Virologist and INSACOG member, Dr V Ravi, explains how genome sequencing works, and why results to confirm coronavirus variants take time.

A health worker collects swab sample of an outstation passenger for COVID-19 testImage for representation/pti
Delve Omicron Wednesday, December 22, 2021 - 17:15

Three weeks since the first case of Omicron was detected in India, the number of COVID-19 patients with this variant has risen to over 200. Recently, four girls from a cluster of around 13 cases at a residential school in Karnataka’s Dakshina Kannada district were found to have contracted COVID-19 from the Omicron variant. While the cluster was identified in November, the source being Omicron was confirmed about a month later.

How is India detecting Omicron and why does it take so long to confirm the variant after detection of COVID-19? And does the S gene drop really help detect Omicron from RT-PCR tests?

We asked Dr V Ravi, retired head of virology from NIMHANS, Bengaluru and present member of the INSACOG Steering Committee as a representative of the Ministry of Health and Family Welfare (MoHFW). INSACOG or the Indian SARS-CoV-2 Genomics Consortium is a joint initiative put together by the MoHFW, the Department of Biotechnology (DBT) with the Council for Scientific & Industrial Research (CSIR), and the Indian Council of Medical Research (ICMR).

Why genome sequencing takes time

Dr Ravi explains that at present genome sequencing is the only way to detect if a person who has COVID-19 contracted it from the Omicron variant.  

“Genome sequencing is highly resource-intensive and very expensive. This is why you cannot test every single sample as and when each comes; it has to be done in batches of 24, 96, or 384. Testing 384 samples on one sequencing chip costs around Rs 10,000 per sample. The cost is higher when the number of samples is lower,” he says. “So, sometimes we have to wait for enough samples to be collected to do the test. Further, only samples with a CT value less than 25 can be used for genome sequencing. If the value is higher, it is tougher to get the full gene sequence, which compromises the accuracy of results.”

Read: Omicron: Karnataka to send samples with Ct value less than 25 for genome sequencing

Dr Ravi adds that the process of gene sequencing takes up to 12 hours, but that is not all – the subsequent analysis and manual confirmation takes 3-4 days. “These are the limitations for a country like India, compared to wealthy ones which have more resources to do this more frequently for a smaller number of samples. But nowhere does the result come in a couple of hours,” he states.

To reduce the delay, he notes that India could set up a dashboard where labs log the number of samples that they have for genome sequencing. This could facilitate transporting a balance of samples from other labs to reach a minimum number of RT-PCR test samples needed to run genome sequencing.

Can the S gene target failure confirm Omicron?

With the emergence of the Omicron variant, there are suggestions that the failure to detect an ‘S gene’ on the RT-PCR test could indicate infection by the variant. The RT-PCR test, which is used to detect COVID-19, does so by detecting targeted genetic materials particular to a virus from samples to confirm its presence in a person’s body.

However, this is not a foolproof way to detect Omicron. “The amino acids which have the gene sequence may differ for two variants like Alpha and Delta. Sometimes, the S gene is amplified in tests and others are not, which shows that the person is overall coronavirus positive but we don’t know the variant. As of now, genome sequencing is the only sure-shot way to zero down on the variant,” Dr Ravi says.

How mutations work

Dr Ravi, like many other virologists, reiterates that mutations are natural in any virus, and SARS-CoV-2 is no exception. We have already seen variants like Alpha, Beta, and Delta, which were caused by changes in the virus’s spike protein. The spike protein on the surface of the SARS-CoV-2 virus is what engages with the human cell receptors. “Being a surface protein, it is subjected to a lot of pressure from the human system. As a result, the virus adapts and devices escape strategies by changing its appearance, which, in technical terms, is a mutation,” says Dr Ravi.

“We saw the first mutation in the original strain, detected in Wuhan, in March 2020 itself. This spike protein was much more adaptable to human cells, which caused a surge of infections. This strain replaced all others till about September 2020. Then the UK reported another set of mutations, and over time, we saw Alpha, Beta, Gamma variants. Then we had Delta which was, at the time, the most lethal variant, so it spread quickly, wiping out the other variants,” he adds.

The SARS-CoV-2 virus also mutates because it has poor “proofreading abilities,” says Dr Ravi, meaning it makes mistakes in copying itself when multiplying. “If there’s a change in the virus that is beneficial to it, it will become the dominant variant, which will replace all others. Now, Omicron is the fastest spreading of all; it has advantages from the mutations for Alpha, Beta, Gamma, and Delta,” he notes.

Vaccination for one and all the only way

Dr Ravi concurs with the epidemiologists and virologists who have been saying since the early days of the pandemic that COVID-19 is here to stay and will become endemic. He adds that the only way to tackle the pandemic is to have global vaccination coverage for one and all. “While Omicron has increased the chances of reinfection, vaccines will largely protect one from severe disease and death,” he notes.

Many health experts have argued that new variants are bound to emerge as long as vaccine access remains inequitable. Even if individual countries have vaccinated enough of their population to reach a threshold immunity, in a globalized world, even these populations will remain susceptible to new variants. This is why public health advocates have been pushing for patent waivers and relaxations on COVID-19 vaccines to quickly ramp up production, lower costs and increase accessibility.

Dr Ravi asserts that people need to continue wearing masks and avoid crowding. However, these practices are on the decline, especially among people who have been vaccinated. “But even vaccinated people need to remember that they are not protected from contracting COVID-19 itself. Besides, if the disease spreads to a vulnerable, unvaccinated person, they have a higher chance of serious illness.”

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