Johannesburg, South Africa (CNN)In the early days of November, laboratory technicians at Lancet Laboratories in Pretoria, South Africa, found unusual features in samples they were testing for the coronavirus.
Essentially, a gene was missing in what would be a normal genome profile of the virus. PCR tests weren't detecting one of their expected targets, a signal that something about the virus had changed.
Just a few days later, the same phenomenon was reported at Lancet's Molecular Pathology Department in Johannesburg.
Dr. Allison Glass, a pathologist with Lancet, said the discovery coincided with an increase in positive cases of Covid-19 in parts of South Africa.
In the province of Gauteng, which includes Johannesburg, fewer than 1% of people were testing positive at the start of November, but this rose to 6% within a fortnight and to 16% by Wednesday.
The discovery "raised concerns that we were in for another surge," Glass told CNN. "Our first thought was: There goes our quiet December and a Christmas break."
Three weeks later, what the South African scientists had stumbled across would be known worldwide as the Omicron variant of the coronavirus.
The spike in Gauteng didn't go unnoticed at the Network for Genomics Surveillance in South Africa (NGS-SA). Its director, Tulio de Oliveira, called a meeting for November 23. He told the New Yorker: "We heard from one member in our network that a private lab, Lancet Laboratories, had sent in six genomes of a very mutated virus. And, when we looked at the genomes, we got quite worried because they discovered a failure of one of the probes in the P.C.R. testing."
CERI rapidly upscaled testing of samples in Gauteng and found the variant appearing very frequently. Tulio later observed on Twitter that in less than two weeks the new variant "dominates all infections following a devastating Delta wave in South Africa."
People queue for Covid-19 tests at Lancet Laboratories in Johannesburg, South Africa, on Tuesday.
Origin a mystery
Just where and when Omicron first emerged is still unknown. There is no identifiable "Patient Zero," a first person known to have been infected with the variant.
As the director of the Africa Centres for Disease Control and Prevention, John Nkengasong, told CNN on November 30, "We just cannot assess where this originated."
"The first cases were recognized and identified in Botswana and subsequently in South Africa," Nkengasong said. But he pointed out: "Identifying a virus, a new strain or a new variant doesn't mean it came from there."
"It might well be a consequence of an outbreak, probably in some parts of sub-Saharan Africa, where there's not a huge amount of genomic surveillance going on and the vaccination rate is low," Michael Head, a senior research fellow in global health at the University of Southampton, told CNN in a phone interview.
Trying to trace Omicron's origins may be futile if it has already been in circulation for a while.
Trevor Bedford, from the Department of Epidemiology at the University of Washington, said on Twitter that based on genomic analysis from Botswana and South Africa, "the Omicron variant likely arose much earlier than when it came to our notice, probably in early October."
Kristian G. Andersen, a virologist at the Andersen Lab in California, took a similar view, tweeting: "We can estimate that based on the diversity in sampled genomes and most estimates land ~mid October (with wide uncertainty), so we believe it's relatively young."
There was also a sharp increase detected in the viral load of wastewater in the Pretoria area at the very end of October and the beginning of November.
Speaking to CNN's Becky Anderson on Wednesday, Michelle Groome of South Africa's Institute for Communicable Diseases said: "Our wastewater surveillance actually alerted us as relatively early to these cases in the Pretoria district."
But virologists acknowledge they are dealing with very preliminary information at the moment on the evolution and characteristics of Omicron.
Transmitted via travel
The rise in infections in early November may have set the stage for the many cases now being identified elsewhere. Most of the international cases tracked by CNN through the end of November involved people who traveled from or through South Africa or from Mozambique, Malawi, Botswana and Namibia.
For example, on November 11, four foreigners leaving Botswana tested positive for the coronavirus -- tests that would later (on November 24, according to the Botswanan Health Ministry) reveal the Omicron variant.
Also on November 11, a 36-year-old man from Hong Kong arrived home from a 20-day trip to South Africa, traveling via Qatar. Two days later, while in quarantine, he tested positive. Genome sequencing confirmed Omicron.
Several people who traveled home to Europe then infected members of their household, including in Germany and Italy.
A CNN analysis of publicly available data shows that some 90% of the Omicron infections so far recorded in Europe involved individuals who had traveled through or from southern Africa.
However, sequencing is in many countries quite limited. Only a very small percentage of Covid tests are subject to sequencing, which takes longer than a simple test. Current data almost certainly underestimates the spread of the variant.
Not all roads lead to southern Africa
While some travelers from southern Africa certainly carried the variant, there are other puzzling instances. One involves a Belgian woman who had traveled to Egypt via Turkey. She arrived home on November 11 -- and tested positive for the variant 10 days later.
Several cases confirmed in Canada are related to travelers from Nigeria. The case identified in Saudi Arabia on December 1 was of a traveler from north Africa. And an Israeli doctor tested positive when got home from a conference in London. He had not been to South Africa.
None of the nine cases reported in Scotland as of November 30 had travel history, and all had attended the same event on November 20. Scottish First Minister Nicola Sturgeon said that "the lack of any known travel or overseas connection to these cases suggests that there is community transmission of Omicron in Scotland."
She also said it was unlikely the cases were a result of the COP26 climate change conference held in Glasgow from October 31 to November 12.
It's now becoming clear that, however it reached Europe, Omicron was on the continent for much of November. In the Netherlands, the RIVM health institute said it found Omicron in samples dating from November 19 and 23 -- the earliest of them more than a week before passengers on a KLM flight arriving from Johannesburg were identified as the first known Omicron cases in the country.
"It is not yet clear whether the people concerned [in the earlier cases] have also been to southern Africa," RIVM said Tuesday.
There is so much still to discover about the new coronavirus variant -- how quickly it can spread, whether it can evade or blunt existing vaccines, whether it will result in only mild symptoms for the majority of those infected.
For now the Delta variant remains the dominant strain, accounting for 99.8% of the global sequences uploaded to the GISAID database, according to WHO's latest bulletin.
But that bulletin also notes that "South Africa, where Omicron was first detected, has experienced a recent sharp increase in the number of cases in multiple provinces, coinciding with the detection of the Omicron variant."
In the past fortnight, South Africa has gone from a weekly average of 290 cases per day to almost 3,800 daily cases. On Wednesday, authorities reported 8,561 new cases nationally. Authorities said three-quarters of sequenced positive tests in Gauteng province were Omicron.
"Our cases are increasing very rapidly, I think probably at the fastest rate we have seen since the start of the pandemic, but it is unclear whether this is due to increased transmissibility of the omicron variant or due to immune escape," Michelle Groome told CNN.
WHO's Director General, Tedros Adhanom Ghebreyesus, said this week that "We still have more questions than answers about the effect of Omicron on transmission, severity of disease, and the effectiveness of tests, therapeutics and vaccines," he added.
But the emerging evidence -- albeit preliminary -- indicates that Omicron has a head start. The world is still getting to grips with a new variant of the coronavirus that has already spread to nearly thirty countries on four continents.
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