The SARS-CoV-2 UK Mutation

Published on December 21, 2020

Dr. Sarah Zaidi, the editor and co-author of “Breaking Down Covid-19,” a comprehensive review of the SARS-CoV-2 virus and pandemic, who has kindly contributed her epidemiology expertise to our clients throughout the course of 2020, has provided below a rapid analysis of the latest virus mutation that has been ripping through the UK.

As with the other SGH COVID reports, the contents of this report were generated by Dr. Zaidi and were not produced or edited except for formatting and flow purposes by SGH Macro Advisors.

On September 20, a distinct phylogenetic cluster (named lineage B.1.1.7) was detected within the COVID-19 Genomics UK Consortium surveillance dataset. Over the past few weeks, the cluster of cases with this new variant has grown rapidly in South East England and London. In mid-November only 26% of cases accounted for the B.1.1.7 variant but by the week of December 9, the new variant accounted for 60% of all cases in London. The variant has been identified in cases from Australia (1), Belgium (4), Denmark (9), and the Netherlands (1) suggesting that international spread has occurred, although the extent remains unknown.

At this time, the variant does not seem to result in poorer clinical outcomes or higher mortality, but it is more highly transmissible than previously circulating variants, with an estimated potential to increase the reproductive rate (R) by 0.4 or greater with an estimated increased transmissibility of up to 70%. The variant is largely seen in people younger than 60 years old, but this age group is driving the increase of overall COVID-19 cases in the U.K.

The fear of increased transmissibility of B.1.1.7 SARS-CoV-2 variant forced 30 countries to impose a trade and travel bans on December 20 against the U.K. The British government also imposed a travel ban in the four nations of the UK along with a strict lockdown of London and surrounding areas. While the bans may seem extreme, it will help to slow down transmission if the B.1.1.7 variant turns out to be much more transmissible than the original SARS-CoV-2 virus that emerged a year ago.

Origins and genomic properties of the new SARS-CoV-2 variant

The B.1.1.7 lineage carries 17 mutations of which 8 are on the Spike protein and one of the mutations (N501Y) is located within the receptor-binding domain (RBD). The cluster differs from the original Wuhan strain by 29 nucleotides, which is higher than the estimated changes of two mutations per month.

It is speculated that the unusual genetic divergence of lineage B.1.1.7 may have resulted from virus evolution with a chronically infected individual. Another explanation suggests that the virus jumped from a susceptible animal such as the one leading to the variant observed in Denmark during transmission among mink. But the U.K. reported that there is no clear epidemiological link to animals.

The Spike protein comprises 13% of the viral genome and it is the main entry point of the virus into the host cell. The mutations of significance on the Spike protein include spike position 501 that increases ACE2 receptor affinity and increased infectivity and P681H that creates a cleavage site between S1 and S2 in spike promoting entry into respiratory epithelial cells and transmission in animal models. Both these mutations have been observed independently but not in combination. In the B.1.1.7 variant, these mutations may provide the virus with a selective advantage, such as increased transmissibility through an increase in receptor binding or the ability to evade the host immune response by altering the surface structures recognized by the antibodies.

As yet there is no evidence that resulting mutations in the B.1.1.7 variant impacts on increased risk for reinfection or lower vaccine effectiveness. There is also no evidence of the variant resulting in increased severity of illness or mortality.  The U.K. continues to monitor the spread of the new virus variant.

Implications for human health

Viruses, especially RNA viruses, are constantly changing as a result of genetic selection, and the emergence of a new variant is not unusual or in itself a cause for concern. Most mutations do not provide the virus with selective advantage. Earlier in April, the D614G mutation, which was predominant lineage in Europe, and described as ‘alarming and dangerous’ turned out to be a process of natural selection and replaced the original SARS-CoV-2 that emerged from China.  The mutation had no significant impact on the spread of the virus. Although preliminary modeling suggest that the B.1.1.7 variant is significantly more transmissible than previously circulating variants, further epidemiological and virological investigations are needed to fully quantify the increase in transmissibility and better understand the biological mechanism.

However, at this time public health and non-pharmaceutical interventions are necessary to reduce transmission and prevent this variant from eventually replacing other currently circulating variants in much of Europe and the world.  There is further reason for concern as an independent and similar lineage with the N501Y mutation in the spike gene has been identified in the Eastern Cape in South Africa (variant 501.V2). This lineage is spreading faster amongst young people, and full details of the variant will be released next week.

The mutations in the variant don’t impact on diagnostic abilities, as the assays don’t target the Spike protein.

You may find more information on the immune system and virology of SARS-CoV-2 in Chapter 2 of “Breaking Down Covid-19,” available at: https://breakingdowncovid19.org/ Carey Kriz, Naiyer Imam, and Sarah Zaidi (eds.) October 2020.

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