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New SARS Like Virus Discovered Before It Causes An Outbreak

Sunday, October 21, 2012 // Uncategorized

Here is a fascinating behind the scene look at the discovery of a novel corona virus, the same family of viruses that caused SARS a few years ago, before it caused an outbreak.  It gives an insight into the networks of scientists that study infectious diseases and how they communicate.

From ProMed Digest:

Date: Sun, 21 Oct 2012 20:45:49 -0400 (EDT)
From: ProMED-mail <[email protected]>
Subject: PRO/AH/EDR> Novel coronavirus – Saudi Arabia (13): history, collateral damage

NOVEL CORONAVIRUS – SAUDI ARABIA (13): HISTORY, COLLATERAL DAMAGE
*****************************************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

Date: 21 Oct 2012
Source: Toronto Star [edited]
<http://www.thestar.com/news/gta/crime/article/1274934–new-sars-like-virus-discovered-before-it-causes-outbreak>

Four months ago, a mucus sample arrived in Dr. Ali Mohamed Zaki’s
laboratory in Saudi Arabia. The mucus had been coughed up by a
60-year-old Saudi Arabian man with a strange case of pneumonia. He had
been admitted to the Dr. Soliman Fakeeh hospital in Jeddah on [13 Jun
2012]; soon after, his kidneys began to fail. Eleven days after being
hospitalized, the man was dead.

When the patient was admitted, Zaki was working in the hospital’s
virology lab, which he helped establish in 1994. He was sent samples
of the patient’s sputum, mucus coughed up from his lungs.

Eventually, this spot of sputum would lead Zaki to the discovery of a
virus never before seen in humans: a novel coronavirus, the same type
of virus behind the SARS outbreak in 2003 that swept across 30
countries and killed approximately 800 people, including 44
Torontonians.

Zaki’s discovery — and his decision to post it online — touched off
a chain of events that quickly unearthed a 2nd patient in another
country and enabled the global health community to gain an upper hand
in the face of a potentially deadly new virus.

Scientists have now learned the virus’s genetic code, discovered its
likely link to bats, and equipped labs around the world with the means
to diagnose it. Virologist buddies from the “old SARS club” have
reunited, collaborating once again across borders, and teams of
experts have been deployed to the Middle East to aggressively
investigate the virus and its origins.

And the World Health Organization currently feels reassured enough to
give its blessing for travel to Saudi Arabia, where millions of
pilgrims are descending this week for the hajj, one of the world’s
largest mass gatherings.

For Zaki, his discovery was fortunate, “a favour for the globe.” Yet,
as of last week, it seems to have cost him his job.

But on [13 Jun 2012], Zaki was still faced with that basic medical
question: What mysterious thing was making this patient so sick?

Zaki 1st ran a battery of tests on the sputum and blood samples.
Initially, he looked for influenza, the usual suspect in a respiratory
ailment. All initial results came back negative.

Zaki decided to culture the samples to see what grew. In late June
[2012], viruses began replicating in the sputum culture, but by this
point, the patient was already dead.

Yet Zaki continued his sleuthing. He had a sense that this was
something bigger than just one patient. So Zaki turned his mind to the
possibility of a paramyxovirus, a class of virus responsible for some
acute respiratory diseases. It was a path that took him to Dr. Ron
Fouchier, a professor of molecular virology at the Erasmus Medical
Centre in the Netherlands.

Zaki has never met Fouchier but knew his reputation as one of the
world’s leading influenza researchers. He also knew Fouchier had
recently developed a test for paramyxoviruses and called him.

Fouchier listened to Zaki and could not help thinking about SARS; the
clinical picture just sounded so similar. Had Zaki tested for
coronaviruses yet?

This was certainly going to be Zaki’s next step. He mailed the virus
to Fouchier in Rotterdam. While he waited for a response, Zaki tested
his virus sample to identify whether it was in the coronavirus family.
It was.

