Covid ‘X Men’ — the 7,000+ mutations in India, how to understand them & where they came from

From 'ancestral' mutation to immune evasion, find out the basics about the many Covid variants prevalent in India.

A health worker arranges slides while conducting Covid-19 sampling, at DDCA in New Delhi on 18 December | PTI Photo

Bengaluru: As the SARS-CoV-2 virus continues to spread and India’s case count climbs once again, there is renewed attention on the different variants of the virus circulating in the country.

These variants and mutations have been found across multiple states in the country, including Delhi, Andhra Pradesh, Maharashtra, Gujarat, Kerala, Karnataka, Odisha, West Bengal and Telangana.

More than 7,000 mutations have been recorded in India. According to the health ministry, some of these are more prevalent in the country but have not contributed to a spike in cases.

Here’s a primer on these variants, their mutations and known abilities.

Understanding the virus word cloud

The word ‘strain’ is often used interchangeably with ‘variant’ and ‘lineage’. However, there is a distinction among them.

A strain is a genetically distinct subtype within a family of virus. While there is no universally accepted definition for what a strain is, it typically describes different kinds of viruses within a virus family.

For example, within the coronavirus family, the SARS-CoV-2 virus is a distinct strain, as are the SARS-CoV virus, which caused an outbreak in 2003, and the MERS-CoV virus that caused an outbreak in 2012. Some other strains of the coronavirus cause mild common cold in humans, such as the 229E, NL63, OC43 and HKU1.

A variant, meanwhile, is a subtype of a strain that is genetically different from the original version of the strain but not different enough to actually be categorised as a strain on its own.

For example, the more transmissible variant B.1.1.17, known as the UK variant, is technically a variant and not a strain. A variant is made up of one or multiple mutations that has caused it to differ from the original version of the virus. The B.1.1.17 variant is known to carry multiple mutations like the N501Y, P681H, etc.

At present, the notable variants circulating globally include the B.1.1.17 UK variant, the P.1 variant from Manaus in Brazil, the P.2 variant (also known as B.1.1.248) also from Brazil and the 501.V2 variant from South Africa.

The terms ‘lineage‘ and ‘clade‘ are used interchangeably with ‘variant’.

A variant is made up of different mutations, which is a specific change in the genetics of a virus.

Coronaviruses are ribonucleic acid (RNA) viruses that multiply continuously. As the viruses multiply, each RNA sequence contains minor errors or modifications in its code and each of these modifications is known as a mutation.

Mutations are written down in the form of nucleotide changes — when the mutated RNA code produces an amino acid, which is different from the one produced by the previous version of the virus, and the position where the change occurs.

For example, the D614G mutation affects the spike protein of the SARS-CoV-2 virus in a way where the D (glycine) amino acid at the 614th position is replaced by the G (glycine) amino acid.

Notable mutations in India

D614G

Of all the mutations that arose, the D614G spread rapidly in countries where the disease was not contained well. It spread to countries like India (as a part of the A2a variant that originated in Europe), France, the US, and became the dominant mutation in these countries.

It is now called the ‘ancestral’ mutation G614 — the D amino acid was replaced by the G amino acid. It is also considered the dominant mutation of the pandemic, replacing the L and S types of the virus that were found in the early days of the pandemic last year.

It has since spawned variants with other mutations that are circulating today.

The mutation, in vitro or in the lab, exhibited the ability to cause higher viral loads and more infectivity (the ability to cause infection) but not an increased severity of disease. In some experiments, it also demonstrated higher transmissibility and replication in animals.

Notably, the mutation is not a concern for vaccine efficacy.

N501Y

This mutation causes a change from asparagine (N) to tyrosine (Y) in the amino acid position 501. It has an increased binding ability because of its position in the spike protein, which binds to our body’s ACE2 receptors — the enzyme on our cell membranes that provides the entry point for the virus to hook into and infect a wide range of human cells. Thus, it is more transmissible and spreads faster.

The mutation evolved independently in the South African, Brazilian and UK variants. It is an immune-evading mutation, which means that it can evade detection by the body’s immune system. Thus, it is not effectively neutralised by antibody treatments.

Since all variants have also been detected in India, albeit only in a handful of sequences, this mutation is present in the country as well.

However, there is no evidence yet to suggest that vaccines will be ineffective against this mutation. However, some reports have indicated that some vaccines, like the Oxford-AstraZeneca one, have reduced efficacy against the South African variant and this mutation could be one of the reasons for it.

N440K

The N440K mutation was discovered in late June in the southern states of India, and has since been spreading with renewed vigour. It was recently found in about 42 per cent of the samples that were sequenced in Andhra Pradesh.

This mutation has not yet displayed increased transmissibility or immune evasion, and is not a concern for vaccine efficacy. Its prevalence in Andhra Pradesh could simply be because of lack of sequencing in other states across the country, experts noted.

This mutation was associated with one case of reinfection in India. However, the health ministry clarified Tuesday that it is not associated with increased transmissibility or the surge in cases in Maharashtra.

E484K

This mutation, where the glutamic acid (E) is replaced by lysine (K) at position 484 has also been discovered in India. It is an immune escape mutation, which means that it has the ability to evade detection by the body’s immune system.

It evolved independently in the two Brazil variants and the South African variant. It subsequently also evolved in the UK variant. It has been detected in three samples in Maharashtra so far.

This mutation, or any other mutation at the site E484, has a reduced susceptibility to neutralisation by antibodies. This means the virus is less likely to be neutralised by the body’s antibodies.

It is believed that this mutation is likely the reason behind the reduced effectiveness of the AstraZeneca, Novavax, and Johnson & Johnson vaccines against the South Africa variant.

This mutation has also been associated with reinfections.

E484Q

This mutation was first detected in India between March and July of 2020 and has now made a re-emergence.

In this mutation, the glutamic acid (E) is replaced by glutamine (Q) at the 484 position and it has been found in 11 other countries such as the USA, UK, Switzerland, Italy, Sweden, and South Africa.

This mutation is positioned at the E484 site, and like the E484K, has a reduced susceptibility to neutralisation by antibodies. The E484 mutations have also emerged in the South African and Brazil variants.

Other mutations

As the virus evolves continuously, mutations occur constantly and in the thousands.

India has identified over 7,000 mutations so far, including ones like N439K and Q493K. None of these seem to indicate increased transmissibility (ability to spread), infectivity (ability to infect) or immune evasion yet.

However, it is likely that many other mutations and variants, and their true spread is underestimated because of lack of sequencing.

“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%),” said a recent paper from the Council of Scientific and Industrial Research, India’s apex scientific research organisation.

The study authors added that increasing monitoring and sequencing efforts after a region records a spike in cases will help in identifying the virus mutations effectively. This will also help stay on top of mutations of concern while their effects are studied in greater detail.