Inflammation in the lungs combined with high viral loads of the novel coronavirus create a perfect storm for obese patients with COVID-19, scientists say

Date:
September 16, 2020
Source:
UT Southwestern Medical Center
Summary:
Conditions related to obesity, including inflammation and leaky
gut, leave the lungs of obese patients more susceptible to COVID-19
and may explain why they are more likely to die from the disease,
scientists say.

They suggest that drugs used to lower inflammation in the lungs
could prove beneficial to obese patients with the disease.



FULL STORY ========================================================================== Conditions related to obesity, including inflammation and leaky gut,
leave the lungs of obese patients more susceptible to COVID-19 and may
explain why they are more likely to die from the disease, UTSW scientists
say in a new article published online in eLife. They suggest that drugs
used to lower inflammation in the lungs could prove beneficial to obese patients with the disease.


========================================================================== COVID-19, caused by the novel coronavirus SARS-CoV-2, varies widely
in clinical severity: Some patients are asymptomatic while others have devastating forms that have led to more than 905,000 deaths worldwide.

Several pre-existing conditions have been shown to increase the risk
of COVID- 19 severity, including obesity and Type 2 diabetes -- two
conditions that often go hand-in-hand, says Philipp Scherer, Ph.D.,
director of the Touchstone Center for Diabetes Research and a professor
of internal medicine and cell biology at UT Southwestern.

For example, he highlights the Dallas County data that reports the
disturbing fact that 47 percent of patients who have died from COVID-19
from March to August had diabetes. In addition, 31 percent of patients hospitalized with COVID-19 in the county during that same period had
diabetes and 17 percent were obese without diabetes (see graphic).

Correlations have been found in many other countries between obesity and
COVID- 19 deaths. However, the mechanisms behind why obesity contributes
to severe COVID-19 are unknown.

Scherer and his colleagues, including Manasi Shah, M.D., an endocrinology fellow at UTSW, and Ilja L. Kruglikov, Ph.D., Dr.Sci., a researcher at Wellcomet GmbH in Karlsruhe, Germany, explore this phenomenon in the
new opinion piece.



==========================================================================
One idea for the increased risk, they suggest, is that fat has high
amounts of ACE2 receptors, entryways for the SARS-CoV-2 virus on
cells. The increased numbers of these receptors in obese patients could
lead to a higher viral load, a factor thought to lead to poor outcomes
for COVID-19 patients.

These ACE2 receptors can be shed into circulation and end up in the lungs, specifically increasing SARS-CoV-2 concentration in lung tissue. In
addition, the increased ACE2 expression in obese individuals spurs an
imbalance in chemical signals that induce inflammation, fibrosis, and
leaky blood vessels, all of which have the potential to cause a more
severe COVID-19 infection.

However, Scherer and his colleagues note other conditions linked
with obesity are even more powerful contributors to increased disease
severity. One of these is a higher overall inflammatory state that tends
to accompany obesity, which primes many tissues -- including the lungs --
for a poor response to infection.

Another is the "leaky gut" that's also typically present in obese
individuals: Their intestinal cell lining develop gaps, allowing small
amounts of intestinal contents to spill into circulation.

Among these contents leaking out are intestinal bacteria and their
toxins, including lipopolysaccharide (LPS), a protein produced by
gram-negative bacteria such as intestinal Escherichia coli that cause a
severe inflammatory response. Studies have shown that obese individuals
have elevated levels of both bacteria and LPS in their lung tissue --
even in the absence of infection.

When these patients are infected with COVID-19, Scherer and his
colleagues hypothesize, it pushes an already vulnerable system over
the edge. Synergistic interactions between damage caused by the virus,
damage already present from intestinal flora that migrated to the lungs
from a leaky gut, and an elevated inflammatory state could lead to a
more severe infection than in the absence of these factors.



========================================================================== "It's all about the system already being primed," Scherer says. "When
the virus comes into this system, the lungs are already at risk. More
damage and more inflammation could push these patients over the edge and
cause a perfect storm." He notes that dexamethasone, a steroid that's
already shown promise in clinical trials, could be especially helpful in
obese patients. This treatment reduces inflammation systemically, taking a broad approach to reducing this damaging state. A more targeted approach
might be to use PPAR? agonists, a class of drugs that have multiple
effects including lowering inflammation, reducing ACE2 expression,
lowering blood sugar, reducing LPS levels in circulation, and preventing
fat cells in the lung from converting into a fibrotic cell type that
can impair breathing. Unlike dexamethasone, PPAR? agonists don't impair immunity and have fewer common side effects.

"There may be an overabundance of currently proposed treatments for
COVID-19," Scherer says. "However, we believe our suggestions are very
much based on facts and could have a high chance of improving outcomes
while avoiding any harm." Scherer holds the Gifford O. Touchstone,
Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research
and the Touchstone/West Distinguished Chair in Diabetes Research.

This research was supported by National Institutes of Health grants R01- DK55758, R01-DK099110, RC2-DK118620, P01-DK088761, P01-AG051459.


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


========================================================================== Journal Reference:
1. Ilja L Kruglikov, Manasi Shah, Philipp E Scherer. Obesity and
diabetes as
comorbidities for COVID-19: Underlying mechanisms and the
role of viral- bacterial interactions. eLife, 2020; 9 DOI:
10.7554/eLife.61330 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200916094240.htm

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