SARS-COV-2 is a novel coronavirus first reported in Wuhan, China in December 2019 which caused an epidemic of acute respiratory syndrome (1, 2). Since then, the coronavirus disease 2019 (COVID-19) has spread quickly all over the world causing great casualties and property losses (3, 4). By mid-March 2022, nearly 460 million cases of COVID-19 were diagnosed with over 6 million deaths around the world (https://coronavirus.jhu.edu/map.html). All viruses, including SARS-CoV-2, change over time. Most changes have little to no effect on virus properties, but some changes especially the mutation accumulation may affect the propagation, pathogenicity, performance of vaccines, diagnostic tools, and so on (5). In order to prioritize global monitoring and research, and ultimately inform the ongoing response to the COVID-19 pandemic, the world health organization (WHO) classified important variants into two categories: variants of concern (VOC) and variants of interest (VOI) (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants). VOC means that the Virus strains have a wide range of influence, and data supports it enhancing the transmissibility and detrimental change or reduces the vaccine effectiveness and therapeutic effect. VOI means that the Virus strains are predicted or known to change characteristics, and have been found in many countries with an increasing number of cases over time. Given the continuous evolution of the virus and the constant developments in our understanding of the impacts of variants, these definitions may be periodically adjusted. Currently, there are five designated VOCs (Alpha from the UK, Beta from South Africa, Gamma from Brazil, Delta from India, and Omicron from Multiple countries) and two VOIs (Lambda from Peru and Mu from Colombia). Each strain contains its unique characteristic mutation spectrum and also has the same mutation sites among strains. Alpha, Beta, and Gamma have the same mutation N501Y within the receptor-binding domain (RBD) of the spike protein, which can increase the affinity to human angiotensin-converting enzyme 2 (hACE2) (6, 7). This may play an essential role in the higher transmission of these strains. Beta and Gamma have another shared mutation, E484K, in their spike protein, this mutation can not only enhance the receptor binding affinity but also can escape the neutralization by vaccine-induced humoral immunity or some therapeutic monoclonal antibodies (8–10). Focusing on the mutations of the Delta strain, it hosts L452R T478K P681R mutations in RBD, these can greatly improve the transmission ability and immune system evasion (11, 12). Since April 2021, Delta has expanded rapidly in the world until the emergence of Omicron in December 2021. Omicron contains more than 15 mutations in RBD, these mutations greatly changed the structure of Spike protein, enhanced its binding ability to ACE2, and invalidated many antibody binding sites (13, 14). In addition, Omicron also got rid of the dependence on cellular protease TMPRSS2 and made it reproduce rapidly and massively in airway cells above the lungs that do not express TMPRSS2, which not only increased the viral load but also accelerated the transmission speed of the virus (15, 16). At present, Omicron has almost completely replaced Delta all over the world.

China was also troubled by the SARS-COV-2 Delta strain. Since June 2021, it has been found in new outbreaks in Yunnan, Guangdong, and Jiangsu. The outbreak started at Lukou Airport of Nanjing with related epidemics in many provinces and cities. Because of omissions in cleaning and disinfection of an inbound Russian aircraft CA910 which arrived at Lukou Airport in Nanjing from Moscow on July 10, the cleaning staff were infected with SARS-COV-2 and then caused the spread of the infection. The investigation showed that the SARS-COV-2 outbreak in Yantai was also closely related to this source. The first Lukou-related case in Yantai was diagnosed on 31 July 2021 and a total of 13 patients were finally diagnosed in 5 days. It was worth noting that the epidemiological investigation showed that the transmission relationship among the 13 people was complex. So in order to determine the virus strains type and the transmission relationship between cases, we sequenced the whole genomic nucleic acids of these 13 cases based on second-generation high-throughput sequencing technology (NGS), analyzed the gene characteristics and variation of the virus from the molecular level, and traced the source of the virus.

Delta VOC was first identified in October 2020 and has become a major variant globally since April 2021. According to WHO research, the transmission rate of the Delta virus has increased by nearly 100% compared to other strains not listed as “of concern,” and a recent study of the transmission dynamics of the Delta variant virus that caused the COVID-19 outbreak in Guangdong, China, also suggests that it is twice as infectious as previous pandemic strains (22). The Delta variant also spread faster than other strains. In the past, the incubation period of the Novel Coronavirus has been 5–6 days, and that of the Novel Coronavirus Delta variant is 4 days. The passage interval used to be 4 or 5 days, but now it is about 3 days (23, 24).

Thirteen cases of this outbreak, caused by a Delta variant in Yantai have been locally transmitted. During the study period, the local government implemented an epidemiological follow-up, and we sequenced all confirmed patients. This provides an opportunity for our study to understand its transmission characteristics.

In this outbreak, we found that patient 1 has been to YEDA and infected one close contact, there may be track crossing with other cases in YEDA. So only investigating the track of the action could not determine the transmission relationship of this epidemic. At this time, whole-genome sequence information may provide evidence for genotyping and phylogenetic analysis which help us to resolve this difference (25, 26), of course, this must also be based on a certain basis: their sequences must have enough differences. Fortunately, the virus transmitted this time meets this prerequisite. Through sequence analysis, we determined that this epidemic situation had two transmission routes (Figure 1) and obtained the mutation spectrum (Figure 2) of each virus. Based on this information, the prevention and control work was carried out in two ways immediately and simultaneously. By the end of this epidemic, there were only 13 cases, which was a great achievement for a city with 3 million people. Like other similar studies, it fully illustrates the importance of rapid virus genome analysis in epidemic prevention and control (27–30).

As SARS-CoV-2 continues to spread around the world, the dynamics of virus evolution and mutation are still changing, and new viruses are constantly acquiring new mutations in their genomes. Although some mutations provide the virus with the advantage of resisting human immune response, these mutations may lead to changes in pathogenicity and virulence (31). Therefore, future prevention and control work should strengthen screening of close contacts, investigation of infection sources, investigation of clusters of outbreaks, and active detection of people in high-risk areas.

The original contributions presented in the study are publicly available. This data can be found here: GISAID, the accession numbers can be found in the Supplementary Material.

Written informed consent was not obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

YS: data curation, investigation, and writing original draft preparation. YZ: data curation, formal analysis, investigation, and resources. ZL: formal analysis, investigation, and methodology. XL and JL: data curation, methodology, and resources. XT, QG, PN, and ZH: data curation and investigation. ZS: methodology, data curation, writing original draft preparation, writing review and editing, and project administration. YT and JW: methodology, data curation, writing review and editing, and project administration. All authors have read and agreed to the published version of the manuscript.

This work was supported by the Yantai scientific project (No. 2020YD081), Technological Innovation Project in Shandong Province (No. 2020SFXGFY02-1), National Natural Science Foundation of China (No. 42177418).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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