A doctor handles vials during a swab test in a laboratory in Milan.
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An unanswered question about Covid-19, the illness caused by the new coronavirus, is how many people with the disease are circulating freely because their infection has not been detected.
More than 80 countries have confirmed at least 97,800 cases of the virus, according to Johns Hopkins University, including more than 14,800 outside of mainland China, where the disease originated in the city of Wuhan.
But researchers at Harvard and Imperial College London estimate that, on average, only one-third of the illnesses exported from China have been observed, a calculation that is still likely to be incomplete.
“It’s not accounting for those who are asymptomatic,” said James Hay, a postdoctoral research fellow at Harvard T.H. Chan School of Public Health. “The number including those without symptoms or with mild symptoms is likely to be higher than that.”
The estimate is based on assessments of how many infected people traveled to other countries from Wuhan before movement was restricted.
“Let’s imagine a scenario,” Dr. Hay said.
According to Dr. Hay, if there was a 1% probability that someone traveled from Wuhan to Singapore, and Singapore then detected five cases of Covid-19, researchers would expect other countries with the same travel probability to import the same number of cases. If they detected fewer, it would suggest they were underreporting.
Because Singapore historically has very good detection capabilities, it can be used as a benchmark. But estimates like this are based on confirmed cases, which involve only the sickest people.
“The asymptomatic fraction is the big thing we usually don’t know,” said Christopher N. Mores, a professor at the Milken Institute School of Public Health at George Washington University.
To get a sense of how many of these people might exist, researchers can use examples like the Diamond Princess cruise ship, where hundreds of passengers got sick while on board.
“There were around 3,700 passengers and 600 who tested positive for the virus,” Dr. Hay said. “Only half had the symptoms. Some of those asymptomatic people might go on to develop symptoms later. So the final percentage of infections that are asymptomatic will end up a bit less than 50%.”
Among those who got sick, six have died.
If the demographics of the passengers and the way they mingled aboard ship resemble the general population, their transmission patterns could help experts estimate the total number of asymptomatic people.
“You know the full spectrum,” said Joseph Lewnard, an assistant professor of epidemiology at the Berkeley School of Public Health. “The proportion of who become infected, the proportion of who have symptoms and the proportion who die.”
In reality, the passengers probably aren’t representative of the larger population, and the conclusions researchers have drawn from their transmission statistics are limited.
“All we know is there are more cases than we’re seeing, and the number is a fair bit larger,” Dr. Hay said.
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Despite the uncertainty, the estimates help researchers anticipate what sort of health-care burden to expect, including the potential number of fatalities. So far, the virus has killed more than 3,300 people globally, including twelve in the U.S.
“The number you see and hear talked about is the case fatality ratio,” Dr. Hay said. “That’s the proportion of people who are classified as a case and who die. You get 2% to 4%, and it varies massively by age.”
Accounting for the total number of infections could substantially alter the ratio.
“What we really want to know is the infection fatality ratio,” Dr. Hay said. “If you use only the number of people who are quite sick and who fit the restricted case definition, it’s a small denominator. If we had a better idea of how many people as a whole are infected, the denominator would be higher, and the infection fatality ratio may be much lower.”
The Imperial College, accounting for both symptomatic and asymptomatic cases, has estimated the infection fatality ratio to be approximately 1%.
At this stage, the researchers caution that all Covid-19 estimates should be taken with a pinch of salt.
Imperial College warns that its fatality ratio is based on limited data. It’s unclear how readily individuals with mild or no symptoms infect others. And international efforts to identify, contain and treat cases will, hopefully, curtail the spread of the disease.
Like the virus, questions about the escalation of Covid-19 have proliferated. But many of the answers are yet to come.
Write to Jo Craven McGinty at Jo.McGinty@wsj.com
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