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SARS-CoV-2 Delta variant

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Total number of B.1.617 sequences by country as of 21 April 2021[1]
Legend:
  100+ confirmed sequences
  2–99 confirmed sequences
  1 confirmed sequence
  None or no data available
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Lineage B.1.617, also known as G/452R.V3,[2] is one of the known variants of SARS-CoV-2, the virus that causes COVID-19.[3] It was first identified in Maharashtra, India on 5 October 2020.[4][5] It has been referred to, unhelpfully,[6] as a double mutation variant.[1][7][8]

As of May 2021, three sublineages have been found. Despite its name, B.1.617.3 was the first sublineage of this variant to be detected, in October 2020 in India. This sublineage has remained relatively uncommon compared to the two other sublineages, B.1.617.1 and B.1.617.2, both of which were first detected in December 2020.[9] There were few known cases of B.1.617 (of all sublineages) until early February 2021 when there was a significant increase.[1]

On 6 May 2021, Public Health England escalated B.1.617.2 from a Variant Under Investigation to a Variant of Concern based on an assessment of transmissibility being at least equivalent to B.1.1.7.[10]

On 11 May 2021, the World Health Organization classified the variant as a Variant of Concern, and said that it showed evidence of higher transmissibility and reduced neutralization. The variant is thought to be partly responsible for India's devastating second wave of the pandemic beginning in February 2021.[11][12]

Name

"Double mutation" refers to B.1.617's mutations in the gene encoding the SARS-CoV-2 spike protein[13] causing the substitutions E484Q and L452R.[14] It is identified as the 21A clade under the Nextstrain phylogenetic classification system.[15]

The use of the term "double mutant" has been criticised by infectious disease scientists due to SARS-CoV-2 being in a state of perpetual mutation with numerous mutations occurring around the world, so use of this misleading term is being discouraged.[16][6] A further issue is that the term "Indian variant" is used in many countries' news reporting due to the variant having been first discovered in India.[17][18][19] This is contrary to the WHO's own recommendation that advises against using terms such as "Indian variant" that identify variants etc. with locations as these stigmatise countries and people for the important work of genome sequencing.[20] The WHO are instead asking that the agreed scientific term be used.[21][22]

Characteristics

Emerging research suggests the variant may be more transmissible than previously evolved ones.[23] Whether the effectiveness of currently-deployed vaccines is affected remains under investigation.[24][25][26]

Surveillance data from the Indian government's Integrated Disease Surveillance Programme (IDSP) shows that around 32% of patients, both hospitalised and outside hospitals, were aged below 30 in the second wave compared to 31% during the first wave. Among people aged 30-40, the 20-39 bracket increased to 25.5% from 23.7% earlier. The data also showed a higher proportion of asymptomatic patients were admitted during the second wave, with more complaints of breathlessness.[27]

On 7 May 2021, British scientists at Public Health England redesignated one of the three sublineages, B.1.617.2, as "variant of concern" (VOC-21APR-02),[28] after they flagged evidence in May 2021 that it spreads more quickly than the original version of the virus. Another reason was that they identified 48 clusters of B.1.617.2, some of which revealed a degree of community transmission.[29][30]

First detection and international spread

In countries other than India, the first cases of the variant were detected in late February 2021, including the United Kingdom on 22 February, the United States on 23 February and Singapore on 26 February.[1][5][4]

Canada's first confirmed case of the variant was identified in Quebec on 21 April 2021, and later the same day 39 cases of the variant were identified in British Columbia.[31] Alberta reported a single case of the variant 22 April 2021.[32]

Fiji also confirmed its first case of the variant on 19 April 2021 in Lautoka, and has since then climbed up to 42 cases and counting.[33] The variant has been identified as a super-spreader and has lead to the lockdowns of five cities (Lautoka, Nadi, Suva, Lami and Nausori), an area which accounts for almost two-thirds of the country's population.

