Coronavirus questions that scientists are racing to answer

The outbreak of a novel coronavirus in China and its spread to more than a dozen countries has presented health experts with a rapidly evolving and complex challenge.
That means there are a lot of unknowns.
Here are some of the outstanding questions that doctors, scientists, and health agencies are rushing to answer. (And a reminder that, already, they’ve learned quite a lot.)

When are people contagious?
One of the luckiest breaks the world got with the SARS outbreak of 2002-2003 was that people weren’t contagious until they developed symptoms. The same is true of MERS. As a result, it became easier for health officials to try to limit spread once they identified a new case.
Public health experts watching this outbreak unfold have been hoping 2019-nCoV, which is a member of the same virus family, would follow that pattern. Now they’re not so sure.
Chinese health authorities said over the weekend they’ve recorded cases where transmission occurred before the transmitting person showed symptoms. And German authorities reported a case Tuesday in which a man was infected by a colleague visiting from China. The colleague only began to feel sick on her flight back home.
If that’s a common feature of this infection, it’s going to cause serious problems.
With some viral illnesses — like influenza for example — people can actually start infecting the people around them a day or two before they start to feel sick. That’s insidious, because it means infected people can go to work, take the subway, go to church or to the movies — unaware that they are emitting viruses that can infect others.
How long is the period between when a person gets infected and when they develop symptoms?
In the past few days several papers from China describing the illness have been published or posted on preprint websites (sites that share papers before they have been peer-reviewed or published in journals). In a paper posted to bioRxiv, scientists from Guangdong province estimated the incubation period — the time from infection to symptoms — to average between four and five days, which was also the case with SARS. There is clearly a range, though; on Monday, the WHO said the information to date suggests two to 10 days.
Another paper, published last Friday in The Lancet, estimated the incubation period in a cluster of six family members to be three to six days. These estimates are compatible and suggest it takes a few days for people to start feeling ill — which explains how a number of travelers who have brought the virus to other countries only realized they were sick a day or two after getting home.

Are there mild cases that aren’t being detected? How big a proportion of the overall cases are they?
Most diseases have a spectrum of illness, ranging sometimes from asymptomatic infection — symptom free — to very severe disease and death. But some diseases tend to tilt toward one end of the spectrum.
With SARS, most of the cases were seriously ill. While that was bad for anyone infected, it made detecting where the virus was spreading easier. In this outbreak, it’s starting to look like there are mild and even asymptomatic cases.
How often they occur still isn’t clear. Nor is it known yet if they are able to transmit the virus, or how often they do. With some illnesses, mild and asymptomatic cases don’t contribute much to spread.
How dangerous is this infection?
The reports emerging suggest a pretty significant portion of cases are seriously ill. For instance, in a report China’s national health authorities posted Monday, about 17% of total cases were severely ill. And about 3% of confirmed cases had died.
Those are frightening numbers. But if the confirmed cases represent only a fraction of the total cases — and they likely do — that could really change the math. Until we have a better handle on the total number of cases it’s premature to draw conclusions.
How far has the virus spread already?
It’s hard to get a clear picture.
On Monday, infectious diseases experts from Hong Kong University said they believe the virus is now transmitting person-to-person, in a sustained way, in all major cities in mainland China.

Epidemiologists who use mathematical modeling to calculate disease spread have been looking at how many cases have been found in other countries. There are formulas that give you an idea of how many infections probably occurred in China before a case was exported.
As of Sunday, when the number of exported cases was approaching 60, Neil Ferguson of Imperial College London estimated there were likely already 100,000 cases in China. But that was two days ago.
Ferguson told STAT it’s getting hard to run that calculation, “given the exit screening and then quarantine of Wuhan,” the central Chinese city where the outbreak is believed to have started.
To date, about 14 countries and territories outside of mainland China have detected cases, but none has yet reported seeing sustained human-to-human transmission of the virus.
China is taking unprecedented and draconian measures to stop the virus from spreading, cutting off transit to cities with millions of people. Can these measures work?
Nothing like this has ever been tried before.
During the 2003 SARS outbreak, the World Health Organization issued what were called “travel advisories” — telling people around the world not to go to affected cities. The travel advisories, which the WHO has never used since, were loathed by the locations battling SARS, which saw tourism dry up and hotel vacancies soar. Though they certainly had the desired effect of driving away tourists, the travel advisories were advice only.
In China, this isn’t advice. The country is cutting off travel between cities. Is it possible to enforce? Can the Chinese economy sustain this? Big, big unknowns right now.

And will these measures stop the spread of the disease? When draconian restrictions are imposed, desperate people tend to use underground efforts to get around them. Still, spread of the virus may happen at a lower or slower rate than if the measures weren’t put into place.
In the end, it may turn out these measures were imposed too late. Analysis of the genetic sequences of viruses from more than two dozen cases suggest the virus had been transmitting person-to-person for a couple of months now — maybe starting in November or early December.
Was there initial transmission outside of the seafood market that authorities tied many of the first cases to?
Now that the virus appears to be spreading effectively among people, tracking down the initial source has become secondary to trying to contain the outbreak. But both as a scientific curiosity and for possible insights about how to prevent the next outbreak, it’s useful to know when and how the virus started infecting people.
Early in the outbreak, local authorities in Wuhan said that most of the early cases were linked in some way to a large seafood market that also had live animals for meat. This seemed like a logical source for the outbreak; coronaviruses can jump from animals to infect people. These viruses are thought to originate in bats, but can use a middleman as they hopscotch to humans. The 2002-2003 SARS outbreak, for example, was traced to palm civets, while MERS infections come from camels.
But then last week, in some of the first analyses of the initial cases, a team of researchers reported that the first patient in Wuhan hospitalized with pneumonia caused by the virus had no tie to the market. The patient’s symptoms also started a week earlier than later cases who were tied to the market.
That raises several possibilities: Perhaps the virus was spreading among people earlier than first noticed or reported by Wuhan health officials, and that one of these patients brought the virus to the market. Or, perhaps there was a group of infected animals that could have seeded the outbreak at different locations.

The coronavirus questions that scientists are racing to answer