Opinion: The Urgent Questions Scientists Are Asking About Coronavirus

By Gabriel Leung

Let’s start with what we don’t know.

Dr. Leung is an infectious disease epidemiologist and dean of medicine at the University of Hong Kong.

Around the world and around the clock, scientists are trying to figure out what must be done to end the global health emergency unleashed by the new coronavirus. As the outbreak accelerates and spreads, dozens of countries have deployed increasingly stringent measures to try to contain the epidemic. Almost as quickly, in a herculean effort, an international network of researchers at data and wet laboratories has started gathering and analyzing data to unmask and disarm this perplexing new disease.

In magnitude, scale and velocity, this coronavirus, known as 2019-nCoV, is too big a problem for any one team to solve. On Monday, China reported its largest single-day death toll, 97, pushing the total reported dead worldwide to 910, with more than 40,500 people infected on four continents.

On Tuesday, I’m joining my fellow scientists at the World Health Organization headquarters for an urgent meeting to piece together, like a giant jigsaw puzzle, our findings so far. We need to get a clear view of the contagion and plug the holes in our understanding of the disease to inform public health decisions that affect hundreds of millions of lives. Science has a critical role to play in restoring calm.

Let’s start with what we know. The new coronavirus is a close cousin of viruses that infect bats. It jumped from an unconfirmed wild source (most likely bats) to an intermediate host, possibly pangolins or other small mammals, being sold as food at a market in Wuhan, a transportation and commercial hub in central China. The infected people unknowingly spread it to others, setting off the outbreak’s deadly journey. We now estimate that it takes about five to six days — possibly upward of 14 days — for someone to show symptoms after becoming infected.

What do we most need to know next? For epidemiologists who track infectious diseases, the most pressing concerns are how to estimate the lethality of the disease and who is susceptible; getting detailed information on how it spreads; and evaluating the success of control measures so far.No. 1 is the “clinical iceberg” question: How much of it is hidden below the surface? Because the outbreak is still evolving, we can’t yet see the totality of those infected. Out of view is some proportion of mildly infected people, with minor symptoms or no symptoms, who no one knows are infected.

A fleet of invisible carriers sounds ominous; but in fact, an enormous hidden figure would mean many fewer of the infected are dying. Usually, simple math would determine this “case fatality” ratio: divide the total number of deaths by the total number of people infected. In an emerging epidemic, however, both numbers keep changing, and sometimes at different speeds. This makes simple division impossible; you will invariably get it wrong.

In 2003, during the early days of the SARS outbreak, the medical community got the math wrong. At first, we believed that case fatality hovered between 2 percent and 3 percent. It took two pages of longhand algebra, written in Oxford, England, coded into a computer in London and then applied to data from Hong Kong, to get it right. The actual case fatality for Hong Kong was staggering: 17 percent.

That’s not to suggest we’re facing as dire a scenario now. Several groups, including mine, are each using our own methods to calculate a preliminary estimate of the new virus’s lethality. If there’s near agreement among our findings, expected within the week, we’ll be more confident in describing the new coronavirus. Does it resemble the seasonal flu, SARS or one of the largest plagues in human history, the 1918-19 “Spanish flu” pandemic?

Knowing the number of people likely to die, or who get seriously sick or have zero symptoms, will help health authorities determine the strength of the response required. They can better estimate how many isolation beds, heart-lung machines and medicines, among other things, are needed.Last month, to start understanding the severity of this illness, my team assisted Chinese experts in analyzing the initial 425 confirmed cases of infection. We learned that 65 percent of people had neither visited a market nor been exposed to another person showing pneumonialike symptoms, which implied, among other things, the possibility that some infected people don’t suffer from obvious symptoms — meaning the illness isn’t always severe.Along with getting a grasp on the level of severity is figuring out susceptibility, or who is most at risk for infection. The data so far indicates that this would include older adults, the obese and people with underlying medical conditions. There are few reports of children becoming infected. But are they not showing symptoms, or are they immune? And could they infect others as silent carriers? We must study those under 18 to find out; the answers could help us fine-tune public health measures. For example, should schools in China and Hong Kong remain closed?

Returning to the big picture, we must also refine what we know about how the new coronavirus is passed between people. Even as the outbreak appears to keep escalating, we believe the rapid — sometimes necessarily draconian — response of governments and health authorities has made a dent in transmission. In another recent study, we estimated how many people could get infected if there were no drastic public health interventions. Our goal with this report was to sound the alarm over what could be, so that it wouldn’t be.

Scientists are working toward quantifying effectiveness of the response. We need to find out if the virus’s basic reproductive number, the R0 or R-naught, has dropped. While our earliest estimates showed that typically every person infected by the new coronavirus passes it to 2 to 2.5 others, it’s still too early to know if measures have reduced the number to below the critical threshold of 1.

Simultaneously, we’re closely watching the rest of the world for any large, sustained outbreaks that might resemble ground zero in Wuhan. We expect more clarity within days or weeks. As of Monday, the largest concentration of infected patients in a single location outside mainland China, at more than 130 people, is on a cruise ship, the Diamond Princess, quarantined at Japan’s Yokohama port.

Finally, scientists need to appraise the control, or social distancing, measures deployed since the outbreak began. The challenge involves trying to quantify how many infections were actually prevented through measures such as wearing masks, closing schools and locking down cities. One possible approach to this assessment in China could involve using location services data from cellphones.