A research that proposes that ancestors of the fast-spreading Omicron coronavirus variant had been circulating undetected in Africa for months earlier than the alarm was raised has prompted fierce dialogue. The paper, printed final week in Science, identifies sequences that the authors say are from Omicron’s predecessors, which they are saying had been spreading from August 2021, some three months earlier than researchers in South Africa and Botswana famous the variant’s arrival in November that yr1. However many researchers suppose the sequences are in all probability the results of contamination within the laboratory.
“I’m considerably sceptical of this paper,” says Angela Rasmussen, a virologist on the College of Saskatchewan in Saskatoon, Canada. Rasmussen just isn’t satisfied that the evaluation guidelines out contamination throughout pattern preparation and sequencing, which is a familiar problem for researchers within the subject.
Researchers have been puzzled by Omicron’s emergence. The variant comprises a number of bizarre mutations that had not been seen earlier than. There are presently three theories for the circumstances that might have given rise to Omicron: that it step by step advanced in part of the world the place testing and genomic sequencing is restricted; that it unfold undetected in animals; and that the mutations collected in individuals with compromised immune techniques contaminated for lengthy durations2,3.
Analysis over the previous yr has supported the third concept, however the newest evaluation means that Omicron might have advanced undetected in western Africa, the place sequencing is uncommon.
As a part of the research, labs throughout 22 African international locations analysed greater than 13,000 virus samples taken from individuals who had COVID-19 between mid-2021 and early 2022. These samples had not been sequenced on the time of assortment. The crew developed a speedy and particular check to determine the BA.1 Omicron subvariant and the Delta variant. “This can be a actually cool means of doing variant-specific surveillance,” says Joshua Levy, an utilized mathematician at Scripps Analysis in La Jolla, California.
The researchers discovered that, by the tip of December 2021, Omicron had changed Delta because the dominant variant throughout Africa, beginning within the south and transferring up in the direction of the west and east, earlier than taking up in northern Africa.
In addition they sequenced 5 virus samples from Benin in West Africa that had been collected between 22 August and 27 October 2021, months to weeks earlier than Omicron was first detected. Genomic evaluation of the evolutionary relationship between these early sequences and Omicron means that they may very well be its shut ancestors.
The early sequences contained among the mutations that make BA.1 so transmissible, says research co-author Jan Felix Drexler, a virologist on the Charité College hospital in Berlin. They’re “snapshots of what the virus regarded like when it was attending to Omicron”. Drexler says Omicron in all probability advanced step by step by spreading from individual to individual, lots of whom would possibly have already got developed some immunity to the virus.
However researchers who’ve reviewed the research and the virus sequences from Benin, which have been posted in a public repository, say that the sequences are in all probability false positives.
The sample of evolution noticed within the viral samples doesn’t observe a sequential order, which might be anticipated if the virus step by step advanced over time, says Joel Wertheim, a molecular epidemiologist on the College of California, San Diego. “This doesn’t appear like SARS-CoV-2 evolution, it seems like SARS-CoV-2 contamination.”
One other warning sign is that most of the sequences from Benin appear to hold a number of mutations particular to Delta, says Levy. “It’s most unlikely that these mutations would have popped up in a non-Delta pattern.”
To clarify a few of these observations, researchers say that both the virus needed to undergo intensive recombination — wherein viruses swap chunks of RNA with one another — or the sequences are the results of contamination within the lab. Richard Neher, a computational biologist on the College of Basel in Switzerland, thinks that recombination is unlikely and never according to what has been noticed within the evolution of SARS-CoV-2 up to now.
Another rationalization that wants additional investigation is that samples containing very small quantities of Delta variant had been contaminated with Omicron, says Darren Martin, a computational biologist on the College of Cape City in South Africa.
“I think about this the extra probably rationalization,” says Neher. “Given how quickly Omicron unfold as soon as it entered the overall inhabitants, it’s unlikely that it had circulated for a number of months undetected throughout” Africa.
Drexler says he and his crew used a number of strategies to make sure their sequencing was as sturdy as potential. He says they’re now re-checking their knowledge fastidiously. “Ought to there have been a mistake regardless of all our precautions, we are going to deal with this appropriately in fact.”
A number of researchers have requested detailed sequencing knowledge from the paper’s authors, and lots of are withholding judgement till they’ve interrogated the uncooked knowledge. Drexler says they’re getting ready to add that knowledge to a public repository.
In the end, the research factors to the significance of genomic sequencing for monitoring infectious ailments. Researchers in South Africa detected Omicron early and this paper highlights the power of their genomic surveillance, says one among them, Tulio de Oliveira, a bioinformatician at Stellenbosch College’s Centre for Epidemic Response and Innovation, who helped to sound the alarm about Omicron.