That is the question that I think we should all be thinking very carefully about when we’re thinking about COVID-19 and what it means for us. Exactly how dangerous is this thing? What does it mean for us? What should we do with the data we’re receiving and should we take it with a grain of salt? And what do we still not know?
Because, there’s so much we don’t know. What plays out in the next few days is going to be crucial to understanding how serious this situation is.
So, what is the denominator? In public health epidemiology, we talk about the case fatality ratio, the CFR. Simply put, it’s the number of deaths divided by the number of cases.
This number is the reason people have become so worried about COVID-19, and the reason the whole world has fallen off a cliff into some sort of economic and social freefall.
This is how they’ve worked it out. If you look at data from, for example, Johns Hopkins University (they’ve got the most up-to-date data) it says there has been around 18,900 deaths worldwide. Quite a lot of people. For 423,000-odd cases, that gives you a case fatality rate of 4.5%. That sounds bad, right? The seasonal flu has a case fatality rate of about 0.1%, so that is 45 times more deadly than the seasonal flu.
So, is that number right? Well, some would say it’s an underestimate because, if you measured those 423,000 cases that are known today, and there were 18,900 deaths today – those deaths are all due to people who were infected a couple of weeks ago. It was the known infected back then, so it’s an underestimate.
But I don’t think it’s that simple. Are the known and tested cases actually representative of all of the number of cases out there? That’s a massive unknown and that makes a massive difference. With the H1N1 swine flu in 2008, the initial estimates of case fatality rate were between 5-11%, so it made it a horrendously deadly flu. At the end of the day, when it was all worked out, when they actually knew exactly how many people had had it and been infected, the case fatality rate was 0.02%. It was five times less deadly than the seasonal flu. Initial estimates can often be high and that may be the case here, too. There is some evidence for that, but exactly how high is the question. We need to understand this data very carefully and think about what we’re doing. I’m not seeing that debate in public at the moment. We need to start talking about it and having that debate, because it makes a massive difference to what we do and what the worst looks like.
So let’s take you through where the data is at the moment. In China, they’ve had 3,281 deaths and 81,591 known cases, 4% mortality. Sounds like the rest of the world. Did we get everyone in China that had had it? We don’t know that. Maybe we did. Maybe China is getting on top of things. They’ve locked down and they’ve slowed down a really deadly flu.
The South Koreans have done some 300,000 tests. They’ve had 126 deaths for 9,000-odd known cases. Their case fatality rate is 1.4%, which is substantially different than 4.5%. That’s still a lot of people, and that still makes it 14 times more deadly than the seasonal flu.
There is only a small amount of data from the Diamond Princess, the ship that originally got stuck in Japan. Of 3,711 people on board, 712 ended up getting COVID-19, which is only 20%. Twenty percent of the population got it when they were almost certainly all exposed to it. There were eight deaths. The case fatality rate therefore was 1.1%, still 11 times more deadly than the flu, but with the added factor that it was an older population – the median age was 64.
We’ve all read the news and seen the images from Italy of people ending up in coffins, being wheeled off. It that normal? No, I don’t think it is. Are those people old and have comorbidities? Yes. Were they going to die of something anyway? Perhaps, but not at this time, at that rate. How many people in Italy have actually had COVID-19? That’s a massive, massive unknown.
To put the cat amongst the pigeons today, researchers at Oxford modelled what they thought the likely infection rate in the UK was. They think up to 50% of people in the UK have COVID-19 or have had it, with very light symptoms, or asymptomatic. I think that’s unlikely. We have very little evidence for that. If that was the case though, the UK has had 422 deaths, and if half the population is infected, that’s 33 million people infected, which makes the case fatality ratio very, very low.
What we don’t know is how many people worldwide have actually been infected and how many have been asymptomatic.
There is an answer and this is what we need to be talking about as a matter of urgency – serological surveys.
This could be an on-the-spot test with a drop of blood in a little vial, a reactive protein, which is now being developed, and we could say, because of the antibody response, whether you’ve had COVID-19 or whether you, in fact, still have it. If you did that with random populations, in the same way that we do political polls, you can get a lot of information and you can be reasonably confident about the numbers that you get.
We need to know the denominator. When we know the denominator, we can be much more certain of what is going to happen.
This is the scary part, isn’t it? We know Italy exists. We should watch New York City in the next five to six days – I think what happens there will be hugely telling. And we should watch China. There is an interesting paper that was published in the Lancet a couple of days ago. It talks about the herald wave. It’s the little wave that comes before the big tsunami. Because that’s what happened in 1918. There was an initial wave of the Spanish flu, and then came the second and third waves, which were more deadly. So should we worry and should we continue to be worried? Absolutely. It’s hard to know exactly how cautious to be when we don’t have all the data.
I think we’ve done the right thing. We value human life and health more than having our economy working.
There will be consequences with what we’ve done – chuck it off a cliff and see what happens – but we’re doing it to protect us.
What will the numbers eventually say? I think it’s unlikely to be like the H1N1 swine flu of 2008, where the case mortality proved to be very low. It could be more like the Diamond Princess scenario or South Korea, or even lower. Or it could be that the deaths are going to soar and soar because, actually, fewer people than we thought are infected, and even if we get it under control, it could come back later. We have no answers to any of those, so the idea is to be cautious.
Frankly, I’m seeing the next four weeks as an opportunity – an opportunity to learn more; to spend more time with my family; to do some biking with my boys, so I’ll be fitter and healthier. So, I think there’s a good side to this.
In the meantime, if you’re a researcher in this area and you know how to do serological surveys and you’ve got some access to that, then we should be doing that. If you’re in government, while we’re chucking billions at everything, chuck a few million at doing some serological surveys. Get that up and running as a matter of urgency, because that is the number that we need to know. Only then do we know what we’re dealing with. Otherwise, we are dealing with incomplete data. When you deal with incomplete data, you make bad decisions.