Mitigating lung damage, mortality due to SARS-CoV-2
Pre-clinical study shows potential of drugs that target specific immune pathways

Date:
October 5, 2021
Source:
University of Illinois at Chicago
Summary:
Researchers report that a drug approved for treating patients with
autoimmune disease helped to prevent lung damage and death in mice
infected with the SARS-CoV-2 virus, which causes COVID-19 in humans.



FULL STORY ==========================================================================
In a new paper, researchers at the University of Illinois Chicago report
that a drug approved for treating patients with autoimmune disease helped
to prevent lung damage and death in mice infected with the SARS-CoV-2
virus, which causes COVID-19 in humans.


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The results of their study provide strong evidence that inflammatory
lung vascular leakage -- or leaky lungs -- is a key feature of COVID-19 illness.

Vascular leakage can be caused by severe inflammation and results in a
buildup of fluid in the lungs, which interferes with oxygen uptake. Mice infected with SARS-CoV-2 showed very clear and early signs of leakage
from the blood vessels of the lung.

The research also suggests targeted drug treatments that suppress only
select immune system pathways, like the rheumatoid arthritis drug used
in the study that targets the molecular receptor called IL-1, might be
a more suitable therapy for COVID-19 patients than drug treatments that suppress the entire immune system.

The study was led by senior author Asrar Malik, head of the department
of pharmacology and regenerative medicine at the College of Medicine,
and by co- senior author Jalees Rehman, professor of medicine in the
department of pharmacology and regenerative medicine.

"With COVID-19, we need to strike a balance. On the one hand, we need a
strong immune system to eliminate the virus. On the other hand, several
studies suggest that in patients with severe COVID-19, the immune system
can go overboard and even cause damage to our own body," Rehman said. "So, while we need the immune system to work efficiently, we also need to
prevent it from becoming hyperactive and causing collateral damage."
The need for balance is why the UIC researchers decided to study the
effects of a drug that works on only one targeted immune system pathway
and see if that would help prevent SARS-CoV-2-induced leaky lungs.



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For the study, the researchers observed mice infected with the virus and tracked the progression of illness. They saw that the mice quickly showed symptoms like weight loss, fluid buildup in the lungs from leaky lung
blood vessels, and even indicators of lung scarring, such as increased
collagen levels in lung tissue.

"This is important evidence that blood vessel leakage in the lungs is
a key feature of severe COVID-19 and that treatments which prevent or
reduce vascular leakage warrant further study," Rehman said.

The researchers also treated some of the mice with the approved autoimmune disease drug, called anakinra, to block the IL-1 receptor, a key molecule regulating inflammation.

"We saw that the mice who received the drug had reduced signs of disease
- - including less lung fluid buildup and less scarring of the lungs --
and better survival," Rehman said.

Rehman said these findings pave the way for helping COVID-19 patients
and illuminate the need for more research on targeted, personalized
treatments.

"Obviously, the best approach to reducing short-term and long-term
damage as a result of COVID-19 is to get vaccinated and reduce the risk
of SARS-CoV- 2 infection as well as the risk of severe disease. However,
the hesitancy of many individuals to get vaccinated as well as the lack
of access to vaccines in many parts of the world means that we will
continue to see patients with severe COVID-19 in the near future. Our
results suggest that it is possible to identify a select a vulnerable
COVID-19 patient population that is most likely to benefit from this
therapy," Rehman said.

In their paper, "Interleukin-1RA Mitigates SARS-CoV-2-Induced Inflammatory
Lung Vascular Leakage and Mortality in Humanized K18-hACE-2 Mice,"
the researchers hypothesize that by assessing the level of certain
inflammatory signals in patients, such as the activation of the IL-1
receptor pathway, scientists could identify when a patient's immune system might be heading into overdrive and use a targeted immunosuppressant,
like anakinra, to keep inflammation at the right balance.

"It is important to get the right drug to the right patient at the
right time, and this study shines a light on a path forward for clinical
trials that are investigating this drug and others that target specific components of the immune system," Rehman said.

Co-authors of the study, which is published in the journal
Arteriosclerosis, Thrombosis, and Vascular Biology, are Shiqin Xiong,
Lianghui Zhang, Justin Richner and Jake Class, all of UIC.

========================================================================== Story Source: Materials provided by
University_of_Illinois_at_Chicago. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Shiqin Xiong, Lianghui Zhang, Justin M. Richner, Jake Class, Jalees
Rehman, Asrar B. Malik. Interleukin-1RA Mitigates SARS-CoV-2-Induced
Inflammatory Lung Vascular Leakage and Mortality in Humanized
K18-hACE- 2 Mice. Arteriosclerosis, Thrombosis, and Vascular
Biology, 2021; DOI: 10.1161/ATVBAHA.121.316925 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211005101918.htm

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