COVID-19 NEWS
that. So we wondered, what’s in these plugs? And it turns out
they’re mainly made up of fibrin, which is exactly what a clot is
made up of.”
“It was all clot with no red cells,” Dr. White adds. “Pure fibrin.”
MUSTARD GAS, SINGLE VENTRICLE HEART
DISEASE AND COVID-19
Funded via CounterACT, a National Institutes of Health-sponsored
counter-terrorism program, Drs. White and Veress specialize
in studying the effects of inhaled chemical weapons and toxic
industrial agents.
“We use our clinical knowledge to understand the injury patterns,
and then we come back to the lab and study animal models,”
says Dr. Veress. “Then we start testing therapies based on what’s
already on the shelf and FDA-approved.”
Some years ago, studying mustard gas inhalation, Drs. White and
Veress noted the persistent presence of a white clot-like substance
in the airways. It looked a lot like plastic bronchitis, rubbery white
strands patients would sometimes cough up after the Fontan
operation, a surgery that reroutes circulation to descend through
the lungs before returning to the heart in patients with singleventricle
heart disease.
“We remembered having these kids in the PICU and having no way
to treat them,” says Dr. Veress. “We’d go in with a bronchoscope to
pull these plugs out of the airways so patients could breathe, but
they’d just come right back. Our animal model looked exactly like
It stood to reason then, that a clot-busting drug might be
effective. After some experimentation, they settled on a
plasminogen activator, plasmin being an important factor
in the breakdown of fibrin. They’re typically administered
intravenously. Dr. Veress had the idea to administer it directly
to the lungs. (For severe cases, they use a bronchoscope to
deliver it.)
The results were striking (5). After dosing an animal model with
mustard gas, the mortality rate for those who didn’t get the
treatment was 100%. Of those that got it, 100% survived.
“It absolutely reversed the acute injury,” says Dr. Veress.
It didn’t take long before the therapy was being tested on
plastic bronchitis after the Fontan operation, with positive
results (6). And it turns out that clotting and fibrin buildup
in the lungs is a complication of many forms of respiratory
distress — including COVID-19.
In fact, preliminary studies have shown that, in patients with
acute COVID-19, aerosolized plasminogen activators were
an effective method of reducing mortality. Dr. Veress helped
published a case report on that in the Journal of Thrombosis
and Haemostasis in July (7).
1. Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin
Immunol. 2020;215:108427. doi:10.1016/j.clim.2020.108427
2. Sriram K, Insel PA. A hypothesis for pathobiology and treatment of COVID-19:
The centrality of ACE1/ACE2 imbalance [published online ahead of print,
2020 Apr 24]. Br J Pharmacol. 2020;10.1111/bph.15082. doi:10.1111/bph.15082
3. Smith JC, Sausville EL, Girish V, et al. Cigarette Smoke Exposure and
Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor
ACE2 in the Respiratory Tract. Dev Cell. 2020;53(5):514-529.e3. doi:10.1016/j.
devcel.2020.05.012
4. Giaha SM, Cheng J,Halpern-Felsher B. Association Between Youth Smoking,
Electronic Cigarette Use, and Coronavirus Disease 2019. J Ado Health. 2020;
doi.org/10.1016/j.jadohealth.2020.07.002
5. Veress LA, Anderson DR, Hendry-Hofer TB, et al. Airway tissue plasminogen
activator prevents acute mortality due to lethal sulfur mustard inhalation.
Toxicol Sci. 2015;143(1):178-184. doi:10.1093/toxsci/kfu225
6. Wakeham MK, Van Bergen AH, Torero LE, Akhter J. Long-term treatment
of plastic bronchitis with aerosolized tissue plasminogen activator in a
Fontan patient. Pediatr Crit Care Med. 2005;6(1):76-78. doi:10.1097/01.
PCC.0000149320.06424.1D
7. Wang J, Hajizadeh N, Moore EE, et al. Tissue plasminogen activator (tPA)
treatment for COVID-19 associated acute respiratory distress syndrome
(ARDS): A case series. J Thromb Haemost. 2020;18(7):1752-1755. doi:10.1111/
jth.14828
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