In the shadow of delta: Why getting the samples early & right for sequencing matter the most

Surveillance is about statistically sampling positive cases and sequencing a fraction of them, ideally 5 per cent of them. (Representational image: IE)

When trying to understand things we know we don’t know about a virus, scientists often turn to the mantra of heightened surveillance and enhanced study of the genetic makeup of a virus, a process known as genomic sequencing. Surveillance is about statistically sampling positive cases and sequencing a fraction of them, ideally 5 per cent of them.

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India has a set system in place to conduct surveillance and sequencing to help track the covid-19 virus mutations. It is largely government-led and controlled with a clear sampling model. But if the experience of the delta variant that teared across the country, is anything to go by, there is clear message on how samples need to rightly and quickly sourced. But first, why intense surveillance and sequencing matters? Where is India in this journey? Are there any lessons to be learnt from the delta variant so we ensure that Omicron or any other variant does not supplant delta and pose a new threat? And why these questions need answers now?

Lessons From Delta

One big lesson from India’s devastating delta experience is a clear imperative to catch upticks early on. As an FT analysis points out, the share of delta cases in the total sequenced cases increased from 0.1 per cent to 1 per cent in less than a month between February and March last and in the subsequent month showing a 10 fold increase yet again. After all, as scientists often remind us, a virus variant may come in slowly, incubate and then could just explode. It is therefore crucial that any uptick is picked up early and tracked. For example, in February this year, Bhramar Mukherjee, professor of epidemiology and biostatistics at the school of public health, University of Michigan began tweeting about upticks in three Indian states and the need to take note of them. Back then, she said, the total cases were just about 10,000 and around 200 deaths but then later it exploded. That is because, as she points out, this virus has an incubation period, comes in slowly and then explodes.

Right Sampling

If sequencing shows rise in Omicron cases then early on measures can be taken with those infected closely monitored for greater insights on transmissibility and virulence of the variant. While all the government laboratories are equipped to handle them and there is enough capacity to take on more, the challenge is really around getting the right samples – over-representation in some cases, travel, clusters, vaccine breakthroughs. Again, while the government set up has a defined approach on this, involving the private sector can help ensure nimbleness and richer sampling.

Role of Private Sector

Given that much of the public health in India is in the private sector, sourcing of samples from private sources, would arguably help get a wider representation. Agreeing therefore that perhaps there is a strong case to involve the private sector, a government official, who prefers not to be quoted, also reminds that within the government system there is also the added burden of consensus building, which each time may not lead to a desired outcome.

Beyond The Sentinel Sites

Currently, the method used for sequencing in India is that of the sentinel site system, wherein there are identified locations with a fixed count from where samples are collected and this can become very slow because it involves a lot of coordination. Therefore, many spoken to by Financial Express Online, were of the view that at the moment, it may be faster if large number of samples were sourced from large private laboratory networks and sequenced fast to understand how much Omicron has penetrated. One could argue that opening it up to private sector may lead to situations in some cases where vested interests could raise false alarms and trigger panic. But then, India already has several leading private sector players with some states like Karnataka for instance, already leveraging the skills of some of these entities. There is a long list of players and includes names like Strand Life Sciences, MedGenome, Lifescell, Clevergene, Mahajan Imaging, Nucleome, NMC Genetics and several others. These could be vetted and then roped in.

Tracking The Upticks

If in the sequencing of say 1000 samples, one is a new variant today but in a fortnight or a month from now, there are 10 cases of the new variant found in a sample of yet another 1000 then the flag ought to be raised about the new variant and its transmissibility. Whether it is more virulent or not will again depend on the information on the health monitoring of the patients whose samples were collected.

A Government-led Model

For handling surveillance and sequencing, India has in place a system that goes under a rather baffling acronym: INSACOG – Indian SARS-CoV-2 Genomics Consortium – a joint initiative of the ministry of health, department of biotechnology, the Council for Scientific & Industrial Research and the Indian Council of Medical Research. It is a consortium of 28 national laboratories to monitor the genomic variations in the SARS-CoV-2.

Imported Machines

But the challenge is not just about right sampling, there is also the component of imported machines and costly reagents.

Those within the industry and some within the government talk of India having roughly about 13 government centres equipped with NovaSeqs sequencing systems. These are arguably the most advanced instruments (with costs estimated at around Rs 6 crore a piece) and are described as big capacity sequencing machines and on each of them about 3000 odd samples could be put through per run and repeated in 48 hours thereabout. So, in about 10,000 samples could be potentially sequenced in a week on each of the 13 sequencing platforms.

Then there are the NextSeq machines, which are next level (costs roughly around Rs 2 crore each) and could do about 1000 samples a week and apparently there are some 11 of these. The rest are the smaller MiSeqs costing roughly around Rs 1 crore. Most of these are from a US-based major company called Illumina. There are some also have Oxford Nanopore.

The key point is that there is enough capacity for surveillance. For instance, it could even go up to sequencing around 1,00,000 samples per week.

Expensive Reagents

The cost of the machines is a one-time expense and only one element of the cost, an added component is that of the imported reagents. If these are imported in large quantities then rough estimates by the industry suggest costs getting to their lowest at around Rs 3500 per sample. But, other components of handling and manpower are added, it could all add up to nearly Rs 6,000 per sample. While most in the industry do point to high costs as a challenge, they do not seem to see it as a major impediment as there are global philanthropic entities also ready to extent grants to back efforts to track the virus mutations globally. Some are already helping out in India.

While most costs are back-of-a-large-envelope calculations, most do point to real increase in costs on account of customs duties, GST (Goods and Services Tax) and expenses on account of middlemen – a point that has not missed the attention of India’s top virologist Dr Gangandeep Kang, who points out: “We have plenty of machines but reagents are very expensive because of middlemen and GST and making it at least nearly twice as expensive to sequence in India as elsewhere.”

USA and Europe is where all the tools to sequence the genomes are concentrated. Recognising the challenges, Dr Soumya Swaminathan, the chief scientist at the World Health Organisation (WHO), says: “One area of concern for low and middle income countries, including India, will be the expensive reagents, which may be sometimes difficult to get in time, this puts researchers and developers in the developing countries at a disadvantage.”

Time To Act

When the two cases were found of the Omicron variant in Bengaluru recently, it became amply clear that it has entered India and there is certain level of community transmission. The spread was in the very nature of the virus and Dr Gagandeep Kang, who also is a professor at the Christian Medical College, says, “I am not surprised” and calls for enhanced surveillance and sequencing. Seen purely from the perspective of absolute numbers, those within the government point out that South Africa by now has only done about 40,000 sequences and therefore India compares well with its little over 1,00,000 samples processed but then it is important to remember the larger size of India and the caseload and while in South Africa it was Omicron, it has been delta in India and therefore even if India is sequencing 1 or 2 per cent of the positive cases it is argued as still a decent number given that roughly around 10,000 get sequenced every month with enough capacity and scope to rapidly increase sequencing, if required.

For the moment, what is clear about the new variant is its source outside India and therefore linkages to travel and thereby to be found, at least initially, in clusters from big cities and from well-connected urban centres. Any which way, it all boils down yet again to how samples are gathered and the turnaround time taken in sequencing them. For, in the shadow of the debilitating experience with delta variant, upticks matter most as do the duties that impact the costs of reagents used for the much needed sequencing.