At a time when the health experts are busy arresting the spread of foreign strains of the novel coronavirus , a scientific study has revealed that there are more than 7,000 mutations of the virus in India, of which some could pose a serious risk.

NITI Aayog Member (Health) VK Paul has said that 187 people have tested positive for the UK strain of SARS-CoV-2 in the country so far, while six people have detected with the South Africa variant. Also, one person has tested positive for the Brazil variant strain.

A study published by the scientists of the Hyderabad-based Council for Scientific and Industrial Research Centre for Cellular and Molecular Biology states that some of the 7,684 mutations detected so far can render the virus more infectious.

Dr Rakesh Mishra, Director of the CCMB, said among the variants, N440K is spreading a lot more in the southern states, including Andhra Pradesh.

He stressed that it is necessary to step up genome sequencing in India to stay on top of the progressive changes in the virus’ structure and to develop a treatment and prevention strategy per these changes.

India has so far not been sequencing SARSCoV-2 isolates to full capacity, having deposited only about 6,400 genomes of the over 10.4 million recorded cases (0.06 percent).

After the evolution of the UK and Brazilian strains of coronavirus which are found to be more transmissible, the Indian government has been trying to step up the sequencing of the genomes.

An Indian SARS-CoV-2GenomicConsortia (INSACOG) comprising 10 institutes was also formed for this purpose. The CCMB is a part of the consortium.

What are the key findings of the study?

The CCMB scientists published their findings in a research paper titled SARS-CoV-2 genomics: An Indian perspective on sequencing viral variants.

The study found that a variant carrying the N440K mutation — is spreading a lot more in the southern states of India, and deeper surveillance is needed to understand if it has worse symptoms or immune-escape capacities.

“We now have emerging evidence that the N440K variant is spreading a lot more in southern states. Closer surveillance is needed to understand its spread properly,” said Mishra in a statement.

Accurate and timely detection of new variants that may show greater infectivity or worse clinical symptoms, including “immune escape”, will be extremely important to pre-empt disastrous consequences, he said.

The paper has also listed out the top 61 non-synonymous Indian variants with details of the genomic mutation and the corresponding amino acid change in the associated viral protein.

The study points out that the virus has transformed to an extent that it now differs at around 20 points in their genome from the variant first reported in Wuhan, China.

“Over time, viruses accumulate mutations that alter the genomic sequence, either due to random replication errors or via a defense mechanism of the host called RNA editing (Van Dorp et al. 2020a, b). The mutations are called synonymous when there is no change to the amino acid encoded and non-synonymous when the protein acquires a change due to the mutation. SARS-CoV-2 has acquired new mutations at the rate of ~2 changes per month so far. Thus, the viral sequences seen today differ from the Wuhan variant at around 20 points in their genomes,” the study explains.

These transformations, the study adds, can render the virus more infectious or likely to evade immunity.

“The evolution of SARS-CoV-2 can render it more infectious via adaptive mutations that increase affinity or enhance binding to host cells, while escape mutations that can help it evade the immune response have serious implications for vaccines and therapeutics and can adversely impact the severity and mortality of the disease,” the study says.

“Our immune systems cannot identify them from previous infections because of the changes in their protein structures,” the paper added.

Mishra, who is also one of the co-authors of the paper, however, added that not every mutation becomes a variant.

“The take-home of this comprehensive work is that due to the natural process of mutation, variants will keep emerging. The best way to control the potential damage is to exercise extensive genome surveillance and take measures to prevent the spread of new variants as and when detected,” the paper said.

What is the difference between mutation and variants?

When a virus replicates itself, errors often occur during the process of replication. This means that the resulting cells of the virus are similar but not exact copies of the original strain first detected in any geographical area.

However, when a mutation occurs at a single point, it won’t necessarily change any of the building blocks (called amino acids) or how the virus is built.

If and when a mutation (or a collection of mutations) alters the building blocks of a virus to change the way it behaves or replicates, it is termed a new strain.

How can mutations affect the COVID-19 fight?

The increasing mutation in the coronavirus can mean that herd immunity will be difficult for Indians. AIIMS director Randeep Guleria, Sunday said that one should not think of it in “practical terms” in India, especially in the times of “variant strains” of COVID-19 and “waning immunity”.

“Herd immunity is something that is going to be very, very difficult to achieve and it is something one should not really think of in practical terms… because the variant strains and varying immunity with times can lead to a chance where people may have reinfection or get the infection again,” the All India Institute of Medical Sciences (AIIMS) director said.

