NEW DELHI – Scientists have sequenced a new “double variant” of the coronavirus first identified  in India – along with a handful of other variants of concern that are appearing during the second biggest wave of the virus since the pandemic began.

The new double variant, bearing two significant mutations in the coronavirus spike protein, dubbed E484Q+L452R, could be associated with higher infectivity and with a capacity to evade antibodies, government experts have warned. Alone or together, the mutations E484Q and L452R “have been found in about 15-20% of samples and do not match any previously catalogued VOCs”,said the Ministry of Health and Family Welfare in a press release, 

The two variants both appear to “confer immune escape and increased infectivity”, the Ministry said; immune escape refers to the ability of a variant to evade immunity conferred by a prior infection. 

The government also said that there is not yet sufficient evidence to establish a link between the new mutation and the surge of COVID-19 cases occurring now in some states of India. India reported 53,476 new cases in the last 24 hours, of which 31,855 are from Maharashtra.  “The variants of concern and a new double mutant variant..have not been detected in numbers sufficient to either establish a direct relationship or explain the rapid increase in cases in some states,” the press statement issued by India’s Ministry of Health and Family Welfare.

The double mutation has been found mostly in the Western state of Maharashtra which is seeing a massive surge in COVID-19 cases. Several cities in Maharashtra including Mumbai and Pune had massive number of cases in the first wave of the pandemic last year. However, since mid-February, the state has seen a massive spike of cases yet again. 

“We have seen this double mutant E484Q+L452R in 206 samples in Maharashtra and a varied number in Delhi. In Nagpur, we found a substantial number of samples with this mutation- about 20%. But, the data so far does not show that the surge is related to this mutant,” said Dr Sujeet Kumar Singh, Director of India’s National Centre for Disease Control, speaking at a press conference on Wednesday.

Nagpur is one of the cities in Maharashtra which saw the beginning of the surge of  Covid-19 cases in India from mid-February. 

Variant of ‘Interest’, Not Yet ‘Concern’ According to WHO Criteria

Speaking at the press briefing, however, Singh also downplayed the significance of the double mutation at this point. 

He said that according to WHO criteria, the double mutation could be called a “variant of interest”, but it has not yet been  established as a “variant of concern” in the same way as the variants first identified in the United Kingdom, Brazilian and South Africa – also circulating in India. 

The WHO has established three classifications for the identification of SARS-CoV2 mutations, including variants under investigation, variants of interest and variants of concern. 

Singh said that further investigations of the Indian mutations are underway. “Only when the variant has public health impact, increases severity of the disease does it become cause of concern,” explained  Singh of the classifications. 

In an interview with Health Policy Watch, Dr Shahid Jameel, chair of the scientific advisory committee of the Indian SARS-CoV-2 Consortium on Genomics (INSACOG), echoed that message. The consortium is a group of 10 laboratories that carry out genomic sequencing and analysis of circulating COVID-19 viruses. The consortium tests international travellers, their contacts, and   community samples. It has so far tested more than 10,000 cases.

“We do not need to worry about the double mutation, but we have to be concerned,” Jameel said. “Both these mutations allow the virus to infect better and evade antibodies. But we do not know how much it will affect the surge on the ground.” 

Variants of greatest concern are typically associated with a higher viral load,  increased transmissibility and  also “immune escape” – referring to variants that can evade immunity conferred by a prior infection. 

The Genomic Consortium is primarily concerned with variants that carry mutations in the characteristic spike protein of the coronavirus, which eases the virus’s way into cells, allowing it to infect individuals with COVID-19. On that spike protein, one region of greatest interest is the “receptor binding domain”, said Jameel.  

In the cases of mutations that facilitate “immune escape”  changes occur in that receptor binding domain, Jameel explained: “In the [spike protein’s] receptor binding domain, there is a path called the ‘receptor binding motif’. It contacts the cell, and from there the virus is able to enter the cell. However, antibodies [built from previous infection or immunization] can prevent its binding to the cell. 

“If the virus changes the process slightly, so that it is not recognised by antibodies it is able to enter cells more effectively,” said Jameel.

Another variant associated with “immune escape” -N44OK- also has been found in the country’s southern states of Kerala and Telangana. This variant, however, has also been reported in 16 other countries including the United Kingdom, Denmark, Singapore, Japan and Australia. 

Sequencing Is Simple – Linkage to Community Spread Is More Difficult

“While sequencing is simple, linking the sequences to community spread depends on various reports and the kinds of samples taken,” said Jameel. “To link it epidemiologically is time consuming and difficult. The mutant strain will be figured out in time, but the important thing is to stop the spread of the virus,” said Jameel.

Even in Nagpur, the cases are spreading in areas of the city that were relatively unaffected in the first wave last year, and that the population in these areas were susceptible to the virus.

A nation-wide survey showed only one out of 5 people have been exposed to the virus. But in cities such as Mumbai, Pune, Delhi the sero-surveillance shows high levels of high levels of sero-positive cases, of more than 50%.

“The most important thing to remember is that viruses will not mutate if they are not allowed to replicate. Therefore, we have to only suppress the chain of transmission to stop mutations of the virus. Testing, quarantine, and containment will limit the spread of the virus,” said Dr Vinod Paul, chairperson of India’s Covid-19 task force.

Mutations Will Not Affect India’s Vaccination Drive

These variants should  not, however, impact India’s vaccination drive, other government officials have said . “It is well established by research studies in literature and published literature, that both the vaccines that are available in our country are effective against both the UK and Brazil variants. The research regarding the South African variant is ongoing at the moment,” Balram Bhargava, director general of Indian Council of Medical Research (ICMR), said.

More than 50 million people have been vaccinated with one dose so far in the country. Much has been said about the slow pace of vaccination in the country covering only about 3% of the population. 

In the first drive of vaccination which started in January, the government only allowed healthcare workers to take the vaccine. In March, the government started the vaccination drive for people above 60 years old and people above 50 years old with co-morbidities. It has now announced that those who are 45-years and more are eligible for the vaccine.

Covid-19’s Second Wave in India

Since mid-February COVID-19 cases have been steadily rising in India. From an average of about 12,000 cases a day at the time, more than 40,000 are getting reported in the last few days.

Just six states in India – the western states of Maharashtra and Gujarat, the central state of Chhattisgarh, the northern state of Punjab and the southern states of Kerala and Karnataka –  have accounted for some 80.63% of the new cases reported in the last 24 hours, said India’s Health Ministry.

Along with any locally emerging variant, another major concern is the high number of samples identified with the UK variation (B.1.1.7) in the northern state of Punjab. The Punjab government said that 81% of the samples examined between January and early March have been found to be from that coronavirus lineage. The explanation for that is likely to be international travel – insofar as the UK is home to a large Punjabi diaspora. 

In the press conference, Singh attributed the rise in cases to the large number of people that were not infected in the first wave, and have not been vaccinated either, and so they are still  susceptible to COVID-19. With a year of the pandemic, pandemic fatigue has set in and people are perhaps lax about COVID appropriate behaviour, he said. 

Image Credits: Flickr – NIAID.