One of the great mysteries of the coronavirus is how quickly it rocketed around the world.
It first flared in central China and, within three months, was on every continent but Antarctica, shutting down daily life for millions. Behind the rapid spread was something that initially caught scientists off guard, baffled health authorities and undermined early containment efforts — the virus could be spread by seemingly healthy people.
As workers return to offices, children prepare to return to schools and those desperate for normalcy again visit malls and restaurants, the emerging science points to a menacing reality: If people who appear healthy can transmit the illness, it may be impossible to contain.
"It can be a killer and then 40 percent of people don't even know they have it," said Dr. Eric Topol, head of Scripps Research Translational Institute.
Researchers have exposed the frightening likelihood of silent spread of the virus by asymptomatic and presymptomatic carriers. But how major a role seemingly healthy people play in swelling the ranks of those infected remains unanswered — and at the top of the scientific agenda.
The small but mighty coronavirus can unlock a human cell, set up shop and mass produce tens of thousands of copies of itself in a single day. Virus levels skyrocket before the first cough, if one ever arrives. And astonishing to scientists, an estimated 4 in 10 infected people don't ever have symptoms.
The slyness of the virus remains on the minds of many scientists as they watch societies reopen, wondering what happens if silent spreaders aren't detected until it's too late.
Travelers with no coughs can slip past airport screens. Workers without fevers won't be caught by temperature checks. People who don't feel tired and achy will attend business meetings.
And outbreaks could begin anew.
As early as January, there were signs people could harbor the virus without showing symptoms. A 10-year-old boy in China who traveled to Wuhan had no symptoms but tested positive, along with six others in his family who had coughs and fevers. More troubling was a report out of Germany: A business traveler from China spread the virus to colleagues in Munich, even though she appeared healthy.
Still, many scientists remained unconvinced.
The concept of people unwittingly spreading disease has never been an easy one to grasp, from the polio epidemic of mid-century America to the spread of HIV decades later.
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At the turn of the 20th century, a seemingly healthy New York cook named Mary Mallon left a deadly trail of typhoid infections that captivated the public and led to her being forced into quarantine on an East River island. "Typhoid Mary" remains a haunting symbol of silent spread.
As COVID-19 emerged, health officials believed it would be like other coronaviruses and that people were most infectious when showing symptoms like cough and fever, with transmission rare otherwise.
"We were thinking this thing is going to look like SARS: a long incubation period and no transmission during the incubation period," said Lauren Ancel Meyers, a disease modeler at the University of Texas at Austin.
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Behind the scenes, scientists like Meyers were sharing their alarming finding with health officials. By scouring the websites of Chinese health departments, Meyers and her team found more than 50 cases between Jan. 21 and Feb. 8 where the person who brought the virus home didn't develop symptoms until after infecting a family member.
"When we looked at the data, we said, 'Oh no, this can't be true,'" Meyers said. "It was shocking."
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Rebecca Frasure, who contracted the virus while aboard the Diamond Princess cruise, sat in bed in Japan in late February, frustrated to be kept hospitalized even though she didn't have any symptoms.
"I'm perfectly healthy except having this virus in my body," Frasure said.
Without widespread and frequent testing, it's impossible to know how many people without symptoms might carry it. The Diamond Princess, which idled in the Port of Yokohama, while the virus exploded onboard, enticed researchers.
After an ill passenger tested positive, only those with symptoms initially got tests.
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Rein Houben, a disease tracker at the London School of Hygiene and Tropical Medicine, set out to build a mathematical model to estimate how many infected people without symptoms were being missed. After four weeks, it indicated a startling three-quarters of infected people on the Princess were asymptomatic.
At first, the researchers worried they had done something wrong. But they hadn't, and they had their answer: Asymptomatic carriers "may contribute substantially to transmission."
In Washington state, similar clues emerged for Dr. Jeff Duchin as a team of investigators examined the Life Care nursing home — where the first major U.S. cluster of coronavirus cases broke out —and found health care workers were spreading the virus to other elder care facilities. They believed at least some of them were working while infected but before feeling symptoms.
In March, more than half the residents at another nursing home who tested positive didn't have symptoms, though most would go on to develop them.
That underscored the need to shift gears and acknowledge the virus couldn't be totally stopped.
"This disease is going to be extremely hard to control," Duchin recalled thinking.
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The nose and mouth are convenient entryways for the coronavirus. Once inside, the virus commandeers the cell’s machinery to copy itself, while fending off the body’s immune defenses. Virus levels skyrocket in the upper airway, all without symptoms early on. Many scientists believe that, during these days, people can spread virus just by talking, breathing or touching surfaces.
In the truly asymptomatic, the immune system wins the battle before they ever feel sick. That may have been what happened with Jessie Cornwell. After an outbreak at her Seattle assisted living facility, Cornwell tested positive for coronavirus, although she never had symptoms. She may have infected the Rev. Jane Pauw, who drove Cornwell to a Bible study meeting and later ran a high fever and tested positive.
As it became clearer that healthy people could spread the virus, U.S. health authorities opted not to wait for scientific certainty. In early April, the Centers for Disease Control and Prevention recommended people wear masks.
Days later, Chinese researchers published a paper saying patients are most infectious two to three days before developing symptoms. Evidence continues to accumulate, and the CDC now estimates 40% of transmission is occurring before people feel sick.
Still, doubt remains among scientists, most notably among the World Health Organization, which has discounted the importance of asymptomatic infection, though it recently began to acknowledge that possibility and advised people to wear masks.
U.S. health officials blame China for delays in sharing information on silent spread. But Topol contends the U.S. could have mounted its own testing program with viral genome sequencing.
That's no small matter: Gaining scientific clarity earlier would have saved lives.
“We’ve been slow on everything in the United States,” Topol said. “And I have to say it’s shameful.”
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