Opinion

Peter Doherty
The pandemic we had to have

Over the past 18 years or so we’ve had periodic public health warnings about one or another bad bug that’s out to get us. In 2002-03, there was severe acute respiratory syndrome (SARS-1), H5N1 bird flu in 2002, the H1N1 swine flu pandemic in 2009 and then Middle Eastern respiratory syndrome (MERS) in 2012.

Australia had almost no cases of SARS-1 and none of MERS. With H5N1, although 60 per cent of those who were directly infected from chickens with the highly pathogenic virus did die, it never “jumped” to start spreading between humans, and again, we had no infections here.

The H1N1 swine flu, which did “jump” from pigs to us – never kiss a pig! – was a bit of a fizzer, likely because many who were alive in 1977, when the H1N1 “Russian flu” hit, had protective antibodies. Unusually, the most severe swine flu cases were in school-aged children, adolescents and young adults – especially heavily pregnant women – with the elderly being relatively protected.

Understandably, this pattern of media blitz and relative non-event led to a measure of scepticism. Some of the radio shock jocks first called Covid-19 yet another example of an academic “‘We’ll all be rooned,’ said Hanrahan” syndrome. But now, even these guys have changed their tune, and broadcast remotely from their opulent rural estates.

With Covid-19, the scenes from Wuhan, then Iran, Lombardy, Spain and so forth are horribly real. This virus is dangerous. If we’re elderly and/or have other underlying health issues, it’s very dangerous. And, although otherwise fit young people will mostly be okay, some in this group – even the occasional small child – will die.

We don’t want Australia to be another Italy or Spain. Avoiding that is basically up to each and every one of us. Our state and federal governments may have got a few things wrong at first, but the message is now clear, their actions have been both informed and forceful and we all need to listen, learn and act accordingly.

The best advice I’ve seen is to pretend that you have the infection, then do whatever’s necessary to avoid transmitting it to others. That will protect you. In particular, we must do everything possible to keep Covid-19 out of remote Aboriginal communities, as Australia’s Indigenous people always have a worse time with influenza.

But what’s so special about SARS-CoV-2, or severe acute respiratory syndrome coronavirus 2, which causes Covid-19? Well, even those of us who are in the “infectious disease and death game” have only known about this virus for fewer than four months. Much of our thinking is based on global experience of the original SARS, then MERS. We’re learning fast.

What is clearly different with this outbreak is that SARS-CoV-2 is completely new to us. Unlike with flu viruses, to which we all have some prior immunity due to pre-existing antibodies or something called “cross-reactive T-cell memory”, the world is experiencing a “virgin soil” pandemic, where everyone is both susceptible and a potential transmitter. This doesn’t mean it’s unstoppable, though. The latest “virgin soil” event most of us knew of was the 2015 Zika virus explosion in South America. Five years on, there is still no vaccine for Zika but now, with more and more people having been infected, they have “herd immunity” and we hear nothing about that virus.

Covid-19, SARS-1 and MERS are all caused by beta coronaviruses (βCoVs). One of our common cold viruses is also a βCoV but it causes few problems and has received little attention, especially from immunologists. A key difference between the CoVs and the influenza viruses is that flu strains A and B, unlike the CoVs, lack any “editorial” proofreading mechanism and thus throw off many more mutants.

The flu B strains that infect us are maintained solely in humans, while pandemic flu A viruses “jump” – as in 2009 – from animal reservoirs. The flu A genome is in eight different bits, which can “reassort” to give a novel pandemic strain if, for instance, a cell in the nose of a pig is infected simultaneously with two different flu A viruses.

Once established in humans, both the A and B viruses change by mutation to give the familiar “seasonal” epidemics. Typically, the inactivated, non-infectious vaccines used in Australia contain two flu As – H1N1 and H3N2 – and one or two flu B strains. This year, it’s vital to get the flu vaccine as soon as possible. You don’t want to have influenza then Covid-19, or vice versa.

SARS-1, MERS and Covid-19 are all maintained in nature as subclinical infections in various bat species. The best understood is SARS-1, which jumped from horseshoe bats to a little forest-dwelling mammal called the civet cat and then to humans. The transmission point for humans was live animal wet markets in southern China, with the virus being widely disseminated as many travelled to visit family during the Lunar New Year.

