(1), Denmark (1), Czech Republic (1), Turkey (1), Australia (1), Curacao (1), and Zimbabwe (1). Epidemiology There have been a small number of cases, primarily imports, of Lambda (C.37) in the United Kingdom (UK). As of the 22 June 2021, there have been 6 cases of Lambda in the UK between 23 February and 7 June 2021. Four cases were from London, one from the South West and one from West Midlands. Five cases have history of travel overseas, for one case travel status is unknown. No deaths have been reported within 28 days. Cases are managed in line with the approach for emerging variants with review of contact tracing, additional data collection, testing of identified contacts, and consideration of targeted case finding as required where there is evidence of community transmission. 2 Romero PE and others (2021). Novel sublineage within B.1.1.1 currently expanding in Peru and Chile, with a convergent deletion in the ORF1a gene. (Δ3675-3677) and a novel deletion in the Spike gene (Δ246-252, G75V, T76I, L452Q, F490S, T859N). Virologica.org, 24 Apr 2021. 3 Weekly epidemiological update on COVID-19 to 15 June 2021 SARS-CoV-2 variants of concern and variants under investigation 67 Sources and acknowledgments Data sources Data used in this investigation is derived from the COG-UK dataset, the PHE Second Generation Surveillance System (SGSS), NHS Test and Trace, the Secondary Uses Service (SUS) dataset, Emergency Care Data Set (ECDS), and the PHE Case and Incident Management System (CIMS). Data on international cases are derived from reports in GISAID, the media and information received via the International Health Regulations National Focal Point (IHRNFP) and Early Warning and Response System (EWRS). Repository of human and machine-readable genomic case definitions A repository containing the up-to-date genomic definitions for all VOC and VUI as c 1 INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China in December 2019, and is responsible for the current pandemic of ‘coronavirus disease 2019’ (COVID19) [1, 2]. As of 23 February 2021, there have been over 111,279,860 cases worldwide, with more than 2,466,639 confirmed deaths, affecting 223 countries [3]. SARS-CoV-2 is a positive-sense, single-stranded RNA virus, with a genome that is approximately 30kb in length and reported to contain 14 open reading frames encoding 27 proteins [4]. Genome sequencing of SARS-CoV-2 has taken place since the beginning of the pandemic, contributing to an understanding of viral evolution and enabling genomic epidemiology investigations into COVID-19 disease origins and spread. As of 23 February 2020, 595,339 SARS-CoV-2 genome sequences have been uploaded and shared via the GISAID database [5]. These sequencing efforts, and monitoring and surveillance of variation within the SARS-CoV-2 genome, enabled the rapid identification of the first of a number of variants of concern (VOCs) in late 2020, where genome changes were having observable impact on virus biology and disease transmission. Several initiatives that use available sequencing data, mostly from GISAID, to monitor variants and provide further analysis are summarized in Appendix 1. Here we outline how genomic surveillance and sequencing have supported the recent identification of new SARS-CoV-2 variants and the impact that these variants have had on currently available diagnostic tests and public health measures. We also summarize the role of sequencing in the development of currently available vaccines. 2 SARS-COV-2 VARIANTS AND MUTATIONS SARS-CoV-2, like all viruses, accumulates mutations – changes in its genetic code – over time as it replicates. This virus has inherent RNA repair mechanisms, and therefore accumulates mutations at a relatively slower rate than most other RNA viruses. On average, a genome from a virus collected in October 2020 has around 20 mutations compared to the first strain sequenced in January 2020 (Wuhan-Hu-1) [6]; the virus evolves at a rate of ∼1.1 × 10−3 substitutions per site per year, corresponding to one substitution every ∼11 days [7]. This compares to a rate of ∼4 × 10−3 substitutions per site per year for the HIV virus [8]. Across all virus genomes sequenced to date, thousands of mutations have emerged since the start of the pandemic, which in turn have given rise to thousands of different variants. The majority have had no perceivable impact on the virus or disease biology and can act as a useful genetic ‘barcode’ for tracking viral spread and evolution. However, more recently, several variants have been identified that appear to increase transmissibility, and potentially have an impact on disease severity. As a result, they have been labelled VOCs. Currently, four internationally confirmed VOCs have been identified − B.1.1.7, B.1.351, P.1 and Cluster 5 (table 1). These are the best characterized and studied so far, and there is supporting evidence of an impact on virus biology available from several countries. As the pandemic continues to unfold, it is likely that more VOCs will be identified, particularly in the presence of new selection pressures, such as vaccination. SARS-CoV-2 variants 4 2.1 Definitions of variants of concern On 25 February 2021, WHO released a document outlining working definitions of VOCs