El mapa de arriba muestra los casos confirmados de infección por el Coronavirus en todo el mundo al día de ayer. A esta altura resulta poco creíble que no existan casos en América Latina o Africa (un solo caso en Egipto). Ayer los mercados globales reaccionaron feo ante las noticias sobre la expansión global del virus. Seguimos con cuidado las noticias, que van desde el ninguneo hasta el Apocalipsis. Habrá que ver. Leemos la siguiente nota de James Hamblin para el diario estadounidense The Atlantic:
Título: You’re Likely to Get the Coronavirus
Epígrafe: Most cases are not life-threatening, which is also
what makes the virus a historic challenge to contain.
Texto: 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.
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 around 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
are both 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.
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 Wuhan City 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 the 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, around 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.”
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 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 if 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, 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,
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.
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 are, like influenza viruses, a single strand 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.
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.