Footprint of B.1.617 now spreads to 44 countries
- The World Health Organization (WHO) said in its weekly Covid-19 epidemiology update that the B.1.617 variant with its three sub-lineages has been found in 44 countries.
Three lineages of a variant of the SARS-Cov-2 virus first seen in India now account for 66% of all samples tested in the most recent 45 days, according to data from India submitted to a global repository (GISAID) even as other data submitted to the same repository indicates that the variant has now spread to several parts of the world with a rapid increase in prevalence in several regions.
The data adds to evidence that the variant could be more infectious, pointing to the public health challenge across the world, but in India, especially, where many scientists and epidemiologists believe that variants such as this one, named B.1.617, may be behind the surging second wave of the coronavirus disease pandemic that has seen the country add almost 10 million cases of Covid-19 in the past month, with the last five being added in two weeks.
The World Health Organization (WHO) said in its weekly Covid-19 epidemiology update that the B.1.617 variant with its three sub-lineages has been found in 44 countries.
While studies on the extent of protection offering by existing vaccines against the variant continue, preliminary research in India suggests that vaccinations using the two vaccines widely used in the country do continue to protect even those infected by the variant against severe illness and death.
The variant’s rapid rise has now triggered alarm in several countries, including the UK which has found it to be responsible for the second highest number of infections and where experts have urged the government to rethink the May 17 lifting of curbs.
B.1.617 -- first detected in India last October and described by Indian officials in late March by the misnomer “double mutant” -- was classified as a variant of concern (VOC) globally by WHO on Monday, and a particular sub-lineage – the B.1.617.2 – was similarly flagged by authorities in the UK last week.
“In consultation with the WHO Sars-CoV-2 Virus Evolution Working Group, WHO has determined that viruses within the lineage B.1.617 have been characterised as a VOC,” the world body explained in its Covid-19 Weekly Epidemiological Update released on Wednesday. WHO said its decision was based on two reasons: “B.1.617 sub-lineages appear to have higher rates of transmission, including observed rapid increases in prevalence in multiple countries (moderate evidence available for B.1.617.1 and B.1.617.2)” and “preliminary evidence suggests potential reduced effectiveness of Bamlanivimab, a monoclonal antibody used for Covid-19 treatment, and potentially slightly reduced susceptibility to neutralisation antibodies (limited evidence available for B.1.617.1).”
Wider Indian spread
According to an analysis of genomic data from India to the GISAID global repository, the B.1.617.1 and B.1.617.2 account for two-thirds of the samples uploaded in the last 45 days – with the latter’s rise particularly stark.
The outbreak.info analysis estimates B.1.617.2 may have grown in prevalence from 9% of cases at the end of March to over 80% at the end of April, although the assessment is dependent on the samples submitted to GISAID and is unlikely to be a random selection.
Gujarat, Delhi, Bihar and Chhattisgarh are the top states where the proportion of B.1.617.2 samples is high, although the number of samples sequenced varies significantly between states. Uttar Pradesh, the largest state by population, has sequenced only 83 samples since the start of the pandemic, while Maharashtra has done over 3,300.
Experts have flagged the low genome sequencing in India, a problem also recognised in the WHO report: “Approximately 0.1% of positive samples in India have been sequenced and uploaded to GISAID to identify Sars-CoV-2 variants,” the report released on Wednesday said.
Globally, there are now four VOCs – B.1.617, B.1.1.7 (first seen in the UK), B.1.351 (first recorded in South Africa) and P.1 (first seen in Brazil). Of these, the variant from UK demonstrated a transmission advantage unlike any Sars-Cov-2 version before, triggering new waves of infection where it was first seen and in several other European nations.
Experts say that the India-linked variant now appears to be outcompeting it in epidemiological terms, which could indicate it to have an evolutionary advantage.
“Tracking frequencies over time in sequence data shared to @gisaid shows a continued increase in B.1.617, while recent weeks have shown a decline in B.1.1.7,” said Trevor Bedford, a scientist at the Fred Hutchinson Cancer Research Center, in a series of tweets analysing the genomic clues.
“The observed rapid growth of this (sub)-lineage in India and elsewhere would suggest that this virus is potentially highly transmissible. If faster growth than B.1.1.7 in India and in the UK is conclusive, it would suggest that this lineage will spread widely,” he added.
Christina Pagel, director of the clinical operational research unit at University College London, said the rise in B.1.617.2 cases was concerning enough to delay the next stage of the UK’s reopening roadmap.
“Under ‘current restrictions’, within a context of [very] infectious B117 (”Kent” variant) and ‘high population immunity’ B.1.617.2 seems to be spreading quickly. Numbers still low(ish) but for how much longer? What will happen after 17th May when so much more opens?” she said in a tweet on May 10, urging the government to step-up surveillance.
Mutation under lens
A variant of a Sars-Cov-2 typically has multiple changes in its genome – or mutations – which change how the virus can behave. The B.1.617 lineage is split into three -- B.1.617.1, B.1.617.2 and B.1.617.3 -- that largely have the same set of mutations, except for some small variations.
Among these, two are common: L452R and P681R (these letters mean the amino acid at site 452 changed from leucine to arginine and at site 681 from proline to arginine). Except for B.1.617.2, the other two variants also have the E484Q mutation.
“...Mutations in these variants may result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility, and possibly capacity to escape binding and neutralization by some monoclonal antibodies. In a preliminary study on hamsters, infection with B.1.617.1 resulted in increased body weight loss, higher viral load in lungs and pronounced lung lesions as compared to B.1 variants (D614G),” WHO said.
Several studies released by scientists in recent days have shown that some of B.1.617 family of the virus are more transmissible, lead to more severe disease, and be somewhat resistant to some lab-grown antibodies, but it isn’t clear yet if they can make vaccines or immunity from a past infection redundant to any significant degree.
In one of the studies, published late on Sunday, on Biorxiv, the researchers zeroed in on the P681R, which has also been seen in the variant first spotted in UK. “We find that P681R is associated with enhanced capacity to induce cell-cell fusion and syncitia formation, and that P681R alone confers this ability on the B.1.617.1 spike with RBD mutations L452R and E484Q ,” said the team of researchers led by scientists from Cambridge.
Syncitia is a phenomenon where multiple cells fuse to create what are known as giant cells. The scientists explained that the P681R mutation occurs at a location of the virus that takes the shape of a spike to first latch onto human cells, before it splits – or cleaves – in order to enter the cell. This site is known as the polybasic cleavage site (PCBS). “Virus infectivity and fusogenicity mediated by the PBCS is a key determinant of pathogenicity and transmissibility and there are indications that giant cells/syncitia formation are associated with fatal disease,” the authors said.
Among the assessments they carried out was the case analysis of 33 staff members of a Delhi health facility who were infected by the coronavirus after having been vaccinated, most of whom had contracted the new variant, although none developed severe symptoms.
“The loss of neutralisation of B.1.617 (by vaccinated serum) has likely contributed to an epidemic wave in India where background infection to the Wuhan-1 D614G in 2020 was between 20-50%,” said the authors in the study, which is yet to be peer reviewed.
“What we found was a reduction in the ability of the antibodies to neutralise this variant, but they weren’t ineffective. There are infections reported in vaccinated individuals but all vaccines protect against severe disease,” said Dr Anurag Agarwal, one of the authors of the paper and director of Institute of Genomics and Integrative Biology. “Breakthroughs are being seen with both (all) vaccines though. Not rare anymore, clearly. In vast majority, but not all, disease is mild,” he added.