A new study by led by researchers from Stanford University School of Medicine along with scientists from University Hospital and Comprehensive Cancer Center Tübingen-Germany, University Hospital of Basel-Switzerland, Beth Israel Deaconess Medical Center-USA and Chan Zuckerberg Biohub, San Francisco-USA has found that the SARS-CoV-2 coronavirus also infects the human adipose tissue especially the mature adipocytes and adipose tissue macrophages, in the process eliciting an inflammatory response 2 consistent with severe COVID-19.
The study findings were published on a preprint server and is currently being peer reviewed.
Obesity has emerged as an independent risk factor for infection, severe disease, and mortality (2–6). While obesity is associated with comorbid conditions also related to severe COVID-19, the independent relative risk of obesity is higher than that of hypertension and type 2 diabetes (2, 5, 7). Further, obesity is a risk factor even in young adults and children who do not have other comorbid conditions (8).
Several distinct mechanisms could underlie this association. Impaired respiratory mechanics may result from a heavy chest wall, airway resistance, and/or presence of obstructive sleep apnea (9). The metabolic milieu in obesity, particularly among individuals with insulin resistance, is characterized by systemic inflammation and hypercoagulability (10–12) and could thus stimulate a more robust inflammatory response to SARS-CoV-2.
Impaired immune responses to viral infection are another possibility, as obese individuals exhibit altered immune cell profiles at baseline (13) and in response to influenza infection (7, 14).
Furthermore, a recent report demonstrated that SARS-CoV-2 can infect adipocytes in vitro (15); it is not known whether SARS-CoV-2 infects other adipose tissue-resident cells and/or drives an inflammatory response in adipose tissue.
Other viruses have been shown to infect several cell types within adipose tissue, including adipocytes (influenza A virus), adipose-stromal cells (adenovirus 36, human cytomegalovirus), macrophages (simian immunodeficiency virus (SIV)), and T cells (human immunodeficiency virus (HIV))(16–19).
Complex interactions between various cell types and adipocytes can drive significant inflammation, with reports of adipocyte-derived chemoattractants such as monocyte chemoattractant protein-1 (MCP-1) leading to macrophage infiltration (20), tumor necrosis factor alpha (TNF-ɑ) activating nuclear factor kappa B (21, 22), and free fatty acids driving toll-like receptor 4-mediated inflammation and insulin resistance (23).
Thus, pronounced and/or prolonged SARS-CoV-2 viral replication and inflammation might occur in those with obesity and contribute to severe disease. Of particular concern is the possibility that viral infection of peri-organ fat could contribute to organ damage via inflammation and downstream processes such as extracellular matrix deposition/fibrosis, edema, impaired cellular function, endothelial dysfunction, and hypercoagulability (11, 13).
To date, COVID-19 profiling studies have generally excluded adipose tissue from analyses; in other cases adipose tissue may have been lumped in with analyses of adjoining tissues (24, 25)
These studies have shown that SARS-CoV-2 RNA and proteins are detected across numerous tissues, including the lung, brain, intestine, and pancreas (24, 26, 27).
Thus, we undertook a study to test the hypothesis that SARS-CoV-2 infects cells within human adipose tissue and incites an inflammatory response. We harvested adipose tissue from multiple depots in uninfected obese humans for in vitro infection and obtained autopsy specimens of various adipose depots in individuals who died from COVID-19.
Our results clearly show SARS-CoV-2 infection in macrophages and adipocytes from multiple adipose depots, with an attendant increase in inflammatory profile.