Emerging COVID-19 variants in China are unlikely: a warning flag from the first two years of the pandemic and why it is important to look elsewhere
When China abruptly dropped its zero-COVID policy in December, most of its population had little immunity against the dominant Omicron variant in circulation worldwide. Jodie McVernon, Epidemiology Program leader at the Doherty Institute states that the emergence of a dangerous new variant is unlikely. She says that there should be less selection pressure for immune-evading variant to emerge in a population.
However, the European Centre for Disease Prevention and Control has called on European countries to set up random testing of travellers from China, and sequence the virus from all positive samples, so that emerging variants can be detected. Other nations, including the United States, Japan and Australia, have also put surveillance measures in place for travellers from China.
When it comes to the first two years of the Pandemic, some countries like the United Kingdom and Norway have more than 10% of their COVID-19 cases out of their system. The earlier such data are gathered and shared, the faster scientists can run laboratory tests to look at the new variant’s immune evasion, resistance to antiviral drugs and ability to infect cells, says Sintchenko.
Over the past year, the testing landscape has changed dramatically according to evolutionary virologist Verity Hill at the Yale School of Public Health. Broad-scale population-based screening was feasible in countries such as the United Kingdom because researchers could tap into samples collected at community-based PCR testing facilities. In many countries authorities are no longer offering such services because of the cost and decreasing demand. People are using rapid diagnostic tests or not using a test at all.
Experts look for mutations in the SARS-CoV-2 spike protein, which allows the virus to enter host cells and is the main target of the body’s immune responses. There’s a chance that there will be a jump in the number of mutations in a new variant. “That’s a warning flag,” she says. There were more than 30 different changes to the spikeProtein in the Omicron variant.
If a new variant is better at evading immune system protections or causes more severe disease, then it is designated a new variant of concern by the World Health Organization.
Omicron not only contained many mutations, but also rapidly became a dominant variant in the population, suggesting it was spreading faster than, and out-competing, other variants in the community. Omicron was designated as a variant of concern by the WHO in a day or so after South African researchers notified the international community. Three weeks had elapsed since the first Omicron sequence was deposited.
The first known sample of the Delta variant was collected in India seven months after being designated a variant of concern. The first sign that there could be a concerning new variant around was a rapid rise in case numbers, hospitalizations and deaths in India at the start of 2021. “It’s connecting case counts and genetics as much as you can,” says Hill.
The majority of the sequence China has submitted since the beginning of December belong to Omicron subvariants. There are five new lineages — descendants of those subvariants — but these are unlikely to gain a foothold outside China, because of pre-existing immunity.
Hill says it’s more likely that a variant that emerges in China might be undetected because there’s less population-wide surveillance outside of China.
There are also concerns that China is not sharing enough. At a 3 January meeting of the WHO’s Technical Advisory Group on Virus Evolution, scientists from the Chinese Center for Disease Control and Prevention presented data based on more than 2,000 genomes collected and sequenced since 1 December 2022. But only around one-quarter of that number — 564 sequences — has been uploaded to GISAID’s database over the same period.
According to a virologist in China, until the current outbreak, all mammals can be traced back to direct contact withviruses. Animals that eat wild- bird droppings or prey on others can develop the disease. But its spread between mammals “implies that this H5N1 virus may pose a higher risk to public health”, Chen says.
The new variant may have genetic material from the gull flu, which could explain why it’s hard to tell that it’s coming from the mink farm. This means that a strain containing those mutations is probably still circulating in the bird population. If the new strains of the disease spread, the health authority would probably be able to produce a vaccine and reduce the severity of the disease.
William Schaffner, an infectious-disease specialist at the Vanderbilt University Medical Center in Nashville, Tennessee, says that the measures taken to prevent the new strain from spreading beyond the farm seem to have been successful.
