Yale SARS-CoV-2 Genomic Surveillance Initiative

New variants of SARS-CoV-2 not yet detected in Connecticut

Over the past weeks, variants of SARS-CoV-2 isolated in the United Kingdom (UK; lineage B.1.1.7) [1,5] and South Africa (B.1.177) [2] were associated with increased incidence of COVID-19 [1] (Figure 1A). In response, government officials imposed tougher restrictions to curb the spread of these variants [1]. While these specific variants have not yet been identified in the United States, one specific mutation shared between both the UK and South Africa variants has also been identified in some U.S. samples [3]. This mutation, called “N501Y”, has been associated with increased infectivity in human and mouse cells [4]. From the 473 SARS-CoV-2 genomes that were sequenced from Connecticut, we have not yet found the N501Y mutation. However, COVID-19 samples from Connecticut have not been sequenced since October, and N501Y has only recently been detected in 8 viruses sequenced from the US. 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.1.177 as well as the N501Y mutation should be a top priority in our region.

The variant found in the UK (B.1.1.7) contains 17 unique mutations [5]. 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 led 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 (hence the “N501Y” name) and the deletion of two amino acids at positions 69 and 70 of the protein.

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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.1.177). 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 [5]. Most nonsynonymous mutations were detected in regions that encode the Spike protein, and deletions were also detected.

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 detection of rapidly spreading viruses, in two distinct countries, both sharing at least the N501Y mutation, suggests that we should remain vigilant. Many studies are being conducted to uncover the true impact of those mutations, and we will have more answers soon.

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.

For media inquiries, please contact Dr. Anderson Brito (anderson.brito@yale.edu).

References

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. 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.
4. Gu, H. et al. Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy. Science 369, 1603–1607 (2020).
5. 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).