Stanford's new finding: SARS-CoV-2 infects adipose tissue, creating an inflammatory storm cloud

Is SARS-CoV-2 hidden in your fat cells?

A study by researchers at the Stanford University School of Medicine showed that SARS-CoV-2 can infect human adipose tissue
.

Obesity is an established independent risk factor for SARS-CoV-2 infection and a risk factor
for patients to develop severe illness and death once infected.

But the new study offers a more immediate cause: The SARS-CoV-2 virus that causes COVID-19 can directly infect adipose tissue (which most of us just call "fat" in general
).

Tracey McLaughlin, MD, professor of endocrinology, said: "2 out of every 3 American adults are overweight and more than 4/10 are obese, which is a potential cause for
concern.

The findings were published online in a study published online on September 22 in
Science Translational Medicine.

In medicine, obesity is defined as a body mass index (weight (kg) divided by the square of height (meter) greater than 30
.

"Adipose tissue's susceptibility to SARS-CoV-2 infection may have played a role in making obesity a risk factor for COVID-19," Blish said
.

The scientists took adipose tissue samples from 22 patients who underwent bariatric or cardiothoracic surgery at the Stanford School of Medicine Bariatric Surgery and Cardiothoracic Surgery clinics
in different parts of their bodies.

Adipose tissue contains not only fat cells, but also a variety of immune cells, including a type of immune cell
called macrophages.

The researchers found that a subset of macrophages in adipose tissue was infected with SARS-CoV-2, albeit briefly
.

"Once infected, these macrophages not only become inflamed themselves, but also secrete substances to summon more inflammatory immune cells, in addition to inducing inflammation
in neighboring 'bystander cells' that are not infected," Blish said.

Adipose tissue surrounds our heart, internal organs, kidneys, and pancreas, and they are adversely affected by inflammation of the tissues
.

Almost without exception, the genetic material encoding SARS-CoV-2 appeared in adipose tissue in
different parts of the body of the 8 patients who died of COVID-19.

McLaughlin said: "This is very important for us because the epicardial fat is right next to the heart muscle and there is no physical barrier to separate
them.

Missing ACE2

Curiously, ACE2 — a cell-surface molecule that is considered the main receptor for SARS-CoV-2 — appears to play little or no role
in the virus's ability to infect fat cells.

The method by which SARS-CoV-2 enters fat cells and macrophages in adipose tissue remains a mystery
.
When the virus binds to the ACE2 protein located on the surface of many body tissue cells, the already identified primary entry pattern occurs
.
Although ACE2 performs important, legitimate functions, the virus doesn't care what it does for a living—it only uses the protein on the surface of the cell as a stop
.

This is the most ironic for McLaughlin and Blish, who initiated the study because they saw reports suggesting that ACE2 may be present in adipose tissue, although this has not been demonstrated
.
(No one claims to have discovered the protein itself
.
) But to the researchers' surprise, they found that ACE2
is almost non-existent in cells in adipose tissue.

Blish said: "It is unlikely that the virus will enter the body through ACE2 because we cannot detect functional proteins
in adipose tissue.
" This means that clearing SARS-CoV-2 from adipose tissue may require new drugs
.
For example, licensed monoclonal antibody therapies for COVID-19 often work by interfering with ACE2/SARS-CoV-2 interactions
.
The potential of adipose tissue as a hiding place for SARS-CoV-2 also increases the likelihood
that it may contribute to the symptoms of a persistent infection known as long COVID.

SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages