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Insights into Editorial: Identifying mutants

 

 

Context:

In early March, members of the Indian SARS-CoV-2 Genomic Consortia (INSACOG), an advisory group to the Central government, warned of a new and contagious form of the novel coronavirus.

Last week, Shahid Jameel, eminent virologist and head of INSACOG, resigned from his post unexpectedly.

Though he did not cite the reasons for his exit, Dr. Jameel has been a critic of aspects of the government’s handling of the COVID-19 pandemic, particularly on data sharing, the emergence of new variants and their role in the second wave of infections.

 

What is INSACOG?
INSACOG is a consortium of 10 labs across the country tasked with scanning COVID-19 samples from swathes of patients and flagging the presence of variants that were known to have spiked transmission internationally.

  1. It has also been tasked with checking whether certain combinations of mutations were becoming more widespread in India.
  2. Some of these labs had begun scanning for mutations in April 2020 itself, but it was not a pan-India effort.
  3. The institutes involved were those with expertise in genome sequencing and included laboratories of the Department of Biotechnology, the Council of Scientific and Industrial Research (CSIR), the Indian Council of Medical Research (ICMR) and the Ministry of Health & Family Welfare (MoHFW).
  4. The National Centre for Disease Control (NCDC) under the MoHFW was tasked with coordinating collection of samples from the States as well correlating disease with the mutations.
  5. The work began in January by sequencing samples of people who had a history of travel from the United Kingdom and a proportion of positive samples in the community.

What are the challenges being faced by INSACOG?
Given that the novel coronavirus is spreading, mutating and showing geographical variations, the aim of the group was to sequence at least 5% of the samples.

  1. For many reasons, this has so far been only around 1%, primarily due to a shortage of funds and insufficient reagents and tools necessary to scale up the process.
  2. While some of these issues can be explained as teething troubles, the INSACOG, in spite of being peopled by expert scientists, is ultimately an advisory group to the Central government and part of its communication structure.
  3. Warnings about emerging variants were not made public with sufficient urgency and the sharing of datasets, even within constituent groups of the INSACOG, was less than ideal.

 

What are the findings?

Recent note from the Department of Biotechnology (DBT) said 20,000 samples had been sequenced and about 3,900 variants had been identified.

The “foreign” variants identified were primarily the B.1.1.7 (first identified in the United Kingdom) and the B.1.351 (first found in South Africa) and a small number of P2 variants (from Brazil).

However, some labs flagged the growing presence of variants identified in India that were clubbed into a family of inter-related variants called B.1.617, also known as the ‘double mutant’ variant, primarily due to two mutations— E484Q and L452R — on the spike protein.

These have been individually identified elsewhere but not together.

Mutant virus will increase infectivity:

  1. There are many more mutations that contribute in different measures, in ways not fully understood, to the virus being able to adapt to human hosts.
  2. The B.1.617 family was marked as an international ‘variant of concern’ after it was linked to a recent spike in cases in the United Kingdom.
  3. In March, it was linked to a spurt in cases in Maharashtra. But there is no evidence yet to show that the variant is associated with increased disease severity.
  4. INSACOG labs also found that the B.1.1.7 variant, which is marked by increased infectivity, is distinctly more prevalent in several northern and central Indian States in comparison to southern States.

Are some mutations more important?

Yes. Scientists pay most attention to mutations in the gene that encodes the SARS-CoV-2 spike protein, which plays a key role in viral entry into cells.

Targeted by vaccines, this protein influences immunity and vaccine efficacy. The B.1.1.7, 501Y.V2, P.1 and B.1.617 variants all carry multiple mutations affecting the spike protein.

That raises questions about whether people who have developed antibodies to the “regular” strain will be able to fight off the new variants.

 

Beyond identifying patterns, why is genome sequencing useful?

  1. The purpose of genome sequencing is to understand the role of certain mutations in increasing the virus’s infectivity.
  2. Some mutations have also been linked to immune escape, or the virus’s ability to evade antibodies, and this has consequences for vaccines.
  3. Labs across the world, including many in India, have been studying if the vaccines developed so far are effective against such mutant strains of the virus.
  4. They do this by extracting the virus from COVID-19-positive samples and growing enough of it.
  5. Then, blood serum from people who are vaccinated, and thereby have antibodies, is drawn.

 

Way Ahead: India’s genome project on low gear:

  1. Sequencing of the genomes of viral strains is important from a ‘know-thy-enemy’ point of view.
  2. A genome is the complete set of genetic instructions that is present in an organism, in the form of its DNA.
  3. Sequencing refers to knowing the exact sequence of occurrence of the four nucleotide bases—A, C, G and T, which are the first letters of the names of four bio-molecules.
  4. Since each mutation is caused by a change in the genome sequence, knowing the sequences helps keep track of the mutations.
  5. In other words, genome sequencing can provide information on mutations or genetic variants that cause the disease or can increase the risk of disease in a person.
  6. The effort of genome sequencing was happening in a sporadic and un-coordinated way and it was not until the first report of a UK ‘variant of concern’ was published in December that the government sat up.
  7. The government immediately initiated the network of large-scale sequencing of viral genome.

 

Conclusion:

The poor progress in genome sequencing also affects India’s image abroad, as all countries are required to upload data into a common global repository, called the ‘Global Initiative on Sharing all Influenza data’, or GISAID.

This is to alert the world about new mutants. The world is watching apprehensively at India’s massive sweep of the second wave and would be expecting India to capture variants and put the data into the common database.

There were fewer antibodies produced against the South African, Brazil and the ‘double mutant’ variant.

Antibody levels are not the only markers of protection and there is a parallel network of cellular immunity that plays a critical role in how vaccines activate immunity.

The current evidence for most COVID-19 vaccines is that they have almost 75% to 90% efficacy in protecting against disease but less so in preventing re-infection and transmission.