September 29, 2022
3 min read
Source/Disclosures
Published by:
Disclosure:
Stanford does not report relevant financial information. Blish reports that he serves on scientific advisory boards for Catamaran Bio and DeepCell. Please see the study for any other authors relevant financial disclosures.
SARS-CoV-2 infects adipose tissue, where it can act as a constant source of viral replication and inflammation, according to a study that may indicate why obesity has proven to be such a significant risk factor for severe COVID-19.
Although the researchers involved in the study said they could not determine whether the infection of adipose tissue contributes to long-term COVID, their findings suggest that adipose tissue may act as a reservoir for SARS-CoV-2 to cause ongoing health concerns .
“Here we report that SARS-CoV-2 infects human adipose tissue, targeting both mature adipocytes and a subset of adipose tissue macrophages, resulting in immune activation and the secretion of inflammatory factors associated with severe COVID-19 are,” the researchers wrote in the study, published this month in Science Translational Medicine.
The researchers examined adipose tissue and lung, heart and kidney samples from eight COVID-19 autopsy cases and detected SARS-CoV-2 in epicardial, visceral and subcutaneous adipose tissue in seven of the eight cases. In the one patient whose adipose tissue was not positive for viral RNA, the researchers reported that they could not detect the coronavirus in lung, heart, or kidney samples either.
The virus was best detectable in lung samples, but the researchers said levels were just as high in adipose tissue and heart and kidney samples. Having detected SARS-CoV-2 in the cytoplasm of adipocytes in epicardial fat with an associated mononuclear inflammatory infiltrate, the researchers raised particular concerns about infection of this tissue in the heart itself.
Researchers infected adipose tissue samples from 22 participants undergoing bariatric or cardiothoracic surgery at Stanford with SARS-CoV-2 and confirmed that the virus can infect fat cells, cause inflammation and evoke an immune system response.
Although the analysis suggests that adipose tissue could serve as a potential reservoir for SARS-CoV-2 as well as a “potentiator of regional or systemic inflammation,” the researchers were unable to support this from their data, the researchers said Catherine A Blish, MD PhD FIDSA, Associate Program Director of Stanford University’s MD-PhD program.
“The primary finding of the study is that adipose tissue can be a source of infection and inflammation. This infection and inflammation could contribute to a serious illness, [particularly] in the context of obesity, but our results fail to establish causality,” Blish, a professor of medicine in Stanford’s Department of Infectious Diseases and Geographical Medicine, said in an email to Healio.
“Infection of this tissue could also contribute to a long COVID, but we have not evaluated that directly and it is a critical area of future investigation,” she said.
Blish said she is not aware of any studies that have looked at the link between body reservoirs of COVID and long-term COVID. However, the results of the current study increase the value of the data on COVID-19 in patients with obesity.
“We have strong data demonstrating that patients with obesity are at higher risk of illness and death related to COVID-19,” Fatimah C Stanford, Mdkm/h, an assistant professor of medicine at Harvard Medical School and obesity medicine physician at Massachusetts General Hospital, Healio said in an email.
In the first year of the pandemic, people with obesity had a 46% increased risk of COVID-19 and those diagnosed with the disease had a 113% increased risk of hospitalization, a 74% increased risk of admission in the ICU, a 66% increased risk of requiring intensive mechanical ventilation and a 48% increased risk of death, according to Stanford, who was not involved in the new study.
Obesity, as Stanford explained at a 2020 Nature conference, brings with it various immune problems and comorbidities, including chronic inflammation.
The new study found that when SARS-CoV-2 infects adipose tissue, it starts a virus replication cycle that causes inflammation in immune cells in the tissue, which then induces nearby, uninfected cells into an inflammatory state, the researchers said.
The researchers said they weren’t sure how the virus infects fat cells because they could detect virtually no angiotensin-converting enzyme-2 — the cell-surface molecule that SARS-CoV-2 commonly uses to infect cells — in the fat tissue samples .
Although the study suggests that infection and inflammation in adipose tissue may be linked to more severe COVID, which is supported by previous studies, Blish said it’s difficult to establish a direct link.
“To prove that fat infection contributes to severe COVID, we would need a model where we only block infection in fat and then show that the disease is less severe. Currently we don’t understand how to do this and frankly it probably isn’t feasible any time soon. So associations like the ones we and others have observed are probably all we have,” Blish said.
References:
