Anatomy of a Killer
What the Coronavirus Does Inside the Body
SARS-CoV-2 does much more damage to the human body
than initially assumed. It can attack any number of organs and even penetrates
the brain. But why do some people experience worse symptoms than others?
By Philip
Bethge
15.05.2020,
11.01 Uhr
The
pathogen has already done a fair bit of damage. It has only been five days
since the patient began exhibiting typical COVID-19 symptoms, but already,
menacing shadows can be seen in the CT scans of the lungs.
"It's
like frosted glass," is how Christian Strassburg, a professor of internal
medicine at the Bonn University Hospital, describes the changes made visible by
the scan. "The lung tissue is saturated with fluid." Secretions and
dead cells are gumming up the walls of the pulmonary alveoli "like Jell-O,"
he says.
"It is
extremely difficult for oxygen to permeate a layer like that to get from the
lung into the bloodstream," the professor explains. It is a phenomenon he
has been seeing frequently in recent weeks and it is caused by the novel
coronavirus, SARS-CoV-2. The number of confirmed COVID-19 patients worldwide is
now well over 4.2 million and the number of deaths is approaching 300,000.
Meanwhile, doctors and biologists are doing all they can to gain a better
understanding of the pathogen behind the pandemic.
SARS-CoV-2
behaves differently than almost any other virus that humans have faced before,
and even now, several months into the pandemic, there is disagreement as to
what percent of COVID-19 patients experience severe symptoms. Estimates tend to
come in at around 5 percent of all infections. And in those cases, the virus
unfolds unfathomable destructive power.
The
epicenter of such infections is almost always the lungs. But as medical
professionals now realize, the virus can also affect other organs and tissues -
including the heart, the brain, the kidneys and the bowels. In the worst case,
the body begins attacking itself. When the immune system spins out of control
like that, doctors call it a "cytokine storm," and when patients die
as a result, multiple organ failure tends to be the cause.
Over 100
vaccine candidates are currently being developed worldwide to combat
SARS-CoV-2, but in the worst-case scenario, it could take years before a
vaccine is available. Until it is, the virus will still be with us. Even if the
pandemic does weaken a bit, experts believe a second wave is just around the
corner.
Early talk
of COVID-19 as being mostly a mild illness has been proven to be
"dangerously false," Richard Horton, editor-in-chief of the medical
journal The Lancet, has written. At the bedside, he says, it is "a story
of terrible suffering, distress and utter bewilderment." U.S. cardiologist
Harlan Krumholz described the ferocity of COVID-19 in the magazine Science as
"breathtaking and humbling." The disease, he continued, "can
attack almost anything in the body with devastating consequences."
The best
way to learn more about SARS-CoV-2 is to start small. Coronaviruses are a mere
160 nanometers in size. In order to multiply, the tiny pathogens are reliant on
the cells belonging to a different organism.
The novel
coronavirus likely comes from bat viruses, and it is thought that, even before
it made the jump to humans, it developed the mechanism allowing it to bind with
human cells. Some bat viruses are able to bind to a receptor called ACE2. This
molecule can be found on the surface of human cells and helps regulate blood
pressure. But it also functions as a kind of doorway to the interstices of the
cell, and viruses that have the key can get inside.
Researchers
believe that bats carry around 3,200 different coronaviruses. Chance, time and
opportunity fueled the creations of the SARS-CoV-2 virus, which ultimately
managed to jump to humans.
The Attack
But how
exactly does the virus find its way into the human body? Internal medicine
professor Strassburg is quite familiar with the process. At the Bonn University
Hospital, he is currently in charge of between 10 and 20 COVID-19 patients. On
one day recently, eight of them were intubated, having become so ill that they
were forced to rely on ventilators. "Luckily, that is the minority,"
Strassburg says. "Most of those infected by the virus get away with only
mild symptoms."
Early on,
virologists thought that the novel coronavirus would spread only slowly, in
part due to the similarities between SARS-CoV-2 and the SARS coronavirus that
appeared in China in 2002. From November 2002 and July 2003, almost 800 people
died of the disease, the full name of which is Severe Acute Respiratory
Syndrome. But then, the epidemic disappeared. It was a stroke of luck for
humanity: That pathogen appears to have been more deadly than SARS-CoV-2, but
it focused its attentions on the lungs. The virus multiplied deep within the
body, making it less contagious. Furthermore, it was easy to identify and
isolate those who had fallen ill from the virus.
Experts
initially hoped that the same would hold true of SARS-CoV-2, but they were
mistaken. The novel coronavirus doesn't just attack the lungs. Throat swabs
from patients revealed early on that the pathogen first goes after the mucous
membrane in the upper respiratory tract.
