Trickery of transmission: Silent spread leaves scientists clueless

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 per cent of people don’t even know they have it,” said Dr. Eric Topol, head of Scripps Research Translational Institute. “We have to get out of the denial mode, because it’s real.” Researchers have exposed the frightening likelihood of silent spread of the virus by asymptomatic and pre-symptomatic 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.

“For control, to actually keep the virus from coming back, we’re going to have to deal with this issue,” said Rein Houben, a disease tracker at the London School of Hygiene and Tropical Medicine. The dire toll of more than 580,000 worldwide deaths from the coronavirus has faded to the background as cities lift restrictions. But the slyness of the virus remains on the minds of many scientists, who are watching societies reopen, wondering what happens if silent spreaders aren’t detected until it’s too late. Travellers 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 harbour the virus without showing symptoms. A 10-year-old boy in China who travelled 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 traveller from China spread the virus to colleagues in Munich, even though she appeared healthy. Still, many scientists remained unconvinced. Some questioned whether the Chinese businesswoman truly didn’t have symptoms. They suggested she might have had mild ones she attributed to jet lag.

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. 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.

At US airports around the country, travellers returning from hot spots including China who didn’t have symptoms were allowed to go on their way. “We were reassuring ourselves and the public that contact with an asymptomatic person was not a risk,” said Dr Jeff Duchin of King County, Washington, where the first major US cluster of coronavirus cases broke out at the Life Care nursing home.

Behind the scenes, scientists like Meyers were sharing their alarming finding with health officials. Meyers had assembled a team of students who scoured websites of Chinese health departments looking for dates of symptom onset in situations where there was enough information to figure out who infected whom. Between Jan 21 and Feb 8, they found several cases where the person who brought the virus home didn’t develop symptoms until after infecting a family member. For example, a woman in a Chinese city with few cases got sick after her husband returned from a trip to a city with a large outbreak. He didn’t get sick until later. “When we looked at the data, we said, ‘Oh no, this can’t be true,’” Meyers said. “It was shocking.” Finding more than 50 such cases, Meyers immediately shared the analysis with the US Centers for Disease Control and Prevention — on Feb 20 at precisely 1:18 a.m., according to her records. The agency responded a few hours later with questions. Meyers and the CDC exchanged extensive emails, going over what could be behind the numbers. Was the virus really spreading that fast and before people felt sick? The Diamond Princess, which idled in the Port of Yokohama, Japan, while the virus exploded onboard, enticed researchers. After an ill passenger tested positive, only those with symptoms initially got tests. Houben and his London research team set out to build a mathematical model to estimate how many infected people without symptoms were being missed. After four weeks, their model indicated a startling three-quarters of infected people on the Princess were asymptomatic.

Could that really be right? At first, the researchers worried they might have done something wrong. They continued fine-tuning the model, directing a post-graduate student to locate any error. “Check for this, check for that,” Houben said. They spent weeks making sure it was foolproof. It indeed was right. They had their answer: Asymptomatic carriers “may contribute substantially to transmission.”

Elsewhere, as testing efforts have widened, huge proportions of asymptomatic people have shown up, from a neighbourhood in San Francisco to an aircraft carrier in the Pacific. An outbreak linked to a South Korean nightclub showed more than 30% of cases were asymptomatic. At one New York maternity ward, some 88% of those who tested positive had no symptoms. 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 in the early days of an infection. Scientists believe during these days, people can spread virus by talking, breathing, singing or touching surfaces. In the truly asymptomatic, the immune system wins the battle before they ever feel sick.

As it became clearer that healthy people could spread the virus, US health authorities opted not to wait for scientific certainty. During a meeting in early March, top US health officials said they believed transmission could be occurring before people displayed symptoms, according to an email obtained by The Associated Press. A few weeks later, the CDC recommended people cover their nose and mouth in public with masks, bandanas, even T-shirts.

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. The agency is telling public health officials in states that rely on mathematical models to use that number in their calculations.