and variants of interest (VOI), including recommended actions for member states if a VOI or VOC is identified [9]. A VOI is defined as an isolate of SARS-CoV-2 that has genotypic and/or phenotypic changes compared to the reference genome. The threshold for defining a VOI is quite low, in order to support surveillance efforts. A VOC is defined as a VOI which has a demonstrable increase in transmissibility, increase in virulence and/or is not being controlled effectively by current public health measures. The threshold of evidence for defining a VOC is quite high, to ensure focussed attention and resources on the variants with the greatest health implications. The full VOI and VOC working definitions as given by WHO are included in the glossary of this report. Other contextual data, such as further characterization in the laboratory, will also support the identification of VOIs and VOCs, since this can help scientists understand whether there are phenotypic changes that improve viral fitness (replication capacity) or impact disease severity. Variants possessing one or more mutations suspected of improving viral fitness can be searched for, flagged, and monitored as VOIs. For example, mutations arising in the spike protein – a common vaccine target – or those which result in changes to an amino acid may be monitored and investigated further. However, due to the variety and number of mutations in the SARS-CoV-2 genome, it is not practical to monitor them all, and prioritizing which variant to follow up is important. In addition, collation of all the genomic, epidemiological and laboratory information about a new variant to determine if it is a VOC can take some time. There is still some variability around the terms and naming systems used to describe the genetic diversity of SARS-CoV-2; for example, the words ‘variant’, ‘strain’ and ‘lineage’ have been used interchangeably. There is some debate around the use of the term ‘variant’, with some suggesting that a description of the ‘constellation’ of mutations is more important to define than just naming the variants themselves. A summary of these definitions is provided in the glossary. Several naming systems for VOCs have also been proposed. Public health authorities have taken to naming VOCs by the date of their identification. For example, Public Health England dubbed the variant they identified that was enhancing transmission, VOC202012/01, after the date it was first identified. This is also known as VOC B.1.1.7. Researchers in South Africa who identified a VOC named it after a defining mutation at the 501st amino acid site, 501Y.V2 (also known as VOC B.1.351) [10]. However, naming a variant after a mutation might cause confusion since it is not always clear, when it was first identified, and which mutations may be of concern, since it is possible that a combination of several mutations is more important in terms of defining the VOC. A naming system proposed by researchers at NextStrain uses a year and letter system to define different SARS-CoV-2 clades [11]. In April 2020, Rambaut et al. proposed a lineage naming system for SARS-CoV-2 [12] which is currently the most commonly used when referring to current known VOCs, e.g., B.1.1.7, B.1.351 and P.1. This is the naming convention followed in this report. Discussions initiated by the WHO Virus Evolution Working Group are underway to produce a standardized nomenclature for SARS-CoV-2 [13]. SARS-CoV-2 variants 5 2.2 Initial variants of concern identified Genomic data is essential in supporting the identification of VOCs and having an effective genomic surveillance system in place can allow VOCs to be identified as rapidly as possible. Both the United Kingdom and South Africa, where VOCs have been identified, established genome sequencing initiatives early on in the pandemic: COG-UK [14] and NGS-SA, respectively [15]. Surveillance systems in Denmark, The Netherlands and Japan also contributed to the identification of VOCs. In the UK, the B.1.1.7 variant was first identified as a VOC by COG-UK in December 2020, as it was increasing in frequency during a nationwide lockdown, whilst other variants were decreasing in frequency. A retrospective examination of the data determined that the variant had been in circulation since September, but at that time there were insufficient data to suggest that it was a VOC. The B.1.1.7 variant is currently the most highly sequenced and well-characterized VOC, and has been shown to have increased levels of transmissibility at a rate of between 40 and 70% [16]. In addition, a paper from the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) and presented to the UK Government’s Scientific Advisory Group for Emergencies (SAGE) outlined the results from several preliminary analyses of B.1.1.7, suggesting that there could be an increase in mortality rates as a result of the variant [17, 18]. The COG-UK mutation tracker outlines the spike protein mutations seen circulating in the UK [19]. It also details the scientific evidence to date on the impact of different mutations on immune evasion. In South Africa, the B.1.351 variant was identified after frontline clinicians alerted NGS-SA to a rapid increase in cases, which prompted genomic investigation. The B.1.351 variant is a concern as it has been shown to have increased transmissibility and to reduce the efficacy of