Several cases of the SARS-CoV-2 variant B.1.617 have now been detected in the UK.
Prof Sharon Peacock, Director of COG-UK, and Professor of Public Health and Microbiology, University of Cambridge, said:
What do we currently know about B.1.617?
“This variant has been around for some time. The first B.1.617 genome in the global database (GISAID) dates back to 5 Oct 2020. India has submitted the most B.1.617 genomes, following in frequency by UK and the US. Based on genome information, B.1.617 was first detected in the UK on 22 Feb 2021, and in the US on 23 Feb 2021. B.1.617 has been identified from genome data submitted by 21 countries as of 19 April 2021. The relative frequency of genomes from different countries is biased because of the different amounts of sequencing being performed in different countries; a country sequencing a high number of genomes may be more likely to detect variants.
What is a ‘double mutant’? Do we know for sure that B.1.617 is one? How worrying is a double mutant?
“B.1.617 has 13 mutations that result in amino acid changes. B.1.617 has been described as a ‘double mutant’. This term is used to refer to two mutations in spike (E484Q and L452R) but is inaccurate, has no specific meaning and should be avoided. The variant has also been referred to as the ‘India variant’ but this should also be avoided – it is unlikely to be able to say definitively where the variant first arose.
“B.1.617 has several mutations that are present in other variants of interest/concern or that have been shown to have antigenic escape in laboratory experiments. Discussed here are changes in positions 484, 452 and 681. E484Q is present in B.1.617. Mutations in position 484 are present in the three global variants of concern, but these variants contains E484K. There is limited evidence for the role of E484Q in immune escape – it was shown to have 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). L452R is present in B.1.617. This is present in several variants of interest, including B.1.429 (associated with California). This 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. P681R is present in B.1.617. P681R or P681H is also present in several variants under investigation in the UK, including A.23.1/E484K, B.1.1.7 and B1.318. This is located adjacent to the furin cleavage site of the spike protein, which could mean a change in spike protein processing or other changes in biology. More evidence is needed to understand the virus changes that result from the specific combination of mutations present in B.1.617.
Is B.1.617 driving the current wave in India or do we not know yet?
“India is currently witnessing a surge in marked surge in COVID-19 cases. The question is whether this is associated with the variant, with human behaviour (for example, the presence of large gatherings, and/or lack of preventive measures including hand washing, wearing masks and social distancing) or whether both are contributing. It is not clear at the present time whether B.1.617 is the main driver for the current wave.
“B.1.617 accounts for almost 70% of genomes submitted by India to GISAID, indicating that the variant is common in the isolates that went on to be sequenced – although this is a very small proportion compared with the total number of cases of infection. Most isolates sequenced by India originated from Maharashtra and West Bengal, but B.1.617 has been identified in several other states. An important caveat is that these data can be influenced by selection of samples for sequencing that are uneven across locations.
Will putting India on the government travel red list help prevent spread of this variant in the UK?
“The Prime Minister announced yesterday that India has now joined the UK government travel red list (as from this Friday). This means that people returning from India will be required to go into government-approved hotel quarantine for 10 days where they will undergo testing and any positive isolates sequenced. This is an important step in controlling further introduction of this variant into the UK. The number of B.1.617 genomes detected in the UK has risen in the last 3 weeks. Even though this is at or less than 1% of the genomes sequenced in the UK overall, the upward trend in cases warrants action whilst ongoing uncertainties over the level of threat posed by this variant are evaluated. PHE indicated on Sunday that a few cases are not linked to travel – but the vast majority of cases have been in people who have travelled. Contact tracing, testing and genomic surveillance of people with COVID-19 will provide essential information on the extent of transmission in the UK that is no longer related to travel (community transmission), which will in turn inform public health actions.
What do we need to know to decide if B.1.617 should be classified as a ‘variant of concern’?
“B 1.617 is a currently a variant under investigation by PHE, which is defined as ‘a variant with mutations for which there is high confidence predictive data, or laboratory data, supporting significant adverse phenotypic change, but which do not meet the definition of a variant of concern, and there is evidence of community transmission in the UK or abroad’.
“To be classified as a variant of concern by PHE, the following need to be met:
“Ongoing study of B.1.617 in the UK and elsewhere is required and underway, to determine whether or not this threshold will be reached for B.1.617.”
Dr Jeffrey Barrett, Director of the Covid-19 genomics initiative at the Wellcome Sanger Institute, said:
“When we see a new variant of the virus appear, there are generally four kinds of information that we can use to evaluate it. One of those is laboratory experiments which we haven’t had time to do yet on B.1.617 and another is real world vaccine evidence which takes even more time. The third source of information is to look at the specific mutations in a variant and to compare that to other variants that we know more about, and the fourth is see how fast it is spreading.
“It can be difficult to get virus samples to do experiments on internationally as you need fairly recent samples, but I’m sure various international authorities are collaborating as best as they can to get these samples to be able to do the experiments.
“This variant has a couple of potentially concerning mutations but these are probably not as serious as some of the mutations present in the variants first seen in Kent, South Africa and Brazil. This could be because we have had less time to study them, so these mutations should be watched carefully. And in terms of spread, clearly this variant has increased in frequency in India around the time of their very large and tragic recent wave but I don’t think we yet know how much B.1.617 is driving that spread versus its spread coincidentally happening at the same time.
“It is certainly possible that there is a cause and effect relationship but there have only been about 1000 sequences published from India out of about 4 million cases in this wave so far. So we only have a tiny window into which variants are becoming the most common and it’s not clear if they are fully representative. Also, we did see some sequences of this B.1.617 variant late last year so if it is driving the wave in India it has taken several months to get to this point which would suggest it’s probably less transmissible than the Kent B.1.1.7 variant.”