SARS-CoV-2 infects fat tissue, possibly explaining obesity risk factor
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SARS-CoV-2 infects adipose tissue, where it can act as an ongoing source of virus 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 researchers involved with the study said they could not determine if the infection of adipose tissue contributes to long COVID, their results suggest adipose tissue can act as a reservoir for SARS-CoV-2 to cause prolonged health concerns.
“Here, we report that SARS-CoV-2 infects human adipose tissue, targeting both mature adipocytes and a subset of adipose tissue macrophages, leading to immune activation and the secretion of inflammatory factors associated with severe COVID-19,” the researchers wrote in the study, published this month in Science Translational Medicine.
The researchers examined adipose tissue, as well as lung, heart and kidney samples, from eight COVID-19 autopsy cases, detecting 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 also did not detect the coronavirus in lung, heart, and kidney samples.
The virus was most detectable in lung samples, but the researchers said levels were just as high in adipose tissue, and in 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 specifically aired concern for infection of this tissue on the heart itself.
The researchers infected samples of adipose tissue from 22 participants undergoing bariatric or cardiothoracic surgery at Stanford with SARS-CoV-2 and confirmed that the virus can infect adipose cells, cause inflammation and draw 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 could not prove this based on their data, 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 severe disease, [particularly] in the setting of obesity, but our findings cannot establish causation,” Blish, a professor of medicine in Stanford’s division of infectious diseases and geographic medicine, told Healio in an email.
“Infection of this tissue could also contribute to long COVID, but we have not evaluated that directly, and it is a critical area of future investigation,” she said.
Blish said she was not aware of studies that have addressed the link between COVID reservoirs in the body and long COVID. The findings of the current study, however, enhance the value of data on COVID-19 in patients with obesity.
“We have strong data to support that patients with obesity are at higher risk for illness and death associated with COVID-19,” Fatima C. Stanford, MD, MPH, an assistant professor of medicine at Harvard Medical School and obesity medicine physician at Massachusetts General Hospital, told Healio in an email.
During the first year of the pandemic, people with obesity had a 46% increased risk for COVID-19, and those diagnosed with the disease were at 113% increased risk for hospitalization, a 74% increased risk for ICU admission, a 66% increased risk for intensive mechanical ventilation and a 48% increased risk for death, according to Stanford, who was not involved in the new study.
Obesity, as Stanford explained at a 2020 Nature conference, carries with it various immune issues and comorbidities, including chronic inflammation.
The new study found that SARS-CoV-2, when it infects adipose tissue, starts a cycle of viral replication that causes inflammation in immune cells in the tissue, which then converts nearby uninfected cells into an inflammatory state, according to the researchers.
The researchers said they are unsure how the virus infects fat cells because they detected virtually no angiotensin-converting enzyme-2 — the cell surface molecule SARS-CoV-2 generally uses to infect cells — in the adipose tissue samples.
Despite the study suggesting that infection and inflammation in adipose tissue could be linked to more severe COVID, which is supported by previous studies, Blish said it would be difficult to establish a direct link.
“To prove that fat infection contributes to severe COVID, we would need a model in which we block infection just in fat, and then demonstrate that disease is less severe. Currently, we do not understand how to do this, and frankly, it’s not likely to be feasible any time soon. Thus, associations like what we and others have observed are likely all we have,” Blish said.
References:
- Martinez-Colon GJ et al. Sci Transl Med. 2022;doi:10.1126/scitranslmed.abm9151.
- Stanford Medicine study: SARS-CoV-2 infects fat tissue, creates inflammatory storm cloud. https://med.stanford.edu/news/all-news/2022/09/stanford-medicine-study--sars-cov-2-infects-fat-tissue--creates-.html. Published Sept. 22, 2022. Accessed Sept. 28, 2022.
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