Epidemiological and Genomic Analysis of SARS-CoV-2 in Ten Patients from a Mid-sized City outside of Hubei, China in the Early Phase of the COVID-19 Outbreak

In this study, we performed a comprehensive epidemiological and genomic analysis of SARS-CoV-2 genomes from ten patients in Shaoxing, a mid-sized city outside of the epicenter Hubei province, China, during the early stage of the outbreak (late January to early February, 2020). We obtained viral genomes with > 99% coverage and a mean depth of 296X demonstrating that viral genomic analysis is feasible via metagenomics sequencing directly on nasopharyngeal samples with SARS-CoV-2 Real-time PCR C t values less than 28. We found that a cluster of 4 patients with travel history to Hubei shared the exact same virus with patients from Wuhan, Taiwan, Belgium and Australia,highlighting how quickly this virus spread to the globe. The virus from another cluster ofhusband and wife without travel history but with a sick contact of a confirmed case fromanother city outside of Hubei accumulated significantly more mutations (9 SNPs vsaverage 4 SNPs), suggesting a complex and dynamic nature of this outbreak. We alsofound 70% patients in this study had the S genotype, consistent with an early studyshowing a higher prevalence of S genotype out of Hubei than that inside Hubei. Wecalculated an average mutation rate of 1.37x10 -3 nucleotide substitution per site peryear, which is similar to that of other coronaviruses. Our findings add to the growingknowledge of the epidemiological and genomic characteristics of SARS-CoV-2 that areimportant for guiding outbreak containment and vaccine development. The moderatemutation rate of this virus also lends hope that development of an effective, long-lastingvaccine may be possible.