Inflammation Can Go Too Far
A common feature for many patients that get severe COVID-19 is serious lung damage caused by an overly vigorous immune response. This is characterized by the creation of lots of inflammatory products called cytokines—the so-called cytokine storm.Cytokines can be really powerful tools in the immune response: They can stop viruses from reproducing, for example. However, some cytokine actions—such as helping bring in other immune cells to fight an infection or enhancing the ability of these recruited cells to get across blood vessels—can cause real damage if they aren’t controlled. That’s exactly what happens in a cytokine storm.
Many white blood cells create cytokines, but specialized cells called monocytes and macrophages seem to be some of the biggest culprits in generating cytokine storms. When properly controlled, these cells are a force for good that can detect and destroy threats, clear and repair damaged tissue, and bring in other immune cells to help.
Glucose Fuels Damage
Diabetes, if not controlled well, can result in high levels of glucose in the body. A recent study showed that, in COVID-19, macrophages and monocytes respond to high levels of glucose with worrying consequences.Once the virus is safely inside these cells, it causes them to start producing lots of inflammatory cytokines—effectively kick-starting the cytokine storm. And the higher the levels of glucose, the more successful the virus is at replicating inside the cells. Essentially, the glucose fuels the virus.
But the virus isn’t done yet. It also causes the virally infected immune cells to make products that are very damaging to the lungs, such as reactive oxygen species. And on top of this, the virus reduces the ability of other immune cells—lymphocytes—to kill it.
Other Risks Tied to Inflammation
The same sort of inflammatory profile that diabetes and obesity cause is also seen in some older people (those over 60 years). This is due to a phenomenon known as inflammageing.Inflammageing is characterized by having high levels of pro-inflammatory cytokines. It’s influenced by a number of factors, including genetics, the microbiome (the bacteria, viruses, and other microbes that live inside and on you), and obesity.
This all means that for some older people, their immune system isn’t only poorly equipped to fight off an infection, but it’s also more likely to lead to a damaging immune response. Having fewer lymphocytes also means vaccines may not work as well, which is crucial to consider when planning a future COVID-19 vaccine campaign.
Studies such as this highlight how different people are. The more we understand these differences and vulnerabilities, the more we can consider how best to treat each patient. Data like these also highlight the need to consider variation in immune function and include people of varied demographics in drug and vaccine trials.
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