‘Need to step up sequencing-based surveillance in country’

Researchers at the Council of Scientific and Industrial Research’s Centre for Cellular and Molecular Biology(CSIR-CCMB), Hyderabad, have made a strong case for keeping a close watch on new and emergent strains of coronavirus, and localised disease outbreaks. “Monitoring and increasing sequencing efforts following local spikes will go a long way in staying on top of mutations of concern,” Dr Rakesh Mishra, director of CSIR-CCMB, told The Indian Express.

While studying SARS-CoV2 under a genomic lens, CCMB researchers have noted mutations in the spike protein used by the virus to enter human cells. “Of concern include E484K found in three samples in Maharashtra and N440K seen in 42 per cent of samples in Andhra Pradesh,” Dr Mishra has said in a new paper to be published online in the Journal of BioSciences- a peer reviewed scientific journal of the Indian Academy of Sciences.

Over time, the viral genome has accumulated mutations and this has implications for disease surveillance and management, vaccines and therapeutics, and the emergence of reinfections. CCMB researchers have reviewed evidence in the past year and highlighted the importance of continued sequencing-based surveillance in the country. They pointed out that India has so far not been sequencing SARS-CoV-2 isolates to full capacity, having deposited only about 6,400 genomes of the over 10.4 million recorded cases (0.06%).

The first case of Covid-19 in India was reported on January 30, 2020, and since then it has affected more than 10 million people and resulted in around 1,50,000 deaths in the country. While most mutations of SARS-CoV2 are of little to no consequence, sometimes the virus acquires a mutation that gives it an advantage over other strains. The Spike protein is used by the virus to enter human cells via the ACE2 receptor.

Some of the spike mutations recently identified in other parts of the world that are of concern include the N439K, N440K, Q493K and E484K, which are prone to immune escape, said Dr Mishra.

“Of these, the N440K variant has been found in 42% of the samples from Andhra Pradesh and E484K in three samples from Maharashtra. The E484K was found in Maharashtra a few months ago. Most of the other mutations are absent in currently sequenced samples from Indian isolates and need to be actively monitored,” Dr Mishra told The Indian Express.

The paper `SARS-CoV-2 genomics: An Indian perspective on sequencing viral variants’ has listed top 61 non-synonymous Indian variants of SARS-CoV-2 , the genomic mutation and the corresponding amino acid change in the associated viral protein.

“E484K, N501Y , S477N are relatively new and hence have a low prevalence among the samples sequenced in India so far. However, they are strong candidates for increased viral transmission and/or immune escape,” CCMB researchers have said.

Dr Mishra referred to recent surveillance studies by European consortia, which had identified strains of SARS-CoV-2 that show increased transmission.”Sequencing and analysis efforts by Spain have identified the EU1 and EU2 strains, which harbour two mutations in their Spike proteins (A222V and S477N respectively) These strains were associated with the surge of cases in various European countries during the summer. In Indian isolates, five samples with A222V and one sample with S477N mutations have been identified till date. Additional studies are required to understand their potential implications in terms of diagnostics, therapeutics and vaccine underdevelopment,” said the CCMB director.

New variants of SARS-CoV-2 that show increased transmissibility were first identified in the UK and S. Africa. Recent reports from South Africa mention concerns regarding lineage B.1.351 which has a mutation in the RBD of the Spike protein (N501Y and E4848K), which may be associated with faster transmission and possible adverse illness in young and healthy individuals.

Even more concerning has been the latest report by the COVID-19 Genomics UK Consortium (COG-UK), detailing the variant VUI-202012/01 (lineage B.1.1.7) that is associated with fast-growing outbreaks across London and a four-fold increase in cases in a span of just 10 weeks prompted immediate monitoring and investigation of the new variant, followed by global measures to limit its spread. This has recently also been identified in the Indian population, with instances of infected travelers from the UK testing positive for the B.1.1.7 lineage fast approaching 180 cases.

“So far, there is no evidence of community transmission of the variant in India but this can only be confirmed once a sufficient number of positive samples have been sequenced across the country. If this strain indeed possesses a transmission advantage, it is likely to overtake the D614G and drive the pandemic in 2021, unless strict measures are adopted for global containment,” cautioned Dr Mishra.

A variant circulating in Manaus, Brazil, was identified from international travellers in Japan in viral genomes sampled from mid-late December 2020 to early January 2021. A new sublineage P.2 (that independently acquired the spike E484K mutation associated with immune evasion) has now been detected in many locations in Brazil including in Manaus. Three cases of reinfection have recently been identified in Brazil. Such variants containing multiple mutations that can drive higher transmission and/or immune escape are strong contenders for enabling reinfections and lowering vaccine efficacy globally.

While a proposed Indian SARS-CoV-2 Genomics Consortium is required to monitor the genomic variations in the SARS-CoV-2 on a regular basis through a multi-laboratory network, the consortium has to be officially launched.

Researchers across some of the 10 institutions under the consortium said that not much sequencing was being done as it was an expensive process. Additional funds have to come in an organised way and overall, in the public domain, close to 6,000 samples have been sequenced so far.

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