Obesity and COVID-19: “What we don’t know is almost everything”
The association between severe COVID-19 and obesity is well established, but how exactly does obesity fit into the COVID-19 picture?
This pressing question was taken up at December’s 18th World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease (WCIRDC) by Tracey L McLaughlin, Professor of Medicine at Stanford University School of Medicine.
Obesity is a major risk factor for severe COVID-19 and increased need of mechanical ventilation, and Professor McLaughlin cited several studies that showed risk increasing as body mass index (BMI) goes up – and one in which there was a sex interaction, with the risk being higher in men.
Age is the strongest risk, but BMI comes second only to age. Why? We don’t have the answer yet, said Professor McLaughlin. “It’s a million dollar question. What we don’t know is almost everything.”
Possible mechanisms include an altered immune response or metabolic syndrome, with hypertension, hypercoagulability, inflammation, endothelial dysfunction and latent coronary artery disease contributing to susceptibility and more severe disease.
Or, Professor McLaughlin suggested, perhaps something else is going on. It’s possible that SARS-CoV-2 enters the human fat cell and infects the reservoir of adipose tissue – for people with a BMI of over 40, this is the vast majority of their body mass. It enters by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, which is thought to be expressed in human adipose tissue.
Their hypothesis is that SARS-CoV-2 infects adipose cells and then promotes inflammation in adipose tissue. Professor McLaughlin set out the two ways in which this may be adverse. Firstly, adipose tissue may act as a viral reservoir for prolonged replication and shedding, and seeding of adjacent organs.
Secondly, it’s a stimulus to inflammation in adipose tissue from direct pathogen insult and/or down regulation of anti-inflammatory ACE2. This can lead to a systemic cytokine storm with inflammation, endothelial dysfunction and hypercoagulability, or it can lead to regional inflammation in visceral/peri-organ fat, which could damage adjacent organs, such as the heart, intestine or kidneys.
She posed a list of questions yet to be answered, such as whether ACE2 is expressed in human adipose cells or other cells resident in adipose tissue, such as macrophages. Does SARS-CoV-2 infect human adipose cells or other resident adipose tissue cells? Can drugs that target ACE2 alter infectivity and/or inflammatory response to infection?
These questions and more are part of a current study at Stanford University, which is using visceral fat samples from bariatric patients and epicardial fat from cardiothoracic surgery to infect with SARS-CoV-2. This work will be extremely important in furthering our understanding of how obesity and COVID-19 interact.
New EASD e-Learning courses on recent literature around diabetes and COVID-19 are currently in development and will be launching in 2021.
For more on insulin resistance, obesity and diabetes, see our course on Insulin resistance.
The opinions expressed in this blog are those of the author, Dr Eleanor D Kennedy.
Sessions at the 18th World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease (WCIRDCD) are now available online at https://www.wcir.org/virtualmeeting