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Can the coronavirus outbreak be contained?

Since a new coronavirus outbreak began in December, Chinese officials have placed millions of people under quarantine, and international airports are screening travelers for signs of the illness in an effort to control its spread. But as scientists learn more about the new virus, which causes pneumonia, it’s unclear how effective these strategies will be at halting the epidemic.  

Cases of the virus, for now called 2019 novel coronavirus, or 2019-nCoV, have rapidly increased since the outbreak was first announced. There are 4,587 confirmed cases of the disease in 16 countries, including 16 health care workers, as of January 28. At least 106 people, all in China, have died.    

U.S.
officials are monitoring 110 people across 26 states for signs of infection,
such as fever, cough and shortness of breath, the Centers for Disease Control
and Prevention announced January 27 in a news conference. Those being monitored
include people who recently traveled to Wuhan — the city at the center of the outbreak
— and others they had direct contact with. So far, five people in the United
States have tested positive for the new virus; 32 have tested negative.

In
response to the spiking case numbers, more than 50 million people in China are
currently under lockdown, likely the largest quarantine in modern history.
Although quarantine and isolation were effective strategies to end the 2003
severe acute respiratory syndrome, or SARS, outbreak, it’s unclear whether
similar methods will be as effective for the new virus. 

Researchers are now scrambling to answer unknown questions about 2019-nCoV that might help control efforts, such as figuring out when people are contagious and how much the virus is changing as it passes from person to person.   

Can people without symptoms spread the disease?

It’s possible that people who aren’t showing symptoms can transmit 2019-nCoV to others, Chinese officials announced January 26. And because people might be infected and not show obvious symptoms, doctors should isolate patients and trace their contacts as soon as possible, researchers report January 24 in the Lancet.  

Asymptomatic
people make outbreaks hard to control because they can spread disease without
signs that they’re sick themselves, making efforts such as airport screenings
less useful. SARS, for instance, had few such cases, which made it easier to
identify and isolate patients, as well as quarantine their contacts.

Although
transmission from asymptomatic people is common for contagious viruses such as
influenza or measles, it would be new for the types of coronaviruses that cause
epidemics, says Stanley Perlman, a virologist at the University of Iowa in Iowa
City.

Coronaviruses responsible for previous outbreaks, including SARS, and Middle East respiratory syndrome, or MERS, infect a patient’s lungs. Because these viruses infect deeper parts of the respiratory tract compared with less-severe coronaviruses that infect the upper portion and cause colds, they’re harder to transmit to other people unless the patient has symptoms like a cough, Perlman says.   

2019-nCoV causes similar symptoms to SARS, though without intestinal symptoms or a runny nose, researchers report January 24 in the Lancet (SN: 1/24/20). The CDC reports that symptoms of 2019-nCoV may appear from two to 14 days after exposure, based on how MERS works. In previous outbreaks, “if somebody was going to get infected from [an] infected person, the virus had to get up into the upper airway so it could spread,” Perlman says, which wouldn’t happen until the patient was sick enough to start coughing.

Scientists don’t yet know how the new virus might spread from asymptomatic people.

How fast the new virus may spread is also uncertain. Researchers are still calculating how many people on average a newly infected person might transmit the virus to — a number called R0. The World Health Organization estimates 2019-nCoV’s R0 is between 1.4 and 2.5, while a study posted January 27 on SSRN reports it could be as high as 6.5. A flurry of additional papers estimate the number to be between 1.4 and 3.8 (SN: 1/24/20)

R0 is a
tricky number to pin down, as the varying estimates reflect. It can also change
as control measures are put in place, suggesting that as more cases emerge,
these estimates will probably continue to shift.

2019-nCoV close-up and viral particles
The 2019 novel coronavirus, or 2019-nCoV, is seen in close-up (left) in a transmission electron micrograph, and viral particles (round, arrows point to some clusters of the virus) infecting human airway cells.N. Zhu et al/NEJM 2020

Will China’s lockdown contain the outbreak? 

China has taken unprecedented actions to try to contain the virus,
shutting down transportation in and out of many cities, closing major
attractions like Disneyland in Shanghai, and postponing the start of school,
among other precautions.

While these measures could help isolate infected individuals and prevent the virus from spreading, many experts caution that quarantine, especially at such large scales, is a largely ineffective, and often counterproductive, public health tool. Before the travel restrictions were fully implemented, at least 5 million Wuhan residents left the city, according to Wuhan’s mayor. Quarantines can also lead to food and medical supplies shortages, as well as other problems that can increase social discord.

“This is an unprecedented situation, nobody knows what the right
thing to do is,” says Allison McGeer, an infectious disease expert at Mount
Sinai Hospital in Toronto who herself contracted SARS in 2003. McGeer says
subduing this outbreak boils down to limiting the virus’s R0 so that on
average, any infected person infects no more than one other person. If that
happens, the virus has a good chance of petering out. 

