The World Health Organisation (WHO) Director-General, Dr Tedros Adhanom, made comments that 3.4% of reported COVID-19 cases have died globally.
Prof John Edmunds, Professor in the Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, said:
“It is surprisingly difficult to calculate the ‘case-fatality-ratio’, or death rate, during an epidemic. This is because it takes some time to die. In the case of COVID-19 the time between onset of disease and death is quite long – 2 to 3 weeks or more – so the number of cases that you should divide by is not the number of cases that we have seen to this point, but the number of cases that there were a few weeks ago. In a rapidly expanding epidemic, that number will be much less, so the true case-fatality-ratio will be higher. However, there is another bias working in the other direction. We do not report all the cases. 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. Estimating what fraction of the cases might be reported is very tricky. So, this long-winded explanation goes to show how difficult it is to get an estimate of the death rate. What you can safely say, however, is that if you divide the number of reported deaths by the number of reported cases you will almost certainly get the wrong answer, unless, of course, both these biases happen to cancel each other out, and the chances of that will be very slim.”
Dr Toni Ho, Consultant in Infectious Diseases at the MRC-University of Glasgow Centre for Virus Research, said:
“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 US (112 confirmed, 10 deaths) and Iran (2336 cases, 77 deaths), have had limited testing. Hence few of the mild cases have been picked up, and what we are observing is the tip of the iceberg. This is supported by sequencing data1 from Washington State, which suggests that there has been ongoing community transmission over 6 past weeks. Furthermore, determining mortality using confirmed deaths over total cases also does not account for the fact that outcome is still unknown for many confirmed cases, as they are still hospitalised. Lastly, since subclinical and asymptomatic infections have been reported, true case fatality ratio cannot be estimated until population seroprevalence (antibody) surveys can be undertaken to estimate the proportion of individuals that were infected but did not manifest symptoms.”
Prof Christl Donnelly, University of Oxford, and WHO Collaborating Centre for Infectious Disease Modelling, Imperial College London, said:
“In an unfolding epidemic it can be misleading to look at the naïve estimate of deaths so far divided by cases so far. Earlier this naïve estimate gave a roughly 2% case fatality ratio. Now it is 3.4%. This increase is due to the delay from the time it takes for individuals to progress from being diagnosed as cases to dying. When we make a robust statistical estimate of the case fatality ratio, we adjust for this diagnosis-to-death interval and the adjustment can substantially increase the naïve estimate. If the case mix of those being diagnosed stays the same, then it is likely that the 3.4% figure will increase further. Our analyses have included estimates of the case fatality ratio, but also the infection fatality ratio. The infection fatality ratio is the proportion of infections (including those with no symptoms or mild symptoms) that die of the disease. Our estimate for this is 1%. This is lower than the observed 3.4% figure because asymptomatic and mildly symptomatic cases are included in the denominator.”
Dr Tom Wingfield, Senior Clinical Lecturer and Honorary Consultant Physician, Liverpool School of Tropical Medicine, said:
“Today, Tedros Adhanom Ghebreyesus has said about 3.4% of confirmed cases of COVID-19 have died. This estimate of case fatality ratio (CFR) is based on 3110 deaths in 90,893 reported cases of COVID-19. Previous CFR estimates included: 2% reported at a WHO press conference on 29 January based on; 2.1% reported by the Chinese National Health Commission on 4 February based on 425 deaths in 20,438 confirmed cases; and 3.8% from the report of the WHO-China Joint Mission on 20 February based on 2,114 deaths in 55,924 laboratory confirmed cases. The CFR most commonly quoted in press articles up until today has been 2%. So, what’s the true CFR for COVID-19?
“Well, that’s hard to answer with any certainty. The CFR is an estimate of the proportion of people with a disease – in this case COVID-19 – who die of the disease over a given period of time. CFRs are difficult to estimate accurately for a number of reasons and COVID-19 is no exception.
