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| DATE | 2020-09-14 |
| FROM | Ruben Safir
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| SUBJECT | Subject: [Hangout - NYLXS] WUHAN-19 Mutations
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wsj.com
‘Really Diabolical’: Inside the Coronavirus That Outsmarted Science
Robert Lee Hotz and Natasha Khan
21-27 minutes
The new coronavirus is a killer with a crowbar, breaking and entering
human cells with impunity. It hitchhikes across continents carried on
coughs and careless hands, driven by its own urgent necessity to survive.
It has a gregarious side that makes it hard to resist. It loves a party.
The persistent social climber claims its victims around the world by
riding on moments of the most innocent of human interactions—a shared
laugh, a conversation, an embrace. And it is a liar. SARS-CoV-2, which
causes Covid-19, often misleads the body’s immune systems.
Taken on its own terms, SARS-CoV-2 is the infectious disease success of
the past 100 years.
Almost unmatched in the annals of emerging human contagions, it has
parlayed a few chance infections into a pandemic of around 27 million
confirmed cases so far.
Doctors long expected the advent of such a virus, but even so, the
shrewdness of the coronavirus caught many by surprise, and goes a long
way to explaining how the world has struggled to contain it ever since.
“We underestimated it,” said Peter Piot, the head of the London School
of Hygiene & Tropical Medicine and a co-discoverer of Ebola, who fell
victim to the coronavirus himself in March.
Dr. Qian Zhang at Rockefeller University retrieves blood samples from a
centrifuge as part of a project to study how the coronavirus affects
different people.
Photo: KHOLOOD EID for The Wall Street Journal
Modern travel made it easy for the new coronavirus to spread to frequent
fliers. It slipped unnoticed aboard a cruise ship in Japan and into
Zumba classes in South Korea. It infected mourners at a funeral in
suburban New York, a choir in Skagit County, Wash., and students on
spring break in Florida.
Initially, it was widely believed the virus made its home in bats, which
harbor hundreds of different kinds of coronaviruses. But it ventured
into new species.
In Hong Kong, Yuen Kwok-yung had been waiting more than a decade for a
virus like this to surface.
The 63-year-old infectious diseases professor at the University of Hong
Kong became enthralled with bat coronaviruses since making the
connection between bats and the original SARS outbreak in 2003, which
was caused by a related coronavirus. He amassed a database of animal
surveillance, showing that 39% of Chinese horseshoe bats could be
harboring SARS-related coronaviruses. In 2007, he wrote in Clinical
Microbiology Reviews that those findings represented “a time bomb.”
Bats’ cells can survive surges in metabolism—their hearts can go from 10
beats a minute during hibernation to 1,000 beats in flight. It is
thought their constitution makes them ideally suited to be a reservoir
where a virus can stay, biding its time before jumping to another host
species, an event known as a spillover.
At the end of December, Dr. Yuen, who has been known to show off his
photo collection of bats in caves, was beginning to suspect his fears
were realized after hearing about a mystery pneumonia afflicting
patients around 600 miles away in Wuhan. He warned Hong Kong officials
that something was coming, helping spur the city’s response.
After Chinese officials posted the gene sequence of the new coronavirus
to share with scientists around the world on Jan. 12, he and others grew
increasingly sure where the killer came from. It was so similar to known
bat SARS-related coronaviruses, it must have once been one of them, Dr.
Yuen said.
Even with spillover, a virus that jumps to a new species doesn’t always
spread. Some, like avian flu, an influenza originally in birds that can
infect humans, largely stop with the new host and don’t move from human
to human.
But around the same time at the HKU-Shenzhen hospital, where Dr. Yuen
also heads the microbiology and infectious-disease department, six
family members had returned to the southern Chinese city after a visit
to Wuhan. They began to feel unwell. The virus had got to them, from the
oldest family member, who eventually died, to a 10-year-old boy.
The cluster suggested the virus had a dangerous trait, Dr. Yuen said: It
was spreading between humans.
Dr. Yuen Kwok-yung in Hong Kong identified a connection between bats and
the original SARS outbreak in 2003, and warned about the new coronavirus.
Photo: Xiaomei Chen/South China Morning Post/ZUMA PRESS
He shared his findings with experts from the Chinese Center for Disease
Control and Prevention, adding to a growing body of evidence that led
China to confirm to the world that the virus was leaping from person to
person.
Even in those early days, said Dr. Yuen, “I suspected that this virus
may spread widely throughout the world like the 1918 Spanish flu.”
