Do most locations have an infection fatality rate less than 0.20% from Covid-19 (and less than 0.05% for those under 70 y.o.)?

Question

This is the (tentative) conclusion of a meta-analysis found on the WHO's website, written by John Ioannidis, which in its abstract says:

Across 51 locations, the median COVID-19 infection fatality rate was 0.27% (corrected 0.23%). [...] In people < 70 years, infection fatality rates ranged from 0.00% to 0.31% with crude and corrected medians of 0.05%.

[... and in its conclusion... ]

Most locations probably have an infection fatality rate less than 0.20%.

Ioannidis also self-cites that in a later paper to say a bit more concisely:

Global infection fatality rate is 0.15-0.20% (0.03-0.04% in those <70 years)

According to Wikipedia, Ioannidis was criticized for some previous (primary) studies on the matter. So is this meta-analysis essentially correct or possibly misleading in some way?

Note 1: according to the mods, this a distinct question from Did WHO publish a bulletin stating that COVID-19 is “equivalent in lethality to seasonal flu”?, although it's obviously related as it was considered in an answer there as being what someone (else) implicitly referred to.

Note 1-bis: That meta-analysis has also been cited in a letter to the editor of the BMJ (by a certain Eshani M King) to say that

A recent peer-reviewed paper by one of the world’s most cited and respected scientist, Professor John Ioannidis of Stanford University, quotes an infection fatality rate (IFR) for Covid of 0.00-0.57% (0.05% for under 70s), far lower than originally feared and no different to severe flu. This paper is published on WHO’s own Bulletin but ignored by UK mainstream media.

(emphasis mine). But Ioannidis himself never seems to make an explicit comparison with flu and there are some other questions here on Skeptics about the appropriateness of the comparison, so let's stick with the original/technical claim in Ioannidis' own paper(s) for this Skeptics question.

(The sub-claim in that letter of the paper being ignored by the press is somewhat inaccurate. The Daily Mail, for instance, did cover the paper in a stand-alone article.)

Note 2: infection fatality rate is not case fatality rate. The former includes in the denominator all those infected, even if asymptomatic.

Answer 1

It is implausible if we assume the estimate of 400,000 USA Covid deaths to date is correct. If the IFR is really 0.2%, we would have 200,000,000 infections, i.e., well over half of the USA population. At that level, we should start seeing herd immunity effects. Although I see the original estimate of 60-70% infected for herd immunity is being revised upward, it's hard to see this as compatible with recent significant growth in the number of daily cases and deaths.

The claim becomes even more dubious when we restrict to a hot-spot. New York City has recorded 26,161 deaths, implying over 13 million infections on 0.2% IFR. However, the population of NYC is only 8.3 million. Some of the differential can be explained by better treatment since the beginning of the pandemic, but the worst NYC test positivity rates are about 10% at the moment. The pieces of the puzzle fit together best by rejecting the low IFR.

Answer 2

If you take a closer look at the paper, then you will notice that the methodology to detect infected people was based on studies which tested more or less randomly selected people for antibodies against SARS-CoV-2, looked at the percentage of people with antibodies, extrapolated that number to the whole population of the region from which the tested people were drawn, and then compared that to the reported number of deaths from COVID-19 in that region.

The assumption is that anyone with antibodies already had an infection with SARS-CoV-2, but might not have realized it because they were asymptomatic and there was no reason for them to get tested during their infection.

This is based on a couple assumption which might or might not be true:

• The antibodies measured in these tests are actually from a SARS-CoV-2 infection and not from an infection with a similar but less dangerous virus (there are lots and lots of coronaviruses, and many of them are not nearly as dangerous as the Coronavirus SARS-CoV-2)
• The antibodies detected are sufficient to prevent a(nother) SARS-CoV-2 infection. (Cases of people getting COVID-19 twice are so far rare, but not unheard of)

The official numbers you can see on various COVID-19 dashboards (like the one from the John Hopkins university) list only confirmed active infections vs. deaths. With that methodology, you come to a fatality rate of ~2% with regional differences ranging from 1% to up to 10%. These regional differences can be explained by prevalence of testing (less testing usually means only obviously sick people get tested and reported, who are usually people who are less likely to survive) and quality of health care.

Answer 3

In interviews, Ioannidis has stated that IFR is not a constant. It varies geographically (which the question implies) and in time. So I think the question also needs to specify a time frame. An example:

Around Boston, USA the current viral peak in wastewater is over twice as high as in the Spring. Yet death rates are less than half as high. An exact geographic match to the wastewater area is unavailable, but state and city numbers confirm this. Apparently, IFR has shrunk considerably since the Spring.

Answer 4

The IFR in Denmark, around April-May 2020, was estimated as 0.089% for patients younger than 70.

This was based on analysis of blood donors, who tend to be healthier than the regular public.

• Estimation of SARS-CoV-2 infection fatality rate by real-time antibody screening of blood donors 4/28/20 Christian Erikstrup et al.

Results: The first 20,640 blood donors were tested and a combined adjusted seroprevalence of 1.9% (CI: 0.8-2.3) was calculated. The seroprevalence differed across areas. Using available data on fatalities and population numbers a combined IFR in patients younger than 70 is estimated at 89 per 100,000 (CI: 72-211) infections.

Conclusions: The IFR was estimated to be slightly lower than previously reported from other countries not using seroprevalence data. The IFR is likely several fold lower than the current estimate. We have initiated real-time nationwide anti-SARS-CoV-2 seroprevalence surveying of blood donations as a tool in monitoring the epidemic.