When Tiger Ye caught the coronavirus in January, his mother and grandmother nursed him back to health. Later that month, both women developed fevers, but with Wuhan’s hospitals overflowing they chose instead to bear it out at home.
Months later, with China’s epidemic appearing under control, the pair took a blood test that confirmed they had in fact contracted and fought off the virus. But they were never counted in the country’s official tally of more than 82,000 infected and nearly 5,000 dead.
"They are lucky to have recovered all by themselves," said Ye.
Now, amid accusations that China has under-reported its virus data, the nation is embarking upon a program that could capture the true scale of their outbreak. If undertaken globally, it could find millions more infections than the 2.1 million currently detected.
The effort, called a serological survey, involves researchers taking blood samples from a representative group of people to see if they have generated antibodies to fight the virus, a sign they’ve been infected. Scientists then extrapolate from there the magnitude of the pathogen’s spread in the broader population. Such studies could also shed light on how the virus transmitted among people, including what role seemingly less-affected groups, like children, have played in its dispersion.
China has refuted charges from US intelligence officials that it concealed the extent of its outbreak, although multiple revisions to its epidemic data have fueled mistrust both domestically and from other countries. This week, the country added more than 1,200 deaths to its official count, including people who died at home without being tested and late reporting from overwhelmed hospitals.
While China has a long history of questionable economic statistics, under-reporting when it comes to the coronavirus is an issue across the world. New York City recently added more than 3,700 previously unreported deaths to its count, and the World Health Organization says many countries will likely have to review their numbers. The lack of widespread testing is one of the main reasons. Besides people like Ye’s mother and grandmother – who choose not to or aren’t able to go to hospital – many countries simply don’t have enough testing kits to detect all their cases.
Another significant factor behind under-counting is the existence of a puzzling group that show no outward signs of illness, known as asymptomatic infections. Such patients are unlikely to be tested because they have no idea they’re even sick. Early indications are that asymptomatic carriers have played a key role in the pandemic spreading as wide and fast as it has.
Even after bringing its official count of new infections to zero, China is still detecting hundreds of asymptomatic cases by testing people who’ve come into contact with infected patients, showing that the virus hasn’t been eradicated even as the country’s biggest cities – including Wuhan, where the pathogen first emerged – start resuming normal activity.
"In all systems, cases are under-reported," said Antoine Flahault, a public health professor at the University of Geneva in Switzerland.
"Some infections are asymptomatic and cannot be detected by the health care system, some test results come back negative when the person is actually infected, and some can be mis-classified as cases of pneumonia or influenza without any proper testing procedures."
As countries that have quelled their first outbreaks worry that the highly-contagious virus will return in subsequent waves, the survey’s findings could help policymakers plan a better defense for its resurgence, including ways to normalize economic activity while controlling infection. China is undertaking serological surveys in a number of regions, Feng Luzhao, a researcher with the country’s Center for Disease Control and Prevention told reporters in Beijing on April 2.
While whole populations are unlikely to have mass immunity, some groups – children, or older people – could be found to have group immunity, allowing economically-costly social distancing measures to be tailored to minimize disruption.
Other countries are making similar efforts on a smaller scale: New York is testing medical and other essential workers for antibodies, while Italy has tested everyone in Vò, a small town of 3,300 near Venice. Their aim is to create a full "epidemiological picture of the outbreak," and findings indicate that many were infected but had no symptoms.
As the outbreak’s original epicenter and the only major country at a mature enough stage of its epidemic to start concertedly looking back, China’s serological effort will be closely tracked by the global scientific community.
In Wuhan, investigators are blood testing a random group of 11,000 people who lived in the city for no less than two weeks between January and March.
Those participating in the survey, which includes all members of chosen households and people like police officers, community workers and taxi drivers, take tests for the virus and for antibodies generated to fight it, according to local newspaper Hubei Daily.
The survey’s findings will be used to "inform adjustment in response strategies," state media CCTV reported.
China has done this before. In 2003, researchers embarked on a serological survey after the Severe Acute Respiratory Syndrome, or SARS, outbreak, which sickened 8,000 people and killed almost 800, mostly in Asia.
The study conducted in southern Guangdong province, where SARS emerged, involved 130 patients diagnosed with the disease along with 119 close contacts and 100 healthy people. It revealed that most of those who have been infected with the SARS virus developed long-lasting antibodies that protected them and likely those around them against future infection.
In 2006, China’s health authorities also launched a nationwide survey of 79,000 people for hepatitis B. It found that the total number of children infected fell by 80 million since 1992 thanks to mass vaccination efforts, and there were still 93 million carriers concentrated in the country’s western hinterland.
In an interview with state news agency Xinhua in mid-January, Wang Chen, the dean of Peking Union Medical College, described a serological survey as "the most pressing task for the country," because it will help policymakers figure out if the coronavirus will disappear like SARS did 17 years ago, or is here to stay like the flu.
It could also determine if the virus can linger in people for a long time the way hepatitis B does in those without sufficient immunity. This tendency to "linger" could be why Korean doctors have found what they termed a "re-activation" of the coronavirus in 51 recovered patients.
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Despite its urgency, serological surveys are challenging to conduct right, especially in populations as vast as China’s.
A key determinant of the survey’s accuracy is whether the sample of people chosen best represents the population at large, said Jeffery Gilbert, an epidemiologist on the Covid-19 incident management team at the World Health Organization.
"China is a mix of European country-sized provinces with very different population densities," Gilbert said. "Without enormous amounts of testing throughout the country, a full picture of China is exceedingly challenging to get."
China has disclosed that it is testing 11,000 in Wuhan but not how many people are involved in other provinces and cities. China’s CDC didn’t respond to questions from Bloomberg on the survey.
Another challenge lies in the antibody test employed. Western biotech companies have launched tests that have been found to be inaccurate after countries had ordered millions.
"It must be highly specific and sensitive – that is, it must identify only SARS-CoV-2 and not cross-react with antibodies from other coronavirus infections," said David Heymann, a professor of infectious disease epidemiology at the London School of Hygiene & Tropical Medicine, referring to the scientific name of the new coronavirus.
An average person’s blood could also have antibodies for common viruses like influenza, which is from the same coronavirus family as SARS-CoV-2.
This difficulty in differentiating antibodies is what’s stopping South Korea, which has also shown success in curbing its outbreak, from kicking off its serological survey. The country’s CDC told Bloomberg it is testing whether certain antibodies are reacting only to the new virus, and not others.
The agency won’t initiate a serological survey until researchers have verified the antibody test’s specificity, it said.
"If the Chinese test is validated and meets sensitivity and specificity standards, then the results will be a valid reflection of previous infection in the community," Heymann said.
Beyond the true number of infections, a serological survey will be able to ascertain the exposure of various groups to the virus. It could also yield insight into the susceptibility of those with previous medical conditions.
"One of the burning questions has been about younger people and how much of a part they played in the virus’s spread," the WHO’s Gilbert said. While official infection tallies skew toward older people, the survey could find that children were just as infected but their immune systems acted more quickly to fight the virus, preventing serious symptoms from developing, he said.
Hotly-debated questions, such as whether school closures are necessary to stem the virus’s spread, could be answered definitively with these sorts of findings.
"A lot of people are waiting with anticipation to learn more," Gilbert said. "It will help us develop or change guidance for other countries where they haven’t been hit so hard."