17 February 2021 — Dr Malcolm Kendrick
I have spent large chunks of my life trying to untangle medical data and research. COVID19 has long since defeated me. I have been unable to make any sense of the information we are bombarded with daily. So, I decided to go back to basics.
At the start of the COVID19 saga, I was interested to know what the infection fatality rate (IFR) was likely to be. I felt I could then have a go at comparing it to other diseases, primarily influenza.
The infection fatality is the number of people infected with the virus who then die. This is very different to the case fatality rate (CFR), which is the number of people infected with the disease who become unwell enough (sometimes, but not always) to be admitted to hospital – the ‘cases’. Who then die.
Before COVID19 appeared, there used to be a reasonably clear distinction between the infection fatality rate (IFR), and the case fatality fate (CFR) and it is important that they should not get mixed up. Because the case fatality rate is almost always far higher than the infection fatality rate – as you would expect. People who are ill enough to go into hospital are far more likely to die than people who do not suffer any symptoms. Bear this in mind.
Another thing to bear in mind is that, at the start of any epidemic it is simpler to establish the case fatality rate, because most people who are seriously ill end up in hospital and/or will have tests to see if they have the disease in question. Those with no symptoms may never cross the path of a medical professional and are very unlikely to be tested.
What is the ratio between the two? It depends on the virus. With Ebola the infection fatality rate and case fatality rate are closely matched – more than fifty per cent of people who are infected, die. With the common ‘coronavirus’ cold, the spread is far wider, maybe a hundred to one, or a thousand to one – perhaps more.
The fact that most infections are never noted, is one of the reasons why the infection fatality rate for previous flu epidemics can vary so wildly from paper to paper. However, with influenza the CFR/IFR ratio has generally been estimated to be about ten to one. By which I mean that, for each ten infections, one will be severe, and it is amongst the severe infections that you get the deaths.
Armed with such knowledge, and assuming COVID19 had a similar case: infection ratio to influenza you could have a go at working out the infection fatality rate. Always bearing in mind that people with no symptoms, who are not tested, are very unlikely to appear in any figures.
You are always guessing – to some degree or another.
However, you always know three things:
- The infection fatality rate must always be lower than the case fatality rate.
- The case fatality rate will appear to fall as less severely infected people are tested.
- The infection fatality rate will also appear to fall as more people with no symptoms are found to have had the infection.
For example, in China, at the start of the COVID19 pandemic, the infection fatality rate was reported to be three to four per-cent. This rapidly fell. Then it went up a bit, then it fell, then it went up. Then, everyone started giving different figures. The highly influential Imperial College group, led by Professor Neil Ferguson, decided to use an infection fatality rate of 0.9% for their modelling.
Somewhat later on, John Ioannidis, an influential figure in the world of medical research, estimated the infection fatality rate to be 0.27%. This was a couple of months after the Imperial College figure was published. 
Peter Gotzsche, who established the highly regarded Nordic Cochrane collaboration, put the figure even lower than this. He looked at a study in Denmark, where blood donors were tested for antibodies. Using these data, the researchers established an infection fatality rate of 0.16%.  Other figures came in higher, some lower.
The most tested population in the World – per head of population – is Iceland. Last time I looked, Iceland had 6,033 ‘cases,’ and twenty-nine deaths. This represents a case fatality rate of 0.5%, which suggests an infection fatality rate of 0.05%. 
However, these figures I am quoting from Iceland come from a time after everything changed. At some point, difficult to put an exact date on this, it was decreed that if you had a positive PCR COVID19 test, with or without symptoms, you were to be defined as a case. No matter if you had symptoms, or not. This had the result of making the infection fatality rate, and case fatality rate, the same thing. Suddenly, all cases are infections, and all infections are cases.
Which means that any comparisons of the infection fatality rate with COVID19, and other diseases became virtually meaningless. The infection fatality rate suddenly shot up to match the case fatality rate, which point I gave up trying to work out the infection fatality rate. I doubly gave up when I tried to find out the accuracy of the PCR tests. Were these tests over-diagnosing, or under-diagnosing?
So, I thought I would turn my attention to the population fatality rate instead. That is, how many people has COVID19 killed in a population, or country. This figure is the bald, unvarnished, death rate. It does not, necessarily, tell you how many people have been infected. It does not tell you the percentage of cases, that die. It simply tells you how many people have died… with COVID19 written somewhere on their death certificate. [Or even not written on their death certificate]
At present, in the UK, the total number who have died is one hundred and seventeen thousand. This represents a population death rate of 0.17%. if you knew how many people had been infected, in total, you could work out the infection fatality rate from this. But we don’t know how many people were infected, and now we never will. Because so many people are now being vaccinated. They will show antibodies, and it will not be known if that is because of an infection, or due to vaccination.
So, where to turn to next. If you look at the entire world, the current figure of COVID19 deaths, on the fourteenth of February, stood at 2,406,689 3. Which is a little over one in three thousand, or 0.033%. How many people in the world have been infected? Nobody knows that answer to this question. There are some countries that have done very little testing, others far more.
On the basis that there are so many questions, with very few clear-cut answers, I thought I would try to compare the two point four million figure with previous influenza epidemics.
A study was done in 2016, looking at the influenza epidemic of 1957 – one of the worst in recent history. They extrapolated the mortality figures from 1957 to 2005, because the World’s population doubled during that time period (I am not entirely sure why they chose 2005). Their conclusion was that a flu epidemic of similar magnitude to that of 1957 could kill two point seven million people.
‘In conclusion, our study fills a gap in the availability of global mortality estimates for historical influenza pandemics, which can help guide pandemic planning. Our model extrapolates 2.7 million influenza-related deaths (95% CI, 1.6 million–3.4 million deaths) should a virus of similar severity to the 1957 pandemic influenza A(H2N2) virus return in the 2005 population, which is intermediate between global estimates for the 2009 pandemic (0.3 million–0.4 million deaths and a devastating 1918-like pandemic (62 million deaths; range, 51 million–81 million deaths)’.
Extrapolating onwards to 2020, where the population is significantly greater than in 2005, then the figure from the 1957 epidemic would now be just over three million deaths. Which means that, up to this point COVID19 has been thirty per-cent less deadly than the influenza epidemic of 1957 – per head of population.
If the Imperial College infection fatality rate of 0.9% is accurate, once around eighty per cent of the world’s population has been infected [at which point population wide immunity would be reached] we should see fifty-four million deaths. We are currently nowhere near that figure, and at the current rate of deaths, per year, it will take twenty-two and a half years to reach the fifty-four million figure.
Of course, people will argue that this outbreak is far from over, and millions more will certainly die. Yes, more people will die, but the current number of new cases and deaths is falling pretty rapidly worldwide, rather than rising. We may reach three million, we may not. It is exceedingly hard to believe we would ever have reached fifty-four million even without any vaccines.
So, how deadly is COVID19? It seems, so far, to be equivalent to a bad flu pandemic. Worse than most in recent times. However, it seems to have had an extremely variable impact.
In Singapore, there have been nearly sixty thousand ‘cases’ and twenty-nine deaths. A case fatality rate of around one in two thousand, or 0.02%. The UK has had four million cases and one hundred and seven thousand deaths. A case fatality rate of 3%. Therefore, if you get COVID19 you are one hundred and fifty times more likely to die of it in the UK, than in Singapore 3.
Yes, I went back to basics and the figures still didn’t make any sense.