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Health


YOU’RE LIKELY TO GET THE CORONAVIRUS

Most cases are not life-threatening, which is also what makes the virus a
historic challenge to contain.

James Hamblin February 24, 2020
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Updated at 7:43 p.m. on Feb. 25, 2020.

In May 1997, a 3-year-old boy developed what at first seemed like the common
cold. When his symptoms—sore throat, fever, and cough—persisted for six days, he
was taken to the Queen Elizabeth Hospital in Hong Kong. There his cough
worsened, and he began gasping for air. Despite intensive care, the boy died.



Puzzled by his rapid deterioration, doctors sent a sample of the boy’s sputum to
China’s Department of Health. But the standard testing protocol couldn’t fully
identify the virus that had caused the disease. The chief virologist decided to
ship some of the sample to colleagues in other countries.



At the U.S. Centers for Disease Control and Prevention in Atlanta, the boy’s
sputum sat for a month, waiting for its turn in a slow process of
antibody-matching analysis. The results eventually confirmed that this was a
variant of influenza, the virus that has killed more people than any in history.
But this type had never before been seen in humans. It was H5N1, or “avian flu,”
discovered two decades prior, but known only to infect birds.

By then, it was August. Scientists sent distress signals around the world. The
Chinese government swiftly killed 1.5 million chickens (over the protests of
chicken farmers). Further cases were closely monitored and isolated. By the end
of the year there were 18 known cases in humans. Six people died.


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 * 


 * HOW STRESS MAKES YOU SICK
   
   Olga Khazan



This was seen as a successful global response, and the virus was not seen again
for years. In part, containment was possible because the disease was so severe:
Those who got it became manifestly, extremely ill. H5N1 has a fatality rate of
about 60 percent—if you get it, you’re likely to die. Yet since 2003, the virus
has killed only 455 people. The much “milder” flu viruses, by contrast, kill
fewer than 0.1 percent of people they infect, on average, but are responsible
for hundreds of thousands of deaths every year.



Severe illness caused by viruses such as H5N1 also means that infected people
can be identified and isolated, or that they died quickly. They do not walk
around feeling just a little under the weather, seeding the virus. The new
coronavirus (known technically as SARS-CoV-2) that has been spreading around the
world can cause a respiratory illness that can be severe. The disease (known as
COVID-19) seems to have a fatality rate of less than 2 percent—exponentially
lower than most outbreaks that make global news. The virus has raised alarm not
despite that low fatality rate, but because of it.



Coronaviruses are similar to influenza viruses in that they both contain single
strands of RNA.* Four coronaviruses commonly infect humans, causing colds. These
are believed to have evolved in humans to maximize their own spread—which means
sickening, but not killing, people. By contrast, the two prior novel coronavirus
outbreaks—SARS (severe acute respiratory syndrome) and MERS (Middle East
respiratory syndrome, named for where the first outbreak occurred)—were picked
up from animals, as was H5N1. These diseases were highly fatal to humans. If
there were mild or asymptomatic cases, they were extremely few. Had there been
more of them, the disease would have spread widely. Ultimately, SARS and MERS
each killed fewer than 1,000 people.

COVID-19 is already reported to have killed more than twice that number. With
its potent mix of characteristics, this virus is unlike most that capture
popular attention: It is deadly, but not too deadly. It makes people sick, but
not in predictable, uniquely identifiable ways. Last week, 14 Americans tested
positive on a cruise ship in Japan despite feeling fine—the new virus may be
most dangerous because, it seems, it may sometimes cause no symptoms at all.



Read: The new coronavirus is a truly modern epidemic

The world has responded with unprecedented speed and mobilization of resources.
The new virus was identified extremely quickly. Its genome was sequenced by
Chinese scientists and shared around the world within weeks. The global
scientific community has shared genomic and clinical data at unprecedented
rates. Work on a vaccine is well under way. The Chinese government enacted
dramatic containment measures, and the World Health Organization declared an
emergency of international concern. All of this happened in a fraction of the
time it took to even identify H5N1 in 1997. And yet the outbreak continues to
spread.




