“More die in the United States of too much food than of too little.”
- John Kenneth Galbraith
“Our work provides the first in vivo evidence of SARS-CoV-2 infection in human adipose tissue and describes the associated inflammation.”
- GJ Martinez-Colon, et al, biorxiv.org October 25, 2021
From the outset of the COVID-19 pandemic two years ago, researchers began searching for clinical factors that increased the risk of developing severe disease and hypothesized that obesity was a critical risk factor. Another year of research has backed this hypothesis. (For a review see “Obesity as a risk factor for COVID-19: an overview,” Critical Reviews in Food Science and Nutrition, 2021.) In addition, a recent publication in biorxiv.org provides a potential mechanism on how “SARS-CoV-2 infects human adipose tissue and elicits an inflammatory response consistent with severe COVID-19.”
On October 28, 2020, I wrote the Germ Gem post, “COVID-19: Does Obesity Matter?” but had no definitive answer. This Germ Gems post sets the record straight: obesity is a major risk factor for severe COVID-19.
Obesity is a big problem. The world is currently facing an unprecedented increase in the number of people who are overweight or obese. A staggering 33% of the world’s population over the age of 20 is overweight (body mass index [BMI] 25.0-29.9) or obese (BMI 30.0 and above). (The Center for Disease Control and Prevention’s Adult BMI Calculator can be found at this link. According to the World Health Organization, these numbers are projected to grow in coming years.
Low- and middle-income countries hold the highest rankings, Nos. 1-11, for obesity worldwide. But the U.S. comes in at No. 12, suggesting that income alone isn’t a major driver behind obesity. (The factors involved in the pathophysiology of obesity are complex and beyond the scope of this Germ Gems post.)
Adipose tissue is an immune organ. Fat tissue is composed mainly of adipocytes—cells that contain large globules of lipid or fat that serve as a source of energy. But evolutionarily adipose tissue also functions as an immune organ, and fat is a rich source of stem cells.
Immune cells located in adipose tissue are important for maintaining metabolic homeostasis. Excess fat accumulation can lead to insulin resistance, and insulin resistance has been linked to meta-inflammation—a chronic and low-grade inflammatory state. With insulin resistance, there is an increase in cells of the immune system—macrophages, neutrophils, T lymphocytes, and B lymphocytes—within adipose tissue.
Adipose tissue macrophages (ATMs) have captured a lot of research attention. As was shown almost two decades ago, the percentage of macrophages within adipose tissue ranges from 10% in lean mice and lean humans up to 50% in extremely obese mice and people. ATMs can exhibit either pro- or anti-inflammatory properties, including responses to and production of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukins, and toxic free radicals.
Macrophages are specialized cells that remove dying or dead cells or cellular debris. Within adipose tissue, presence of dead adipocytes is a hallmark of obesity. In addition to an increased number of macrophages within adipose tissue, obesity also induces a switch in macrophages’ ability to produce different types of cytokines. Suffice it to say that research interest in defining the role of ATMs is increasing dramatically with regard not only in obesity and weight loss but also tumor growth.
SARS-CoV-2 targets adipose tissue. Within the first month of the COVID-19 pandemic it was determined that ACE2 receptors on cells served as a portal of entry of SARS-CoV-2 via engagement of its spike protein. In April 2020, ACE2 gene expression was found to be higher in both human subcutaneous adipose tissue and human visceral adipose tissue than in human lung tissue. Therefore, it didn’t come as a big surprise when researchers at Stanford University School of Medicine provided this report on-line on October 25, 2021, “SARS-CoV-2 infects human adipose tissue and elicits an inflammatory response consistent with severe COVID-19."
These researchers demonstrated that human adipose tissue from multiple body sites supports SARS-CoV-2 infection and that infection elicits an inflammatory response akin to that seen in the “cytokine storm” that characterizes severe COVID-19. They also discovered two cellular targets for SARS-CoV-2 within adipose tissue—mature adipocytes and ATMs. They postulated this pathogenic inflammation may explain the link between obesity and severe COVID-19.
As New York Times staff writer Roni Rabin pointed out in a December 8 article, “The Coronavirus Attacks Fat Tissue, Scientists Find,” because of the U.S.’s high rate of obesity, the results of the Stanford University study are particularly relevant to America, especially to Black, Hispanic, and Native Americans who have higher rates of obesity than white and Asian American adults. Also, COVID-19-related death rates in these minority communities are double those of white Americans. In addition to acute effects like disease severity, the Stanford University researchers speculate that infected body fat may even contribute to the debilitating chronic illness referred to as “long Covid.”
Translating these research findings into improved clinical outcomes. The findings reported in this Germ Gems post give me an enhanced appreciation of adipose tissue. They also give me hope that someday these basic science discoveries will be translated into improved treatments of COVID-19 as well as other medical conditions.
