In a press briefing on March 3, 2020, the Director-General of the World Health Organization (WHO), Dr. Tedros Adhanom Ghebreyesus, reported a 3.4% mortality rate from COVID-19. But how reliable is this figure? We take a look at what British experts have to say on the matter.

In the media briefing, Dr. Ghebreyesus reported a total of 90,893 cases of COVID-19 globally, with 3,110 resulting in death.

Dr. Ghebreyesus also made some comparisons with the common flu in his statement. These included the facts that COVID-19 “does not transmit as efficiently” as influenza, there are no vaccines and therapeutics for COVID-19, and containment strategies could work for COVID-19 but would not be possible for the flu.

An additional and important observation that Dr. Ghebreyesus made regards the severity of the two illnesses. Unlike the flu, nobody is immune to COVID-19. As a result, more people are prone to infection, and many are susceptible to “severe disease.”

“Globally, about 3.4% of reported COVID-19 cases have died. By comparison, seasonal flu generally kills far fewer than 1% of those infected.”

But how was this mortality rate calculated? And what are the unique challenges of determining the death rate during an epidemic?

Some of the world’s leading health experts have weighed in. Below, we summarize their opinions.

## Why calculating the death rate is so ‘tricky’

“It is surprisingly difficult to calculate the ‘case fatality ratio,’ or death rate, during an epidemic,” says John Edmunds, a professor in the Centre for the Mathematical Modelling of Infectious Diseases at the London School of Hygiene & Tropical Medicine in the United Kingdom.

This difficulty is due to the long period between the onset of the illness and the fatality, explains Prof. Edmunds.

For COVID-19, this length of time is 2–3 weeks or more, he says. Therefore, to calculate the case fatality rate, we should use the number of confirmed cases from a few weeks ago, rather than at the present time.

Experts define the case fatality rate as “the ratio of deaths occurring from a particular cause to the total number of cases due to the same cause.”

But, continues Prof. Edmunds, in the case of a “rapidly expanding epidemic,” the number of cases from a few weeks ago will always be much smaller than the current one, so “the true case fatality ratio will be higher.”

On the other hand, another bias evens the scale in the opposite direction.

“We do not report all the cases,” says Prof. Edmunds. “In fact, we only usually report a small proportion of them. If there are many more cases in reality, then the case fatality ratio will be lower.”

In conclusion, estimating the true case fatality ratio is “tricky,” says the researcher.

“What you can safely say […] is that if you divide the number of reported deaths by the number of reported cases [to get the case fatality ratio], you will almost certainly get the wrong answer.”

– Prof. John Edmunds

## Why 3.4% is likely an overestimate

Dr. Toni Ho, a consultant in infectious diseases at the Medical Research Council (MRC)–University of Glasgow Centre for Virus Research, U.K., echoes similar sentiments.

She goes on to suggest that the figure of 3.4% is likely an exaggeration, mainly due to the challenges of calculating mortality rates outlined above.

“The quoted mortality rate of 3.4% is taken from confirmed deaths over total reported cases. This is likely an overestimate, as a number of countries, such as the United States (112 confirmed, 10 deaths) and Iran (2,336 cases, 77 deaths), have had limited testing. Hence, few of the mild cases have been picked up, and [the total number of cases] we are observing is the tip of the iceberg.”

In fact, the overestimation could be 10 times higher than the reality, notes Mark Woolhouse, a professor of infectious disease epidemiology at the University of Edinburgh, U.K.

“[I]f a significant number of mild cases have been missed or not reported, then this [3.4%] estimate is too high.”

“Though there is disagreement about this, some studies have suggested that it is approximately 10 times too high. This would bring the death rate in line with some strains of influenza.”

– Prof. Mark Woolhouse

## Importance of regionality and other factors

Another factor that confuses the calculations is regionality. “[T]he number of reported cases and deaths is likely to vary depending on the population in question,” says Tom Wingfield, a senior clinical lecturer and honorary consultant physician at the Liverpool School of Tropical Medicine, U.K.

“For example, earlier in the outbreak, reported COVID-19 cases and deaths from Hubei province were predominantly among people admitted to hospital, which may not have captured less severe cases in the community.”

“[T]he evidence suggests that [case fatality ratios] were higher in the earlier stages of the outbreak than in the most recent weeks and higher within than without China.”

Paul Hunter, a professor in medicine at the University of East Anglia (UEA), U.K., also offers his opinion, saying, “We […] don’t know whether the Chinese experience will apply elsewhere — in the U.K., we hopefully won’t have such an intense outbreak in a small area.”

Additional factors that could influence the case fatality ratio include “how cases and deaths are classified,” says Wingfield.

He gives the example of the “spike in cases in China when the case definition was broadened to include those diagnosed clinically rather than confirmed through testing.”

Furthermore, the researcher continues, the case fatality ratio “may change over time during the course of the outbreak.”

“The factors contributing to this may include: mutations in the virus […]; host-related factors, such as immune response of different subpopulations infected; and epidemiological factors, such as levels of exposure and repeated exposure.”

Finally, the actual number of deaths may be underreported, says Wingfield.

## Death rate may only be known at the end

“Early estimates of fatality rates tend to be higher and then drop as the outbreak progresses,” says biological anthropologist Jennifer Cole, from the Royal Holloway, University of London, U.K.

This is mainly because early figures are based on the more severe cases only — those that seek hospital treatment — and so don’t capture mild cases.”

“It’s not until later in the outbreak, when large numbers of people […] such as all the passengers on the quarantined ships, everyone an infected person has been in contact with, or the entire population of a town is tested that more accurate numbers start to emerge, and the figures settle down.”

The scientist goes on to stress the importance of early intervention. “Early cases may also be more likely to result in death, as people’s symptoms may be more advanced before they seek treatment. The earlier people receive treatment, the better chance they may have of making a full recovery.”

“Scientists don’t always consider explaining why figures change as more information about a situation emerges, which can leave people feeling confused and not sure whether figures are reliable or not. Estimates and projections should always be put into context. If figures and estimates change, it’s important to clearly explain why this has happened.”

– Jennifer Cole