Abstract
The rapid emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in unparalleled public health and economic implications worldwide. In Kuwait, the virus was first detected in February 2020, after which it rapidly spread and caused over 600 thousand infections, reinfections, and over 2500 deaths until early 2023. While the pandemic has passed its emergency stage and been declared endemic, continuous molecular surveillance for rapidly evolving pathogens like SARS-CoV-2 is critical for early intervention efforts, as the emergence of new variants is the most essential component in shaping the dynamics of the pandemic. Thus, the main objective of this study is to investigate and compare the variant-specific evolutionary epidemiology of all the Delta (B.1.617.2 and descendant lineages) and Omicron (B.1.1.529 and descendant lineages) complete genome sequences collected between 2021 and 2023 in Kuwait. Here, we reconstructed, traced, and compared the two variants' demographic, continental phylogeographic origins, and the role of sex and age in shaping their transmission history between infected patients using a discrete-trait Bayesian phylodynamic analytic pipeline. We found that the Delta variant had a higher evolutionary rate than the Omicron variant. While both variants went through periods of sequential growth and decline, likely linked to air travel, intervention measures and the development of natural immunity. Our results indicate that the delta variant and descendant lineages were frequently introduced into Kuwait from Asian countries between mid-2020 and early 2021, while those of the Omicron variant were most likely from Africa and North America between late 2021 and 2022. For Both variants, our between-patient discrete-trait analysis revealed statistically significant (Bayes Factors > 1000) asymmetric unidirectional and intense transmission routes from adult patients aged between 20 and 50 years on one side and patients aged less than 20 and older than 50 years on the other. In contrast, no significant evidence was found for the role of sex in shaping the evolutionary transmission history of both variants between males and females. Our analysis highlighted the importance of implementing risk-based genomic surveillance programs to uncover important epidemiological aspects of SARS-CoV-2 that may improve the efficiency of future decision-making related to allocating intervention resources toward relevant emerging variants. Finally, we discuss the importance of unifying molecular surveillance efforts in humans and companion animals to improve the inferences derived from our phylodynamic models.