On 29 April 2021, health officials from Finland's the Ministry of Social Affairs and Health (STM) and the Finnish Institute for Health and Welfare (THL) reported that the variant had been detected in three samples dating back to March 2021.[34]

The Philippines confirmed its first two cases of the variant on 11 May 2021, despite the imposed travel ban of the country from the nations in the Indian subcontinent (except for Bhutan and Maldives). Both patients have no travel history from India for the past 14 days, but instead from Oman and UAE.[35]

Mutations

Defining mutations in B.1.617
Gene Nucleotide Amino acid
ORF1ab T749I
T77A
P323L
M429I
K259R
T93M
Spike G142D
E154K
L452R
E484Q
D614G
P681R
Q1071H
H1101D
orf3a S26L
orf6 I33T
orf7a V82A
Source: Haseltine/ Forbes[36]

The B.1.617 genome has 13 mutations (15 or 17 according to some sources,[which?] depending on whether more common mutations are included) which produce alterations in the amino-acid sequences of the proteins it encodes.[37] Three of them, all of which are in the virus's spike protein code, are of great concern:

  • E484Q. The substitution at position 484, a glutamic acid-to-glutamine substitution, confers the variant stronger binding potential to hACE2 (the human ACE2 receptor), as well as better ability to evade hosts' immune systems, for B.1.617 in comparison to other variants.[36][38]
  • L452R. The substitution at position 452, a leucine-to-arginine substitution, confers stronger affinity of the spike protein for the ACE2 receptor and decreased recognition capability of the immune system.[14][39] These mutations, when taken individually, are not unique to the variant; rather, their simultaneous occurrence is.[14][7]
  • P681R. This is a substitution at position 681, a proline-to-arginine substitution, which, according to William A. Haseltine, may boost cell-level infectivity of the variant "by facilitating cleavage of the S precursor protein to the active S1/S2 configuration".[36]

Sublineage details

There are three sublineages of B.1.617 categorized so far.

B.1.617.1 (VUI-21APR-01) was designated a Variant Under Investigation in April 2021 by PHE. Later in April 2021, two other variants B.1.617.2 (VUI-21APR-02) and B.1.617.3 (VUI-21APR-03) were designated as Variants Under Investigation. While B.1.617.3 shares the L452R and E484Q mutations found in B.1.617.1, B.1.617.2 does not have the mutation E484Q. B.1.617.2 has the T478K mutation, not found in B.1.617.1 and B.1.617.3.[40][41] On 7 May 2021, B.1.617.2 was reclassified by Public Health England to a Variant Of Concern under the name VOC-21APR-02 due to evidence that it is at least as transmissible as B.1.1.7.[3] On 11 May 2021, the World Health Organization also classified it as a VoC.[11][12] Simultaneously, the ECDC released a brief maintaining all three B.1.617 variants as VoI, estimating that a "greater understanding of the risks related to these B.1.617 lineages is needed before any modification of current measures can be considered".[42]

Vaccine efficacy

ICMR found that convalescent sera of the COVID-19 cases and recipients of Bharat Biotech's BBV152 (Covaxin) were able to neutralise VUI B.1.617 although with a lower efficacy.[43]

Anurag Agrawal, the Director of the Institute of Genomics and Integrative Biology (IGIB), said the study on effectiveness of the available vaccines on the B.1.617 variant of SARS-CoV2 suggests that post vaccination, the infections are milder. He tweeted:

Initial positive neutralization studies of B.1.617, with both post-Covaxin or Covishield sera, are correlatable with milder disease during post-vaccination breakthrough infections. This is a positive while we get quantitative data for better understanding of infection protection.[44]

Anthony Fauci, the Chief Medical Advisor to the President of US, has also expressed his confidence regarding the preliminary results. In an interview he said:

This is something where we're still gaining data on a daily basis. But the most recent data, was looking at convalescent Sera of COVID-19 cases and people who received the vaccine used in India, the Covaxin. It was found to neutralise the 617 variants.[45]

Another study by the Centre for Cellular and Molecular Biology (CCMB) in Hyderabad found Covishield (Oxford–AstraZeneca) vaccinated sera offers protection against the B.1.617 variant. Rakesh Mishra, the Director of CCMB, said in a tweet:

Very preliminary but encouraging result: #Covishield protects against #B1617. Early results using in vitro neutralisation assay show that both convalescent (prior infection) sera and Covishield vaccinated sera offer protection against the B.1.617 variant, aka #DoubleMutant.[46]

