Health officials in China, racing to try to contain a fast-growing
coronavirus outbreak,
are principally recording severe cases of disease, using a case
definition that cannot capture patients with mild illness, according to
experts familiar with the surveillance efforts.
The approach, the experts told STAT, is likely resulting in both an
underestimate in the total number of cases and flawed assumptions about
fatality rates calculated by those who ignore the repeated caution that
it’s too soon to do that math.
The experts were quick to note that the Chinese are not willfully
underreporting cases. Rather, the approach is a testament to how
challenging data collection can be during the early days of an epidemic.
When thousands of sick people show up at hospitals looking for care,
there is no time to go searching for people who have mild symptoms and
who have stayed home.
“I think right now things are so chaotic in China it may be hard to
collect data on the whole spectrum of illness,” said Michael Osterholm,
director of the Center for Infectious Diseases Research and Policy at
the University of Minnesota.
Officially, an estimated 20% of cases in China are severely ill,
according to the World Health Organization. But that calculation is
derived based on known cases, and would not reflect mild, undetected
ones.
Without knowing for sure what percentage of cases is severe — and how
easily the pathogen that causes the disease can be transmitted — it’s
impossible to forecast what might happen if the virus continues to
spread globally, the WHO’s emergencies chief, Mike Ryan, told reporters
Wednesday.
“We don’t understand either of those parameters well enough to make
accurate predictions,” he said. Still, he added a warning for people who
are concluding that the virus may be less fatal than some other known
pathogens: “A relatively mild virus can cause a lot of damage if a lot
of people get it.”
The outbreak has infected upward of 7,700 people on the Chinese
mainland, and killed 170 since the new virus, known provisionally as
2019-nCoV, was reported to the WHO on Dec. 31. Nearly 20 other countries
have reported diagnosing infections in travelers from the Chinese city
of Wuhan, the epicenter of the outbreak, but to date there has been
little local spread of the virus in other countries.
WHO Director-General Tedros Adhanom Ghebreyesus and Ryan, who were in
China earlier this week to consult with the Chinese government and
assess the situation, praised the response by officials there. “The
challenge is great but the response has been massive,” Ryan told
reporters.
The effort, which is of an unprecedented scale, involves quarantining
whole cities that are home to tens of millions of people to try to stop
spread of the virus. The WHO is still hopeful, Ryan said, that China
will be able to stop the outbreak.
If it cannot — or if exported infections seed outbreaks in other
parts of the globe — the world could be looking at a more disseminated
epidemic, admitted Tedros, as he is called.
Among other factors, epidemiologists are interested in the severity
of the outbreak and what is known as the virus’ “attack rate.” The
attack rate means the percentage of people who will develop the disease
if it spreads.
With seasonal influenza, the Centers for Disease Control and
Prevention estimates between 3% and 11% of people become sick with flu
every year. But immune systems have experience with influenza; the
attack rate might be higher with a virus that is wholly new to humans.
Likewise it’s unclear how many mild infections are being missed. The
Chinese are currently only testing people who are sick enough to seek
medical care because they have pneumonia — a criterion that
automatically excludes anyone on the mild end of the disease spectrum.
With some diseases, there isn’t much mild illness. In the case of the
2002-2003 SARS outbreak, for example, most people who became infected
ended up in hospital, noted Dr. Gabriel Leung, dean of medicine at Hong
Kong University and a veteran of that city’s battle against the disease.
It’s clear there are at least some mild cases with this new
infection. Many of the 100 or so exported cases are people with mild
illness; to date there have been no deaths among these cases. Some of
the five cases in the United States are only in hospital to ensure they
don’t infect anyone else. Such cases would not be tested in China using
the current case definition.
“The look and feel of the exported cases, I think, really support the
argument that there’s a lot of mild disease that is not being detected
in China at the moment for the very good reason that they just can’t do
it,” said Dr. Allison McGeer, who fought SARS in Toronto and helped
contain hospital outbreaks of MERS in Saudi Arabia. Both SARS and MERS
are coronaviruses, related to the new virus.
McGeer, an infectious diseases researcher at Toronto’s Mount Sinai
Hospital, noted the types of studies needed to estimate how much mild
disease this virus causes are very difficult to do.
Infectious diseases experts use the analogy of an iceberg when they
talk about the spectrum of a disease. The most severe cases represent
the tip of the iceberg; they are visible, because they are sick enough
that they seek health care.
But the portion of the iceberg that is under water is harder to
calculate, especially with a new disease. And without having a clear
picture of total cases, it’s difficult to come up with an accurate
fatality rate.
Wang Linfa, director of the program in emerging infectious diseases
at Duke-NUS Medical School in Singapore, is convinced there are a lot of
mild infections. “Mild cases don’t go to hospital and there’s many,
many cases that remain to be confirmed,” he said, noting laboratories
are struggling to keep up with testing amid a reported shortage of test
kits.
Leung agreed: “It looks like the submerged bit of the iceberg is fairly large for this thing.”
Some of the answers China cannot currently generate will come from
watching what happens with the exported cases, said Dr. David Heymann,
who oversaw the WHO’s SARS response and now teaches at the London School
of Hygiene and Tropical Medicine. “Now we are really going to begin to
see things,” he said.
Countries outside of China are using a broader approach to testing,
looking for anyone who has recently traveled to or from Wuhan who has
respiratory symptoms. These people, who the CDC calls “persons under
investigation” or PUIs, do not need to have pneumonia in order to be
tested.
Limited data may be skewing assumptions about severity of coronavirus outbreak, experts say
