Longitudinal Genomic Surveillance of SARS-CoV-2 Evolution and Immune Escape Variants in Nigeria: A National Phylogenomic Study

Genomic surveillance of SARS-CoV-2 evolution is essential for tracking variant emergence, characterising immune escape mutations, and informing vaccine update decisions. Nigeria, as the most populous country in Africa, represents a critical surveillance node, yet the completeness and analytical depth of its national genomic surveillance programme have been limited. This dissertation conducted the most comprehensive longitudinal phylogenomic analysis of SARS-CoV-2 evolution in Nigeria, integrating 1,200 sequenced genomes collected from all six geopolitical zones between January 2020 and December 2023. Nasopharyngeal swab samples were collected from confirmed COVID-19 cases at sentinel surveillance sites in Lagos, Kano, Abuja, Enugu, Port Harcourt, and Maiduguri. Viral RNA was extracted and whole genome sequencing was performed using the ARTIC amplicon protocol on Illumina and Oxford Nanopore platforms. Lineage classification used the Pangolin nomenclature system, and phylogenetic analysis used maximum likelihood and Bayesian approaches in IQ-TREE and BEAST2. Temporal Bayesian analysis estimated substitution rates and origin times of variants. Import and export events were reconstructed using ancestral state reconstruction. Multiple immune escape mutations in the spike receptor-binding domain were characterised in Nigerian-predominant lineages. Periods of local cryptic transmission preceding reported waves were identified in multiple states. This dissertation establishes the first national-scale phylogenomic account of SARS-CoV-2 evolution in Nigeria. Keywords: SARS-CoV-2, phylogenomics, genomic surveillance, immune escape, Nigeria