Coronaviruses can infect many animals and humans and are named for
their distinctive crown-like appearance under a microscope. Before
2003, there were only 2 coronaviruses known to infect humans, and both
were associated with the common cold. The discovery of SARS 9 years
ago [2003] changed everything and opened the world’s eyes to the
coronavirus’s deadly potential and the ominous possibility that new
strains were lurking undiscovered.

Zaki did not have the equipment to sequence the genome, in other
words, to determine its genetic code and identify it specifically. But
Fouchier did.

In 2003, Fouchier had played a major role in identifying the SARS
genetic sequence, a process that took 3 or 4 weeks. Sequencing the
virus’s genome allows scientists to perform their life-saving work —
developing antivirals, vaccines and diagnostic tests — more easily
and quickly.

This time, with advanced technologies and resources, it only took
Fouchier a few days to sequence Zaki’s virus. He found it was closely
related to a coronavirus found in bats, the same animal from which
SARS is believed to have sprung. But this was not the SARS
coronavirus.

“It was a new kind,” Zaki said, admitting that at this point he began
to worry about his own exposure to the virus. “I became afraid it
could (spread) like SARS, and I listed it on ProMED-mail.”

ProMED-mail is an infectious disease reporting website that had been
used during the SARS outbreak. Designed to quickly disseminate
information, every message is vetted by a panel of experts before
being posted online and sent to more than 60 000 subscribers
worldwide.

Zaki’s email, which described his and Fouchier’s findings in 3 short
paragraphs, went online on [20 Sep 2012].

“NOVEL CORONAVIRUS — SAUDI ARABIA,” the summary read in capital
letters. “HUMAN ISOLATE.”

Zaki’s inbox was immediately flooded. Some congratulated him on his
discovery but most were anxious queries.

“The coronavirus is really not like any other virus,” said Dr.
Christian Drosten, who runs the virology department at the University
of Bonn in Germany. “This is not a thing that you see every day,
popping up new. If it’s a new coronavirus that has never been seen
before in humans, that is ringing the bell.”

The ringing of this bell was heard in every corner of the globe. Most
importantly, it reached a north London lab in England, where doctors
and scientists were scratching their heads over a puzzling case.

On [12 Sep 2012], 8 days before Zaki’s email went live on ProMED-mail,
a 49-year-old Qatari man with “atypical pneumonia” was airlifted to a
London hospital. The patient had fallen sick in Qatar but had visited
Saudi Arabia in August [2012].

Within days, the United Kingdom’s public health organization, the
Health Protection Agency (HPA), was notified of the case.

Initially, as had Zaki, they figured this could be influenza. The HPA
began conducting tests on [20 Sep 2012], the same day Zaki’s
ProMED-mail email went online.

That same night, 2 HPA employees working on this case — a clinician
and a scientist — independently noticed Zaki’s post. “They both had a
sort of light-bulb moment,” said Maria Zambon, the HPA’s director of
reference microbiology. “Should we test for this new virus?” The next
day, Friday [21 Sep 2012], the HPA clinicians tested for
coronaviruses. The test was positive. But they needed to figure out
which coronavirus. The team quickly began sequencing a tiny snippet of
the virus’s RNA, working through the night.

Early Saturday morning [22 Sep 2012], Zambon decided to contact Dr.
Albert Osterhaus, a long-time colleague with whom she had worked
during the SARS outbreak. Osterhaus is a flu expert and one of the
world’s leading virologists, but that is not why Zambon contacted him
exactly. Osterhaus works at the same Rotterdam laboratory as Fouchier,
the doctor contacted by Zaki who now had a sample of the new
coronavirus. Zambon emailed Osterhaus and asked him to call her. About
20 minutes later, her phone rang. “So, that tells you 2 things. One,
that he reads his emails at 7 o’clock in the morning,” Zambon said,
chuckling. “And secondly, that he takes messages from me quite
seriously.”

Osterhaus hung up the phone with Zambon and called Fouchier, who was
actually in Canada at the time, attending a flu conference in Bromont,
Quebec, with post-doctoral students. “That is the moment where you’re
really shocked,” Fouchier said. “Once you hear about a 2nd case you
think, ‘Whoa. We’re not going to get another SARS.'”

