Genomic surveillance of COVID-19 in Hong Kong (2020-2023): Analysing SARS-CoV-2 variants, mutations, and their impact on viral entry.

We analysed 15,982 quality-controlled SARS-CoV-2 genome sequences from Hong Kong, obtained from NCBI and GISAID between 2020 and 2023, to characterize lineage dynamics, mutational profiles, demographic distributions, and variant-specific viral entry. Genomic surveillance identified 543 lineages and 5,982 unique mutations. Lineages A, B, and B.4 dominated the initial epidemic waves, whereas Delta and Omicron emerged and predominated in later waves. Omicron BA.1 and BA.2 exhibited distinct distributions across gender and age groups, while JN.1 harboured several novel mutations. Molecular simulations comparing spike receptor-binding domain (SRBD)-ACE2 interactions revealed significant differences in binding affinity among variants (F = 4.404, p = 9.12 × 10⁻⁷). JN.1 demonstrated enhanced ACE2-binding affinity, suggesting increased viral entry and potential transmissibility. By integrating genomic, demographic, and molecular evidence, this study provides a comprehensive account of SARS-CoV-2 evolution in Hong Kong and highlights the public health relevance of emerging variants. These findings support sustained genomic surveillance and demographic monitoring to strengthen pandemic preparedness. Future research should evaluate public health strategies and adopt holistic frameworks integrating population characteristics with genomic evidence to mitigate the effects of future variants.