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. 2020 Oct 30;11(1):5503.
doi: 10.1038/s41467-020-19345-0.

Genomic surveillance of COVID-19 cases in Beijing

Affiliations

Genomic surveillance of COVID-19 cases in Beijing

Pengcheng Du et al. Nat Commun. .

Abstract

The spread of SARS-CoV-2 in Beijing before May, 2020 resulted from transmission following both domestic and global importation of cases. Here we present genomic surveillance data on 102 imported cases, which account for 17.2% of the total cases in Beijing. Our data suggest that all of the cases in Beijing can be broadly classified into one of three groups: Wuhan exposure, local transmission and overseas imports. We classify all sequenced genomes into seven clusters based on representative high-frequency single nucleotide polymorphisms (SNPs). Genomic comparisons reveal higher genomic diversity in the imported group compared to both the Wuhan exposure and local transmission groups, indicating continuous genomic evolution during global transmission. The imported group show region-specific SNPs, while the intra-host single nucleotide variations present as random features, and show no significant differences among groups. Epidemiological data suggest that detection of cases at immigration with mandatory quarantine may be an effective way to prevent recurring outbreaks triggered by imported cases. Notably, we also identify a set of novel indels. Our data imply that SARS-CoV-2 genomes may have high mutational tolerance.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. The COVID-19 cases in Beijing and sequenced in this study.
a The geographic sources of the cases in our hospital. b The number of cases in Wuhan group (from or passed by Wuhan), local group (onset locally and without Wuhan or overseas travel history), and imported group (overseas imported) in our hospital. The histograms represent the daily case numbers and the lines show cumulative case numbers in the three groups. c The number of well-sequenced cases (n = 102). The histograms represent the sequenced case numbers on each day and the orange line shows the cumulative case numbers. d The average sequencing coverage among the sequenced cases (n = 102). The shadow represents the lower and upper quartiles. Source data are provided as a Source Data file.
Fig. 2
Fig. 2. Genotype analysis and lineage determination of the viral genomes and the difference among the three groups.
a The viral genotypes from our data and public genome data. The heatmap shows genome clustering based on 17 high-frequency SNPs. The purple lines above the heatmap indicate the genomes sequenced in this study. The sublineages are marked on the top, and the geographic sources of the genomes are marked below the lineage. b The minimum-spanning tree of the seven clusters. The genomes from different continents are displayed on the pie by colors. The SNP differences are displayed on the lines between two clusters, and those caused by non-synonymous mutations are in red. c The histogram on the top displays the numbers of genomes we sequenced from each group in each cluster, and that at the bottom displays the early major lineages corresponding to each cluster. d The numbers of viruses from different clusters emerged in the three groups during the outbreak. The pie charts at the right show the proportion of the clusters in the three groups. Source data are provided as a Source Data file.
Fig. 3
Fig. 3. The distribution of SNPs and iSNVs in the viral genomes sequenced in this study.
a The numbers of SNPs and iSNVs in each cluster. The number of genomes in each cluster are displayed in the brackets. b The distribution (left) and frequency (right) of SNPs identified in the 102 genomes of the three groups and seven clusters. The red dots represent the positions of SNPs. The histogram shows the frequencies of the SNPs in each cluster. c The distribution (left), frequency (middle), and minor allele frequency (right) of iSNVs identified in the 102 genomes of the three groups and seven clusters. The green dots represent the positions of iSNVs. The histograms show the frequencies of the iSNVs in the enrolled population. The boxplots and scatter plots show the minor allele frequency of iSNVs. Boxplots indicate median (middle line), the first and third quartiles (box), the first quartile minus 1.5-fold the interquartile range, and the third quartile plus 1.5-fold the interquartile range. Source data are provided as a Source Data file.
Fig. 4
Fig. 4. The indels identified in the viral genomes sequenced in this study.
a The loci of the indels and their distribution in the sequenced genomes. The arrow chart on top represents the protein-coding genes of SARS-CoV-2, and the vertical lines below mark the loci of the indels. bd The read coverage of the three long fragment deletions in ORF6, ORF7a, and ORF8, respectively. Arrow charts in the middle represent the protein-coding genes, and the curves of read coverage and split reads supporting the deletions are displayed above. Forward and reverse mapping reads are in blue and red, respectively. Sanger sequencing results of corresponding PCR fragments are displayed below; resulting protein mutations are shown at the bottom.

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