Dubai: Indian scientists tracking the coronavirus recently found something interesting —a "double mutant" COVID-19 variant. It was at the Center For Cellular & Microbiology, in Hyderabad, where this particular strain was first sequenced.
The variant was initially detected in Maharashtra's Nagpur district in December last year. Recently, other cases were also reported from Delhi, Gujarat and Punjab, among others. It has now reportedly spread to 18 states in the subcontinent.
What’s this 'double mutant' strain all about?
Dr Rakesh Mishra, the centre’s director, explained it is the result of the E484Q and L452R strains coming together to form a third strain. The L452R strain was first reported in California and the E484Q is an “indigenous” strain found in India. There's no name/code assigned to it yet.
On Wednesday (March 24, 2021), scientists under the Indian SARS-CoV-2 Consortium on Genomics (INSACOG) confirmed an “increase in the fraction of samples with the E484Q and L425R mutations” compared with December last year.
Since its founding in December 2020, the consortium has been carryring out genomic sequencing and analyses of COVID-19 variants circulating in India. INSACOG groups 10 labs in the country and correlates their findings with data on genomic mutations gathered in a common global scientific database. Viral genome sequences on GISAID come from different corners of the planet, uploaded at a rate of about 5,000 per day.
Is India's double-mutant strain deadlier?
Dr Mishra told Indian media the new strain is “efficient”... but “not yet a superspreader”. And there’s is no reason to believe that it is more deadly — just yet.
He stressed, however, that more investigation is needed to fully understand it, as well as future mutations of the SARS-CoV-2 in the country.
56,211number of new cases of coronavirus reported by Indian health authorities on Monday, March 29, 2021.
Do available vaccines work against them?
At the moment, there is no evidence to show that vaccines in India — Covishield and Covaxin — will not work against these new strains, according to him.
Is this double mutation responsible for a spike in COVID cases in India?
So far, there's been no link between the double mutant virus with the surge in COVID-19 cases in several states, according to INSACOG.
Why do viruses mutate?
Viral mutation is a natural phenomenon. They mutate all the time. As a virus it keeps changing in small ways. Most of the time, such minute changes don’t matter, if they don’t change how the virus behaves in general. Single mutations may occur in a part of the virus RNA that causes a change in a particular building block. There could also be many mutations — that eventually alter an entire viral RNA.
271number of COVID-19 related deaths reported on March 29, 2021 in India (162,000 total deaths)
Why are some strains labelled as 'variants of concern'?
While tens of thousands of minor SARS-CoV-2 mutations had been seen by scientists, rare block-altering mutations can trigger changes in its viral structure. For example, they could confer greater efficiency in the spike protein, bumping up its ability to hijack human cells. Such variants could potentially be more infectious and cause more severe disease.
When enough mutations happen in a viral family tree (or a lineage), the virus can begin to function differently. That lineage can be classified as a so-called “variant of concern”. That’s why constant global surveillance is necessary, and global leaders have called for a new pandemic treaty to boost surveillance and coordinated action.
• These shared databases would help determine whether the "double mutant" is the same lineage as the one found in the UK, or whether this combination of mutations independently emerged, as was the case for the K417N/T, E484K, and N501Y trio of mutations that came together in Brazil and South Africa to give rise to their strains, P.1 and B.1.351.
How many mutations in SARS-CoV-2 had been found?
Since it was first sequenced in early January 2020, SARS-CoV-2 has been mutating. Researchers have catalogued more than 12,000 mutations in SARS-CoV-2 genomes, according to a Nature article published in September 2020. Scientists say the virus's mutation rate is actually “sluggish”.
12,000number of SARS-CoV-2 mutations catalogued by researchers around the world so far, according to the journal "Nature".
What are examples of sub-strains?
On March 3, 2021, a group led by Dr Rui Wang, a mathematician at Michigan State University, analysed 45,494 complete SARS-CoV-2 genome sequences gathered from different parts of the the world to understand mutations (12,754 sequences came from the US).
“Our analysis suggests the presence of four sub-strains and 11 top mutations in the US,” Wang wrote in the open-access "Communications Biology” journal. “These 11 top mutations belong to 3 disconnected groups. The first and second groups consisting of 5 and 8 concurrent mutations are prevailing, while the other group with three concurrent mutations gradually fades out.”
12.1mnumber of coronavirus cases recorded in India as of March 29, 2021.
Researchers also found that female immune systems are more active than those of males in responding to SARS-CoV-2 infections. “One of the top mutations, 27964C > T-(S24L) on ORF8, has an unusually strong gender dependence.” More importantly, Wang’s group uncovered that two of four SARS-CoV-2 sub-strains in the US were “potentially more infectious.”
What is the most transmissible variant?
