all provinces during the first wave of infections in South Africa. Insights included the description of three local lineages that caused over half of infections in the first wave and the establishment of surveillance baselines that enabled rapid characterization of variants of concern in upcoming waves. Chapter 3 provides a description of, for the first time in the world, the emergence of a SARS-CoV-2 variant of concern. The study gives an overview of the detection of the Beta variant, its association with an accelerating epidemic in the Eastern Cape province and the inferred phylogeography of how the variant spread to coastal provinces during summer holidays in South Africa. Chapter 4 describes the characterisation and phylodynamics of the Omicron variant of concern in record time at the start of the 4th wave of infections in southern Africa. Chapter 5 provides insights into the continued evolution of Omicron into sublineages BA.4 and BA.5, which went on to dominate the epidemic in other parts of the world in mid-2022. Finally, Chapter 6 and 7 are comprehensive studies of continental genomic surveillance in Africa, giving insights into establishment of epidemics from introductions from external sources, cross-border viral movements and the expansion of genomic surveillance on the continent to cover blindspots. This thesis also contributed to a number of other studies where genomic sequencing of SARSCoV- 2 helped to answer critical questions during pandemic response, which is described in the last chapter. In conclusion, this thesis exemplifies how genomic epidemiology can be utilised in real-time to track the evolution of a pandemic pathogen as well as rapidly raise alarms of detected global health threats.