Like the rest of the country, Andhra Pradesh too is in the midst of a raging second wave of COVID-19, with hospitals being flooded with critical patients. Over the past week, on a daily basis, around 70 COVID-19 deaths on average have been officially recorded in the state (between April 28 and May 4), while the total official death toll stands at 8,289 as of May 4.
Amid the crisis, several reports have emerged in recent days, suggesting that the rise in infections in Andhra Pradesh was the result of a more dangerous variant of the SARS-CoV-2 virus, native to the state. These reports have claimed that the ‘AP variant’ was several times more damaging or deadly than other prevalent variants. These claims are inaccurate, according to experts studying the genomic variants of the coronavirus.
According to scientists from the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, these reports were a misinterpretation of a study carried out by researchers from CCMB and Academy for Scientific and Innovative Research (AcSIR), Ghaziabad. The study, available on the preprint server bioRxiv had found that variants with the N440K mutation had higher ‘infectious fitness’ or ‘infectivity’. The researchers, however, have said that this does not necessarily mean that the virus is more deadly.
While variants with N440K could be more infectious than other variants that came before it, scientists say that it seems to have now been overtaken by other variants like B.1.1.7 (first detected in the UK and commonly known as the UK variant) and B.1.617 (first detected in India and widely known as ‘double mutant’).
The variant with the N440K mutation, now being called the ‘AP variant’ and ‘N440K variant’, was first detected in India in Andhra’s Kurnool district, back in June 2020, during the first wave of COVID-19. According to Divya Tej Sowpati, a scientist at CCMB, most of the viruses carrying this mutation fall under the lineage B.1.36.29.
It is normal for RNA viruses, like the novel coronavirus, to undergo changes or mutations in its genetic code, as it makes more copies of itself in the host cells of infected people. These mutations generate new variants of the original virus. While many insignificant mutations which are unfavourable to the virus end up disappearing, a few mutations which offer benefits to the virus persist. Such variants, which could possibly worsen the pandemic situation, are classified as variants of interest, concern, or high consequence.
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The CCMB-AcSIR study found that the variant with the N440K mutation had more ‘infectious fitness’ than previously prevalent strains like A2a and A3i (without the N440K mutation). This means that in the controlled environment of cell culture, the ‘N440K variant’ was able to make more copies of itself. Specifically, it could make ten times more copies of itself than the A2a variant, and a thousand times more copies than the A3i variant.
However, Divya Tej said that the behaviour of the variant in cell culture may not necessarily be the same among humans. “In a cell culture, everything is controlled, there is no competition (with other variants) and other such factors,” he noted.
2. Though in controlled cell culture this variant makes more copies, it does not necessarily mean that it can compete with other variants just the same way in a real life pandemic where new variants keep coming up. Our genome studies say that N440K is now diminishing
— CCMB (@ccmb_csir) May 5, 2021
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Moreover, the variant being able to replicate more or being more infectious does not mean it is more lethal or deadly, he added. Clarifying the findings of the study, one of its authors, Vishal Sah wrote, “No need to panic about N440K being more 'deadly'. Being more infectious and being lethal are two totally different things.”
Totally agree with the fact that UK and double mutant will ultimately take over N440K at their current rate of spread, and no need to panic about N440K being more 'deadly'
— Vishal Sah (@acurious_one) May 4, 2021
Being more infectious and being lethal are two totally different things.
As of March 2021, the Ministry of Health had called the N440K a variant under investigation, while noting that it is associated with immune escape (the virus’ ability to escape the human immune response). However, scientists have noted that the ‘N440K variant’ seems to be on the decline. “N440K variant of SARS-CoV-2 is diminishing and likely to disappear soon,” CCMB director Rakesh Mishra noted on May 3.
N440K variant of SARS-CoV-2 is diminishing and likely to disapear soon. pic.twitter.com/Su13gflHqs
— Rakesh K Mishra (@3RakeshMishra) May 3, 2021
Commenting on the reports on N440K, Department of Biotechnology Secretary Renu Swarup said on May 5 that the study was published by an independent researcher based on samples collected last year. “N440K was found but quickly diminished. Not seen now, no clinical impact at all,” she said.