By 2 p.m. London time, Zambon’s team had a genetic sequence for the
virus from the Qatari patient. It was indeed a new coronavirus. But
was it the same that had sickened the Saudi patient? She sent the
sequence to Fouchier.

As Fouchier’s post-doctoral students spoke at the conference, he
hovered over his laptop at the back of his room, analyzing the 2
viruses. He remembers a crowd gathering around him as the sequences
began to align.

“We were with quite a lot of people in Canada. They were all sitting
very excited up on my table as we were analyzing the sequences,” he
recalled.

At about 4 p.m. London time, Fouchier reported his result: a 99.5 per
cent match. It was the same virus. And with that revelation, the
situation took on a new level of urgency. “There was this kind of
concern that you may be looking at the tip of an iceberg,” Zambon
said.

That night, Zambon had a meeting with the HPA’s incident control team.
Fouchier also participated via teleconference, calling from a bus
taking him to the Montreal airport, where he caught his flight back to
Rotterdam.

The HPA declared a Level 3 incident, indicating a public health event
with potential national impact, and the news began to make its way
around the world (the HPA has 5 levels of alert for public health
threats, with 5 being the most serious). The World Health Organization
was also notified.

“At that point, the machinery started,” said Dr. Maurizio Barbeschi,
with the WHO’s global capacity, alert and response department.

One of the cogs in the machine was Drosten, the energetic 40-year-old
University of Bonn virologist. Drosten had shot to international
recognition in 2003 when he worked furiously (and mostly without
sleep) to develop the 1st diagnostic test for SARS just 11 days after
the WHO had issued a global alert, thus beating several other
high-performance labs racing toward the same goal.

Drosten, by this point, was well aware of the new coronavirus; about a
week before Zambon was emailing Osterhaus about the Qatari patient,
Fouchier and Drosten were discussing the virus from the Saudi.

Fouchier knew that Drosten, a friend and colleague, had done a lot of
work with bat coronaviruses. They are also both members of EMPERIE, a
European Commission-funded project coordinated by Osterhaus and
created post-SARS to establish a network of experts and medical labs
capable of mobilizing quickly in the face of a new virus.

The new coronavirus was reuniting scientists who were in the trenches
together during SARS. “This is the old SARS club,” Drosten commented
to Nature earlier this month [October 2012].

Two days after the 2nd confirmed case was announced, Fouchier sent
Drosten the virus so he could begin developing a diagnostic test. If
this virus were to spread, labs around the world would need tools for
diagnosing it.

Drosten’s capacity has also been hugely improved since SARS. In 2003,
it took him about 5 days to develop a diagnostic test; this time, it
took just over 2.

Drosten actually developed 3 diagnostic tests and shipped them to
Zambon, who tested them on the Qatari patient to confirm which ones
worked (2 did, one failed).

On [27 Sep 2012], the team published a paper — a detailed description
of how they developed a diagnostic test for identifying the new
coronavirus — in Eurosurveillance, a scientific journal that
emphasizes the rapid publication of papers on ongoing outbreaks.

“We sent the paper in the morning. I wrote it overnight, and it was
reviewed during the day by 2 proper reviewers, and it was out at
midnight,” Drosten said. “We published a complete scientific paper —
I think about 2800 words or something — showing all of this
validation data.”

For Zambon, she believes this “must be a world record” of some sort
(she notes, however, that the team barely slept that week). “That’s
e-publishing,” Drosten said. “This speeds up everything.”

In their paper, the team included information on how laboratories can
order materials for diagnosing the virus. Shipments have now been made
to approximately 150 labs around the world, according to Drosten.

On [4 Oct 2012], exactly 2 weeks after Zaki’s ProMED-mail post, public
health officials in the United Kingdom had tracked down 64 people who
had come into contact with the Qatari patient. Their finding likely
unleashed sighs of relief: nobody had developed serious symptoms.