--------------------------------------------------------------------------------

The Harvard epidemiology professor Marc Lipsitch is exacting in his diction,
even for an epidemiologist. Twice in our conversation he started to say
something, then paused and said, “Actually, let me start again.” So it’s
striking when one of the points he wanted to get exactly right was this: “I
think the likely outcome is that it will ultimately not be containable.”



Containment is the first step in responding to any outbreak. In the case of
COVID-19, the possibility (however implausible) of preventing a pandemic seemed
to play out in a matter of days. Starting in January, China began cordoning off
progressively larger areas, radiating outward from the city of Wuhan and
eventually encapsulating some 100 million people. People were barred from
leaving home, and lectured by drones if they were caught outside. Nonetheless,
the virus has now been found in 24 countries.

Despite the apparent ineffectiveness of such measures—relative to their
inordinate social and economic cost, at least—the crackdown continues to
escalate. Under political pressure to “stop” the virus, last Thursday the
Chinese government announced that officials in Hubei province would be going
door-to-door, testing people for fevers and looking for signs of illness, then
sending all potential cases to quarantine camps. But even with the ideal
containment, the virus’s spread may have been inevitable. Testing people who are
already extremely sick is an imperfect strategy if people can spread the virus
without even feeling bad enough to stay home from work.



Lipsitch predicts that within the coming year, some 40 to 70 percent of people
around the world will be infected with the virus that causes COVID-19. But, he
clarifies emphatically, this does not mean that all will have severe illnesses.
“It’s likely that many will have mild disease, or may be asymptomatic,” he said.
As with influenza, which is often life-threatening to people with chronic health
conditions and of older age, most cases pass without medical care. (Overall,
about 14 percent of people with influenza have no symptoms.)

Lipsitch is far from alone in his belief that this virus will continue to spread
widely. The emerging consensus among epidemiologists is that the most likely
outcome of this outbreak is a new seasonal disease—a fifth “endemic”
coronavirus. With the other four, people are not known to develop long-lasting
immunity. If this one follows suit, and if the disease continues to be as severe
as it is now, “cold and flu season” could become “cold and flu and COVID-19
season.”



At this point, it is not even known how many people are infected. As of Sunday,
there have been 35 confirmed cases in the U.S., according to the World Health
Organization. But Lipsitch’s “very, very rough” estimate when we spoke a week
ago (banking on “multiple assumptions piled on top of each other,” he said) was
that 100 or 200 people in the U.S. were infected. That’s all it would take to
seed the disease widely. The rate of spread would depend on how contagious the
disease is in milder cases. On Friday, Chinese scientists reported in the
medical journal JAMA an apparent case of asymptomatic spread of the virus, from
a patient with a normal chest CT scan. The researchers concluded with stolid
understatement that if this finding is not a bizarre abnormality, “the
prevention of COVID-19 infection would prove challenging.”




Read: 20 seconds to optimize hand wellness

Even if Lipsitch’s estimates were off by orders of magnitude, they wouldn’t
likely change the overall prognosis. “Two hundred cases of a flu-like illness
during flu season—when you’re not testing for it—is very hard to detect,”
Lipsitch said. “But it would be really good to know sooner rather than later
whether that’s correct, or whether we’ve miscalculated something. The only way
to do that is by testing.”



Originally, doctors in the U.S. were advised not to test people unless they had
been to China or had contact with someone who had been diagnosed with the
disease. Within the past two weeks, the CDC said it would start screening people
in five U.S. cities, in an effort to give some idea of how many cases are
actually out there. But tests are still not widely available. As of Friday, the
Association of Public Health Laboratories said that only California, Nebraska,
and Illinois had the capacity to test people for the virus.

With so little data, prognosis is difficult. But the concern that this virus is
beyond containment—that it will be with us indefinitely—is nowhere more apparent
than in the global race to find a vaccine, one of the clearest strategies for
saving lives in the years to come.

