Editor’s note: This article was first published on December 9, 2021, after an earlier version of the study was published in the preprint database. bioRxiv (opens in a new tab). The article was updated on September 23, 2022 to reflect new information contained in the peer-reviewed journal.
The SARS-CoV-2 coronavirus directly infects fat cells and specific immune cells found in fat tissue, causing inflammation that can then spread to nearby uninfected “bystander” cells.
In a study, published on September 22 in the journal Scientific Translational Medicine (opens in a new tab)scientists experimented fat tissue obtained from patients undergoing bariatric, cardiac and thoracic surgery, to see if the tissue could be infected by coronavirus. They found that the virus could infect and replicate inside mature fat cells, known as adipocytes, and these infected cells became inflamed. They also found that specific subsets of immune cells housed within fat tissue, called macrophages, also became infected and caused a much more intense inflammatory response.
Remarkably, the virus was unable to make new copies of itself inside macrophages—the pathogen could enter immune cells, but the buck stopped there. However, even this short-term invasion caused a significant change in the macrophages, causing them to expel inflammatory substances into the surrounding tissue. There, immature fat cells, called pre-adipocytes, reacted to the onslaught of chemical signals by becoming inflamed.
These pre-adipocytes cannot be directly infected by SARS-CoV-2, the team found, but through this chain reaction, they were indirectly affected by the virus.
Related: Study suggests that COVID-19 can infiltrate insulin-producing cells in the pancreas
In addition to these experiments, the team examined fat tissue from patients who died of COVID-19 infections and found genetic material of the coronavirus in the fat surrounding various organs. Viruses like hiv i flu they can squirrel in the fatty tissue, as a way to hide from the immune system. Similarly, “adipose tissue could serve as a potential reservoir for SARS-CoV-2,” and in theory, this hidden reservoir could contribute to the long-lasting symptoms seen in people with long-term COVID, the team wrote in their report
Additionally, in two patients who died of COVID-19, the team found that inflammatory immune cells had gathered around infected adipocytes in the fatty tissue surrounding the heart. “This was very concerning to us because epicardial fat is right next to the heart muscle, with no physical barrier separating them,” said lead co-author Dr. Tracey McLaughlin, a professor of endocrinology in the College of Stanford University Medicine, in a statement (opens in a new tab). “So any inflammation there can directly affect the heart muscle or the coronary arteries.”
Since the early days of the pandemic, people with obesity have faced a higher risk of developing severe symptoms, requiring hospitalization and dying from COVID-19, Previously reported by Live Science. Several theories emerged to explain why fat increased the risk of poor outcomes from COVID-19.
For starters, excess fat in the abdomen can push on the diaphragm and thus restrict airflow to the lungs; if people are already struggling to get enough oxygen into their lungs on a good day, they may fare worse against COVID-19, informed science (opens in a new tab). In addition, the blood of obese people tends to clot more easily than those with lower fat levels, another major issue in the context of COVID-19, which can trigger extensive blood clotting.
Also, 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 effectiveness of the immune cells produced. Excess fat can also lead to chronic, low-grade inflammation throughout the body, as 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 may worsen the outcomes of COVID-19 for people with obesity, there is now evidence that the virus directly infects fat cells.
“Infected fat tissue pumps out precisely the inflammatory chemicals seen in the blood of severe COVID patients,” co-senior author Dr. Catherine Blish, a professor of infectious diseases at the University’s School of Medicine, said in the statement from Stanford. “It is reasonable to infer that having a large amount of infected fat could contribute to the overall inflammatory profile of severely ill COVID-19 patients.”
It is not yet clear how the virus infiltrates immune cells carried by adipose tissue and fat. That’s because the study authors found negligible amounts of ACE2, the main “gateway” the virus uses to enter cells, in their tissue samples. “It’s very unlikely that the virus enters through ACE2, because we couldn’t detect the functional protein in adipose tissue,” Blish said.
Originally published in Live Science.