How coronavirus kills: Q&A with infectious diseases expert Josh Davis

He is a career development fellow of the National Health and Medical Research Council and president of the Australasian Society for Infectious Diseases.

He spoke to the Newcastle Herald about the clinical progress of COVID-19 and how an overzealous immune response called a cytokine storm can have deadly consequences.

NH: Overseas doctors are reporting that COVID-19 patients can crash fast in intensive care. What happens when patients go from being relatively healthy to requiring ventilation?

Professor Davis: "What we've observed is that they do crash fast, as in over a number of hours people can go from just needing a little bit of oxygen to needing to go on a ventilator, that sort of progression that normally happens over days in other conditions.

"We think early in the illness people have a lot of virus in their respiratory secretions, high viral loads, but not all that much immune response. In the second week of illness the viral loads are lower and there's a lot more immune response happening.

"From animal models, we know that a lot of immune cells are migrating into the lungs. We think that why people suddenly get really sick is that there's this massive immune activation and this vicious cycle of more immune activation and this cytokine storm which can cause a lot of lung inflammation and low blood pressure and other organ failures.

"What a lot of people don't realise is that with a lot of infectious diseases it's the human immune response that does the damage and not the infection itself. That's also likely here when people get the severe lung injury the second week."

NH: Can you describe the clinical progress of the disease?

PD: "The first thing to say is, just on one end of the spectrum, a significant proportion of people are asymptomatic.

"We don't know yet what that percentage is because we haven't had widespread testing of people without symptoms. But from a couple of published studies, one from Iceland and one from the cruise ships where they tested everybody, we think at least half of infections are asymptomatic.

"Of the 50 per cent who get symptomatic, about 80 per cent have very mild symptoms, a cold, sore throat, runny nose, maybe a mild cough.

"That generally will last much longer than a normal cold, 10 to 14 days of symptoms, whereas a normal cold might be three to five days. Those sort of people never need to come to hospital.

"Of those that need hospitalisation, the illness can last quite a long time, 10 to 14 days of fever and cough. And finally there's the 1 to 5 per cent who get really sick and need intensive care. That usually happens in the second week, so after seven to 10 days of symptoms is when people get severe pneumonia and potentially need ventilation."

NH: Are younger people not getting sick because they have a less developed immune system?

PD: "That can't be the whole explanation. It might explain why young children don't get all that sick, because young children certainly have less mature immune systems and don't respond as well to vaccines.

"But it shouldn't apply to people in their 20s and 30s. They still have a much lower rate of getting severe illness than people in their 50s and 60s. But people in their 20s and 30s have a very robust immune system, and, in fact, as you get older, past 50 or 60, your immune system starts to get less and less efficient.

"The other potential explanation is that there's these receptors in the lungs called ace receptors, which is what the virus binds to to get in, and kids seem to have less density of those in their lungs than adults. It might be harder for the virus to get into the cells of children."

NH: Some studies from overseas suggest the mortality rate is quite high once a patient is ventilated. Will we see the same thing here?

PD: "It's heavily age-dependent. With people over 80, yes, they've got about a 50 per cent mortality if they get on a ventilator, but people under 50 they've only got about a 10 per cent mortality if they end up ventilated. That's based on data from the US and China.

"The handful of people who have been admitted to ICUs in Australia, very few have died. Certainly nothing like 50 per cent.

"I think the reason the mortality has been so terrible in Italy and now New York is that their health systems were overwhelmed.

"I think with really good-quality, supportive care, mortality rates should be significantly lower than in a health system that's overwhelmed."

NH: What are the long-term outcomes for people who have recovered from a severe case of COVID-19?

PD: "We don't really know long-term outcomes yet from COVID, but we do know that people with acute respiratory distress syndrome often end up with some loss of lung function and other quality-of-life problems like muscular weakness and depression over time. It can take over one to two years for their lung function to plateau. Usually it improves and improves then plateaus after a year, but they'll probably be left a lot less fit than they were before.

"The lung's definitely the key organ. The second organ that's been noted to be a problem in the really sick patients is the heart. Those who end up dying, they often end up with a myocarditis, so the heart becomes involved and gets badly affected. Those who survive don't end up with a myocarditis."

NH: What's your message to people using untested medication to prevent or treat COVID-19?

PD: "We don't want people using experimental anti-viral drugs at the moment outside the context of clinical trials.

"There's been a lot of stuff in the media about certain drugs possibly being effective, and Donald Trump went on and promoted hydroxychloroquine. As a result people are using these things off label left, right and centre, and they're all sold out, like toilet paper.

"I'm involved in running a national clinical trial of some of these medications. It's possible they're harmful, it's possible they do nothing, and it's possible they're of a small benefit."

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