--------------------------------------------------------------------------------

Over the past month, stock prices of a small pharmaceutical company named Inovio
have more than doubled. In mid-January, it reportedly discovered a vaccine for
the new coronavirus. This claim has been repeated in many news reports, even
though it is technically inaccurate. Like other drugs, vaccines require a long
testing process to see whether they indeed protect people from disease, and do
so safely. What this company—and others—has done is copy a bit of the virus’s
RNA that one day could prove to work as a vaccine. It’s a promising first step,
but to call it a discovery is like announcing a new surgery after sharpening a
scalpel.



Though genetic sequencing is now extremely fast, making vaccines is as much art
as science. It involves finding a viral sequence that will reliably cause a
protective immune-system memory but not trigger an acute inflammatory response
that would itself cause symptoms. (While the influenza vaccine cannot cause the
flu, the CDC warns that it can cause “flu-like symptoms.”) Hitting this sweet
spot requires testing, first in lab models and animals, and eventually in
people. One does not simply ship a billion viral gene fragments around the world
to be injected into everyone at the moment of discovery.

Inovio is far from the only small biotech company venturing to create a sequence
that strikes that balance. Others include Moderna, CureVac, and Novavax.
Academic researchers are also on the case, at Imperial College London and other
universities, as are federal scientists in several countries, including at the
U.S. National Institutes of Health. Anthony Fauci, the head of the NIH’s
National Institute of Allergy and Infectious Diseases, wrote in JAMA in January
that the agency was working at historic speed to find a vaccine. During the SARS
outbreak in 2003, researchers moved from obtaining the genomic sequence of the
virus and into a phase 1 clinical trial of a vaccine in 20 months. Fauci wrote
that his team has since compressed that timeline to just over three months for
other viruses, and for the new coronavirus, “they hope to move even faster.”




New models have sprung up in recent years, too, that promise to speed up vaccine
development. One is the Coalition for Epidemic Preparedness (CEPI), which was
launched in Norway in 2017 to finance and coordinate the development of new
vaccines. Its founders include the governments of Norway and India, the Wellcome
Trust, and the Bill & Melinda Gates Foundation. The group’s money is now flowing
to Inovio and other small biotech start-ups, encouraging them to get into the
risky business of vaccine development. The group’s CEO, Richard Hatchett, shares
Fauci’s basic timeline vision—a COVID-19 vaccine ready for early phases of
safety testing in April. If all goes well, by late summer testing could begin to
see if the vaccine actually prevents disease.

Read: Coronavirus is devastating Chinese tourism

Overall, if all pieces fell into place, Hatchett guesses it would be 12 to 18
months before an initial product could be deemed safe and effective. That
timeline represents “a vast acceleration compared with the history of vaccine
development,” he told me. But it’s also unprecedentedly ambitious. “Even to
propose such a timeline at this point must be regarded as hugely aspirational,”
he added.



Even if that idyllic year-long projection were realized, the novel product would
still require manufacturing and distribution. “An important consideration is
whether the underlying approach can then be scaled to produce millions or even
billions of doses in coming years,” Hatchett said. Especially in an ongoing
emergency, if borders closed and supply chains broke, distribution and
production could prove difficult purely as a matter of logistics.

Fauci’s initial optimism seemed to wane, too. Last week he said that the process
of vaccine development was proving “very difficult and very frustrating.” For
all the advances in basic science, the process cannot proceed to an actual
vaccine without extensive clinical testing, which requires manufacturing many
vaccines and meticulously monitoring outcomes in people. The process could
ultimately cost hundreds of millions of dollars—money that the NIH, start-ups,
and universities don’t have. Nor do they have the production facilities and
technology to mass-manufacture and distribute a vaccine.



Production of vaccines has long been contingent on investment from one of the
handful of giant global pharmaceutical companies. At the Aspen Institute last
week, Fauci lamented that none had yet to “step up” and commit to making the
vaccine. “Companies that have the skill to be able to do it are not going to
just sit around and have a warm facility, ready to go for when you need it,” he
said. Even if they did, taking on a new product like this could mean massive
losses, especially if the demand faded or if people, for complex reasons, chose
not to use the product.