Officials can bring a virus’s R0 down by
identifying and isolating infected people, canceling large gatherings of people
or limiting the spread of the virus to other cities so that authorities can
focus their attention and effort on one specific area, McGeer says. “China
tried to do those things, but we just don’t know if they’ll work.” 

Personal actions, like wearing masks, could help contain the
spread of the virus, though experts say the evidence is inconclusive. “If
you’re infected and you wear a mask, you’ll shed less virus into the air around
you,” McGeer says, and potentially reduce the risk that others get infected.
For uninfected people, the effects of a mask are less clear, since they usually
aren’t sealed tight around the nose and mouth.

McGeer says it could be a couple more days before scientists will
be able to see whether the lockdown measures implemented January 23 have any
effect. Because it takes time for the virus to incubate and become detectable,
she says that the recent spike in cases likely reflects infections that
happened before the mass quarantine.

Even if the lockdowns yield some benefits in China, it may not be
enough to prevent further global spread. “We may have to learn to live with
this new virus, just like we live with winter waves of influenza,” she
says. 

While the 2019-nCoV has killed at least 106 people and infected
thousands more, its ultimate impact depends on the overall severity of illness
caused by the virus. “We still don’t really know that,” McGeer says. 

Most cases reported to date have been mild, with around 20 percent of those infected experiencing severe illness, the WHO reports January 28. So far only a few other countries have reported person-to-person spread. McGeer adds that countries like the United States had time to put proper screening procedures in place, giving them a leg up in keeping the virus from spreading.

How much is the virus changing?

All
viruses change as they spread, including 2019-nCoV, which could make future
versions more or less virulent, affecting efforts to control its spread.

As
viruses replicate, mistakes are sometimes incorporated into their genes. Coronaviruses
are RNA viruses, which have notoriously error-prone replication machinery, says
Perlman, the virologist at the University of Iowa. Such viruses also easily
swap parts with other viruses. “They can change a lot,” he says.

But
coronaviruses have proofreading enzymes that make them more stable than other
RNA viruses, says Mark Denison, a pediatric infectious disease specialist and
coronavirologist at Vanderbilt University in Nashville. “They are certainly
capable of change,” he says. “But in general once they’ve established a virus
that works well, they stabilize that.” Additional changes are more likely to
have no effect or to be detrimental to the virus’s success.

Researchers have posted the genetic makeup of more than two dozen samples of the new coronavirus to the GISAID database. Comparing the RNA makeup, or genome, of the viruses can help researchers trace where it came from and keep track of changes that might make it more or less virulent in the future, Perlman says.

There
is no indication that this virus is becoming more dangerous, or changing much
at all. 

So far, versions of the new coronavirus isolated from patients in China, Thailand and the United States aren’t much different from each other. Only five or fewer of the more than 29,000 genetic letters of the virus’s genome differ from patient-to-patient, says Trevor Bedford, an evolutionary biologist at the Fred Hutchinson Cancer Research Center and the University of Washington in Seattle. Of the 27 viruses examined, eight had no changes from the original. The small number of changes indicates the virus hasn’t had time to change much.

“This lack of genetic diversity fits with an origin in the human population in mid-November,” Bedford says. The data also suggest that the virus made the leap from animals to humans just once and has been passing from person to person since. The viral sequences don’t suggest multiple spillover events from animals to people associated with a seafood market as originally thought, he says. If the virus leaped from animals to humans multiple times, the researchers would expect a greater number of mutations. Bedford and colleagues posted their conclusions and supporting data January 25 at nextstrain.org.

The virus appears most closely related to a SARS-like coronavirus found in bats, Na Zhu of the Chinese Centers for Disease Control and Prevention and colleagues report January 24 in the New England Journal of Medicine. That doesn’t mean that bats passed the virus directly to humans, Bedford says. Another animal could be an intermediate host. “It’s not snakes, though,” he said, referring to a study suggesting that snakes could be a reservoir for the virus (SN: 1/24/20).

Bats
have probably been carrying a similar virus for years. It’s a mystery why the
virus suddenly made the leap to humans in 2019, Perlman says. Researchers will
continue to collect virus genomes to monitor how the virus changes over time,
he predicts. 

SARS
developed mutations that helped it latch on to human cells more readily, he
says, but ultimately that didn’t help the virus survive. The last human case of
SARS was recorded in 2004. Even if 2019-nCoV develops mutations people might
think are dangerous, only time will tell if such changes really make the virus
more infectious or deadly. Neither is necessarily success from the virus’s
point of view. “The goal of a virus is not to kill people; it’s to make more
virus,” Perlman says.

“We
could see a change today and we might think ‘Aha! It’s adapting better to
humans,’ but then in two weeks it’s gone,” Perlman says. Something similar
happened with MERS. Researchers detected mutations in the virus that might make
it better able to infect humans, but viruses carrying those mutations
ultimately couldn’t compete with strains that didn’t have those changes.