Editor’s Note: This article first appeared on December 9, 2021, after an earlier version of the study was posted to the preprint database bioRxiv (opens in new tab). The article was updated on September 23, 2022 to reflect the new information in the peer-reviewed journal.
The coronavirus SARS-CoV-2 directly infects fat cells and specific immune cells found in adipose tissue, causing inflammation that can then spread to nearby uninfected “bystander” cells.
In a study published Sept. 22 in the journal Science Translational Medicine (opens in new tab)what scientists experimented with fat tissue obtained from patients undergoing bariatric, heart and chest surgery to see if the tissue can be infected by the coronavirus. They found that the virus could infect and replicate in mature fat cells, known as adipocytes, and these infected cells became inflamed. They also found that specific subsets of immune cells residing in the adipose tissue, called macrophages, also became infected, triggering a much more intense inflammatory response.
Specifically, the virus couldn’t make new copies of itself in the macrophages — the pathogen could break into the immune cells, but that’s where the buck stopped. But even this short-lived invasion caused a significant change in the macrophages, causing them to spew inflammatory substances into the surrounding tissue. There, immature fat cells called pre-adipocytes responded to the onslaught of chemical signals by becoming inflamed themselves.
These pre-adipocytes cannot be directly infected by SARS-CoV-2, the team found, but this chain reaction caused them to be affected indirectly by the virus.
Related: COVID-19 may infiltrate insulin-producing cells in the pancreas, study suggests
In addition to these experiments, the team examined adipose tissue from patients who died from COVID-19 infections and found the genetic material of the coronavirus in the fat surrounding various organs. Viruses like hiv and influenza squirrels can hide in fatty tissue as a way to hide from the immune system. Likewise, “fat tissue could serve as a potential reservoir for SARS-CoV-2,” and in theory this hidden reservoir could contribute to the lingering symptoms seen in people with long-term COVID, the team wrote in their report.
In addition, in two patients who died from COVID-19, the team found that inflammatory immune cells had gathered around infected adipocytes in the fatty tissue surrounding the heart. “This was a major concern for us, as epicardial fat is right next to the heart muscle, with no physical barrier separating them,” said co-senior author Dr. Tracey McLaughlin, professor of endocrinology at Stanford University School of Medicine, in a pronunciation (opens in new tab). “So any inflammation there can directly affect the heart muscle or coronary arteries.”
Since the early days of the pandemic, obese people have been at a higher risk of developing severe symptoms, requiring hospitalization and dying from COVID-19, Live Science previously reported. A number of theories arose to explain why fat increased the risk of bad COVID-19 outcomes.
For starters, excess fat in the abdomen can press on the diaphragm, restricting airflow into the lungs; if people are already struggling to get enough oxygen into their lungs on a good day, they could be doing worse against COVID-19, Science reported (opens in new tab). In addition, the blood of obese people tends to clot more easily than those with lower fat levels – another major problem in the context of COVID-19, which can cause extensive blood clotting.
In addition, as fat accumulates in the body, fat cells infiltrate the spleen, bone marrow and thymus, where many immune cells are produced. This can weaken the immune system by both reducing the number and undermining the efficacy of the immune cells produced. Excess fat can also stimulate chronic, low-grade inflammation throughout the body because fat cells release inflammatory substances called cytokines and macrophages do the same, in an effort to remove dead fat cells from the body, Science reported.
While all of these factors could worsen the COVID-19 outcomes for obese people, there is now this evidence that the virus directly infects fat cells.
“Infected adipose tissue pumps out exactly the inflammatory chemicals you see in the blood of severe COVID patients,” said co-senior author Dr. Catherine Blish, a professor of infectious diseases at Stanford University School of Medicine, said in the statement. “It is reasonable to conclude that having a lot of infected fat may contribute to the overall inflammatory profile of critically ill COVID-19 patients.”
It is still not clear how the virus infiltrates fat and adipose tissue-borne immune cells. That’s because the study authors found negligible amounts of ACE2 — the main “doorway” the virus uses to enter cells — in their tissue samples. “The virus is highly unlikely to enter via ACE2, because we were unable to detect the functional protein in adipose tissue,” Blish said.
Originally published on Live Science.