“First, the calculation relies on numbers of cases and deaths reported to organisations such as WHO. Modelling studies have suggested that there are likely to be a significant proportion of cases and, to a lesser extent, deaths that go unreported.
“Second, the number of reported cases and deaths is likely to vary depending on the population in question. For example, earlier in the outbreak, reported COVID-19 cases and deaths from Hubei province were predominantly amongst people admitted to hospital, which may not have captured less severe cases in the community. How cases and deaths are classified can also impact on CFRs as was seen with the spike in cases in China when the case definition was broadened to include those diagnosed clinically rather than confirmed through testing.
“Third, the CFR may change over time during the course of the outbreak. The factors contributing to this may include: mutations in the virus which cause a change to its potency; host-related factors such as immune response of different subpopulations infected; and epidemiological factors such as levels of exposure and repeated exposure.
“Fourth, the best estimates of CFR would have to occur once an epidemic was over. Estimating CFR in real-time during the COVID-19 epidemic is therefore fraught with difficulties including not taking into account those who currently have COVID-19 but for whom we do not yet know the outcome.
“While we might not be able to accurately estimate the true CFR, we can use the information on cases and deaths we have to recognise patterns that might help us to identify at risk groups and trends in CFR rates over time. In terms of patterns, the evidence suggests that CFRs were higher in the earlier stages of the outbreak than in the most recent weeks and higher within than without China. The evidence also suggests that, as Tedros Adhanom Ghebreyesus noted today, while COVID-19 may not be as transmissible as seasonal flu, the CFR appears higher (seasonal flu CFR is approximately 0.1%). Those with the highest risk of severe COVID-19 illness or death are people aged over 60 years old, with pre-existing chronic lung or heart conditions, diabetes, or significantly suppressed immune systems. For this reason, WHO recently advised people who fit this category to take extra precautions to avoid crowded areas, or places where they might interact with people who are sick.
“As we gather and analyse more information about the COVID-19 epidemic, we will begin to get a clearer picture on the true outcomes of those infected. Moreover, we will be able to create more accurate predictions on CFR for specific geographical areas and sub-populations than we are currently able to do. This, along with important general measures such as maintaining good hand and cough hygiene, keeping calm, and being supportive of and vigilant for each other, will help us to tailor our response to meet the needs of those with the greatest risk.”
Biological Anthropologist Dr Jennifer Cole, Royal Holloway, University of London, said:
“Early estimates of fatality rates tend to be higher and then drop as the outbreak progresses. 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 who wouldn’t normally have sought healthcare, 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. 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.”
Prof Mark Woolhouse, Professor of Infectious Disease Epidemiology, University of Edinburgh, said:
“Calculating the death rate for COVID-19 is not straightforward. We believe that we have a good count of the number of deaths among people infected with the virus. That’s the numerator. But we do not believe that we have a good count of the number of infections. That’s the denominator. The WHO is using the official figure for confirmed cases as the denominator, and this gives the estimate of 3.4%. But if a significant number of mild cases have been missed or not reported then this 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. This is an important information gap: accurate estimates of the COVID-19 death rate would help us plan properly for the next phase of the epidemic.”
Prof Paul Hunter, Professor in Medicine, UEA, said:
“3.4% is the figure you get from the current known cases and current known deaths. There are three issues here:
“The first is that people die at the end of the illness but are diagnosed at the beginning. So among the cases known about there will be some people who will eventually succumb and we should expect the 3.4% value to rise.
“BUT we know that not all people who are infected will have been counted in the cases, so the total cases will be an underestimate. There will be people with fairly mild illness we don’t know about – so, this will reduce the percentage death rate.
“We also don’t know whether the Chinese experience will apply elsewhere – in the UK we hopefully won’t have such an intense outbreak in a small area so will be able to provide better care for the most seriously ill to help reduce the death rates.
“So current quotes are estimates based on currently available data with assumptions or models where we do not have exact data.
“Ultimately 1-2% is an estimate based on a number of assumptions which may or may not be true. But in my view 1-2% is still a reasonable estimate.”
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