The meta bloc: Why India faces a data shortage on genome sequencing of coronavirus

Express News Service

CHENNAI: India ranks a distant 102 in genetic sequencing of coronavirus and sharing that data with the rest of the world, says Global Initiative on Sharing Avian Influenza Data (GISAID). Only 3,636 genome sequences have been shared with the GISAID between January 12, 2020, and April 28, 2021.

Sequencing genomes of daily cases will help determine the impact of new variants in the second wave, including the infamous double mutant. The international community has criticised India for not sequencing enough genomes each day, and for what they call “poor infrastructure” in genomic labs.

However, scientists here say the real reason is not the lack of capacity at genomic labs. It is the lack of background data on samples, thanks to the burden on the healthcare system. The labs in India have capacity to sequence far more samples each day than the current rate, says Rakesh Kumar Mishra, director of CSIR-Centre for Cellular and Molecular Biology (CCMB) in Hyderabad. “The problem lies elsewhere.”

The main reasons for this, according to Mishra, are poor logistics and inadequate metadata. Last December, Indian government put together 10 labs under the name Indian SARS-CoV-2 Genomics Consortium (INSACOG), to ramp up the process of sequencing across the country. Mishra’s lab is part of this consortium.

THE NEED
There is extensive speculation that the prime culprit behind the second wave of cases is a double mutant, dubbed B.1.617. Each day, India submits a count of only a couple of hundred sequences  of this variant to the GISAID database, while almost four lakh sequences of the UK-origin B.1.1.7 variant is on the database.

Given that many scientists have found the double mutant sequence variant in their respective countries, they are anxious to know the impact it is causing in India, where it was first detected last October. This way, countries can brace for what they may face in the future and develop better vaccines and drugs. But, why is India struggling to get this data? To understand that, one must know how the genomic study is used to combat the pandemic.

FROM VIRUS TO DATA
When people go for a Covid test, their swab samples are collected. The samples are then analysed using an RT-PCR test. If a sample tests positive, it is sent to a genomic lab along with patient’s records containing metadata – their age, sex, co-morbid conditions, vaccination history, symptoms, and mortality among others.

“Simply put, if there is a Covid mortality rate of X per cent in Maharashtra, and Y per cent of the virus genomes sequenced from the area have the strain B.1.617, using that metadata we can estimate the
mortality rate caused by that specific strain,” says Mishra. Most swab samples come from three sources – airports, hospitals, and random testing. “The third source is most important, as it has to be a collection of samples scientifically randomised from across the country,” says Mishra.

Mishra says that out of the 6,000 genomes sequenced by his lab during the first wave, he found 7,500 variations. “Without metadata, one cannot identify which strain is a variant of concern.” Mishra says
most samples labs receive are from super-spreader events. “But, let’s say we have a thousand samples from one city. It does not say much about the variant. We need samples collected for genome sequencing
with appropriate strategy to get the benefits of the effort.”

WHERE IS THE DATA?
Metadata, unfortunately, has to be collected by frontline workers, who are overloaded and overwhelmed by the sheer number of cases they have to handle. According a ‘Whitepaper’ on “Future of Biomedical
Engineering programs in India released” by IIT Madras recently, in Indian rural areas, there is, “a low number of healthcare facilities and care providers, reliance on informal and private care providers, and high out-of-pocket costs are major barriers that need addressing.”

In a recent interview with Express, Dr Jacob John, renowned virologist from Christian Medical College (CMC) Vellore remarked, “Who has the time to conduct scientific studies when doctors are attending to an
overwhelming number of patients?” He said that healthcare workers have almost no time to dwell on a person who died from Covid to study them as healthcare workers will quickly have to move on to a person, who can be saved.

“Where is the money coming from for these studies? Who has the time to collect data? Are epidemiologists employed to collect and study data?” Dr John asked exasperatedly and opined that finding data is “not the healthcare worker’s job, but the public health system’s – that India has not invested much in.” The problem is exacerbated by the under-reporting of Covid deaths and reinfection incidents along with poor correlation of adverse symptoms with Covid.

INVESTING ON ADVANCED RESEARCH
While sequencing is one part of the game, India also needs to make a crucial investment in labs which can study the virus’ structure and its working mechanism to prepare for a long term solution. For example, Indian Institute of Technology Madras researchers are studying the high transmission rate and mortality of three Covid strains by identifying the mechanism and structure of proteins in the virus. Once they know the mechanism through which it enters and affects the body, drugs can be created to specifically counter it.

Professor Michael Gromiha, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, IIT Madras, who is leading the research said that some important information about the different strains cannot be obtained from the sequence alone. “To know why some strains are more virulent or infectious, you need to know the mechanism of the virus. In order to know that, we need more experimental studies on the virus,” he said.

Puneet Rawat, one of the two research scholars working on the project further added that experimental studies are extremely time-consuming. For example, isolating the viral protein structure, which takes a lot
of time, is important for the development of drugs and vaccines. While such studies are conducted for one strain, conducting them for all variants will require a lot of time, resources and facilities. “Our lab at IIT Madras is addressing these issues through computational analysis,” he said.

When asked how this particular project was funded, Gromiha said that he put together a project fund from the Department of Science and Technology (DST), a grant from IIT Madras and diverted a portion of their previous research funds, as studying Covid, is the need of the hour. While his lab has managed to get the project going, many other labs in India, which have the capacity and researchers to work on such projects, are scrambling for funds.

Mishra too agrees that there is a lack of investment on advanced scientific research on epidemiology, but he says, no matter how much scientists hurry up, they can help with only middle to long term solutions.

“In Punjab and UP, it is the UK variant that is dominant. In Maharashtra it is B.1.617. In South India it is the N-440K strain; and it has been there for several months. Different variants are prominent in different parts of India. But what is common is the human behaviour of gathering in large numbers without masks and the way the virus spreads: from one person to another,” he said, adding that this is an urgent problem that needs to be fixed.