Pedestrians wearing face masks walking across a busy zebra crossing junction in Hong Kong

Strict COVID-19 restrictions have been relaxed in Hong Kong and the Chinese mainland, raising fears that worrying new viral variants will emerge.Credit: Miguel Candela/SOPA Images/LightRocket via Getty

Fears that the massive surge of coronavirus infections in China could immediately spark the emergence of a troubling new variant are unfounded, say researchers. But that could change in the coming months as more people in the country acquire some natural immunity from infection. More widespread immunity could drive the virus SARS-CoV-2 to evolve ways to evade this immune protection. It remains crucial that variants be tracked, yet scientists question how quickly the next variant of concern will be detected as many countries wind down surveillance efforts.

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. Under such circumstances, the emergence of a dangerous new variant is unlikely, says epidemiologist Jodie McVernon at the Doherty Institute in Melbourne, Australia. There should be less selection pressure for immune-evading variants to emerge in a such a population, she says.

Still, China is ramping up efforts to monitor variants circulating in its population, and has announced plans to get 3 hospitals in each of its 31 provinces to genetically sequence virus samples collected from 15 outpatients, 10 people with severe COVID-19, and all people who have died from COVID-19 each week. But experts are divided on whether these plans will be enough to rapidly detect a concerning variant that could cause new waves of infection and death, in part because many other nations have reduced their genomic monitoring.

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.

Tracking a virus

Countries track variants by constantly sequencing a proportion of known infections and sharing those sequences in public repositories such as GISAID. During the first two years of the pandemic, most public-health agencies carried out targeted sequencing, monitoring people who had been hospitalized with COVID-19 with the aim of detecting new variants that might cause more-severe illness. Viruses collected from immunocompromised people, who can harbour infections for weeks or months, were also sequenced, because prolonged infections can give rise to heavily mutated viruses1,2.

Most nations also sequenced a representative sample of viruses from across the community, says Vitali Sintchenko, a microbiologist at the University of Sydney in Australia. In a study he co-authored, the researchers concluded that countries should aim to sequence 0.5% of COVID-19 cases and share those data within 21 days of collecting the samples. That would give them a 34% probability of detecting a new lineage before it infects 100 people3.

The study, which also looked at sequencing efforts in 189 countries up to the end of February 2022, found that during the first two years of the pandemic, 78% of high-income countries sequenced more than 0.5% of their COVID-19 cases, with some, including Denmark, Japan and the United Kingdom, consistently sequencing more than 5% of cases each week. 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.

But the testing landscape has changed drastically over the past year, says evolutionary virologist Verity Hill at the Yale School of Public Health in New Haven, Connecticut. 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. But in many countries authorities are no longer offering such services because of the expense and the decrease in demand, says Hill. And people are increasingly opting to self-test, using rapid antigen tests, or not test at all.

That means that detection of new variants is getting harder everywhere, says Sintchenko.

Red flags

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. A jump in the number of mutations in a new variant is one thing to watch out for, says Hill. “That’s a warning flag,” she says. The Omicron variant, which first appeared in a sequence from Botswana, had more than 30 mutations in its spike protein.

The World Health Organization (WHO) only designates a new ‘variant of concern’ if a variant is better at evading existing immune system protections, causes more severe disease or is much more transmissible than currently circulating variants.

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. The WHO designated Omicron a variant of concern within days of South African researchers alerting the international community to the variant’s rapid spread. But that came nearly three weeks after the first Omicron sequence was deposited into GISAID.

The Delta variant was designated a variant of concern in May 2021, seven months after the first known sample was collected in India. 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.

Wait and see

So far, most of the sequences that China has submitted to GISAID since the beginning of December belong to Omicron subvariants already in circulation elsewhere. There are five new lineages — descendants of those subvariants — but these are unlikely to gain a foothold outside China, because of pre-existing immunity.

But the decreased population-wide surveillance outside China makes it more likely that a variant that emerges in China might initially go undetected, says Hill.

Sintchenko says there are also concerns that China is not sharing enough of its sequences. 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.

A COVID-19 researcher in China, who has asked to remain anonymous to avoid undue attention for weighing in on political matters, says that although current surveillance in China is insufficient, China is building its capacity and ramping up the number of sequences it uploads to GISAID each week.