- Chronic inflammation caused by obesity could be a driver of Covid-19 severity.
- This changes immune response long term, making it less effective when faced with a viral infection.
- It's therefore important to include obese individuals in vaccine trials.
The severity of Covid-19 is generally mediated by the human body's immune response. Everyone's immunity is different – which is why reactions to the virus are so varied – and there are various genetic, environmental and chronic disease factors that can influence this response.
One such factor is obesity. Those who have a BMI of more than 40 are 2.6 times more likely to die from a coronavirus infection.
A new study published by Endocrine Society investigates how this condition exacerbates inflammation in the body, which, in turn, puts strain on the immune system.
Early studies of the virus took place in China, and there was no focus on obesity because it is so rare in that country. But that changed when the virus hit the US, a country with one of the highest rates of obesity in the world.
South Africa also has a high rate of obesity, making it important to understand the interaction between Covid-19 and obesity.
How does obesity affect the immune system?
Metabolic inflammation, or meta-inflammation, is a chronic type of inflammation caused by obesity due to increased tissue and circulating myeloid cells. These cells develop an immunosuppressive environment and have been linked to the promotion of tumour growth.
This meta-inflammation might be part of the reason why obese patients are so susceptible to severe Covid-19.
"While obesity and diabetes may complicate the delivery of supportive care in critical illness, regardless of the underlying disease, lessons learned from the interaction of obesity with other systemic inflammatory syndromes suggest that obesity modifies biologic factors related to SARS-CoV-2 infection and the Covid-19 syndrome," explain the researchers.
They add that obesity also has the potential to do long-term reprogramming of the immune system through this chronic inflammation.
This isn't restricted to Covid-19; the syndrome can also make a patient more prone to other diseases like bird flu and bacterial infections. With global obesity rates expected to rise in the future, understanding endocrine, metabolic, and inflammatory shifts caused by obesity would be vital for future pathological treatments.
Cytokine storms and macrophages
In severe cases of Covid-19, the coronavirus infection induces a cytokine storm that floods the immune system. It also does this by shifting monocyte populations in the body – a type of white blood cell that can influence adaptive immunity – and helps drive the infection throughout the body.
With meta-inflammation, cytokine levels are always at higher levels than normal, including chemokines. Throw Covid-19 into the mix, and you're left with a much more virulent attack on the body.
Another element increased by obesity and Covid-19 are macrophages.
"Macrophages from obese animals and humans have been described as metabolically active, M1 polarised, and pro-inflammatory with both regulatory and detrimental activity. These macrophages produce cytokines, chemokines, reactive oxygen species, and factors regulating fibrosis and metabolism."
A high fat diet morphs obesity myeloid cells into metabolically active macrophages, which in turn, has an impact on organs and hematopoiesis, the process through which the body produces blood cells.
Enhancing hematopoiesis, in turn, impairs the immune response to, for example, a viral infection. The increased cytokine production can also cause tissue damage when the storm is triggered.
Obese people also tend to have high blood sugar, called hyperglycemia, which can concentrate glucose in the lungs and the rest of the respiratory system. This helps colonisation and replication of bacteria, and also damages the intestinal barrier that protects us against infection.
"On top of the direct effects that obesity may have on macrophage function in infection, diaphragm excursion is also inhibited due to obesity, which restricts ventilation and can inhibit the clearance of pulmonary pathogens."
This also prevents the body from effectively identifying and killing off any bad bacteria, maintaining the infection for longer. For similar reasons, an obese person is then just as susceptible to a viral infection.
"Along with possible impairments in pathogen clearance, obese hosts are more likely to experience the breakdown of respiratory epithelium during a pulmonary infection, which leads to increased fluid in the airway space.
"This allows the pathogen to have the opportunity to more easily spread throughout the body and leaves the host with reduced lung function."
ACE2 receptors – one of the main entry points into cells for the coronavirus – are also more prevalent in the fat cells of obese and diabetic patients. This might become a reservoir for SARS-CoV-2 replication that increases Covid-19 severity.
The gut is also another factor to consider, as studies have proven the influence that its microbiota have on health and the immune system. Covid-19 tends to make changes in the gut that encourage more inflammation, but more in-depth research is needed.
It's important to note, however, that not all obese people suffer from meta-inflammation or necessarily develop other chronic conditions, like heart disease or diabetes. But if you're male, you're far more likely than obese pre-menopausal women to develop these conditions, which also helps explain men's susceptibility to severe Covid-19.
Being obese might also impact the effectiveness of a potential coronavirus vaccine.
Flu shots tend to not work as well for them, probably due to impaired T-cell function.
According to the researchers, this makes it vital that obese individuals are included in the vaccine trials to ensure efficacy in this high-risk group.
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