COVID-19: Recombination unlikely to be greater public health threat than mutation, says Shahid Jameel

The recombination of novel coronavirus lineages is unlikely to be a greater threat to public health than mutations, a top COVID-19 expert has told Down To Earth.

Shahid Jameel, virologist and former head of the Indian SARS-CoV-2 Consortium on Genomics (INSACOG), a consortium of 38 laboratories, added that ‘recombination events’ which are the exchange of genetic material between two genomes “happened all the time”, especially in ribonucleic acid (RNA) viruses.

The close proximity of enzymes that are copying RNA molecules in a cell, sometimes results in the enzymes jumping from one template to another. The final product is not an exact replica of the parent RNA strand, but carries pieces from two or more RNA strands, he added.

Co-infection, when an individual is simultaneously infected with two different variants, enables a recombination event. As SARS-Cov-2 continues to spread rapidly across the globe, chances of both a co-infection and recombination increase.

“Any change that does not favour the virus, does not survive in infected populations. Recombination is no different. It survives and therefore we see it only when it offers some selective advantage to the virus,” Jameel said.

Research has revealed that recombination events have likely been a part of SARS-CoV-2 since its genesis.

A July 2020 study published in Science found that “SARS-CoV-2’s entire receptor binding motif (RBM) was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans.” RBM is the part of the virus’ spike protein that aids its entry into human cells.

Recombination is not exclusive to SARS-CoV-2 alone. It has been recorded in HIV, influenza and other coronaviruses as well. Tracking recombination events is not easy. A wider diversity of circulating strains — where they are not too similar to each other — is key.

SARS-CoV-2 recombination was assumed in the early days of the pandemic, but had not been confirmed with data.

“It wasn’t until about a year into the pandemic that there was enough variation to confirm that hypothesis,” Ben Jackson, a postdoc in Andrew Rambaut’s group at the University of Edinburgh, said recently.

‘XD’ and ‘XE’

The heightened focus over recombination comes even as the World Health Organization (WHO) declared recently that further variants of SARS-CoV-2, including ‘recombinants’ will continue to emerge.

The organisation is tracking the XE subvariant as part of the omicron variant of SARS-CoV-2, according to its latest weekly epidemiological update dated April 5, 2022.

XE is a ‘recombination’ of the BA.1 and BA.2 sub lineages of omicron. It is estimated to have a 10 per cent growth advantage over the stealth variant or BA.2, according to the WHO.

Little else is known about the variant’s other characteristics, in terms of the severity of disease it causes and the ability to evade immunity. XE was first detected in the United Kingdom January 19 this year. Some 600 sequences of it have been reported till March 29.

Another variant, XD — a recombination of delta and omicron — is being monitored by the WHO. “Its spread appears to have remained limited at present (26 sequences in the GISAID database). Currently available evidence does not suggest that it is more transmissible than other circulating variants,” the body noted.

It remains to be seen whether XE and XD will be termed as variants of concern. “When you have multiple lineages circulating, the danger is that the viruses could combine one dangerous phenotype with another dangerous phenotype into a single virus that has two dangerous phenotypes,” Penn State biologist Maciej Boni has said. 

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