That is
advantageous for the virus. The distance from one throat to another throat is
much shorter than the distance from one person's lung to another. "That
means that those carrying the virus are highly contagious," says
Strassburg. A huge number of the viruses are found in the nasal cavity and
pharynx, "even in people who aren't yet experiencing symptoms," he
adds, "which is why the pathogen was able to circle the globe so
quickly."
There are
three stages in the attack on the human body. Initially, the coronavirus binds
with club-shaped protein complexes on the ACE2 receptors of human cells. That
opens up the host cell and allows genetic material from the pathogen to enter.
The virus then converts the cell into a virus factory. Huge numbers of viruses
thus produced then leave the host cell and attack other cells.
The
resulting viral load is enormous, particularly in the first week following
infection. And initially, there are hardly any symptoms. Often, there is merely
a dry cough, says Strassburg, with the body's temperature hardly rising at all.
"Even patients who are more severely affected generally have a temperature
below 38 degrees Celsius (100.4 degrees Fahrenheit)." That is a
significant difference to the flu: "For influenza, a sudden rise in
temperature is typical, along with a distinctive feeling of being sick. But
that's not the case here."
In this
initial phase of the illness, much depends on the patient's immune system.
Immune cells attack the invaders, but because the body isn't yet familiar with
the virus, the weapons at their disposal are relatively basic.
A battle of
attrition ensues, one that determines whether the patient will quickly recover
or whether the disease will get the upper hand. Will the immune system stop the
attack in the upper respiratory tract? Or will the pathogen be able to find its
way into the lungs? The answers to those questions determine whether the
illness becomes life threatening or not.
Researchers
are still trying to figure out why the virus is able to reach the lungs of some
patients but is stopped short in others. One of the factors appears to be the
number of pathogens that attack the body at the beginning. More than anything,
though, patients with underlying medical conditions seem to have the most to
fear from SARS-CoV-2. According to estimates, about a quarter of the population
in Central Europe has such an underlying condition.
Those at
risk include people suffering from obesity, diabetes and high blood pressure.
And smokers: "Their mucous membranes and lung ventilation are already
impaired," says Strassburg. Tiny hair-like projections known as cilia,
which normally help keep pathogens and mucous out of the lungs and respiratory
tract, no longer function appropriately.
In such
cases, there are hardly any hurdles for the virus on the way to the lungs.
Gravity is sufficient for the tiny pathogens to reach their target. Once the
virus advances into the smaller, branch-like bronchioles, it meets a
particularly vulnerable layer of cells, the membranes of which are also covered
with ACE2 receptors. Directly in the pulmonary alveoli, the tiny sacs where
oxygen is transferred into the bloodstream, SARS-CoV-2 finds perfect
conditions.
The
Defensive Battle
To depict
the precise damage the virus does in the lungs, thoracic surgeon Keith Mortman
of George Washington University Hospital in Washington, D.C., turned to
computer modelling. The 3-D imagery from the clinic shows the lungs of a man in
his late 50s. Yellow-tinged deposits can be seen in many areas within the
organ.
"The
damage we are seeing is not isolated to any one part of the lung," says
Mortman. Initially, he says, the patient experienced a fever and a cough,
before then developing serious breathing difficulties. He was intubated and
attached to a ventilator, but when that proved insufficient, he was hooked up
to a so-called ECMO machine.
The machine
infuses blood with oxygen outside of the body before pumping it back inside.
The hope is that the procedure will give the lungs the time they need to
recover.
Doctors now
have a deeper understanding of how SARS-CoV-2 damages lung tissue. White blood
cells discover the virus and attract other immune cells to the site, which
attack the infected lung cells and kill them. They leave behind cell detritus,
which clog up the alveoli. If the body isn't able to gain control over the
reaction to the infection, acute lung failure looms.
But other
organs can also be damaged as a result of the infection. The more SARS-CoV-2
patients are treated around the world, the clearer it has become just how
comprehensive the attack staged by the virus is.
According
to data from China, around 20 percent of patients requiring hospitalization
suffer damage to the heart. It remains unclear whether the virus goes after
heart muscle cells directly or if damage to the coronary blood vessels is to
blame. The blood clotting function is also disrupted, leading to clumps that
could result in heart attacks, lung embolisms and strokes.
The kidneys
of some hospitalized patients also come under attack, as evidenced by blood or
protein in urine samples. As a result, dialysis machines have had to join
ventilators in ICUs devoted to treating COVID-19 patients.
Doctors
have likewise observed brain inflammation and seizures in some patients. The
virus apparently advances all the way into the brain stem, where important
control centers are located, such as the one responsible for breathing. The
virus likely gets to the brain via the mucous membrane inside the nose and the
olfactory nerve. This could also be the reason that many patients temporarily
lose their sense of smell.
