COVID-19 is like three different diseases, says New York doctor, from flu-like illness to severe reactions and rare children’s syndrome
Almost 10 weeks into the pandemic, COVID-19 is continuing to surprise and baffle health experts.
In fact, experts’ picture of exactly how COVID-19 might play out in the body is now quite different to what was thought as little as a few weeks ago, with some experts saying it could be better described as three different diseases.
We have known for a while that the mild to moderate form of the disease — a flu-like illness with fever, muscle aches and respiratory symptoms, or often no symptoms at all — is almost like “child’s play” compared to the major damage to organs like the the lungs, heart, brain, and kidneys seen when COVID-19 becomes severe.
Umesh Gidwani, head of cardiac intensive care at New York’s Mount Sinai Hospital, says that trying to treat the severe form of the disease is like facing a terrifying fire, burning out of control.
“The patients we take care of [in intensive care] are those in whom the fire has already destroyed the house. But there continues to be embers and small fires. I can’t enter the house because it’s too hot and things are falling on me,” he says.
“[Severe disease] is almost a completely different animal [compared] to someone who is recovering at home with some chicken soup and paracetamol”.
A man wearing scrubs, a doctor’s cap and glasses sits in a doctor’s office.
Intensive care specialist Umesh Gidwani from New York’s Mount Sinai Hospital warns Australia not to let down its guard in the COVID-19 pandemic.(Supplied: Umesh Gidwani)
And now it seems there is evidence of a third variation in illness that can occur following exposure to the virus — a mysterious new disease given the name paediatric multisystem inflammatory syndrome, with an entirely different set of symptoms again.
The syndrome seems to only affect children, unlike both mild and severe COVID-19, which mostly affect adults. However the link between the inflammatory syndrome and the virus that causes COVID-19 is not yet 100 per cent confirmed.
The bottom line, says Dr Gidwani, is what we have been calling a single disease — COVID-19 — is really looking more like three separate diseases.
He and others draw this conclusion based on how the virus affects the immune system.
“The key disaster is the extent and severity of the immune response,” he says.
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It is now clear the symptoms experienced by people with severe COVID-19 are largely caused by the body’s disordered immune response to the virus rather than the virus itself, Dr Gidwani says.
In fact, the disordered immune response in severe COVID-19 is the disease; they are one and the same thing.
In contrast, with mild to moderate COVID, the immune response is more measured, with symptoms largely confined to the upper respiratory tract.
But with severe COVID-19, the body’s response to the infection goes into overdrive. In particular, substances called cytokines, which tell other parts of the immune system there is a problem that needs fixing in the body, and which coordinate the immune response, are released in excessive amounts.
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This creates what’s known as a “cytokine storm”, which ends up causing damage to healthy tissue.
Doctors have seen similar cytokine storms in people with different kinds of infections or with certain cancers. But the cytokine storm with COVID-19 is wildly different.
As a result, therapies that work for the other cytokine storms don’t control the problem, Dr Gidwani says.
“My brain is thinking ‘what is going on? Is there a way to fix this?’ I don’t know what to do,” he says.
“It is very challenging, very frustrating, very upsetting.”
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‘This is a brand new disease’
Understanding what makes the cytokine storm unique in severe COVID-19 is important as it means there may need to be a different approach to helping patients get better.
“This is a brand new disease. We are seeing more and more that the therapies we are used to working with don’t necessarily produce the same results with COVID,” Dr Gidwani says.
One important difference is that the cytokine storm in severe COVID-19 results in widespread blood clotting, which can in turn trigger heart attacks, strokes, deep vein thrombosis (DVT), pulmonary embolisms (clots in veins in the lungs) and limbs so damaged they may need to be amputated.
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What’s more, Dr Gidwani says the surge in cytokines can last up to 45 days and can wax and wane. Patients may show an improvement, then a worsening — a pattern that can be repeated several times, often for weeks on end.
This can lead doctors to misjudge how sick a patient is and withdraw supportive measures such as a ventilator before they should.
“It is important to realise this is a distinct [immune] syndrome and that you can therefore avoid certain pitfalls,” says Dr Gidwani.
“This is not what we expected at the outset.
“But we never knew what to expect. I don’t know what will happen next either.”
Over-activation of the immune system could be a major “unifying element” that explains a large part of why the disease can play out in such different ways in severe COVID-19 and in PMIS, says Australian cardiologist and blood vessel researcher Jason Kovacic.
An immune attack on blood vessels potentially explains many of the key dangerous features of both conditions, says Dr Kovacic, who is Professor of Medicine and Cardiology both at New York’s Icahn School of Medicine and the Victor Chang Cardiac Research Institute at the University of NSW.
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Rare mysterious illness in children
Paediatric multisystem inflammatory syndrome is an entirely different set of symptoms but it is nonetheless a “post-COVID-19” disease, Dr Gidwani says.
Symptoms may include fever, swollen hands and feet, a red rash that can occur on the skin around the lips and eyes, abdominal pain, diarrhoea and vomiting, resembling a rare condition called Kawasaki disease, thought to be triggered by infections.
But it is inflammation of the heart and blood vessels supplying it that make the condition potentially deadly.
Blonde, curly-haired girl, about 8, wearing pink mask with nurse in blue smock, gloves, glasses getting medical test
Not all children with paediatric multisystem inflammatory syndrome tested positive for current or past infection with the virus.(AAP: Lionel Urman)
Australian health authorities have pointed out the link between the syndrome and COVID-19 is unclear because not all affected children were positive in tests for current or past infection with the virus.
But it’s known “false negatives” — where no signs of current or past virus exposure are detected when that is not actually the case — can occur with these tests.
In all likelihood, the minority of cases who did not show a link with COVID-19 were in fact just undiagnosed cases because of inaccuracies with the tests, says Dr Gidwani.
Further investigation is underway to explore this idea.
The illness has appeared in 102 children from newborns to teenagers in the US in past two months, killing at least three.
Two of those died at Mount Sinai Hospital. Additional cases have been reported in the UK, Spain, France, Netherlands and Italy.
“All of these kids [with paediatric multisystem inflammatory syndrome] have some sort of inflammation of the blood vessels,” Dr Gidwani says.
“It is not due to the COVID itself but to an overblown immune reaction following COVID exposure.”
In this sense, paediatric multisystem inflammatory syndrome seems similar to severe COVID-19, in that it is the result of a disordered immune response, triggered by the virus.
But the timing and nature of the immune response is different in the two conditions (with different outcomes in terms of symptoms).
In severe COVID-19, which occurs in about 10 per cent of patients, the immune over-activation usually occurs eight to 10 days after symptoms begin.
In the children’s syndrome, it seems the immune over-activation occurs either late in the course of infection, or after the virus has been cleared from the body.
“These kids have escaped the symptoms of the acute infection but they may not have escaped the post-infectious reaction to the virus.”
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The condition is much rare than severe COVID, and it is thought that children who develop it may have unusual genetic vulnerabilities.
“Only a very small number of kids who get COVID exposure will get this,” Dr Giwani says.
“We do not have a good handle on what the number is but it’s pretty clear it is extremely rare.”
While treatments for the unique cytokine storm in COVID-19 are currently limited, recognising that it is new and different is nonetheless a vital first step towards tackling the problem and saving lives, Dr Kovacic says.
“It is a very, very, scary virus.”
Me: Coronavirus is totally vulnerable as the virus in your head, however, once it incubates in your head and goes down into your body as Covid-19 then you are potentially fucked.
Use a strong salt water snort or sniffle to kill the virus in your head, which will stop it from ever becoming the disease, which virologists are trying to find a cure for in your body – how silly is that?