## Infection fatality ratios, or why SARS-CoV-2 is not flu, continued

Even after more than 18 months of COVID-19 outbreak, there are still voices questioning the severity of the virus as compared with, for example, the seasonal flu. Although the evidence for adults has been overwhelming and is rarely questioned these days, there is an ongoing debate about children and young adults.

The impact can be measured by the Infection Fatality Ratio, IFR, the per cent of those infected who die of COVID-19. As the name suggests, it is a ratio of two numbers: fatality (numerator), i.e. the number of those who died from COVID-19, and infection (denominator), i.e. the number of those who became infected.

There is a pretty good definition of who counts as dying from COVID-19, including a doctor diagnosis and time from infection. This procedure attempts to exclude that those who acquired COVID-19 but then die from other causes. We will never know the exact number, but with all procedures, we can be sure that the numerator is quite well determined.

The denominator, in contrast, is a bit tricky. As I described elsewhere, the number of those infected – as opposed to those showing symptoms – is not easy to estimate. There are basically two ways to do this, one using models and one using community testing; preferably the two methods are used together. Thanks to massive testing we are now in a reasonably good position to estimate the numbers of people infected at any given point.

Taking the ratio, we arrive at the following graph:

Red points correspond to results of different studies, using different data sets and methodologies, estimating the IFR for COVID-19. In contrast, blue points are for seasonal influenza, as estimated in different years (2014-2019).

The first thing to note is that both flu and COVID-19 are much more deadly to older patients than to young ones. The scale above is logarithmic, and so the difference is actually quite large. 2 in 1,000 of 80-years-old flu sufferers are expected to die (0.2%) from seasonal flu. In my age class, this drops to 0.02% (2 in 10,000), but it is still quite high (on the flu-related deaths, see my post here).

I was astonished to find that many people seem to be quite relaxed about this level of deaths. In fact, a lot of times, the argument goes like this: We have been OK with the flu deaths so far, and COVID-19 is not much worse, so why do we suddenly do all the lockdowns?

I think this argument is wrong in two ways. Firstly, have we been doing enough to protect these people every winter before COVID-19? Or, have we been accepting that the cost of doing more (economically and socially) to protect the vulnerable people from flu-related deaths, is too high?

Secondly, COVID-19 is not flu, as most red points in the graph above are well above blue points – with a possible exception of 1-year-olds and younger. The COVID-19 IFR is the astonishing 10-30% for 90-year-olds, dropping to 0.2-1% in my age bracket, and to 0.005-0.05% for my children (who are young adults). This is as much as 25 times higher than for the seasonal flu for older individuals, but even for young ones, it is 3-5 times higher.

There are some studies that suggest that COVID-19 and flu have similar values of IFR for children and a couple of studies that suggest it might be less deadly, but these studies are in minority. The Perez-Saez study (with a very low IFR for 10-19-year-olds) is actually quite old (February-June 2019) and based on the data which show no deaths in this age range (and therefore the value is heavily influenced by the assumptions of their statistical model). Their credible range in that age class is 0 to 0ยท0033 in that category and so would extend well into the blue range in the graph. Similarly, Molenbergh’s paper is also from the first wave, but at least has some data in that age range.

Why is it so important to understand these numbers? Firstly, COVID-19 is much more deadly than the seasonal flu. It is no wonder that the excess deaths records show such an increase at the peaks of COVID-19 outbreaks.

Secondly, while younger people can fight off the virus much better than older ones, they are still more affected by COVID-19 than by the flu. This extends even to very young children. In other words, even if you are young, you have a much higher chance of dying from COVID-19 than you had a chance to die from seasonal flu in other years.

Thirdly, the chances of severe complications from COVID-19 vaccines are not that well understood for children. However, extrapolating from adults, the overall risk of Astra Zeneca blood clots is approximately 4 people in a million, i.e. 0.0004%. The Perez-Saez study estimates 0.0002% risk of death in the 10-20 years bracket, but it is an outlier. Most other studies of the IFR give results in the range of 0.001-0.01% for this age group – between 1 in 100,00o and 1 in 10,000. These values are much higher than the risk of vaccine complications.

Clearly, we do not know the long-term effects of vaccination for both adults and children, but given that the risk of death is high, there is a good argument for extending the vaccination to that group.

Fourthly, I have not even mentioned the “Long COVID”. There is good evidence that a large proportion of those infected by SARS-CoV-2 ends up with long-term complications. There is mounting evidence that this affects young people as well as old ones.

The lasting effects of COVID-19 are going to cause huge problems in the future, both individually – as people continue to suffer for a long time – and socially – as the public health systems will need to cope with these problems potentially for years to come.

The solution? To act quickly and decisively to suppress the spread and to follow this action with implementing strict border controls and testing to detect and stop any small outbreaks before it is too late. And, keep the vaccinating momentum, both nationally and globally.