SARS-CoV-2
can also attack the digestive tract, with patients complaining of bloody
diarrhea, nausea and abdominal pain.
Doctors
have also reported a possible link between COVID-19 and a rare blood vessel
syndrome in children called Kawasaki Disease. In Britain, the disease has even
killed a few children who became infected with SARS-CoV-2. The disease involves
the inflammation of blood vessels throughout the body and can damage the heart.
Doctors now
believe that SARS-CoV-2 attacks tissue and organs virtually everywhere in the
body. And the disease can also apparently leave behind long-term damage.
Chinese researchers have examined the blood of patients and found that even
after the infection has passed, certain blood values remain abnormal for an
extended period. Despite the virus no longer being present in the body, for
example, their livers still don't exhibit normal functionality.
The lungs,
too, likely suffer lasting damage in severe cases. "When inflammation does
not subside with time, then it becomes essentially scarring in the lungs,
creating long-term damage," says Mortman, the doctor from George
Washington University Hospital.
It is still
too early for a comprehensive understanding of the long-term consequences of
COVID-19. But doctors are familiar with cytokine storms and acute lung failure
from other severe infections. Some of the survivors of the first SARS epidemic,
for example, experienced limited lung functionality for up to 15 years after
the illness.
Life or
Death?
But why do
some people emerge virtually unscathed from this multifaceted attack while
others do not? Thus far, researchers do not have an answer to this question.
There are indications that the virus - similar to the pathogen that causes AIDS
– is able to attack certain white blood cells, thus damaging precisely that
line of defense that is supposed to stop the infection.
Are some
patients more susceptible than others to that phenomenon for genetic reasons?
The biotechnology company 23andMe intends to comb through the DNA of its 10
million customers in the search for sequences that could be predictive of their
susceptibility to severe COVID-19.
Until the
question is answered for sure, however, most patients can continue to rely on
hope. After all, most people do not experience severe symptoms from the
disease. "Among patients without underlying conditions, even severe cases
have an 80 percent survival rate," estimates Christian Strassburg, the
internal medicine specialist. Still, it is by no means time to let down our
guard, he says, particularly now that restrictions on public life are
increasingly being lifted. "The danger remains extremely high that a large
number of patients will soon have to be treated in hospitals."
That will
heap even more pressure on doctors and nurses. The condition of some patients,
after all, can worsen dramatically within just a few days.
Should
death be the ultimate result, it is often not the virus itself that causes it,
but the immune system of the infected patient, which can disastrously overreact
and attack the body.
In such
instances, huge numbers of so-called cytokines are released. These chemical
signaling molecules produced by the body trigger a cascade of biochemical
reactions that affect the immune system. The development of a fever accelerates
the metabolism and helps kill the virus. Blood vessel walls are made more
permeable, allowing easier access for immune cells, such as phagocytes, to
attack the virus. The heartrate speeds up.
"The
reaction is actually quite sensible," says Strassburg. But in cases of
severe infection, the immune system can overreact and trigger a cytokine storm.
"The
result is a reaction that looks like a massive blood infection, but isn't
one," says Strassburg. It can lead, however, to multiple organ failure.
"If the immune system overreaction to the pathogen continues for too long
or is too severe, it will kill the body."
Vast
destruction is the result, as pathologists can attest. Johannes Friedmann is a
professor at Lüdenscheid Hospital just south of Dortmund and has examined the
bodies of several patients who succumbed to COVID-19. In the alveoli of these
patients, he has found epithelial cells in the lung that have been "scaled
off" in addition to protein "deposits" in the blood resulting
from blood vessels that have become permeable. He has also discovered cells
with multiple or enlarged nuclei, a phenomenon that is typical of viral
illnesses.
The walls
of the vast majority of the alveoli in the lungs are "widened to many
times their normal thickness," Friemann says, adding that the lungs of
many COVID-19 casualties are "insufficiently inflated." That impedes
oxygen transfer.
Friemann's
findings have been consistent with those of medical professionals in Hamburg,
the United States, Switzerland and elsewhere: Most of those who died were sick
before they came into contact with SARS-CoV-2. Friemann has found cases of
liver cirrhosis, severe arterial sclerosis and extremely high blood pressure.
Did these
patients die of SARS-CoV-2 or from other maladies? "You can't live with
such a lung, so I would point to the virus as being the cause of death,"
says Friemann. "Many of these people would still be alive without the
infection."
Indeed, a
recent calculation by British epidemiologists casts significant doubt on claims
that most COVID-19 victims would have died soon anyway. They found that female
victims of the disease lose an average of 11 years of life. For men, the
number was 13 years.
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