In early December, a variant of SARS-CoV-2 associated with increased cases of COVID-19 was identified in the UK (B.1.1.7)1.
- Early epidemiological and phylogenetic data in the UK indicates that certain mutations common to both variants increases the ability of infected individuals to transmit the virus.
- A variant with mutation leading amino acid change N501Y (B.1.351) has been identified in South Africa2.
- The first case of the B.1.1.7 variant in the US was identified in Colorado on December 29 with no travel history3.
- There is no evidence so far that this variant causes a more severe infection or has an impact on the effectiveness of vaccines.
Importance of new variants of SARS-CoV-2
In early December, variants of SARS-CoV-2 isolated in the United Kingdom (UK; lineage B.1.1.7) and South Africa (B.1.351) were associated with increased incidence of COVID-19 (Figure 1A). In response, government officials imposed tougher restrictions to curb the spread of these variants 1,2. The first confirmed US case of B.1.1.7 variant was in Colorado on December 293. In addition, one specific mutation shared between both the UK and South Africa variants was also been identified in some U.S. samples retrospectively4. This mutation, called “N501Y”, has been associated with increased infectivity in human and mouse cells5.
The variant found in the UK (B.1.1.7) contains 17 unique mutations6. Among them, eight were found to affect the spike protein, which coronaviruses use for cell entry and is detected by antibodies. Two of these mutations lead to changes in potentially important amino acids of the spike protein (Figure 1B): a replacement of an amino acid asparagine (N) to a tyrosine (Y) in the position 501 of the protein (hence the “N501Y” name) and the deletion of two amino acids at positions 69 and 70 of the protein.
Figure 1. Genomic information about the new SARS-CoV-2 variants. (A) Phylogenetic tree highlighting the two lineages expressing the spike protein variant N501Y, independently observed in viruses circulating in the United Kingdom (B.1.1.7) and in South Africa (B.1.351). An interactive version of this tree (by Hodcroft and Neher) can be found on https://nextstrain.org/groups/neherlab/ncov/S.N501?c=gt-S_69,501,681&m=div&p=full&r=country. (B) List of amino acid changes observed in the variant circulating in the UK (B.1.1.7), provided by CoG-UK. Most nonsynonymous mutations were detected in regions that encode the Spike protein, including substitutions and deletions.
It is not yet known whether any of these mutations individually or in tandem will alter the effectiveness of the current vaccines or drugs, though there is no strong reason to believe that it will make an impact. So far the evidence suggests that they do not make infections more severe, only that it is possible that they make the viruses more transmissible. That is, this variant may be more efficient at infecting cells in the upper respiratory tract (nose, throat, etc), and as a consequence, may be more easily transmitted. However, the true impact of these genetic changes has yet to be determined, but the fact that rapidly spreading viruses in two distinct countries share at least the N501Y mutation suggests that we should remain vigilant. Many studies are being conducted to uncover the true impact, and we will have more answers soon.
From the 473 SARS-CoV-2 genomes that were sequenced from Connecticut, we already found viruses from B.1.1.7 (see our latest report). While further research is needed to determine if any virus containing the N501Y mutation has increased transmission potential, surveillance for lineages B.1.1.7 and B.1.351 as well as the N501Y mutation should be a top priority in our region.
Our group, in collaboration with the Connecticut Department of Health, will intensify the genomic surveillance of SARS-CoV-2 in circulation in our region to detect the presence of these variants as they arise.
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1. Kupferschmidt. Mutant coronavirus in the United Kingdom sets off alarms, but its importance remains unclear. https://www.sciencemag.org/news/2020/12/mutant-coronavirus-united-kingdom-sets-alarms-its-importance-remains-unclear (2020).
2. Tegally, H. et al. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. https://www.krisp.org.za/publications.php?pubid=315.
3. Polis, J. Gov. Polis and State Public Health Officials Announce First Case of COVID Variant of COVID-19 in Colorado. https://www.colorado.gov/governor/news/3856-gov-polis-and-state-public-health-officials-announce-first-case-covid-variant-covid-19
4. Hodcroft, E. & Neher, R. Phylogenetic analysis of SARS-CoV-2 clusters in their international context – cluster S.N501. https://nextstrain.org/groups/neherlab/ncov/S.N501?c=gt-S_69,501,681&m=div&p=full&r=country.
5. Gu, H. et al. Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy. Science 369, 1603–1607 (2020).
6. Andrew Rambaut, Nick Loman, Oliver Pybus, Wendy Barclay, Jeff Barrett, Alesandro Carabelli, Tom Connor, Tom Peacock, David L Robertson, Erik Volz, COVID-19 Genomics Consortium UK (CoG-UK). Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563 (2020).