A borrowed life
All told, there are more viruses than stars in the known universe.
Trillions upon trillions of viruses float in the air and ride on the
clouds. Scientists at the University of British Columbia estimate that
800 million viruses rain onto every square meter of the planet every
day. A coronavirus itself is so small that 500 of them could fit within
the diameter of a human hair.
Many scientists can’t decide whether a virus is actually alive in any
conventional sense. All viruses lead a kind of borrowed life, chemists
say. They are a submicroscopic essence of the need to reproduce that by
nature is at cross-purposes with humankind.
“Viruses don’t think. They don’t have desires,” said Columbia University
virologist Angela Rasmussen.
In the absence of desire, they have purpose: to spread, multiply and
survive.
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THE COVID STORM
The Wall Street Journal is examining the causes of the Covid-19
catastrophe and the bungled response that followed. Get alerts for each
new installment, along with our daily coronavirus briefing.
At least 320,000 different viruses infect mammals. There are 219 virus
species that are known to be able to infect humans. One researcher found
more than a hundred different viruses living inside human lungs. At
least six other types of coronavirus are known to infect humans. Several
cause the common cold.
SARS-CoV-2 isn’t the first virus to have its impact broadened by travel.
Smallpox, which killed 300 million people or more in the 20th century
alone, first traversed the world by sailing with the Vikings a thousand
years ago, new research into the history of epidemics suggests.
The coronavirus belongs to a category of viruses that work by
transmitting chemical code, called RNA, sealed inside a protective
protein envelope. RNA is a nucleic acid present in all living cells that
usually acts as a messenger to relay genetic instructions in DNA,
telling the cells what to do. Once the virus gets inside a host cell, it
seizes the cell’s reproductive machinery.
Without that maneuver, the coronavirus is impotent. It could never
reproduce and churn out the millions of new coronavirus cells in a
spreading infection. When it kills, it is almost out of carelessness.
Its own survival depends on sparing its victims to continue as vehicles
for its propagation.
While estimates vary widely, SARS-CoV-2 appears to kill about 0.6% of
the people it infects—about six times that of a typical flu. By
comparison, two other human coronaviruses are far more lethal but harder
to contract. SARS-CoV, the original SARS in the 2003 outbreak, has a
case fatality rate of 9.6%, while MERS, which stands for Middle East
respiratory syndrome, which was first reported in 2012, has an even
higher case fatality rate of 34%.
But the current coronavirus causes serious symptoms in many of its
victims. As David Hui, a respiratory disease expert at the Chinese
University of Hong Kong, said, it is “mild, until it decides to become
nasty.” He said the effects were severe in approximately 20% of the
people it afflicts.
Investigators quickly realized that SARS-CoV-2 usually seeks out type II
lung cells in the people it hijacks. These coat membranes lining the
nose, throat and sinuses, and deep into the lungs. The coronavirus pries
the cells open with a molecular structure called a spike protein that it
uses like a crowbar to force entry.
In images that scientists made to study it, the round virus bristles
with spikes. The spike protein locks onto a receptor called the
angiotensin-converting enzyme 2, or ACE-2, which typically regulates a
protein that increases blood pressure and inflammation. The receptors
seem to be more numerous among older people and higher generally among
men than women.
Researchers at the Francis Crick Institute in London used a technique
called cryo-electron microscopy to compare this structure to the spike
protein of a bat coronavirus most like that of SARS-CoV-2. They saw
subtle differences in the spike of SARS-CoV-2 that make it able to bind
about 1,000 times more tightly to a human cell than the bat virus, the
scientists said.
How SARS-CoV-2 Multiplies: The virus uses its spike protein to attach to
a receptor called the ACE-2 in a human cell and pries its way inside.
The virus then injects its RNA into the human cell’s nucleus and takes
over. The viral RNA uses the host cell to replicate itself. New virus
cells are released, sometimes destroying the host cell in the process.
(Source: Genome.gov)
Once inside a human cell, the new coronavirus has a rare ability to
silence alarms that would normally alert the immune system to mobilize
antibodies and virus-killing cells, according to microbiologists at the
Icahn School of Medicine at Mount Sinai, New York. To do so, it makes
special proteins that interfere with the cell’s surveillance system,
scientists at the University of Minnesota reported in May.
Bewildering complications
Doctors who first encountered it diagnosed it as a respiratory virus.
