As China emerges from its COVID-zero cocoon, the country is experiencing an unprecedented surge in cases that's fuelling global concern over new variants.
With mass testing clinics shut, and the National Health Commission (NHC) no longer releasing daily figures on COVID-19 infections and deaths, there are growing doubts about the reliability of China's data.
A senior World Health Organization (WHO) official told a briefing this week that the official figures "under-represent the true impact of the disease" in terms of hospital and ICU admissions as well as deaths.
Leaked details from an internal NHC meeting last month suggested as many as 250 million people had been infected in the first 20 days of December, including 37 million in a single day.
While previous outbreaks were largely isolated to one major region at a time, the current wave is reaching across the country, in cities from Beijing to Shanghai to Guangzhou and regions from Sichuan to Inner Mongolia.
The global community's reaction has been swift and stern, with countries, including Australia, clamping down borders and restricting entry from Chinese travellers.
There are longer-term concerns about whether China's recently isolated, high-density population could provide the perfect conditions for a new variant of concern to emerge.
Dartmouth Geisel Medical School's Professor Daniel R Lucey warned the medical community should be on the lookout for what could become Pi, Rho or Sigma — a variant that's potentially more immune-evasive and more virulent than current strains.
"The world should anticipate to recognise early not only more Omicron subvariants but also a new variant of concern after Omicron," he wrote on December 20.
One epidemiologist has warned the world may be about to witness "a billion or more opportunities for the virus to evolve".
Which subvariants are currently circulating in China?
China's current wave appears to be dominated by two main Omicron subvariants already circulating in other parts of the world: BA.5.2 and BF.7 (which is actually short for BA.5.2.1.7).
That's according to genomic sequencing data from GISAID, a global online database that has been tracking how infectious diseases evolve since a deadly strain of avian flu emerged in 2006.
In its latest update on January 5, GISAID's analysis noted that China was ramping up its COVID-19 surveillance efforts, providing data from recent cases in Beijing, Chongqing, Fujian, Guangzhou, Hunan, Inner Mongolia, Jiangsu, Shanghai, Sichuan and Zhejiang Province.
"When compared against the 14.4 million genomes in GISAID's EpiCoV database, all closely resemble globally circulating variants seen in different parts of the world between July and December," it said.
Internal analysis by China's Center for Disease Control, provided to WHO, also showed the same two subvariants accounted for the vast majority of about 2,000 cases it sequenced in December.
Both BA.5.2 and BF.7 are from the same Omicron lineage, and have been bubbling along in North America, Europe, other parts of Asia and Australia since mid-to-late 2022.
Local reports indicate that BF.7 is the dominant subvariant currently circulating inside China, with a shorter incubation period, faster transmission rate, and stronger resistance to immunity than previous strains the country has seen.
Each person with BF.7 appears to infect between 10 and 18.6 other people — far higher than the Omicron average of 5.08.
"The high transmission rate of BF.7, taken with the risk of hidden spread due to the many asymptomatic carriers, is understood to be causing significant difficulty in controlling the epidemic in China," the University of Westminster's Manal Mohammed explained in The Conversation.
However, the data currently available may not be giving the full picture.
La Trobe University's China health program director, George Liu says since the U-turn in China's COVID-19 management strategy, there is now no way for the government to capture all of the country's infections.
"The reporting system can only capture those reported by the health facilities. And the majority of people in China don't do PCR testing anymore, so they're not captured," he said.
Chinese authorities have so far submitted less than 800 recent cases to GISAID for genomic sequencing analysis — a relatively small sample size for what is understood to be a large outbreak.
Given China's lack of transparency in the early stages of the pandemic, many of its neighbours are now operating on the assumption that it is suppressing information to cover up the extent of the outbreak.
The concern is that without a clear picture of China's outbreak, it is difficult to assess threats of new variants.
How do new variants emerge? It's like 'cracking a safe'
To put it simply, COVID-19 is going to keep changing no matter where it's circulating — that's what viruses do.
Infected cells in the body produce billions of copies of the virus, and sometimes that process goes wrong and produces a mutation.
"You always have mutations building up over time. That holds true for China, just like it holds true for the rest of the world," says clinical virologist Siddharth Sridhar, from the University of Hong Kong.
With a population of 1.4 billion — nearly 20 per cent of the entire globe — China provides a lot of opportunities for transmission and mutation.
Every now and again, a mutation gives the virus an advantage.
"It might change the shape so that our antibodies don't recognise it as well, or it might increase how well the virus binds to our cells, making it more infectious," explains epidemiologist Zoë Hyde, from the University of Western Australia.
"It could also increase or decrease the severity of the disease.
"You can think of it as like cracking a safe. The virus is trying out lots of different combinations and most won't work.
"But, if over a billion people get infected, that's a lot of chances for the virus to find a winning combination."
Elsewhere, Omicron subvariants have evolved to evade antibody responses from previous infections or vaccinations.
"That higher level of population exposure to COVID is really driving Omicron to mutate in that direction," Dr Sridhar said.
However, in China — which has until now been cut off from the rest of the world — it's a different story.
"The background is completely different because you have this large population that has never been exposed to Omicron before in any form. The virus doesn't share the same kind of evolutionary pressures," Dr Sridhar said.
That's not to say that the subvariants currently circulating won't make a lot of people in China sick.
Dr Hyde is particularly concerned about China's large number of of immunocompromised people, who are generally at higher risk of severe disease from COVID-19.
"Because their immune system can struggle to clear the virus, they can have infections that last for months rather than just a week or two," she said.
"That gives the virus a long time to keep mutating and finding new ways to get around a person's antibodies."
When does a new variant become concerning?
Not all new variants pose a threat. Trying to predict where the next variant of concern will come from is almost impossible, but tracking the spread of subvariants so far does provide some clues.
Currently, the WHO lists Omicron — including its descendant lineages — as the only "variant of concern", having overtaken the previous Delta strains.
Additionally, there are a number of Omicron subvariants listed as "under monitoring" for distinct characteristics that may warrant their own label as a variant of concern, though neither BF.7 or BA.5.2 are among them.
Dr Sridhar says even if a new variant does emerge in China, it will take some time, and "may not necessarily be as successful in other parts of the world".
Globally, Omicron BA.5 and its subvariants have dominated the sequenced cases lodged with GISAID since May 2022, accounting for about 85 per cent by mid-August.
In late October, health bodies around the world noticed the growing prevalence of two particular subvariants, BQ.1 and XBB — essentially "Omicron cousins".
The most dominant sublineages — XBB.1.5 "Kraken" and BQ.1.1 "Cerberus" — are thought to have gained traction thanks to crafty mutations that help them evade immunity.
The WHO describes XBB.1.5 as "the most transmissible subvariant that has been detected", but there is no indication yet that it causes more severe disease.
Research so far shows they are able to work around immunity from vaccination, previous infection, and in the case of in the case of B.Q.1.1, protection from antibody drugs used for immunocompromised people.
Based on the way Omicron has evolved elsewhere, Dr Sridhar says it's reasonable to expect the virus to eventually do the same thing in China.
"It's fair to assume that a similar process is going to happen in China, well into 2023 when most of the population is already infected," Dr Sridhar said.
However, for that new variant to pose a threat globally, it would need to overcome the dominant strains outside China.
Dr Sridhar says the situation is unlikely to give rise to a strain that could completely knock Omicron off its perch.
"A new variant of concern could still emerge, but it would really be out of left field," he said.
"It's very difficult to track the emergence of a completely new variant of concern in real time.
"It might still happen, but Omicron is just so good at the job already."
