Why Hong Kong may become a living laboratory in search for Covid-19 answers

In the two months since it first hit the world’s Covid-19 radar, scientists have generated an astonishing amount of information on the Omicron variant. Still, key questions remain about Omicron, as well as about a new subvariant, known as BA.2. Among them: How much more transmissible is BA.2 than its wildly transmissible parent?

Answering questions like these can be challenging, sometimes almost impossible, in many locations because such a large proportion of people has been vaccinated, previously infected, or both. That can make it hard to tease out whether certain outcomes are attributable to changes in the virus versus the result of built-up human immunity. But it turns out there is a place where clear answers to key questions may be within reach — if that place is really, really unlucky.

That place is Hong Kong.

The special administrative region, a city of 7.5 million people crammed into 427 square miles in Southern China, has a unique combination of characteristics at this point in the pandemic that could make it a living laboratory, if the city is unable to withstand the onslaught of Omicron.

Hong Kong has a zero Covid policy. Like New Zealand and the Chinese mainland, the city has largely succeeded in preventing Covid transmission from taking hold there by requiring incomers to quarantine for 21 days in designated hotels, aggressively testing for the virus, and tracking down contacts when cases emerge.

As a consequence, few people there have been infected; it’s estimated that less than 1% of residents have immune system weaponry generated by prior infection. And though vaccination rates are high among younger adults, they are dangerously low among the elderly, who are at the greatest risk of dying from Covid. Less than 50% of adults 70 to 79 have received two doses of vaccine. In adults 80 and older, only 20% have received two shots and only about 4% of people in this highest-risk group have received a booster shot, according to the government’s vaccination dashboard.

The vaccination rate among residents of nursing homes is lower still. “The nursing homes, we are looking at 16% — one, six — currently,” Gabriel Leung, dean of medicine at the University of Hong Kong, told STAT.

If Omicron were to breach the city’s formidable Covid barricades, Hong Kong’s elders would be highly vulnerable to the infection. Things that could appear muddled elsewhere could be clear there.

For example, it’s thought that BA.2 may be 30% to 35% more transmissible than BA.1, the original version of Omicron, Leung said. But if that’s true, is that due to something about how the virus behaves when it infects people? Or is it because BA.2 has acquired even more tricks to slip past human immunity than the original Omicron virus, which was already quite adept at the feat?

That question can best be answered where there is no human immunity to evade, so-called virgin territory. “Immune escape is not an issue if you are unvaccinated and you have never been infected,” Leung said.

“Ironically, and, paradoxically, Hong Kong’s nursing homes … would be the perfect laboratory to sort this out,” he continued. “Because 84% of our older folks in nursing homes are not vaccinated, they have never been infected, so they are literally immune naïve. And if we have a BA.1 versus BA.2 in different homes, that’s actually the only place on earth that this could be sorted out definitively.”

Leung was quick to add, though, that he hopes this scenario doesn’t come to pass. “It’s one natural experiment that I’d rather not have the world first on,” he said.

Hong Kong’s low vaccination rate among the elderly stems from hesitancy that arose early in the vaccination rollout when some adverse events were seen after vaccination, explained Ben Cowling, a professor of infectious diseases epidemiology at the University of Hong Kong. Elevated rates of Bell’s palsy or reactivation of shingles were reported among some early vaccinees.

“So that those were reported in the media in the early days and got a lot of attention,” he said.

In countries where Covid transmission rates are high, the risk-benefit ratio of vaccination tilts decidedly toward getting a jab. But in a place like Hong Kong, where for much of the pandemic to date the risk of catching Covid has been very low, some clinicians actually advised their elderly patients against getting vaccinated, Leung said.

“That has set the wrong tone,” he said, adding the hesitancy has solidified over time. “I don’t think this is rational, but it’s real.”

Over the two years of the pandemic, Hong Kong has recorded only 13,000 Covid cases and 213 deaths. That’s fewer deaths than the city suffered during the 2003 outbreak of SARS-1, which claimed 299 lives.

Cowling thinks continued spread of the Omicron variant in the city may be unavoidable, despite the determination of Hong Kong’s leaders to maintain the city’s zero Covid status. And with both the Delta and Omicron variants causing cases, there could be infections in naïve individuals that could generate comparative data.

“The government is working very hard to try and control the current outbreaks — and there are various outbreaks. But it’s difficult to stop Omicron,” he said. “So quite possibly, we will have data fairly soon on the severity profile of Omicron in unvaccinated older people, unfortunately.”

Michael Diamond, a viral immunologist at Washington University in St. Louis, said a growing amount of animal data — including some that his lab helped to generate — points to Omicron being less virulent than earlier variants. There’s also been early human data, but more is needed, he suggested, adding that Hong Kong could be a place to generate it, if the virus takes off there.

“The key measure of whether this is less pathogenic — apart from the animal studies — is in naive people, meaning those who have never been vaccinated and never been infected. Are they getting severe disease or not?” said Diamond. “The preliminary data, I’ve seen one study which suggests now that that is indeed the case, that it is less pathogenic overall. However, in some people it is still pretty pathogenic and people are still dying from it.”

Natalie Dean, an assistant professor of biostatistics, bioinformatics, and epidemiology at Emory University’s Rollins School of Public Health, said one of the challenging things about trying to answer questions like whether one variant is more virulent than another is that we don’t often see both transmitting at the same time.

Trying to stack up death rates from one point in the pandemic, when, say, the original virus was circulating, to those accrued later in the pandemic, after one of the variants of concern had emerged, is not an apples-to-apples comparison. Treatment of Covid has improved and many people have some immunity from vaccination or prior infection.

Seeing both circulating in a population — Hong Kong’s elderly — with little immunity could create a clearer picture, Dean agreed.

“I’ll add too that Hong Kong has excellent data collection, and so another advantage is that capture of infections will be more complete,” she said.

Correction: An earlier version of this story incorrectly stated the percentage of people in Hong Kong who have been vaccinated.