The novel coronavirus, it would seem, is not easily transmitted
between humans. There have been multiple reports of suspected new
cases in recent weeks, everywhere from Hong Kong to Denmark, but none
has ultimately tested positive for the novel coronavirus. As for the
Qatari patient, he is still alive.

Investigations continue at a furious pace, both in laboratories and on
the ground in Qatar and Saudi Arabia, where international experts have
descended in recent weeks. They are searching for more signs of the
virus, both in humans (have other people been exposed?) and the

environment (could bats have passed the virus to other animals who are
now transmitting it to humans?). Fouchier and Osterhaus are also
working to prove the novel coronavirus ultimately killed the Saudi
Arabian victim, who also had bacterial infections that could have
caused the respiratory disease.

For Drosten, the discovery of this new coronavirus reinforces that
mysterious viruses lurk undetected in animal reservoirs, waiting to
spill over into human populations.

“You don’t hear about them for years, and then suddenly they pop up,”
Drosten said. “Chances are, there’s close human-animal contact, and
there’s been a jump.”

As for Zaki, he will also continue work on the novel coronavirus. But
not in Saudi Arabia.

This is not the 1st time Zaki had discovered a new virus in Saudi
Arabia, and, in 1994, he was the 1st scientist to isolate dengue fever
in the country. He found another virus, a tick-borne virus that killed
2 young butchers, in 1995.

But this time around, Zaki said his discovery has made the Saudi
Arabian ministry of health “very angry.”

“They were very aggressive with me. They sent a team to investigate
me,” he said. “And now they force the hospital administration to force
me to resign.”

A spokesperson for the hospital, however, said in an email that Dr.
Zaki is still employed there. She did not respond to follow-up
questions seeking clarification.

Zaki is back in his homeland, Egypt. He said he will now help the
Egyptian government test sick people returning from the hajj, the
annual Islamic pilgrimage to the holy city of Mecca in Saudi Arabia,
which begins Thursday [25 Oct 2012].

The hajj attracts millions of pilgrims every year. In other words,
Mecca will soon become the perfect breeding ground for a virus looking
to cause maximum damage. But so far, this virus is not easily
transmitted, and the WHO has not recommended any travel restrictions
to Saudi Arabia. But rest assured, they will be monitoring the
situation closely.

With this new coronavirus, the world has been much more prepared than
in 2003. But sheer luck has also been on our side.

With SARS, it was the outbreak that came 1st. The virus was only
discovered later. “Now, it’s really the reverse situation,” Drosten
said. “We already have the virus, and we’re waiting for an epidemic to
show up or not show up. It’s a much better scenario.”

[Byline: Jennifer Yang]

– —
Communicated by:
ProMED-mail from HealthMap alerts
<[email protected]>

[The above newswire presents a very interesting “behind the scenes”
account of events to date related to the identification of a novel
coronavirus identified in a fatal severe respiratory disease with
renal failure patient in Saudi Arabia, and a similar clinical syndrome
in a patient with probable exposure in Qatar, presently hospitalized
in the United Kingdom for intensive therapy.

If the information given in the above article is valid, that the
identifying scientist has had negative professional consequences as a
result of releasing this information to the scientific community
through a post on ProMED-mail, it is an unfortunate situation. As a
result of the dissemination of information through ProMED-mail, a 2nd
case was identified. This led to the activation of an international
public health alert and response network, and investigations are
underway to identify the extent of possible background infection rates
with this novel coronavirus in the region. Given the upcoming mass
gathering that will involve approximately 2-3 million people from all
over the world, the possibility of an outbreak of disease caused by a
novel coronavirus is a serious concern. The need for the international
community to be aware of this novel coronavirus — on a laboratory,
epidemiologic, and clinical level — is obvious, and not reporting on
this could potentially have led to a repeat of 2003’s experience with
SARS. – Mod.MPP

A HealthMap/ProMED-mail map can be accessed at:
<http://healthmap.org/r/1HAJ>.]

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