The WHO said current vaccines will continue to be effective against the variant. In an update in May, they said there may be some evidence of "reduced neutralization".[47]

International reactions

After the rise in cases from the second wave, at least 20 countries imposed travel bans and restrictions on passengers from India in April and May. UK prime minister Boris Johnson cancelled his visit to India twice, while Japanese Prime Minister Yoshihide Suga postponed his April trip.[48][49][50]

In May 2021, residents of two tower blocks in Velbert, Germany were quarantined after a woman in the building tested positive for the variant.[51]

Statistics

By 13 May 2021, more than 4,500 sequences of the variant had been detected in about 60 countries.[4][52] Reported numbers of sequences in countries with detections are:

Cases by country (As of 16 May 2021)
Country Confirmed cases
(GISAID)[4] as of 17 May 		Confirmed cases
(PANGOLIN)[1] as of 16 May 		Cases (other sources) First detection
 India 2247 1941 5 October 2020
 United Kingdom 3804 2196 22 February 2021
 USA 883 675 23 February 2021
 Singapore 156 156 26 February 2021
 Australia 99 84 16 March 2021
 Canada 25 - 373[53][54][55][56] 15 March 2021
 Germany 261 111 1 March 2021
 Fiji - - 42[57] 28 April 2021
 Israel 2 - 41[58][59][60] 16 April 2021
 Denmark 66 65 8 March 2021
 Japan 145 29 28 March 2021
 Bahrain 22 19 5 April 2021
 Poland 16 12 16[61] 26 April 2021
 Ireland 80 61 26 February 2021
  Switzerland 44 41 29 March 2021
 Belgium 59 51 25 March 2021
 France 32 32 21 February 2021
 New Zealand 15 15 9 March 2021
 China 17 (incl. Hong Kong) 7 24 April 2021
   Nepal 1 - 9[62] 28 April 2021
 Angola 8 8 14 January 2021
 Hong Kong 10 8 22 April 2021
 Portugal 10 9 5 April 2021
 Sweden 13 13 26 March 2021
 Luxembourg 6 6 15 April 2021
 The Netherlands 27 26 6 April 2021
 Italy 52 51 2 April 2021
 South Korea 6 7 26 March 2021
 Spain 32 22 22 April 2021
 Turkey - - 5[63] 28 April 2021
 Finland - - 12[34][64] March 2021
 Jordan 5 3 21 April 2021
 Russia 5 3 16[65] 21 April 2021
 Bangladesh 5 3 9[66][67] 28 April 2021
 Czech Republic 3 2 24 April 2021
 Greece 2 2 23 March 2021
 Guadeloupe 2 2 10 March 2021
 Indonesia 10 10 3 April 2021
 Argentina - - 2[68] 24 April 2021
 Morocco 1 - 2[69] 3 May 2021
 Thailand 2 - 2[70] 24 April 2021
 Sint Maarten 2 - 19 March 2021
 Algeria - - 6[71] April 2021
 Aruba 3 3 16 April 2021
 Austria 1 - 17 April 2021
 Botswana 1 - 2[72] 28 April 2021
 Cambodia 1 - 5 April 2021
 Curacao 1 - 23 April 2021
 DR Congo 6 - 5[73] 3 May 2021
 Iran - - 3[74] May 2021
 Kenya - - 5[73][75] May 2021
 Malaysia 3 - 10 April 2021
 Mexico 7 4 5 April 2021
 Nigeria - - 1[73] May 2021
 Norway 4 4 1[76] 15 April 2021
 Panama - - 1[77] April 2021
 Romania 6 10 26 April 2021
 Reunion 1 - 4 May 2021
 Slovenia 1 - 20 April 2021
 South Africa 12 7 4[78] 30 April 2021
 Sri Lanka 1 - 1[79] 30 April 2021
 Uganda 5 4 1[80] 26 March 2021
 Philippines - - 12[81][82] 11 May 2021
 Vietnam - - 12[83][84] 18 April 2021
World (64 countries) Total: 8,278 Total: 5,702
incl. B.1.617.1, B.1.617.2, and B.1.617.3		 577 Total as of 16 May 2021.

See also

References

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