A Case Study of Applying Metagenomic Sequencing in Precise Epidemiology for the COVID-19 Pandemic — Sichuan Province, China, 2020

Introduction: Determining the transmission chain of a virus in its incipient stages is extremely time consuming in traditional approaches that rely mainly on case incidence and interview-based contact data. With the development of high-throughput sequencing technology, genome-based epidemiology approach is showing promise in detecting viral transmission. However, there is still insufficient evidence for the relationship between the viral genetic variations and real viral transmission. Methods: To explore the possible relationship between transmission chains and viral genetic variations, we combined both epidemiological data and viral genomes of COVID-19 virus collected from Sichuan Province. A phylogenetic approach was used to infer the transmission chain, which was then compared to the transmission chain that came from epidemiological data. Results: We found that the putative transmission chains were highly concordant to the true transmission chains from epidemiological data, suggesting a strong correlation between viral genetic variations and the viral transmission chain. Discussion: Our results showed advantages of viral genomic sequencing in tracking and perceiving pathogen transmission, which allowed for potential improvements in the design and implementation of population-level public health interventions. INTRODUCTION It is crucial to understand the evolution and transmission of a virus in its incipient pandemic, especially the transmission chains, which can help to design effective strategies for disease control and prevention (1). However, it is time consuming and costly to ascertain transmission chains traditionally, in which the process largely relies on case incidence data and interview-based contact tracing (2). A recent study on the epidemiology of coronavirus disease 2019 (COVID-19) in Guangdong Province, China found the transmissions from epidemiological data were congruent with the phylogenetic cluster patterns that inferred from single nucleotide variations (SNVs) of COVID-19 virus genomes (3), suggesting the possibility to infer transmission chains from viral genomes. To investigate possible correlations between transmission chains and viral genetic variations, we combined both epidemiological data and viral genomes of COVID-19 virus collected from Sichuan Province. We found the putative transmission chains are highly concordant to the true transmission chains from epidemiological data. Given to the low cost and convenience of sequencing viral genomes, this approach showing promise to assist disease control and prevention during viral pandemic.