It's been described as the "second week crash".

About seven days after developing symptoms of COVID-19, some people — even those with mild symptoms — can suddenly start to deteriorate, often with little warning.

"They end up getting admitted to hospital, and about three days afterwards, they're admitted to the intensive care unit (ICU)," said Mark Nicholls, an intensive care specialist from the Australian and New Zealand Intensive Care Society.

This is pretty much what happened to British Prime Minister Boris Johnson, who went from reportedly having a 'mild case' of COVID-19, to being put in the ICU.

While most people who get COVID-19 will have relatively mild symptoms and get over the illness within a week or two, about 15 per cent of people need to be hospitalised, and 5 per cent become critically ill.

Predicting who will decline is difficult, since there are few definitive warning signs.

"It's a puzzling problem, and our understanding of it is still evolving," Dr Nicholls said.

Older people and people with pre-existing medical conditions, including heart disease, type 2 diabetes and some chronic lung conditions, are at higher risk of developing serious illness.

But there have been cases where young, otherwise healthy people have become very ill too.

In some cases — especially when people become severely ill in the later stages of infection — doctors and researchers suggest it may be the body's response to the virus, rather than the virus itself, causing damage.

This immune overreaction, known as a 'cytokine storm', can cause acute respiratory distress, which means less oxygen reaches your bloodstream — depriving your organs of the oxygen they need.

"You see it in patients rarely in the intensive care setting," Dr Nicholls said, "but in the severe patients with COVID-19, we're seeing it much more commonly."

When your immune system goes rogue

When your immune system detects an invader like SARS-CoV-2, it triggers a series of responses to contain and eradicate the infection.

This includes the release of small, signalling proteins called cytokines, which cause inflammation.

In most cases, the immune response works: the body's defences quell the infection and inflammatory response shuts off.

But sometimes the immune system mistakenly goes into overdrive and remains active long after the virus is a threat, said Julian Elliot, director of the National COVID-19 Clinical Evidence Taskforce.

"You get a more severe immune response … and that actually causes problems for you," he said.

In a misguided attempt to keep you safe, the immune system continues to flood the body with cytokines, activating further inflammation and mistakenly ravaging healthy cells.

"There's a whole collection of immune cell types and chemicals that we can measure which increase [in COVID-19] — some of them dramatically," said Dr Elliot, an infectious disease physician at the Alfred Hospital.

What we're seeing in COVID-19 patients

In those with coronavirus who become severely unwell, it's difficult to tease out to what degree the immune system is causing damage and to what degree it's the virus itself.

"The immune system in most people is playing a very beneficial role," Dr Elliot said.

"The hypothesis is that in a specific subset of patients where we're seeing a lot of this inflammation ... perhaps the immune system is overactive and is now part of the problem."

It's typical for people who are developing more serious COVID-19 disease to have markers of increased inflammation, especially in the lungs.

"Sometimes people can feel normal but actually they've already developed pneumonia or inflammation in the lungs, and can have quite low oxygen levels," Dr Elliot said.

Pneumonia is an infection of the lungs in which the air sacs become inflamed and can fill with fluid. As the illness progresses, the pneumonia typically becomes worse.

"In those who get into really very severe and critical illness, [patients] can then start to progress to Acute Respiratory Distress Syndrome," Dr Elliot said.

"This is where there's a lot of inflammation in their lungs, they often have very low oxygen levels, and need to go on a ventilator."

Cytokine storms, though not fully understood, can also occur in influenza and other respiratory diseases. ( Getty Images: Virojt Changyencham )

One of the most worrying aspects of COVID-19 pneumonia is that it can creep up on people without them being aware, Dr Elliot said.

Usually pneumonia makes people feel chest discomfort or they have trouble breathing, but some people with some COVID-19 don't feel short of breath, even as their oxygen levels fall.

"That seems to be one of the distinct presentations of moderate to severe COVID disease ... these quite low levels of oxygen, even though the person doesn't feel particularly breathless," he said.

That's different to other similar infections, and may be why some patients, with seemingly mild symptoms, can suddenly start to decline.

Anti-inflammatory drug trials underway

While it's unclear how common cytokine storms are, some experts believe they may help to explain why some people have a severe reaction to COVID-19, while for others it's relatively mild.

Generally, people who tend to fare worse with COVID-19 are those who are older, have chronic medical conditions or compromised immune systems.

"In the small percentage of young people who develop severe disease, it may be that an overactive immune response is part of the cause, but that might be in older people as well," Dr Elliot said.

"Why a particular person might get that response rather than not, we don't know."

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To treat cytokine storms, doctors may turn to anti-inflammatory drugs that broadly blunt the immune system, such as corticosteroids, or block specific cytokines.

But this comes with inherent risks: you don't want to overly-suppress the body's immune system right when it's trying to fight an infection.

"That's why we need research studies because these treatments have risks," Dr Elliot said.

"In other diseases we're often battling with that same question, where we think there's perhaps an overactive immune response.

"Until we do the study, it's really impossible to know whether the potential benefits in terms of dampening down the immune systems overweighs the potential risks of suppressing someone's it."

There are currently COVID-19 drug trials underway investigating the role of drugs that suppress the immune response.

