“In a lot of chemical labs there’s no link to the human world,” says
Dr. Veress. “The models we create are very human disease relevant.”
Their latest model: a robot that vapes.
Designed by research partners in Canada and manufactured in
China, the robot, the first of its kind, was originally commissioned
to study EVALI, the outbreak of acute lung injuries associated with
vaping. That disease turned out to be the result of an additive in
some marijuana vaping devices sold on the street.
But just as soon as the mystery of EVALI resolved, another new
and dangerous potentially complicating factor of vaping came
up: COVID-19.
THE DOORS OF INFECTION
Every virus comes with a key, an appendage of protein that unlocks
some structure within the cell. For SARS-CoV-2, that structure is
ACE2, a receptor protein on the surface of epithelial cells. It’s the
door that lets the virus inside.
Generally speaking, the cellular function of ACE2 is to break up a
large protein called angiotensin II, or ANG II, which is generated by
another protein called ACE. ANG II promotes vasoconstriction and
inflammation of the epithelia, which line mucous membranes like
those in the nose, mouth and lungs — including the alveoli, the air
sacs that facilitate gas exchange and oxygenate the blood. ACE2
breaks it into smaller proteins that counteract those effects.
“Basically, ACE and ACE2 have a yin-yang kind of relationship,”
Dr. White observes.
One prominent hypothesis for the pathology of COVID-19 is that
the SARS-CoV-2 virus throws the two out of balance (2). The
mechanism carries increased risk for cigarette smokers, because
smoking seems to increase the gene expression of ACE2. In fact,
smokers produce 30 to 55% more ACE2 than nonsmokers (3).
“ACE2 is the receptor, so it’s possible that making more targets for
the virus, you could get a more severe infection and a bigger viral
load,” says Dr. White. “You look at the population that goes into
intensive care or has respiratory distress to the extent they need a
ventilator, if you’re a smoker your odds are at least 2 to 1.”
And new research out this summer shows that adolescents who
vape are five times as likely to be diagnosed with COVID-19 — close
to seven times as likely if they’ve reported vaping within 30 days (4).
But the mechanism remains to be studied.
A MECHANISM FOR ANSWERS
Sixty miles north of Drs. White and Veress’s lab, in Ft. Collins,
Colorado, the Infectious Disease Research Center at Colorado
State University is chasing down one of the world’s most promising
leads for a COVID-19 vaccine. The technology, called SolaVAX,
inactivates viruses using a combination of riboflavin and UV light.
It’s already been validated on other coronaviruses. They’re making
fast progress on SARS-CoV-2.
“Their team has some highly reputed virologists who have been
studying SARS and MERS and all these precursors of COVID-19 for
years,” says Dr. White. “They know how to handle them. And they
have a lot of experience with animal models.”
That’s key, because in certain small animal models ACE and ACE2
operate in much the same way as they do in humans. But an animal
model that tests the effects of a virus coupled with the effects of
a behavior is complicated: You have to find a way to replicate the
behavior first. That’s where the robot comes in.
“It’s programmed for pull times, dwell times, volume of air,” says Dr.
White. “All this is based on published studies developing inhalation
patterns that mimic how humans vape.”
Dr. White and Veress’s study calls for two variations: chronic
vaping, where the models will get “vaped” multiple times a day for
three weeks, and acute, which is based on patient reports of vaping
behavior. A teen might not vape every day, but they might go to a
party and vape all night — and might contract COVID-19 at that
same party.
After the model is vaped, it goes to Ft. Collins, where it’s inoculated
with SARS-CoV-2 virus by CSU’s Angela Bosco-Lauth, DVM, PhD,
and her virology team. Pathology tends to be at its worst around
day six or seven, so they’ll monitor for a week.
The study stands to answer some crucial questions regarding the
relationship between smoking, vaping, and COVID-19, and perhaps
even the mechanism of COVID-19 itself. Does vaping increase
the expression of ACE2, as it does in smoking? Does increased
ACE2 expression in fact lead to a higher viral load? And is there a
through-line from increased ACE2 to worse pathology? If so, the
study could offer insight on potential treatment options, such as
angiotensin receptor blockers, which inhibit the action of ANG II.
“Ultimately,” says Dr. White. “This could answer those kinds of
questions.”
And in the midst of the pandemic, the answers are more crucial
than ever. •
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