New SARS-CoV-2 Variant
SARS-CoV-2 is an RNA virus in which mutations arise naturally as the virus replicates. SARS-C0V-2 acquires about one new mutation in its genome every two weeks. Many mutations are biologically silent because they do not change the structure or function of viral proteins.
Covid-19 Genomics UK (COG-UK) consortium is a partnership of the UK’s four public health agencies, the Wellcome Sanger Institute and 12 academic institutions that was established in April 2020 to randomly sequence the viral genomes from people who test positive for COVID19. The consortium has already sequenced 157,439 virus genomes throughout the UK out of a total of 2.1 million COVID19 cases. The consortium uses this data to track outbreaks, identify variant viruses and publish a weekly report. (https://www.cogconsortium.uk/da- ta/).
On December 14, the consortium detected a new highly mutated variant of SARS-CoV-2. The European Centre for Disease Prevention and Control began an enhanced epidemiologic investigation after noticing a pronounced increase in the infection rate in Southeast England from 100 cases per 100,000 population in early October to 400 cases per 100,000 in December.
The first sample of the UK variant was collected on September 20th, to the southeast of London. The second was found the following day in London itself. The new variant accounted for 28% of new infections in London by the beginning of November 62% of new cases by the first week of December. It probably now comprises more than 90% of new cases.
So far, the variant has mostly infected people younger than 60 years. An increase in the virus reproduction number (R0) from 1.1 to 1.5 suggests that this variant is more contagious than the previous wild type strain.
In order to contain the the new coronavirus variant, U.K. Prime Minister Boris Johnson announced on December 20 that, "It is with a very heavy heart, I must tell you: We cannot continue with Christmas as planned." He imposed a lockdown on more than 20 million people in London and southeast England. On December 30, the UK further announced it would change its vaccination strategy to give as many people in at-risk groups their first dose, rather than providing the required two doses, even though Pfizer said there is no data, demonstrating that a single dose of its vaccine would provide protection from infection after 21 days.
The new strain has already spread to other European countries, such as the Netherlands, Iceland, Denmark, Sweden, Australia, Japan, Italy, Spain, France and Canada. Most of these cases have been linked to travel to the UK. On January 6, CDC reported that 52 cases of UK variant of SARS-CoV-2 had been detected in five states in the US. At least 26 cases were found in California, 22 in Florida, two in Colorado and one case each in New York and Georgia. Michael Osterholm of CIDRAP said the U.K. variant had probably already spread to at least 25 states and would soon be in all 50 states and the District of Columbia.
The actual extent of spread within the US is not known because the US has no large-scale, nationwide system for checking coronavirus genomes for new mutations. Approximately 1.4 million people test positive for the virus each week, but fewer than 3,000 of those weekly samples can be sequenced. Sequencing is being done by a patchwork of academic, state and commercial laboratories rather than a coordinated national surveillance program.
The new variant has been referred to as “SARS-CoV-2 VOC 202012/01” (i.e., the first Variant of Concern from 2020, December) and as B.1.1.7. VOC 202012/01 has accumulated an unusually large number of 23 mutations. Eight of these mutations affect the spike protein. One of the mutations affects the receptor binding domain (RBD) of the spike protein at position 501, where amino acid asparagine (N) has been replaced with tyrosine (Y). The shorthand notation for this mutation is N501Y. This mutation may enhance binding to the angiotensin converting enzyme 2 (ACE-2) receptor on human cells and account this variant’s increased transmissibility.
SARS-CoV-2 VOC 202012/01’s also possesses two other intriguing spike mutations. Mutation 69-70del, deleted two amino acids, and P6815 substituted histidine for proline at position 681. The double deletion is also found in the SARS-CoV-2 variant isolated from Denmark’s mink farms in November. P681H is significant because it occurs at one end of the S1/S2 furin-cleavage site, which helps activate the spike protein for binding to the ACE-2 receptor of human cells. This furin-cleavage site is absent from the spike proteins of related coronaviruses, such as SARS, and may account for SARs-CoV-2 increased infectivity.
Scientists do not believe this highly mutated variant could have evolved so quickly following the usual evolutionary process of a chance accumulation of mutations. COG-UK suggested that the new variant might be the consequence of an evolutionary process in a single human rather than a population. One possibility is that the variant gained its array of new mutations after infecting immunosuppressed COVID19 patient who was unable to clear virus, allowing it to replicate for a prolonged time. Rapid evolution of the variant might have been further driven by treatment of this patient with COVID19 convalescent plasma, monoclonal antibodies, and/or the antiviral drug remdesivir. Over time, natural selection favors mutant viruses that evade the immune system.
On December 18, 2020, the South African government announced that it had also seen the emergence of a new coronavirus strain, designated 501.V2. This strain has been found in 90% of patients that underwent genetic analysis since mid-November. The South African variant has three meaningful mutations, and all are located in the receptor binding domain of the spike protein. It possesses the same N501Y mutation found in the UK variant along with mutations K417N and E484K (K and E are shorthand for lysine and glutamic acid). Preliminary studies indicate that people infected with this variant have higher viral loads. The South African strain emerged completely independently of the UK strain and is not related to it. So far, the variant has been detected in Brazil, the U.K., France, Switzerland, Japan, Austria and Zambia. Former FDA Commissioner Scott Gottlieb, MD believes the South African variant 501.V2 may decrease the effectiveness of monoclonal antibody therapy and may partially avert or weaken existing immunity from a prior COVID19 infection.
Another variant has emerged in Nigeria, but there's no evidence at this time to indicate it has caused more severe illness or increased spread.
Scientists are trying to elucidate the potential consequences of these variants which may include the ability to: spread more quickly, increase the risk of reinfection, increase the severity of illness, decrease accuracy of PCR and antigen tests, decrease response to therapeutics, and evade natural or vaccine-induced immunity.
On January 7, Pfizer scientists published early research on the preprint server bioRxiv suggesting that sera from 20 individuals vaccinated with the BNT162b2 Pfizer/BioNTech mRNA vaccine neutralized the N501Y mutation carried by the South African and UK coronavirus variants.
On January 8, Dr. Tom Frieden warned that “B.1.1.7 was more transmissible and would cause more infections, hospitalizations and deaths in the United States. B117 is a shot across the bow. COVID19 will be here for years. Citizens will have to do much better to avoid indoor exposures and wear masks. The vaccination rate needs to be greatly accelerated.”
References
Wise J. Covid-19: New coronavirus variant is identified in UK. Brit Med J. 2020;371:m4857 | doi: 10.1136/bmj.m4857.
Van Beusekom M. Little certain about UK COVID variant except continued spread, CIDRAP News, December 23, 2020.
CDC Executive summary, Implications of the emerging SARS-CoV-2 Variant 202012/01, December 22, 2020.
SARS-CoV-2 is following the evolutionary rule book: Its new variants are optimized for spreading. The Economist January 2, 2021.
Greaney, AJ et al. Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies. bioRxiv, January 4, 2021, doi: https://doi.org/10.1101/2020.12.31.425021
Zou XXJ et al. Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera. bioRxiv, posted January 7, 2021, doi: https://doi.org/10.1101/2021.01.07.425740.
