Genomic epidemiology of SARS-CoV-2 in Guangdong Province, China

Abstract

Highlights: 1) 1.6 million molecular diagnostic tests identified 1,388 SARS-CoV-2 infections in Guangdong Province, China, by 19th March 2020; 2) Virus genomes can be recovered using a variety of sequencing approaches from a range of patient samples. 3) Genomic analyses reveal multiple virus importations into Guangdong Province, resulting in genetically distinct clusters that require careful interpretation. 4) Large-scale epidemiological surveillance and intervention measures were effective in interrupting community transmission in Guangdong Summary: COVID-19 is caused by the SARS-CoV-2 coronavirus and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain due to low virus genetic variation early in the pandemic. Our results illustrate how the timing, size and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required as the number of cases imported from other countries is increasing.

Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions

“…Although much of the pathophysiology of the novel coronavirus, SARS-CoV-2, remains unknown, studies have reported the virus using the receptor ACE2 for entry into target cells (Hoffman et al, 2020;Lu et al, 2020). Further validating this, we found expression of the ACE2 gene was significantly upregulated in the samples with higher viral load, as well as some cytokine genes, which matches observations found in other betacoronaviruses (Sajuthi et al, 2020).…”

Tracking the onset date of the community spread of SARS-CoV-2 in Western Countries

“…Genomic epidemiology could be a useful tool to track the geographic spread of SARS-CoV-2 over time and to infer the timing of community transmission. Its implementation has enabled to trace back the time of the most recent common ancestor (T MRCA ) of SARS-CoV-2 to late November 2019, (8) consistent with epidemiological findings that show viral local transmission in Wuhan by the middle December 2019. (9) Within this same framework, a recent analysis of SARS-CoV-2 genomes from 21 neighborhoods in New York city (NYC) revealed that the NYC epidemic has been mainly sourced from untracked transmission between the USA and Europe and also pointed that the virus was likely circulating in the city weeks before the first confirmed SARS-CoV-2 infection case.…”

“…Due to the short period of time since the beginning of the outbreak and to the uneven geographic sampling of SARS-CoV-2 genomes, in most cases, there's still not enough phylogenetic signal to define location-specific clusters. (8,11) Here, we aimed to develop a simple inference method to estimate the onset date of the community spread of SARS-CoV-2 in different countries from the cumulative number of reported deaths during the early stage of the epidemic. The cumulative number of deaths could be a reliable tracker of the SARS-CoV-2 epidemic's progress within a country.…”

Revealing COVID-19 Transmission by SARS-CoV-2 Genome Sequencing and Agent Based Modelling

“…Our genomic data have also confirmed the dominance of overseas acquired infections in these early stages of the epidemic in Australia Our findings extend the value of genomic surveillance in depicting transmission pathways and evolution of emerging pathogens 13, 21,22 . They also improve our understanding and support the implementation of genomically enhanced surveillance for more efficient COVID-19 control strategies and the investigation of cases with unclear infection sources and within a short turn-around-time 16,17,21,22 . The initial delay of 21 days between date of collection and sequencing for the first three samples received included the time taken to establish the inhouse amplicon-based WGS method used in this study.…”

“…Importantly, the ongoing analysis of this global data set suggests no significant differences or links between SARS-CoV-2 genome sequence variability and virus transmissibility or disease severity 15 . However, even during these early stages of the global pandemic, genomic surveillance has been used to differentiate currently circulating 4 strains into distinct, geographically based lineages and reveal multiple SARS-CoV-2 importations into geographical regions of China and the USA 16,17 .…”