Omicron threat: Will high seroprevalence help Indians? What experts say

Airports are on high alert and the COVID surveillance mechanism in States has been stepped up, with increased vigil for Omicron. The emergence of the virus variant has been described by Dr VK Paul, Chairman of the National Task Force on COVID, as a ‘pandemic within a pandemic’.

Yet, it’s still too early to get an accurate fix on Omicron and the three key questions we must ask of any variant: is it more transmissible, does it cause more severe disease, will it escape vaccines?

The Federal spoke to several experts to put the Omicron — at least, what we know about it at the moment — in perspective.

So far, 18 countries have reported occurrence of the variant. In all, 215 genomic samples have been submitted to the GISAID database, of which 147 are from South Africa and Botswana. The GISAID is a Germany-headquartered global initiative that aims to promote the rapid sharing of data from all influenza viruses including COVID.

What do the spike mutations mean?

By now, we know that Omicron has more mutations than Delta, which is currently the dominant variant. It has around 50 mutations, of which 30 are in its spike protein area alone. Broadly, this is the region through which the virus attaches itself to cells and gains entry — it’s also the region that antibodies target in order to destroy the virus.

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“Virtually all currently approved vaccines generate antibodies against the entire spike protein,” said biophysicist Raghavan Varadarajan from the Indian Institute of Science (IISc). Within the spikes there are two primary targets for antibodies to prevent infection — the receptor binding domain (RBD) and the N-terminal domain (NTD). “All the variants of concern (VOC) have mutations in both the RBD and NTD, and this one has a lot of them,” said Varadarajan.

What could that point to? “It means that the antibodies that have been generated either by natural infection or a vaccine will likely be less effective in preventing infection with this new variant,” said Varadarajan, who has been working on a protein subunit vaccine for COVID through Mynvax, a start-up he co-founded.

“But we don’t yet know how transmissible this variant is. Especially when people have been previously infected or vaccinated…whether they would come down with severe disease. It seems unlikely because in addition to neutralising antibodies, the immune system has other ways of conferring protection, but we don’t yet know,” he added.

Infectiousness vs virulence

Merely a higher number of mutations doesn’t turn a virus into a monster either. When many changes happen together, do they add up? “The answer is, generally, no. The mutations don’t add up. One mutation in one context will have a certain property. In a different context it may behave differently,” said Rakesh Mishra, former director of the Centre for Cellular and Molecular Biology (CCMB).

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As experts explain, how fast a variant can transmit is a key question. The case in point is Beta, the variant that was detected last year but which, fortunately, didn’t spread. “Beta evaded antibodies the maximum but it didn’t transmit well,” said virologist Shahid Jameel, who formerly chaired the scientific advisory group at INSACOG, India’s network of labs for genomic surveillance. “Delta was something that didn’t evade antibodies very much. It evaded some but it transmitted better. That’s why Delta took over,” said Jameel.

“We don’t still know whether these two properties are mutually exclusive,” he further said, pointing out that it’s not possible to predict how any two mutations will behave when they come together. “I think we should just wait for a week or two. My hunch is that vaccine efficacy will just dip a little bit but it is not going to make vaccines useless.”

The surrogate test

Some of the spike mutations in Omicron were what also helped to detect it early. As Jameel explained, one of the polymerase chain reaction (PCR) tests that virologists in South Africa were using constantly failed to detect the spike gene. But other genes were being detected.

“That’s something called S Target failure. That happens when there are mutations in the region where a particular reagent in the PCR, called a primer, binds,” he said. “So, they thought it was very unusual that the surface gene is failing. When they sequenced it, they found that all of the ones that had failed surface gene detection showed the novel variant.”

Hence, this opens up the possibility of an indirect method of detecting Omicron via a PCR test — without necessarily having to send a positive sample for genome sequencing. “If there is a high prevalence of this particular virus then it is feasible to use this as a method,” said Varadarajan.

Of course, this would mean using PCR kits that look for the S gene particularly. Currently, most PCR tests target many structural proteins to ensure they don’t miss out anything.

“Most of the existing tests, including ours, are not targeting the particular genetic sequence which codes for the spike protein. Because we are not specifically targeting it, any change in that region is not going to have an effect on the efficacy of our test,” explained Dr Gautam Wankhede, Director, Medical Affairs, at Pune-based Mylab Discovery Solutions, which manufactures RT-PCR test kits.

But, in the context of this significant development, Mylab is now working on a new test to detect Omicron in a more direct way, he said. “Every protein present on the surface of the virus is coded by a genetic sequence present in the nucleic acid, the RNA of the virus,” said Wankhede. “So, as we get to know which particular sequence is responsible for this slightly different spike protein in Omicron, we will target that particular sequence. That will be a direct way of diagnostics.”

The current guidelines in India require all positive samples taken from air travellers from ‘at risk’ nations to be sent for genome sequencing. All positive samples from recent clusters of infection within States too have to be sequenced.

Delta vs Omicron

Experts say a clear indication of the threat from Omicron will only come when there is evidence of it displacing Delta to become the dominant variant. At the moment, there’s no indication on whether or not that is happening.

Jameel pointed out that only a small number of genomes have been sequenced globally. “So, it is early days,” he said.

CCMB’s Mishra agreed. “We are at the beginning stages. I would be of the opinion that we should wait for a week or 10 days to see if it is really spreading,” he said.

Experts generally point to the high seroprevalence in India, following the brutal second wave this summer and the vaccination campaign, as the context for the graph of infections. “You are reaching a point where most people have been exposed to either the virus or the vaccine,” said Jameel. “What it means is that even if there is a dip in vaccine protection efficacy from symptomatic infection, people will be continue to be protected from severe disease, hospitalisation and mortality. My hunch is most Indians will be protected from severe disease.”

Vaccine updates

Tests are ongoing worldwide to determine how currently available vaccines hold up against Omicron. “Despite the appearance of new variants over the past year, vaccines have continued to provide very high levels of protection against severe disease and there is no evidence so far that Omicron is any different,” said the University of Oxford, which co-developed the Covishield vaccine with AstraZeneca, in a statement on November 30. “However, we have the necessary tools and processes in place for rapid development of an updated COVID vaccine if it should be necessary.”

Meanwhile, in interviews this week, Moderna CEO Stephane Bancel said that existing vaccines are likely to be less effective against Omicron, a comment that led to considerable nervousness worldwide.

“As long as there is some residual protection from the vaccination or from a previous infection, which then doesn’t render the next infection terribly serious, it is OK. I think that’s really the key question,” said IISc’s Varadarajan.