A novel approach to profile global circulation pathway of SARS-CoV-2 variants by site-based mutation dynamics

TL;DR

This study introduces the S-EPS framework, a new phylogenetic-free method for analyzing SARS-CoV-2 mutation dynamics, revealing key source regions and transmission patterns across the globe.

Contribution

The paper presents the S-EPS framework, a novel bias-correcting, site-based mutation analysis method for tracking viral dispersal without relying on phylogenetics.

Findings

Africa and India are main sources of mutations.

Southeast Asia acts as an early transmission hub.

Mutations reaching 1% prevalence in sources have an 80% chance to spread elsewhere.

Abstract

The genetic evolution of SARS-CoV-2 has caused recurring epidemic waves, understanding its global dispersal patterns is critical for effective surveillance. We developed the Site-based mutation dynamics - Equal Power Sampling (S-EPS) framework, a phylogenetic-free, bias-correcting framework for profiling viral source-sink dynamics. Applying S-EPS to 6.6 million SARS-CoV-2 genomes (March 2020 - June 2024) from 13 regions worldwide, we identified Africa and the Indian subcontinent as the predominant sources of key mutations. Southeast Asia serves as an early transmission hub, while Russia and South America mainly acted as sinks. Key mutations took longer to establish fitness in source regions than externally. Once an amino acid substitution on the receptor-binding domain reached 1% prevalence in major sources, there is an 80% probability it would spread elsewhere, with a 2-month median lead time (IQR: 1-4). Our findings underscore the importance of genetic surveillance, with S-EPS offering enhanced capability for monitoring emerging viral threats.