Public Health England (PHE) have announced that, following a rise in cases in the UK and evidence of community transmission, they have reclassified VUI-21APR-02 (B.1.617.2, classified as a Variant Under Investigation (VUI) on 28 April) as a Variant of Concern (VOC), now known as VOC-21APR-02.
Prof Sharon Peacock, Director of COG-UK, and Professor of Public Health and Microbiology, University of Cambridge, said:
“Three clades of the SARS-CoV-2 lineage B.1.617 have been detected in the UK (B.1.617.1, B.1.617.2 and B.1.617.3), which are differentiated based on the profile of mutations present.
“There has been a steep increase in detected cases infected with B.1.617.2 in England in the last week (total known cases have risen from 202 to 520), with hotspots in London and the North West. The number of cases with a travel history is now a minority of the total (n=157), indicating that transmission is occurring in the community.
“PHE escalated B.1.617.2 from a Variant Under Investigation to a Variant of Concern on 6 May 2021 based on an assessment of transmissibility being at least equivalent to B.1.1.7 (Kent). This assessment is rated as having moderate confidence and is based on biological plausibility of the mutation profile, supported by evidence that it can compete with B.1.1.7 in the population and modelled growth estimates suggesting transmissibility at least equal to B.1.1.7. The analyses performed on transmissibility are not yet in the public domain.
“The other two variants (B.1.617.1 and B.1.617.3) remain Variants Under Investigation.
“All variants can be controlled by standard precautions (hands, face, space, ventilation). This is another reminder that compliance with these practices is vital for ongoing COVID-19 control. PHE report that surge and community testing is underway, with enhanced contact tracing for people testing positive for this B.1.617.2. This is being done to in an effort to limit further spread. India remains on the UK government travel red list.
“The basis for higher transmissibility of B.1.617.2 is under investigation. One mutation under scrutiny is L452R, which has been associated with transmissible variants in the United States (lineages B.1.427 and B.1.429). However, this same mutation is also present in B.1.617.1. and B.1.617.3, which do not appear to be spreading in the UK at the same rate as B.1.617.2. This may indicate that other mutations are involved in B.1.617.2 spread but this will require experimental investigation. As more surveillance data are collected over time, it may become feasible to determine the relative contribution of virus transmissibility versus other modifiable factors that are contributing to community spread.
“There is not enough evidence to comment on vaccine efficacy against B.1.617.2. The L452R mutation has been associated with weaker neutralisation of the virus by convalescent plasma from people who have been infected with SARS-CoV-2, and/or some monoclonal antibodies in laboratory experiments. But it is reassuring that B.1.617.2 does not contain E484Q, which is present in B.1.617.1 and B.1.617.3. Mutations in position 484 are present in two global Variants of Concern (B.1.351 and P1, most commonly detected in South Africa and Brazil, respectively), where the variant contains E484K. There is limited evidence for the role of E484Q in immune escape. E484Q had reduced neutralisation by some but not all convalescent plasma samples from people who have had natural infection with SARS-CoV-2 using an experimental system (Greaney et al., 2021, Cell Host & Microbe 29, 463–476). This is under intensive investigation.
“Looking ahead, if transmissibility of B.1.617.2 is comparable (or less than) B.1.1.7 (Kent variant), current restrictions would be expected to maintain the current progress in COVID-19 control. But more data and data analysis is required to understand whether this is the case, whether B.1.617.2 can out-compete B.1.1.7, and if so, what this means for disease control. There is no evidence at the present time to indicate that vaccines will not work, and it remains essential that people are encouraged to become vaccinated.
“The most important messages remain exactly the same – for people to comply with precautions to prevent infection and prevent spread to others, and to get their vaccination when called.”
Prof Nick Loman, Professor of Microbial Genomics and Bioinformatics, Institute of Microbiology and Infection, University of Birmingham, said:
“The surge in cases in India and scenes witnessed there is of grave concern internationally. The recent PHE report shows that cases from India arriving in the UK are predominantly of the B.1.617.2 variant. Interestingly this is not the so-called “double mutant” (B.1.617.1) although it does have several spike mutations that are concerning and could result in increased transmissibility (specifically L452R and P681R).
“The absolute numbers of cases in the UK remain small but the growth rate is quite high, although at this stage it is hard to say whether this is related to specific biological features of the variant. On the background of declining cases of B.1.1.7 in the UK the growth rate looks alarming when measured as a proportion of cases, however even a variant less or equally transmissible virus to B.1.1.7 could show this effect when there are large numbers of imports in a short period.
“This variant will now be one to watch carefully given the situation in India, although the early data shows that the vaccines are expected to work well against this variant. Although some cases have been hospitalised it is reassuring that no deaths have been reported to date.”
Dr Jeff Barrett, director of the COVID-19 Genomics Initiative at the Wellcome Sanger Institute, said:
“In recent weeks we have seen three subtypes of the B.1.617 ‘Indian variant’ circulating, and of these the B.1.617.2 subtype has become the most common in the UK and other countries around the world. This is consistent with B.1.617.2 being as transmissible as the B.1.1.7 ‘Kent variant’ that’s dominant in the UK. Therefore, B.1.617.2 has now been designated by Public Health England as a ‘variant of concern’.
“Another key question is how well vaccines will work against B.1.617.2, but we don’t yet have much data. However, there is good news about other variants of concern, such as the B.1.351 ‘South African variant’, which was suspected of being less well neutralised by vaccines. There’s now real-world evidence from Qatar that vaccination there protected against the B.1.351 variant almost as well as other variants. This paints a positive picture that the vaccines will be effective against new variants.
“We have built excellent infrastructure in the UK to sequence the genomes of as many positive cases as possible as they are detected in the community. So while the UK has publicly shared the largest number of B.1.617.2 sequences in the world, it doesn’t necessarily mean that there are more cases of this variant in the UK than other countries.
“We need to keep up genomic surveillance of SARS-CoV-2 in the UK, even when cases are low, so we can continue to identify variants and where they are circulating in order to keep them under control.”
All our previous output on this subject can be seen at this weblink: