some vaccines [20]. For B.1.351, there may be some form of enhanced escape from immune pressure and onward transmission, generating a fitness advantage, but the evidence for this is still weak [21]. In the case of the P.1 variant, Japan reported the variant via their surveillance system, after detection in four travellers who had returned from Brazil [22]. The variant was flagged to be of concern due to the presence of spike mutations also found in the B.1.351 variant: N501Y (which increases virus binding affinity to the ACE2 receptor on human cells), E484K (which renders the virus less susceptible to some monoclonal antibodies) and K417N/T (suggested to increase binding affinity to ACE2, in combination with N501Y). The set of mutations/deletions, especially N501Y, shared between the P.1, B.1.1.7 and the B.1.351 variants appear to have arisen independently. P.1 and B.1.351 also appear to be associated with a rapid increase in cases in locations where COVID-19 disease rates were previously high. Therefore, it will be crucial to investigate whether there is an increased rate of recent re-infection, caused by these variants, in previously exposed healthy individuals. The fourth variant, Cluster 5, was a VOC identified on mink farms in Denmark and the Netherlands. Swift action from local public health authorities in these countries stopped the spread of this VOC, and it is now believed to be extinct (see section 4.2). Ongoing monitoring of variants B.1.1.7, B.1.351 and P.1 is being carried out globally. SARS-CoV-2 variants Table 1: Variants of concern. Further information is available via online resources ([23, 24]) that are closely monitoring the main variants identified (B.1.1.7, B.1.351 and P.1). *Information extracted 19 January 2021 [24]. Variant (Bold indicates the most commonly used variant notation; other known notations for each variant recorded below) First identified (location) Date identified Notable mutations Number of defining mutations (number in spike) Clinical changes Number of countries reporting variant Sequence counts Transmissibility Virulence Antigenicity B.1.1.7, VOC-202012/01, 20B/501Y.V1 United Kingdom Nov 20 N501Y, 69–70del, P681H 23 (8) Yes, evidence of increased transmissibility (PHE) >40% Potential evidence emerging suggesting increased virulence No evidence of change 83* 79,434* B.1.351, 501Y.V2; 20C/501Y.V2 South Africa Dec 20 N501Y, K417N, E484K 21 (9) Yes, evidence of increased transmissibility (South African Department of Health) No evidence of change Undergoing investigation (E484K mutant) 41* 1436* P.1, 501Y.V3, B.1.1.28.1 Brazil and Japan Dec 20 N501Y, E484K, K417N 17 (10) Undergoing investigation (N501Y mutant), evidence is suggesting increased transmissibility unknown K417T possibility escaping some monoclonal antibodies 20* 153* Cluster 5, ΔFVI-spike Denmark Oct 20 Y453F, 69– 70del Not described (4) No evidence of change No evidence of change Yes "Moderately decreased sensitivity to neutralizing antibodies" Likely extinct >300 SARS-CoV-2 variants 7 2.3 Variants of interest As the pandemic continues, new variants will emerge. Ongoing surveillance will therefore be required not only for known VOCs, but also for VOIs. Variants of interest that are currently being closely monitored include the P.2 variant in Brazil, of interest because it harbours a E484K mutation seen in other VOCs [25], and the CAL.20C variant in California, with an L452R mutation suggesting increased transmissibility [26]. Multiple variants with mutation Q677P, also suspected to increase transmissibility, have been identified in a number of states in the U.S. [27]. According to the Pan American Health Organization (PAHO) of WHO, three new variants have been detected in 14 countries in the Americas and flagged as possibly causing heightened spread and more severe disease [28]. In the UK, a second variant named VOC202102/02 – that is B.1.1.7 with an additional E484K mutation – has been labelled a VOC by Public Health England, due to it retaining the characteristics of the original B.1.1.7 VOC, but with an additional mutation. It has been associated with a limited number of cases and is being closely monitored. Another variant with an E484K mutation is also being monitored [29]. These and other variants still need to be evaluated further to determine if they are VOCs and if they are having an impact globally. 3 IMPACT OF VARIANTS ON DIAGNOSTICS Sequencing data can be used to understand whether current diagnostic tests remain fit for purpose, as well as inform the development of new diagnostics. As described below, virus mutations have the potential to reduce the accuracy of diagnostic tests. Regular analysis of sequence data can allow researchers to identify any mutations of particular concern, which can then be investigated to see if they impact on test function. Alternatively, if a test appears to not be working as expected, for example continually delivering false negative results, the samples could be sequenced to see if they contain a mutation responsible for test failure. Routine testing for SARS-CoV-2 can be categorized according to the test target, including direct viral detection of either viral RNA or viral antigens indicative of current infection, or indirect detection of anti-SARS-CoV-2 specific antibodies, indicative of current or historic infection [30]. Nucleic acid amplification tests (NAATs), including those based