Slight genetic changes of virus don't change strain, say geneticists

Geneticists from Delhi's CSIR Institute of Genomics and Integrative Biology, Vinod Scaria and Bani Jolly, tell how they are tracking the evolution of SARS-CoV-2 in India

What is a phylogeny study? How would you explain the evolution of SARS-CoV-2?

As the virus mutates and evolves, its genetic structure changes, and the relation between these different SARS-CoV-2 genomes can be represented via a “phylogenetic tree”, akin to the family tree of the virus.

Do you find different variants of the virus, then?

Slight changes in the genetic structure of the virus does not change the strain, but alters only a few characteristics. The group of genomes who share common mutations form a “clade”, akin to a family. Different mutations, and thus various clades, may impact humans differently. The phylogenetic study helps in tracking the disease outbreak by identifying the diversity of the virus and determining how the virus has travelled around the world.

What are the primary insights from the study?

As against 10 globally prevalent clades of SARS-CoV-2, seven “families” of this coronavirus have been observed in India: and they are named A1a, A2a, A3, B, B1 and B4, and I/A3i. The predominant clade A2a, which possibly originated in Europe, is seen in 60 per cent of the spread in India. This variant is defined by a mutation in the spike protein of the virus, a protein that has been shown to be responsible for aiding the virus in infecting a host body.

Vinod Scaria

Is there any “clade” or family that is unique to India?

Yes, the I/A3i did not classify under any of the 10 previously labelled clades, and was the second-largest set of SARS-CoV-2 genomes found in India. It is present in a distinctly large proportion in India (a fourth of the samples), with limited representation outside the country.

Bani Jolly

There seem to be two variants dominant in India, then. How different are they?

For the dominant family A2a, we found that there are multiple points of introduction of the infection — the infections can originate in different places at the same time — followed by the subsequent spread to other regions. However, the transmission pattern of the clade I/A3i suggests that the clade diverged from a single point (or a few points), then spread to other regions, possibly as the result of a large outbreak event.

Would this study help us arrest the spread of Covid-19 in India?

Mutations in genomes helps us do “molecular contact tracing”, or tracing the spread of the virus based on the mutations that it has accumulated while jumping from one human to the other. Thus, the identification of clades is important from a public health point of view. If a large number of genomes is made available in India, the information gained from documented cases of infection in the country can be used to uncover undocumented sources of infection, which can be quarantined to prevent the recurrent spread of the disease.

Can this study help in vaccine development?

Looks possible. Given that the study has shown that the globally most prevalent clade of SARS-CoV-2 is also predominant in India, any vaccine or drug that gets developed in the world should also prove effective in India.

Would a vaccine for a particular strain apply to an infection caused by a different strain? Does the spike protein change its shape in a certain clade? If this is true, would it impair the efficacy of the vaccine?

The most common A2a clade, for instance, contains a mutation in the spike protein of the virus and is located in a highly immunodominant region. This may affect vaccine effectiveness.

However, though many mutations in the SARS-CoV-2 genome have been catalogued, the studies conducted so far do not sufficiently suggest the implications of these mutations on the “fitness” of the virus. It is unlikely that the mutation will have an impact on the efficacy of vaccines currently in development.

How severe, or deadly, is SARS-CoV2 compared to other viruses?

SARS-CoV-2 is shown to have a lower rate of mutation as compared to other RNA viruses. It is mutating at a rate of approximately 25 times per year, which means it accumulates one mutation in 15 days. To put this into perspective, the viruses causing seasonal flu mutate at a rate of 50 mutations per year.

While making a vaccine for flu has always been a difficult task, the relative stability of the novel coronavirus provides hope that it will not mutate into a more dangerous strain that will evade any possible vaccines.

How challenging is this specific study compared to the previous ones?

The study was done using publicly available datasets of SARS-CoV-2 genomes. COVID has led to a culture of “open science.” Global collaborations and increased data sharing helped us evade the challenge of getting data to work with.

The data was taken from a web-based freely accessible global science initiative called GISAID. The resource provides unrestricted access to more than 70,000 genomes that have been sequenced from all over the world. Close to 2000 genomes have been deposited on GISAID from India.

Does phylogeny help in countering future infections? Say, for a recovered Covid-19 patient after a year of infection?

There is no evidence at this point in time to prove/disprove this.