The B.1.1.7 variant — first discovered by researchers in Britain in November 2020 — till now has been the most aggressively transmissible one among the many variants. For example, as cases rise in the US, at least 40 states in US have recorded cases that contracted COVID-19 with the B.1.1.7 variant, according to Dr Wang.
Did the B1.1.7 variant combine with another?
Yes, a concern among US scientists is the 'E484K' mutation combined with B.1.1.7. This specific mutation has been one of the many reasons for the number of cases rising across the world, including India, say experts.
Across Europe, the B.1.1.7 variant continues to grow, said Dr Emma Hodcroft, co-developer of Nextstrain and molecular epidemiologist at University of Basel (Switzerland). She's one of the leading phylogeneticists who put together analytical tools to establish mutation patterns and increase the scientific community’s understanding of the genomic tree of the virus.
Are such double mutants rare? What happens to other mutations?
"'Double mutants' are not rare," says Dr Jeremy Kamil, a virologist, told Gulf News on Tuesday. "'But the combo of L452R + E484Q appears to be a relatively newly emergent lineage/variant. Interestingly, it also has P681R. And at least 3 other Spike mutations. So the term 'double mutant' is a misnomer!"
'Double mutants' are not rare. But the combo of L452R + E484Q appears to be a relatively newly emergent lineage/variant. Interestingly, it also has P681R. And at least 3 other Spike mutations. So the term 'double mutant' is a misnomer.
The associate professor at the Louisiana State University Health Sciences Centre Shreveport recently co-authored a study of seven growing lineages of the novel coronavirus in the US. In a series of tweets he sent out in February, he stated: "Every plague forms a family tree, as it disperses through our species. Out of one comes many, and many don't get along...someone has to 'win' while another fades away to viral obscurity."
"It is now extremely common to see more than one mutation at once - even if we limit ourselves to the spike gene,” he was quoted as saying. Earlier in the pandemic, most spike genes had only one mutation - D614G. Now that mutation is dominant and everywhere, "so we see others on top of it", he added.
What's the use of sequencing the coronavirus genome?
"Imagine if no one was sequencing the coronavirus...we would be speaking and thinking in terms of one virus...there would be no variants in the headlines or in our minds...just poortly explained upticks in casess... handwaving, blaming of human behaviour or seasonality," Dr Kamil stated on Twitter.
What do other scientists know about the double-mutant strain?
GISAID, an open sharing database, lists 43 virus strains that have both the E484Q and L452R mutations found in India. Dr Kamil pointed out that a virus collected in March from UK has nine spike mutations. "That's a lot of mutations.” He asked the Indian scientists if the variant they first sequenced in Hyderabad really has just only two spike mutations.
Its full set of mutations and phylogenetic profile (genetic lineage) will be known once the Indian researchers upload their sequence data to GISAID, Nextstrain, or some other open genome databases.
Dr Kamil belongs to a highly specialised group of virologists and phylogeneticists, researchers concerned with finding the genetic connections and relationships between species. This discipline greatly enhances understanding of SARS-CoV-2 variants.
As for the "coming together" of the E484Q and L452R strains to form a third strain, "this is probably wrong," Dr Kamir told Gulf News. "We already know that the same mutations can recurrently emerge — independently. The most likely explanation is that this E484Q and L452R emerged anew."
"Phylogenetic analysis, as far as I know, doesn’t suggest that the 'California' L452R variants B.1.427 + B.1.429 traveled to India and picked up E484Q," he added. "Look at P.1 and B.1.351, they emerged independently, coming up with the same/very similar set of mutations: E484K, K417N/T and N501Y."
How worried should we be about the new variant?
Dr Kamil said unlike some other variants, India's new “double variant” is not likely to be more deadly or more inherently transmissible. But just to be sure, he said more data would shed greater understanding.
Using open scientific databases like GISAID, researchers from around the world would be able to determine whether the "double mutant" is the same lineage as the one found in the UK, or whether this combination of mutations independently emerged — as was the case for the K417N/T, E484K, and N501Y trio of mutations that came together in Brazil and South Africa to give rise to their strains, P.1 and B.1.351.
• Knowledge of the virus’ RNA sequence was key in characterising it. This made possible an increased surveillance of SARS-CoV-2 viral genome, which enables the research community to identify and track new “mutations of concern”.
What about reinfections with the 'double mutant' virus?
Scientists say “reinfections” will be very mild compared to primary infections in people who are vaccinated or who recovered already from an earlier case of COVID-19.
There's one problem with this: With reinfections, the virus can use asymptomatic people to spread far and wide. This then would help the virus "penetrate" herd immunity (when large portion of a community becomes immune to a disease through vaccination or through the mass spread of the disease.)
This puts the most vulnerable people at risk of severe disease, as the virus can move through the herd to reach them.