They looked for symptoms of fever, cough and shortness of breath. But
Covid-19 triggered bewildering complications.
People complained of nausea or diarrhea. Some had arrhythmias or even
heart attacks. Some suffered kidney damage or liver failure. Some lost
their sense of smell or taste. Other patients turned up at clinics with
blood clots or swollen purple bumps on their toes.
In most countries where the virus triggered outbreaks, it sent people to
the hospital with delirium, blackouts, brain inflammation or strokes,
researchers at the U.K.’s Liverpool University reported in The Lancet
Neurology in July.
In a separate review, researchers at Columbia University Vagelos College
of Physicians and Surgeons found that up to a third of those infected
had neurological symptoms.
By coming into contact with this virus, “you wouldn’t know what kind of
effect a meeting with it would have: Maybe you will be unscathed, but
maybe you would die,” said the University of Oxford’s Sarah Gilbert,
whose team is developing a vaccine against the virus that is in
late-stage human trials.
Heidi Larson first met the virus when her husband started feeling
lethargic and feverish. He lost his appetite and struggled to lift a
spoon. When she touched his forehead, it burned. “But fever can mean
many things,” she said.
Prof. Larson, an anthropologist specializing in vaccines, had spent
years working around the world and has survived typhoid in Nepal and
eosinophilic meningitis in Fiji. Her husband is 71-year-old Dr. Piot,
the virus hunter who co-discovered Ebola. He was the first to run the
United Nations agency to combat AIDS, the condition caused by HIV,
before going on to head the London School, the research university
focused on public health and tropical medicine.
With no signs of Dr. Piot’s fever subsiding over the course of a week,
their suspicions began to sink in. A test confirmed: The man who had
spent his life combating viruses was now besieged by one.
By the 14th day, his fever spiking, they rushed to the emergency room
and he was immediately admitted. He had no breathing difficulties but
his oxygen saturation levels were dangerously low, a condition called
silent hypoxia. In his more lucid moments, he kept thinking: “It got me.
The virus got me.”
Dr. Piot was relieved when he was discharged. But then came a second
wave: He got chills and a form of pneumonia. He thinks his body was hit
by a so-called cytokine storm, a side effect for many victims in which
the body’s immune system goes into overdrive and attacks more than just
the invader.
Dr. Peter Piot, the head of the London School of Hygiene & Tropical
Medicine and a co-discoverer of Ebola, said we underestimated the new
coronavirus.
Photo: mike blake/Reuters
Prof. Larson tested positive for antibodies, suggesting she was also a
victim, but her symptoms were different, too: conjunctivitis and
splitting headaches.
Five months on, Dr. Piot is recovering, though he still experiences
lingering effects. They both are concerned about long-term consequences
yet to be revealed.
“This virus is really diabolical, it came like a thief in the night with
an insatiable appetite for victims to devour,” Dr. Piot said. “It
behaves unlike any other virus. It spreads through our respiratory
system because there are receptors in our noses and throats—but then it
goes through your entire body: blood vessels, the heart, every organ
could be targeted. It’s crazy.”
The virus has infected millions of people who never got sick or were
only mildly ill, which allowed it to reproduce while its victims spread
it in ever-widening circles. By contrast, those who become infected with
the Ebola virus don’t become infectious until they actually show
symptoms and usually are too sick to travel.
When researchers at the University of California, San Francisco tested
people for SARS-CoV-2 in San Francisco’s Mission District, 53% of those
infected hadn’t shown any overt ill effects.
Heart
Nervous System
Inflammation of the heart lining, heart attacks and abnormal heart rhythms.
Loss of smell and taste; seizures, strokes and hallucinations.The virus
has been detected in cerebrospinal fluid, which is found in the brain
and spinal cord.
Eye, Nose and Throat
Runny nose and conjunctivitis, an inflammation of the membranes lining
the eyeball and eyelids. The virus has been detected in eye-fluid samples.
Lungs
The replicating virus damages tiny air sacs called alveoli in the lungs.
Immune cells set off an inflammatory response against the infection, but
too much inflammation can damage lung cells and blood vessels.
1
SARS-CoV-2
infects lung
tissue
Immune
cells produce
inflammatory
proteins
2
3
Inflammation
causes damage
4
Clots form to
repair damage
Capillary
Kidneys
Blood clots in capillaries, leading to acute kidney damage.
Digestive System
Diarrhea and other gastrointestinal issues.
