..............................................................................................................................................................
Smokers And COVID-19
Why COVID-19 hits smokers harder
smokers already
face a heightened risk of catching viral infections, likely due to their having
depressed immune systems, tissue damage and chronic inflammation in the
respiratory tracts
By Nicoletta Lanese - Staff Writer
Smokers may be prone to severe COVID-19 infections, in part,
because their lungs contain an abundance of entry points that the virus can
exploit.
COVID-19 infections begin at the ACE2 receptor, a protein
nestled on the surface of cells throughout the body, including in the upper and
lower respiratory tracts.
The coronavirus that causes COVID-19, known as SARS-CoV-2,
must plug into the ACE2 receptor in order to inject its genetic material into
cells, replicate and spread.
Now, preliminary research suggests that lungs exposed to
cigarette smoke accumulate abnormally large numbers of ACE2 receptors, which
may leave the organ vulnerable to damage inflicted by the coronavirus.
"It has been reported that smokers
who get COVID-19 tend to have more severe infections than individuals who
aren’t smokers," co-author Jason Sheltzer, a research
fellow at the Cold Spring Harbor Laboratory in New York, told Live Science in
an email.
An increase in ACE2 receptors "could
be one reason — of many — why smokers get so sick from coronavirus," he
said.
The study, posted March 31 to the preprint database bioRxiv,
has not been peer-reviewed and its premise remains "fairly
speculative," said Dr. Stephanie Christenson, an assistant professor
in the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine at
University of California, San Francisco, who was not involved in the study.
"If ACE2 expression is high, if
ACE2 expression is low, and what that means toward your overall prognosis — I
don't think we actually know that yet,"
Christenson told Live Science.
"Smoking does a lot of things to
the body," Sheltzer added. "And it’s
possible that [smoking's] effect on ACE2 levels isn’t the most important
factor."
Smoking linked to severe infection
Mounting evidence suggests that, compared with nonsmokers,
people who smoke cigarettes face a higher risk of developing severe
complications and dying from COVID-19 infections.
For instance, a study of more than 1,000 patients in China,
published in the New England Journal of Medicine, found that smokers with
COVID-19 were more likely to require intensive medical interventions than those
who didn't smoke.
In the study, 12.3% of current smokers were admitted to an
ICU, were placed on a ventilator or died, as compared with only 4.7% of nonsmokers.
Smokers may be particularly vulnerable
to COVID-19 for several reasons, but the ACE2 receptor hypothesis "provides
a holistic, mechanistic link" between smoking and severe infection,
Jaber Alqahtani, a researcher in Respiratory Medicine at University College
London, told Live Science in an email.
If future research bolsters the link between receptor
quantity and disease severity, drugs that block or reduce the sensitivity of
ACE2 receptors could potentially be used as treatments, he added.
More gateways into the lung
To draw the connection between ACE2 receptors and smoking,
Sheltzer and software engineer Joan Smith, a member of Sheltzer's lab, examined
lung and respiratory tissue samples from deceased mice, rats and humans, as
well as samples collected during human lung surgeries.
The number of ACE2 receptors in the lungs did not vary
between rodents of different ages or different sexes, and the same trends
appeared in humans.
As age and sex appeared unrelated to ACE2 quantity, the
researchers wondered if cigarette smoke exposure might make a difference.
The team inspected tissue samples from mice that had been
exposed to diluted cigarette smoke for zero, 2, 3 or 4 hours a day over the
course of five months.
They found that, the more smoke exposure, the more ACE2 receptors
studded the animals' lungs.
Compared with unexposed mice, the mice that received the
highest dose of cigarette smoke accumulated about 80% more ACE2 receptors in
their lungs.
The researchers then compared the lungs of human smokers
against those who never smoked, and again, they found a similar trend: Smokers’
lungs contained 40% to 50% more ACE2 receptors than those of nonsmokers.
The quantity of ACE2 receptors varied by pack-years — a
measure of how many packs of cigarettes a person smoked per day multiplied by
the number of years the person smoked.
For example, among smokers who had undergone thoracic
surgery, people who smoked more than 80 pack-years showed a 100% increase in
ACE2 receptors compared with people who smoked fewer than 20 pack-years, the
authors noted.
While smoke-exposed tissues harbored more ACE2 receptors,
the team could not tell which specific cells contained the receptor.
By examining which proteins appeared in what cells, the team
found that ACE2 appeared on cells that process oxygen and carbon dioxide in the
lungs, known as alveolar type 2 cells.
But primarily, the receptors appeared on cells that secrete
a mucus-like fluid into the respiratory tracts, known as goblet and club cells.
Nonsmokers carry most of their goblet and club cells in
their nose and throat, but in smokers, the cells begin to accumulate also in
the lungs, the authors found.
"What they're suggesting is that
when you smoke you have an increase in goblet cells [in the lower respiratory
tract], and that's definitely true,"
Christenson said.
Evidence that smoking boosts the number of secretory cells
in the lungs has been reported for decades, according to a 1999 report in the
American Journal of Respiratory and Critical Care Medicine.
The sticky mucus generated by goblet and club cells acts as
a protective barrier, capturing debris, aerosols, smoke and pathogens that get
sucked into the respiratory system, Christenson said.
When people inhale smoke into their lungs, the organ
reinforces its defenses by building more secretory cells and increasing mucus
production.
The same process occurs in individuals exposed to high
levels of air pollution, Christenson said.
Still a hypothesis
While high numbers of goblet and club
cells, laden with ACE2 receptors, may explain why smokers fall severely ill of
COVID-19, the exact relationship between ACE2 and disease prognosis "remains
to be demonstrated," Sheltzer and Smith noted.
Smoking is associated with many comorbidities — multiple
medical conditions that appear simultaneously — including emphysema and
compromised immune function, which likely exacerbate COVID-19 infections, they
wrote.
In general, smokers already face a heightened risk of
catching viral infections, likely due to their having depressed immune systems,
tissue damage and chronic inflammation in the respiratory tracts, Christenson
added.
High ACE2 levels may not be unique to smokers, but instead
may be common among people with lung conditions, in general, the authors noted.
The team did analyze tissue samples from patients with
asthma and the inflammatory disease sarcoidosis, however, and these did not
contain abnormal quantities of the receptor.
To tease out how ACE2 levels relate to lung disease, in
general, future research could focus on patients with chronic obstructive
pulmonary disease (COPD), bronchitis, pneumonia or lung diseases triggered by
bacterial, viral or fungal infections, Alqahtani said.
If they also have elevated levels of ACE2 receptors on their
cells, that could help clarify whether cigarette smoke poses a singular threat
to COVID-19 patients, or if other lung conditions present risks for the same
reason.
If smoking does prove uniquely dangerous for COVID-19
patients, however, the study does offer a potential solution.
"We show that former smokers have
lower levels of ACE2 than current smokers" — about 30% lower, Sheltzer said.
"It’s conceivable that quitting
smoking could be beneficial to decrease COVID-19 susceptibility, for multiple
reasons."
"Indeed, it also allows us to
consider campaigns and programs aimed at helping smokers quit as a preventative
strategy going forward,"
Alqahtani added.
Nicoletta Lanese is a science journalist and dancer who aims to bring
science to new audiences, whether in print or on stage. She holds degrees in
neuroscience and dance from the University of Florida and a graduate
certificate in science communication from the University of California, Santa
Cruz. Brains are her beat. Follow her on Twitter @NicolettaML.
No comments:
Post a Comment