While many factors contribute to how severely people are affected,  it’s becoming clear that for some  groups, it’s the response of their immune system – inflammation – that explains why they get so sick.

The severity of COVID-19 can vary hugely. In some it causes no symptoms at all and in others it’s life threatening, with some people particularly vulnerable to its very severe impacts.

The virus disproportionately affects men and people who are older and who have conditions such as diabetes and obesity. In the UK and other western countries, ethnic minorities have also been disproportionately affected.

 

Specifically, we’re seeing that the risks associated with diabetes, obesity, age and sex are all related to the immune system functioning irregularly when confronted by the virus.

Inflammation can go too far

A common feature for many patients that get severe COVID is serious lung damage caused by an overly vigorous immune response. This is characterised 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 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 are not controlled. This is exactly what happens in a cytokine storm.

Diabetes, if not controlled well, can result in high levels of glucose in the body. A recent study showed that, in COVID, macrophages and monocytes respond to high levels of glucose with worrying consequences.

The virus that causes COVID, SARS-CoV-2, needs a target to latch onto in order to invade our cells. Its choice is a protein on the cell surface called ACE2. Glucose increases the levels of ACE2 present on macrophages and monocytes, helping the virus infect the very cells that should be helping to kill it.

Once the virus is safely inside these cells, it causes them to start making lots of inflammation 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 lung, such as reactive oxygen species. And on top of this, the virus reduces the ability of other immune cells – lymphocytes – to kill it.

This all means that for some older people, their immune system is not only poorly equipped to fight off an infection, but it is 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 vaccine campaign.

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