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Lineage B.1.351

Lineage B.1.351

The 501Y.V2 variant, also known as 20H/501Y.V2 (formerly 20C/501Y.V2), B.1.351 lineage, and South African COVID-19 variant, is a variant of SARS-CoV-2, the virus that causes COVID-19. One of several SARS-CoV-2 variants believed to be of particular importance, it was first detected in the Nelson Mandela Bay metropolitan area of the Eastern Cape province of South Africa and reported by the country's health department on 18 December 2020.

The new variant was uncovered by whole genome sequencing. Several genomic sequences from this lineage were submitted to the GISAID sequence database.

Researchers and officials reported that the prevalence of the variant was higher among young people with no underlying health conditions, and more frequently causes serious illness in such cases than other variants. The South African health department also indicated that the variant may be driving the second wave of the COVID-19 pandemic in the country, as the variant spreads faster than other earlier variants of the virus.

There are three mutations of particular interest in the spike region of the B.1.351 genome: K417N, E484K, N501Y. five spike mutations have so far generated less concern: L18F, D80A, D215G, R246I, A701V. Away from the spike region, it also carries: K1655N, SGF 3675-3677 deletion, P71L, and T205I.

Scientists noted that the variant is able to attach more easily to human cells because of three mutations in the receptor-binding domain (RBD) in the spike glycoprotein of the virus: N501Y (a change from asparagine (N) to tyrosine (Y) in amino-acid position 501), K417N, and E484K. Two of these mutations, E484K and N501Y, are within the receptor-binding motif (RBM) of the receptor-binding domain (RBD). The N501Y mutation has also been detected in the United Kingdom. Two mutations found in 501.V2, E484K and K417N, are not found in Variant of Concern 202012/01. Also, 501.V2 does not have the 69-70del mutation found in the other variant.

International Spread:
On 23 December, UK health minister Matt Hancock announced that two people who had traveled from South Africa to the UK were infected with 501.V2. 28 December, the variant had been detected in two people in Switzerland and in one in Finland. On 29 December, the strain had been detected in a visitor from South Africa to Japan, and in one overseas traveler to Queensland, Australia. On 30 December the variant was detected in Zambia. On 31 December it was also detected in France, in a passenger returning from South Africa. On 2 January 2021, the first case of this variant was detected in South Korea. Austria reported their first case of this variant, along with four cases of the UK variant on 4 January. The Republic of Botswana also detected their first case on 4 January. The People's Republic of China reported the first case of this variant in southern Guangdong province on 6 January.

On 8 January 2021, the Republic of Ireland reported the detection of 3 cases, all linked to travel from South Africa. On the same day a case of reinfection with the new variant by a woman who had had COVID-19 was reported from Brazil, the first such reinfection reported in the world. Canada reported the first case of this variant in Alberta on 9 January, and Israel reported four cases, all of which were imported in people traveling from South Africa. New Zealand reported the first case of this variant on 10 January. On 12 January, Germany reported the detection of the mutation in six people from three different households. The same day, it was reported that the United Kingdom had a total of 29 cases, two of which were previously reported. The following day, Belgium reported the first case in a person from West Flanders with no travel history, Israel reported four further cases, and Taiwan reported the first case in a Swazi man in his 30s who had tested positive for COVID-19 on 1 January.

On 14 January, Germany detected a further case, and the following day, Canada reported a second case of the mutation which was detected in the Canadian province of British Columbia. A further case was reported in Germany the same day. Denmark and Réunion reported their first cases on 16 January as Israel discovered a further four cases. On 17 January, Israel reported another four cases bringing their total number of cases of this variant to 20. Two further cases were reported in The Netherlands on 18 January bringing the country's total to three. Ghana reported its first case of the variant on 19 January. On 23 January, Panama detected its first case of the strain in a person from Zimbabwe, who had traveled from South Africa. Also on 23 January, Belgium reported at least 15 cases of the variant in Ostend, while 6 cases were confirmed in the Comoros. On 26 January, the Republic of Ireland reported the detection of 6 further cases. The United States reported its first cases of the variant on 28 January 2021, in the state of South Carolina. On 27 January, Israel reported 3 more cases which were the first cases of the variant from samples that were collected in the community randomly, without knowing the source of infection. Preliminary data reported by Africa CDC on 29 January indicated that the variant had reached Ghana. On 31 January, Israel reported its first case of reinfection with the new variant by a man who returned from Turkey.