Making vaccines is so difficult, cost intensive, and high risk that in the
1980s, when drug companies began to incur legal costs over alleged harms caused
by vaccines, many opted to simply quit making them. To incentivize the
pharmaceutical industry to keep producing these vital products, the U.S.
government offered to indemnify anyone claiming to have been harmed by a
vaccine. The arrangement continues to this day. Even still, drug companies have
generally found it more profitable to invest in the daily-use drugs for chronic
conditions. And coronaviruses could present a particular challenge in that at
their core they, like influenza viruses, contain single strands of RNA. This
viral class is likely to mutate, and vaccines may need to be in constant
development, as with the flu.



“If we’re putting all our hopes in a vaccine as being the answer, we’re in
trouble,” Jason Schwartz, an assistant professor at Yale School of Public Health
who studies vaccine policy, told me. The best-case scenario, as Schwartz sees
it, is the one in which this vaccine development happens far too late to make a
difference for the current outbreak. The real problem is that preparedness for
this outbreak should have been happening for the past decade, ever since SARS.
“Had we not set the SARS-vaccine-research program aside, we would have had a lot
more of this foundational work that we could apply to this new, closely related
virus, ” he said. But, as with Ebola, government funding and
pharmaceutical-industry development evaporated once the sense of emergency
lifted. “Some very early research ended up sitting on a shelf because that
outbreak ended before a vaccine needed to be aggressively developed.”

On Saturday, Politico reported that the White House is preparing to ask Congress
for $1 billion in emergency funding for a coronavirus response. This request, if
it materialized, would come in the same month in which President Donald Trump
released a new budget proposal that would cut key elements of pandemic
preparedness—funding for the CDC, the NIH, and foreign aid.  



Read: It’s suddenly cold out. Am I going to get sick?

These long-term government investments matter because creating vaccines,
antiviral medications, and other vital tools requires decades of serious
investment, even when demand is low. Market-based economies often struggle to
develop a product for which there is no immediate demand and to distribute
products to the places they’re needed. CEPI has been touted as a promising model
to incentivize vaccine development before an emergency begins, but the group
also has skeptics. Last year, Doctors Without Borders wrote a scathing open
letter, saying the model didn’t ensure equitable distribution or affordability.
CEPI subsequently updated its policies to forefront equitable access, and Manuel
Martin, a medical innovation and access adviser with Doctors Without Borders,
told me last week that he’s now cautiously optimistic. “CEPI is absolutely
promising, and we really hope that it will be successful in producing a novel
vaccine,” he said. But he and his colleagues are “waiting to see how CEPI’s
commitments play out in practice.”




These considerations matter not simply as humanitarian benevolence, but also as
effective policy. Getting vaccines and other resources to the places where they
will be most helpful is essential to stop disease from spreading widely. During
the 2009 H1N1 flu outbreak, for example, Mexico was hit hard. In Australia,
which was not, the government prevented exports by its pharmaceutical industry
until it filled the Australian government’s order for vaccines. The more the
world enters lockdown and self-preservation mode, the more difficult it could be
to soberly assess risk and effectively distribute tools, from vaccines and
respirator masks to food and hand soap.

Italy, Iran, and South Korea are now among the countries reporting quickly
growing numbers of detected COVID-19 infections. Many countries have responded
with containment attempts, despite the dubious efficacy and inherent harms of
China’s historically unprecedented crackdown. Certain containment measures will
be appropriate, but widely banning travel, closing down cities, and hoarding
resources are not realistic solutions for an outbreak that lasts years. All of
these measures come with risks of their own. Ultimately some pandemic responses
will require opening borders, not closing them. At some point the expectation
that any area will escape effects of COVID-19 must be abandoned: The disease
must be seen as everyone’s problem.  

* This story originally stated that coronaviruses and influenza viruses are
single strands of RNA; in fact, influenza viruses can contain multiple segments
of single-strand RNA.

We want to hear what you think about this article. Submit a letter to the editor
or write to letters@theatlantic.com.




James Hamblin, MD, is a staff writer at The Atlantic. He is also a lecturer at
Yale School of Public Health and author of the forthcoming book Clean.
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