That’s why Lunar New Year celebrations were immediately shut down when Covid-19 was identified in Wuhan. The likely pathway for MERS was bats to camels – never kiss a camel! – to us; while the proposal for SARS-CoV-2 is that it jumped from a bat potentially to a pangolin, likely entering the human population at a wet market in Wuhan.

Through 2002-03, the SARS-CoV-1 infected about 8100 people – mostly in east Asia, including China, Singapore, Taiwan and Vietnam, and the only “Western” spread was to Toronto. The MERS-CoV has so far caused disease in some 2500 people, including 212 in 2019, with the disease largely restricted to the Middle East and Asia, including Thailand and South Korea.

As of March 25, the World Health Organization is reporting 414,179 cases of Covid-19, in 196 countries. A less official number is 450,000 cases.

Covid-19 thus tops the hierarchy for transmission – followed by SARS-1 then MERS – but that is reversed for mortality. The death rate for MERS was 34.4 per cent and 9.6 per cent for SARS-1. Covid-19 will likely kill 1 per cent to 1.5 per cent of those infected. Although the initial report from Wuhan was about 2.5 per cent, the recognition that 30 per cent or more of infections can be asymptomatic brought that down to 1.4 per cent, which rises to 2.6 per cent in the over-60s. Still, even a mortality rate of 1 per cent is 10 times what we see yearly for influenza.

Recent data from the United States suggests that 30 per cent of those in the 75-to-84 age group who present with symptoms need to be hospitalised, with 10.5 per cent needing to be placed in intensive care units. Some of the ICU patients are likely to die – about 4.3 per cent – and, as is the case in Italy where the hospitals are overwhelmed, that proportion will be much higher if there is no access to mechanical ventilation. That’s why we need to “flatten the curve”.

Doing the numbers: if, say, 60 per cent of the Australian population becomes infected over the next six to 18 months, that means some 150,000 people will die. If we can’t “flatten the curve”, the death count will be considerably higher. The number for the US would be well over a million people. By contrast, 40,000 Americans die from influenza in a bad flu year and 40,000 are killed by guns, with 60 per cent of those being suicides.

So, why is Covid-19 so much worse than the flu? The lung is an incredibly delicate organ and, if the mix of damage done by the virus and the resultant host response is too severe, the delicate terminal bronchi become clogged and we just can’t get enough oxygen to survive. At that advanced stage, flu and Covid-19 may be very similar. In 2009, some 50 per cent of those who would likely have died from swine flu were saved by heart–lung machines that breathed for them while they went through the crisis period. That resource will quickly be overrun as the Covid-19 line goes steeply upwards, as will the supply of ventilators to help people breathe in ICUs. We have to flatten the curve.

Apart from the current social distancing and isolation measures, a major priority is to get a safe and effective vaccine out there and into everyone’s arm as fast as possible. Of course, those who’ve already had the infection may not need the vaccine, though my approach is that it never hurts to have a booster. Maybe we will move a bit quicker but even with the fantastic technologies we now have to hand, vaccination could be 12 to 18 months off. With a bit of luck and universal vaccination, we might ultimately see the back of Covid-19.

But what happens the next time one of these viruses makes the jump to humans? At every level – from the laboratory, to the clinic, to the hospital, to policy – we’re on a very steep learning curve. Much of what was in place in Australia has proved to be robust and “fit for purpose”, although there is no way the health system in any country could have built in the capacity to deal with Covid-19.

When it comes to developing new tests for the virus and for the antibodies that tell us people have been infected and recovered, we’re in infinitely better shape than we were during the SARS-1 or MERS outbreaks. Novel vaccines developed with new technologies have already gone into animal trials in Australia, and into people in the US. But we have to be sure any product is both safe and efficacious – and that takes time.

For the future, we may want to look at rebuilding some of our own manufacturing capacity. Once this is over, there will be many questions and, if we’re smart, we’ll be keeping some of the positive changes that are being made right now. Experience is a great teacher, though the lessons can be very painful and difficult.

This article was first published in the print edition of The Saturday Paper on Mar 28, 2020 as "The pandemic we had to have".

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Peter Doherty won the 1996 Nobel prize in physiology or medicine for his research on immunity.