On 1 February 2021, the United Kingdom Secretary of State for Health and Social Care reported the random detection of 11 cases of the variant where there was no connection to international travel. The same day, the Canadian province of Ontario reported the first case of the variant in the Peel Region, with a similar absence of travel history and no contact with anyone who had recently been abroad. On 8 February, the Republic of Ireland reported the detection of 2 further cases

On 8 February 2021, Austria detected the greatest outbreak of 501.V2 variant in Europe so far. A total of 293 confirmed cases and 200 suspected cases have been identified through sequencing, most of them will be confirmed in all probability. All of the cases were found in the Tirol region, where nearly 9% of the positive PCR tests were identified as the 501.V2 variant by sequencing. The active cases were estimated at around 140. After a week of public discussion and political pressure about a possible quarantine of Tirol, the government of Austria abstained from isolating the areas of concern, instead making a formal plea to reduce movement in and out of the region and go for testing after visiting Tirol. Tirolean officials stated their intention to relax the lockdown rules in Tirol in keeping with the rest of Austria. On 25 February, the Republic of Ireland reported the detection of 4 further cases.

On 22 February, the Israeli Health Ministry stated that the variant has genetically sequenced on 1% of community samples. Later on, Israel reported a total of 444 cases of the variant, which makes is the highest infection rate in the world outside South Africa.

Vaccine Evasion:
On 4 January 2021 UK newspaper The Telegraph reported that Oxford immunologist Sir John Bell believed there was "a big question mark" over the new South African variant's potential resistance to COVID-19 vaccines, raising fears that vaccines might not work as effectively on that variant strain. The same day Shabir Madhi, professor of vaccinology at the University of the Witwatersrand, commented to CBS News that "it's not a given" that the new 501.V2 variant would be able to evade the vaccines, but that it should be considered that they "might not have the full efficacy". The additional mutations to the spike protein in variant 501.V2 were raised as a concerning factor by Simon Clarke, an associate professor in cellular microbiology at the University of Reading, in that they "may make the virus less susceptible to the immune response triggered by the vaccines". Lawrence Young, a virologist at Warwick University, also noted that the variant's multiple spike mutations "could lead to some escape from immune protection"

The E484K amino acid change, a receptor-binding-domain (RBD) mutation, was reported to be "associated with escape from neutralising antibodies" which could adversely affect the efficacy of spike protein-dependent COVID vaccines. The E484K spike mutation was linked to a case of reinfection with the 501.V2 variant of SARS-CoV-2 in Brazil, believed by researchers to be the first such case of reinfection involving this mutation. The possibility of an alteration in antigenicity was referred to as an "escape mutation" from a monoclonal antibody with the capability of neutralising the spike protein variants of SARS-CoV-2. This suggests that existing vaccines can and should be updated to counter the new strains without recourse to phased trials.

On 7 January 2021, it was reported that Pfizer researchers had found the Pfizer and BioNTech COVID-19 vaccine in tests involving 20 blood assays to be capable of affording protection, with only slightly less effectiveness, against one of the 501.V2 variant mutations (N501Y, shared with variant B1.1.7). Further investigation was to be undertaken to ascertain the level of protection involved.

Moderna is planning to test an alternate mRNA-1273 vaccine version specially designed to protect against 501.V2. It is reported that NVX-CoV2373 is 60% effective against 501.V2. According to a clinical study of the Ad26.COV2.S vaccine, its effectiveness in southern Africa is 15% lower than in the United States (57% and 72%, respectively), the difference is probably associated with the prevalence of the 501.V2 strain in South Africa. One more vaccine study (related to NVX-CoV2373 by Novavax) showed 60% efficacy (for HIV-negative participants) in South Africa, compared to 90% efficacy in Britain.

On 6 February 2021, The Financial Times reported that provisional trial data from a study undertaken by South Africa's University of the Witwatersrand in conjunction with Oxford University demonstrated reduced efficacy of the Oxford–AstraZeneca COVID-19 vaccine against the 501.V2 variant. The study found that in a sample size of 2,000 the AZD1222 vaccine afforded only "minimal protection" in all but the most severe cases of COVID-19. On 7 February 2021, the Minister for Health for South Africa suspended the planned deployment of around 1 million doses of the vaccine whilst they examine the data and await advice on how to proceed.
On 18 February 2021, Pfizer confirmed that the South African variant could significantly reduce vaccine protection. The following day, Pfizer published its findings, which found that the vaccine produced around 66% fewer antibodies than normal when combating the variant, but was still successful in neutralizing the virus.
On 24 February 2021, Moderna announced the start of a trial of a new vaccine version. The new version is specially developed to help against 501.V.

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