The SARS-CoV-2 virus, which causes COVID-19, has infected over 255 million individuals worldwide. Obesity and related diseases such as type 2 diabetes and hypertension are strong independent risk factors for infection, severe disease, and death. Findings of a new report indicate that SARS-CoV-2 infiltrates adipose tissue, causing inflammation and worsening disease severity.
Severe COVID-19 is characterized by immune hyperreactivity that creates systemic inflammation mediated by excessive production of pro-inflammatory proteins. Obesity is also characterized by excessive immune reactivity and inflammation, potentially putting people with obesity at greater risk of COVID-19 complications. However, further investigation is needed to understand the mechanisms by which obesity increases COVID-19 severity and whether these mechanisms are independent of type 2 diabetes, hypertension, and other obesity-related conditions.
The investigators recruited adults with obesity who were patients of a bariatric surgery center and had not had a SARS-CoV-2 infection. They collected adipose tissue samples from multiple fat depots around the body such as subcutaneous fat (under the skin), visceral fat (wrapped around internal organs), and pericardial and epicardial fat (around the heart) on the day participants underwent bariatric surgery. The researchers also collected adipose tissue samples from adults who had died from COVID-19 illness. They isolated cells from the connective tissue, sorted them based on type (such as mature adipocyte, pre-adipocyte, and adipose tissue macrophage), and characterized their gene expression and surface receptor population. Then, they exposed the cells to the SARS-CoV-2 virus and observed changes.
The authors found that the SARS-CoV-2 virus infects adipose tissue from multiple depots around the body, but that macrophages were the main cell type infected. They found low expression of the angiotensin converting enzyme (ACE)-2 receptor in these macrophages, indicating that the virus enters through a different route than the primary entry point in cells of the lungs and gut. Upon exposure to the SARS-CoV-2 virus, these cells increased production of pro-inflammatory cytokines. In adipose tissue samples from participants who had died of COVID-19, the investigators found SARS-CoV-2 infection in mature adipocytes in addition to macrophages.
These results are the first to show that the SARS-CoV-2 virus can infect adipose tissue in vivo and that this tissue type may contribute to excess inflammation during COVID-19 illness, especially in older adults with a higher BMI.