What have 1 million deaths taught us about COVID-19 and how to treat it?

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In the beginning, we knew almost nothing about the disease sweeping the world.

“We started out by basing treatment and investigations on previous research of similar types of illnesses,” said Steve McGloughlin, director of the intensive care unit at Melbourne’s Alfred Hospital.

But a dearth of evidence about COVID-19 wasn’t a problem for long.

Since January, thousands of research papers have been published about the virus that has now left more than one million people dead.

For doctors and public health officials, part of the challenge has been keeping up the flood of scientific studies, which have varied significantly in quality and scope.

“As time goes on, the number of patients involved in clinical trials has increased, which means the quality of research and the inference you can take from it has improved,” Dr McGloughlin said.

Even so, our understanding of COVID-19 has improved markedly in the past nine months.

Here are five things we’ve learned about the disease and how to treat it — and what we still don’t know.

Drugs can help, but not hydroxychloroquine

When the pandemic kicked off in early 2020, hydroxychloroquine — an antimalarial drug that had shown promise against previous coronaviruses — emerged as an early treatment candidate.

Despite shaky scientific evidence for its use against COVID-19, the drug was touted by US President Donald Trump as a “game changer” and heavily promoted by Brazilian President Jair Bolsonaro.

Australian health authorities held off from recommending its use, which turned out to be a good decision. There is still no robust evidence to suggest hydroxychloroquine is an effective treatment for COVID-19.

Instead, according to infectious diseases physician Steve Tong, research has shown remdesivir (an experimental antiviral medication) and dexamethasone (a corticosteroid drug used for years to reduce inflammation) are most effective at improving recovery and survival rates in seriously ill COVID-19 patients.

“Remdesivir has been shown to reduce the time to recovery,” said Dr Tong of The Doherty Institute and The Royal Melbourne Hospital.

Meanwhile, dexamethasone has been shown to reduce mortality in patients who require ventilation or oxygen.

“The sicker patients seem to benefit most from dexamethasone,” Dr Tong said.

COVID-19 is respiratory, but affects more than lungs

COVID-19 is predominantly a respiratory illness — SARS-CoV-2 binds to the body’s ACE2 receptors, which are mostly found in the lungs and respiratory tract.

This is where the disease typically causes damage, whether patients are mildly, moderately or severely ill, Dr McGloughlin said.

But in recent months, it’s become clear the virus doesn’t just attack the lungs.

ACE2 receptors are also found in the heart, blood vessels and kidneys (among other places), and the disease has been shown to cause damage to multiple organ systems.

“People seem to develop blood clots when they become severely unwell — that seems to be well recognised now,” Dr McGloughlin said.

There have also been reports of cardiovascular damage, stroke, and other neurological symptoms.

Steve McGloughlin standing in the ICU at The Alfred.
Associate Professor Steve McGloughlin is an intensivist, infection diseases specialist, and director of ICU at The Alfred.(Supplied: The Alfred)

Dr Tong said the illness could generally be thought of in two phases.

“There is an initial phase where there is a lot of virus around, a lot of viral replication, and the patient’s immune system then dampens that down,” he said.

“But in some cases, in the second week of the illness, [the immune system] overcompensates and we get this immune-mediated inflammatory response that leads to damage to the lungs and other parts of the body.”

This hyper-inflammatory response — known as a “cytokine storm” — happens when the immune system mistakenly goes into overdrive, releasing extra inflammatory proteins that erroneously attack healthy cells.

It can cause acute respiratory distress, which means less oxygen reaches your bloodstream, depriving your organs of the oxygen they need.

Age is the biggest risk factor for COVID-19 death

The factors that increase your risk of severe illness or death from COVID-19 have been the same since the beginning of the pandemic: older people and people with compromised immune systems are more vulnerable.

We also now know that individuals with diabetes and heart disease are at increased risk, as well people who are overweight.

Still, it’s not always clear why some individuals are hit harder by COVID-19 than others — especially those who experience a severe immune response.

“This is a common problem when dealing with any sort of severe infection,” Dr McGloughlin said.

While not all aspects of the immune response are understood, Dr Tong said clinicians now had a better sense of who was likely to fare well — and who wasn’t.

“Age seems to be, by far and away, the strongest prediction of whether someone will die from the disease,” he said. “If you’re a kid or in your teens or 20s, it’s very rare to die.”

There is some emerging evidence that suggests pre-existing levels of antibodies and T-cell based immunity may influence the likelihood of a person developing a hyper-inflammatory response.

“But it’s going to take quite a bit of teasing out, and even then, there is such variation in people,” Dr Tong said.

Dan Hadley, wearing a mask and gown, touches a screen with medical information
Nurse at Royal Melbourne Hospital ICU operates equipment in a room designated for severe coronavirus patients.(ABC Melbourne: Kristian Silva)

The illness can drag on … and on

One of the more surprising elements of COVID-19, according to Dr McGloughlin, is just how long the illness can last, even after the virus has gone.

“We have learnt that for the people who are unlucky enough to become critically unwell, it’s quite a long time in intensive care,” he said.

The period of time that critically ill patients are on ventilators tends to be longer than it is for other similar diseases, he said, and it can take up to a month or two for people to fully recover.

“On the positive side, many people are making a good recovery … but it is very long.”

It’s not just people in intensive care who experience lingering symptoms, either.

Anecdotal reports and growing research suggest that even those with mild illness can be plagued by persistent fatigue, breathlessness and “brain fog” for months after their infection has cleared.

But Dr Tong said COVID-19 “long-haulers” were generally in the minority.

“That’s maybe 10 per cent of people who get COVID. The majority are recovering and getting back to normal life.”

COVID-19 treatment is getting better

In Australia, COVID-19 outbreaks have tended to emerge slightly later and with less ferocity than in other parts of the world, which has bought clinicians valuable extra time, Dr McGloughlin said.

“We’ve got a couple of things in our favour in Australia, and one is that we’re a little bit behind the rest of the world.”

The other, he said, was Australia’s National COVID-19 Clinical Evidence Taskforce, of which he is a member. The taskforce was set up to help ensure treatment guidelines reflect the best and latest evidence.

“Our [clinical] outcomes reflect this — the outcomes in intensive care in Australia have been good,” Dr McGloughlin said.

Dr Tong agreed that a coordinated, measured approach to COVID-19 treatment had put Australia in a very good position.

With time, both clinicians have also found ways to improve treatment of seriously ill patients beyond proven drug treatments.

Doctors have found positioning patients on their tummy or side works better than if they are on their backs.

“When people lie on their back, their oxygen levels get worse,” Dr Tong said.

They also now delay the use of ventilators where possible, as months of experience had shown them it was difficult to take people off the machines.

“That’s something that’s changed and I think that’s been beneficial,” he said.

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