The N440K mutant is not new to the state. It was detected as early as June 2020, and has been found in south India since the first wave of COVID-19. It is not unique to Andhra Pradesh either. It has been found in several states including Telangana, Karnataka, Chhattisgarh and Maharashtra, as well as other countries including the UK, US, Denmark, Singapore, Japan, Germany and Australia.
Moreover, scientists studying the genomic variants of the coronavirus have pointed out that N440K’s presence has gone down in samples lately, to be replaced by variants like the B.1.1.7 (UK variant) and B.1.617 (‘double mutant’).
Lineages with #N440K are NOT the dominant ones in the second wave of #Covid19inIndia. While N440K was a indeed mutation of concern in South India during and after the first wave, current data shows that it is essentially replaced by new VoCs such as #B1617 and #B117 pic.twitter.com/3mbjLNijny
— Divya Tej Sowpati (@TejSowpati) May 3, 2021
B.1.617 (blue) and B.1.1.7 (green) lineages seem to be edging out every other lineages which were prevalent in India.
— Vinod Scaria (@vinodscaria) May 2, 2021
Plot: @Arvinden3 from @GISAID Data. pic.twitter.com/UwXrYcv1Oi
Specific to Andhra Pradesh and the Vizag region too, data from recent samples sequenced at the CCMB showed that N440K did not have a dominant presence, according to Divya Tej. “#N440K is not circulating in Vizag as suggested by some news reports. Looking at the data from recent samples sequenced by us, only 2 out of 36 Vizag samples carry the N440K mutation. In fact, it's <5% of all AP samples from Mar and Apr,” he wrote on Twitter.
#N440K is not circulating in Vizag as suggested by some news reports. Looking at the data from recent samples sequenced by us, only 2 out of 36 Vizag samples carry the N440K mutation. In fact, it's <5% of all AP samples from Mar and Apr. https://t.co/NQijjzJ198
— Divya Tej Sowpati (@TejSowpati) May 4, 2021
According to Divya Tej, N440K was present along with A2a and A3i (the three variants the study has compared) during the first wave. While the A2a variant was more prevalent worldwide, the A3i variant (which was found to replicate 1000 times less than N440K) was already declining when N440K was detected. “Eventually, N440K possibly took over A2a. We saw that N440K was indeed prevalent during the first wave, and it continued to be prevalent up until December-January. By the time the second wave began, the lineage B.1.617 seems to have become more prevalent at the expense of N440K,” he said.
The CCMB-AcSIR study does not compare N440K with the UK and ‘double mutant’ variants.
We did not compare the infective titer of N440K with UK or double mutant in this study. We compared it with its parent strain which did not have N440K mutation and with another strain which is now almost lost among the population.
— Vishal Sah (@acurious_one) May 4, 2021
According to Divya Tej, the B.1.617 (double mutant) variant has been the dominant one among the samples from Andhra Pradesh as well as other southern states and Maharashtra. While studies on the double mutant variant and its effect on the current surge are still underway, the WHO (World Health Organization) in a recent update said, “Preliminary modelling by WHO based on sequences submitted to GISAID suggest that B.1.617 has a higher growth rate than other circulating variants in India, suggesting potential increased transmissibility, with other co-circulating variants also demonstrating increased transmissibility."
While the N440K may not be a cause for panic in Andhra Pradesh right now, the state is faced with similar problems as the rest of the country, with increased infections, hospitalisations and deaths, and an overburdened healthcare system. But no matter which variant of the virus is in circulation, experts say that the precautions remain the same: slowing transmission with masks, distancing and vaccine coverage. “The more the virus circulates, the more possibility of mutations and more harmful variants coming up,” Divya Tej said.
3. Our main focus as a community should be on reducing the spread of coronavirus. The more it spreads, the more variants come up, the more mess we create by increasing uncertainties and fear.
— CCMB (@ccmb_csir) May 5, 2021
So, see
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