“And one should also remember that a large number of people have had mild infections and we do know that those with mild infection tend to have fewer antibodies production, their antibodies tend to wane over a period of time,” he added.

Experts say herd immunity is said to have been developed in a population segment if at least 50-60 percent of those are found to have the presence of antibodies in a seroprevalence survey.

Herd immunity implies that in any set of people in a community, after becoming affected by the virus, a lot of them become immune to it, on account of antibodies developed in response to it. And, hence, such people become a protective layer between the infected person and unaffected people, thereby breaking the chain of viral transmission.

India has released three nationwide serological surveys, the latest of which suggests that one out of every five Indians (20 percent) may have been exposed to the novel coronavirus and there is still a large number of people who are susceptible to get the infection.

Impact of COVID variants on vaccine manufacturing

Vaccine makers in India have asserted that they can quickly adapt their shots according to the new variants emerging in the country.

Bharat Biotech and Biological E Ltd said on Monday they could quickly rework their COVID-19 vaccine products to fight new variants once their genetic sequence is known, Reuters reported.

“As we are seeing a lot of resurgence of cases, we are picking up samples from hotspots and clusters and we are trying to sequence them,” Nivedita Gupta, deputy director-general of the Indian Council of Medical Research (ICMR), told the BioAsia conference.

What is genome sequencing?

According to Genome News Network, genome sequencing is the process of figuring out the order of DNA nucleotides, or bases, in a genome — the order of As (adenine), Cs (cytosine), Gs (guanine), and Ts (thymine) that make up an organism’s DNA. The human genome is made up of over 3 billion of these genetic letters.

In the case of the novel coronavirus , the first genome sequences became available on the global public repository, Global Initiative on Sharing All Influenza Data (GISAID) around 10 January 2020, named as the original virus from Wuhan.

According to the paper, since then the repository has amassed over 3,20,000 sequences from all over the globe. India was the 5th country in the world to sequence the viral genome (isolated from the first patients in Kerala) for inclusion in GISAID.

Delhi, Maharashtra and Kerala step up sequencing efforts

Delhi Lt Governor Anil Baijal Monday directed officials to launch cluster-based genome sequencing testing in the National Capital as cases spiked. There was no official confirmation, however, if the mutant variants have emerged in the National Capital so far.

Likewise, news reports said that samples from Kerala, Maharashtra, Punjab and Bengaluru may also be sent for genome sequencing.

An Indian Express report published Saturday states that three Maharashtra districts, Yavatmal, Amravati and Akola, have sent samples for genome sequencing to check if the mutation is responsible for the rapid rise in cases in these districts.

The report claimed that the decision came after four of 12 samples from Amravati showed a point mutation (E484Q) similar to the one found in South Africa, Brazil, and the UK. One of four samples from Yavatmal showed a local mutation (N440K) which was also found in parts of north India and Andhra Pradesh.

NDTV reported that 800 to 900 samples from Maharashtra and Kerala have been sent for genome sequencing in the last one month, while more samples are being sought from Punjab and Bengaluru.

Mutant variants linked to the United Kingdom, South Africa and Brazil have been detected in India so far.

Exploiting advances in genomic epidemiology by monitoring and increasing sequencing efforts following local spikes will go a long way in staying on top of mutations of concern while their biology and effects are studied in greater detail, the paper said.

Govt says hike in cases in Kerala, Maharashtra not due to new variants 

Two variants of SARS-CoV-2 — N440K and E484K — have been detected in Maharashtra and Kerala but there is no reason to believe presently that they are responsible for the surge in cases in some districts in these two states, the Centre said on Tuesday. One of the two variants has also been detected in Telangana.

Only detection does not lead to any attribution for a phenomenon on the ground because to relate the occurrence of a virus mutation to change in disease pattern, other epidemiological information and clinical information has to be linked to these mutants, Paul said, adding, because otherwise these (mutations) happen but they have no influence on the pandemic.

“Today, based on the information and as analysed and understood by a very eminent scientific advisory group of Indian SARS-CoV-2 Genomics Consortium (INSACOG), we would like to underline the fact that we do not see attribution of mutant strains to the upsurge of the infection being seen in some districts. But this is a work in progress. We will continue to watch the situation with full responsibility,” Paul said.

He said the behaviour of mutations is being constantly and closely watched in the country and 3,500 strains have been sequenced so far. “When we are doing sequencing, we are looking for any abnormal shift in the virus character. We have been watching mutants.”

With inputs from PTI