The WHO’s Disease Outbreak News is one of the most influential when it comes to tracking infectious-disease outbreaks. The researchers at Georgetown University collected all of the 2,797 DON reports issued between 1996 and 2019. The database includes the metadata pulled from each report, such as the location of the outbreak, type of disease and timeframe over which it progressed.
Saudi Arabia, with 179 documented cases of the Middle East Respiratory Syndrome, was the second most reported disease outbreak, after China, which had a total of 262 outbreaks, of which 218 were of flu. There were very few reports about countries in Eastern Europe.
Putting COVID-19 in the public domain: The H5N1 girl is the first to have been sequenced by Karlsson and his colleagues
The database will allow researchers to look at the factors that determine how much money is spent to suppress a specific outbreak, or how external circumstances such as conflicts or weather events affect them, says Katz. However, the study notes that DON reports do not mention all known outbreaks in every region.
The WHO has the ability to improve the reports by increasing transparency, creating more specific criteria for an outbreak and showing more information about animal populations.
I don’t know why the virus has spilled over from poultry to people in this case, after some ten years of it not being detected. A lot of factors still need to be investigated, but there have been a lot of global changes in agricultural practices owing to the COVID-19 pandemic that could have created the conditions for a spillover.
Carol Cardona, a vet and professor at the University of Minnesota College of veterinary Medicine, says that the heroic effort may not be sustainable given the current building styles and workforce. “The reason I say it can work is that companies that had [highly pathogenic avian flu] in 2015 had fewer cases in 2022. So they learned some lessons and changed some things—but very few of them kept it out completely.”
Erik Karlsson, a virologist at the Pasteur Institute of Cambodia in Phnom Penh, spoke to Nature about how he and his colleagues sequenced the full genome of the virus sample from the young girl in less than a day before sharing the data on the public repository GISAID. The girl is not the first person in nine years to be diagnosed with H5N1, but she is the first one to have a sequence of the virus.
The sample was first tested at the National institute of public health in Phnom Penh and transferred to us. We received a sample at 5 p.m. on February 22, and we were able to read it within 24 hours. This really exemplifies the way that the COVID-19 pandemic has increased our capacity to sequence and share data very quickly.
The viral load in the sample was high enough that we could amplify the whole influenza genome in one go. If the viral load had been low, which is often the case, we would have had to wait about three days to grow it in cells or eggs to get enough virus to sequence. Our goal has been to get the virus up and running in the public domain.
Researchers have been keeping an eye on 2.3. 2.1c for quite a while and have information to make reasonable judgements regarding its transmissibility and pathogenicity. But anytime there is a zoonotic spillover, we must treat it with the utmost importance.
Viruses, especially RNA viruses such as influenza, are extremely promiscuous and will quickly adapt to a new host. We’ve seen this with the virus that causes COVID-19. The chance to adapt to a new host has been indicated by a spillover. That is concerning because that adaptation could result in a virus that could potentially transmit between people. It is vital that we block any potential for transmission, as well as understand what a new host does to the virus, in order to inform the outbreak response.
We are attempting to sequence samples from the father, but he seems to have had a lower viral load, which makes it a little bit harder to rapidly get a sequence. We will try to find ways to target the virus. But often, there isn’t enough viral load to get more than just partial sequences.
The Cambodian Pandemic (Singapore) Chicken Infections: Isolating and Growing the Virus at Biosafety Level-3
We know that, in Cambodia, the pandemic increased the amount of backyard poultry farming. Tour guides have to supplement their incomes and sources of food for their families, because they can’t work. Changes in agricultural practices that can increase spillover risk have been caused by people being still struggling. Changes to people’s health, for example being overweight, can cause them to be more susceptible to getting infections.
We will also isolate and grow this virus in our biosafety-level-3 facility, which will help us to develop tools to better understand the epidemiology of this case and the virus in the region. For example, we could develop blood tests for the presence of antibodies — a marker of past infection — in samples collected from the father, other people living in the girl’s home and the broader community. The isolating of the virus will be needed for animal models, such as ferrets, to be studied.