Cardiovascular System
Blood clots that can lead to stroke or pulmonary embolisms, and
microclots that can make it hard for lungs to oxygenate blood.
Musculoskeletal System
Muscle and joint aches; painful, purplish swelling in the toes.
In the early days of the pandemic, researchers thought children might be
less affected by the coronavirus, with lower rates of hospitalization
and few deaths. But the very young are more vulnerable than initially
suspected.
By the end of July, nearly 340,000 children in the U.S. had tested
positive for Covid-19, or 8.8% of all reported cases. No one is sure yet
how readily children transmit the virus or whether they are highly
contagious when they show no symptoms.
The virus’s own internal chemistry alone wasn’t enough to account for so
much variation of symptoms, severity and deaths.
Forensics team
There is no shortage of possible contributing causes: old age, gender,
underlying chronic diseases such as diabetes, lack of health care and
poor diet. Investigators also turned their attention to gene variations
that might make some uniquely vulnerable.
“The immune system in people is as diverse as beauty, height,
intelligence and any other human feature,” said molecular immunologist
Michel Nussenzweig at Rockefeller University in New York. “Not everybody
is the same in their ability to fight infection.”
At Rockefeller and the New York Genome Center, scientists are comparing
the entire genomes of those most severely affected by the coronavirus to
those who experience only mild symptoms—and then to the coronavirus
itself. They are part of a network in 50 countries that is studying the
new disease by analyzing the DNA from millions of people.
Like a crime scene forensics team, these scientists extract the virus
from nose swab mucus collected from the people it infected and, through
high-speed genome sequencers, reduce it to biochemical code for
analysis. Some samples are drawn from people who suffered no more than a
fever and a cough. Others come from autopsies.
At this level of molecular biology, the virus and its victim are one,
their genetic material intermingled in a tiny vial awaiting processing.
Wearing a blue mask, purple gloves and a blue lab coat, Melissa Marton,
the associate director of the New York Genome Center’s research
sequencing lab, opened a biosafety box with a razor and gingerly removed
a rack holding 94 tubes of virus samples. Each one was labeled with an
identifying bar code.
A robot sorted them behind a plexiglass barrier inside a biosafety hood
with a specialized ventilation system. The possibility for the virus to
break out at this point in processing is small but not zero. “That’s why
we take extra precautions,” she said.
Every few days, shipments of RNA from the virus and DNA from the
patients it infected arrived at the center in Manhattan’s SoHo district
from regional hospitals. The genome consortium so far has collected
1,600 samples for sequencing.
They can already tell the virus is evolving.
The four bases of virus RNA are written in an alphabet composed of
nucleotide chemicals: adenine (A), cytosine (C), guanine (G) and uracil
(U). In its rush to make new copies of itself, the virus is prone to
random errors.
“The virus changes on a fairly clockwork basis,” said computational
biologist Michael Zody at the genome center. “Every two weeks or so, it
seems that the virus picks up a new mutation.”
Melissa Marton and Robert Furatero at the New York Genome Center.
Photo: KHOLOOD EID for The Wall Street Journal
That adds up to about 25 random changes a year, much less than the
seasonal flu, which has a mutation rate of almost 50 mutations a year.
Most of the changes in the coronavirus don’t make any difference now.
In time, it is possible that some might make it easier to transmit from
person to person or become deadlier. So far, more than 1,200 natural
variations in coronavirus strains around the world have been identified.
Recently, researchers led by biologist Bette Korber at Los Alamos
National Laboratory in New Mexico identified a single change in the
30,000 chemical characters of the coronavirus RNA. In a section of code
that affects its spike protein, a single “A” had turned to “G,” the
scientists said.
That version has become more common in almost every country, compared
with the original version that first arose in Wuhan. It may have
out-competed the original strain, but may not be making patients any
sicker, the scientists said.
“Any of these mutations could functionally make the virus different,”
said Emma Hodcroft at the University of Basel in Switzerland who tracks
its global transmission. “But this virus is very young and we haven’t
seen any evidence of this happening yet. It’s only been in humans a few
months, and it’s doing very well.”
—Graphics by Kevin Hand/WSJ
—Illustration at top by Jessica Kuronen/WSJ
Write to Robert Lee Hotz at sciencejournal-at-wsj.com and Natasha Khan at
natasha.khan-at-wsj.com
--
So many immigrant groups have swept through our town
that Brooklyn, like Atlantis, reaches mythological
proportions in the mind of the world - RI Safir 1998
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