Genomic epidemiology, evolution, and transmission dynamics of respiratory pathogens during the COVID-19 pandemic in The Gambia

Large-scale genomic sequencing during the COVID-19 pandemic advanced understanding of SARSCoV-2. However, less than 1% of publicly available genomes were sequenced in Africa, about a third (32%) of which were generated from one country, South Africa, limiting representation of the continent’s geographical and epidemiological diversity. Furthermore, many previous African-based genomic studies relied on a few sequences, mainly used for diagnostic or to assess small transmission chains. This thesis addresses part of this gap by analysing one of the largest SARS-CoV-2 genome datasets from sub-Saharan Africa to investigate the genomic, temporal, spatial, and clinical dynamics of the virus in The Gambia between March 2020 and January 2022. This work was part of the SARS-CoV-2 genomic surveillance in The Gambia, during which ~1600 high-quality near full-length viral genomes were generated and analysed using phylogenetic and Bayesian phylodynamic methods (objectives 1 and 2, respectively). In addition, hospital-associated transmission dynamics were explored using viral genomes with clinical and epidemiological data (N=63) to untangle transmission chains among staff and patients across two epidemic waves by Bayesian inference (objective 3). Phylogenetic and detailed genomic epidemiological analysis (objective 1) showed that the first and third national SARS-CoV-2 waves were characterised by intense local transmission. During this period, PANGO lineage B.1.416 and Delta/(AY.34.1) were the most dominant and coincided with the rainy season (July – October), consistent with increased indoor gathering during rainfall, which may have facilitated viral transmission. The high viral diversity observed during the second wave reflected the country’s exposure to international travel with high viral introductions when the national lockdown was eased and international borders reopened. Bayesian phylodynamic inference (objective 2) estimated high and continuous rates of viral imports between March 2020 and January 2022. At least 94 independent introductions of SARS-CoV-2 lineages into The Gambia were inferred mainly from Southern Europe, Western Africa, and Southern Asia. Some lineages or variants introduced prior to lockdown persisted longer in the population, suggesting sustained viral circulation despite containment measures. Post-vaccination, phylodynamic analyses showed evidence of reduced persistence of observed transmission clusters, most probably attributable to population acquired immunity. Using Bayesian framework which integrates genomic and epidemiological data (objective 3), the analysis showed that staff-to-staff transmission was dominant during wave 1 but its relative contribution markedly decreased during wave 2, with patient-to-patient and patient-to-staff transmissions becoming more prevalent. Notably, two-thirds of all transmission events in wave 1 were associated with only two staff that worked in the same department, highlighting the possible role of workplace clustering in sustaining nosocomial transmission. The findings suggest that although control practices reduced staff to-staff transmission, IPC measures failed to reduce patient-driven transmission. This thesis provides one of the most comprehensive genomic reconstructions of SARS-CoV-2 transmission in Western Africa, from a national to a micro-epidemiological (hospital-level) scale. Collectively, this thesis provides insight into how viral importation, local transmission, and infection control measures have shaped the trajectory of SARS-CoV-2 in The Gambia. The methods and insights developed in this thesis could strengthen national capacity for epidemic preparedness and help establish a genomics-informed response for future emerging pathogens in low-resource settings.