Last updated: February 11, 10:25 GMT
At present, it is tempting to estimate the case fatality rate by dividing the number of known deaths by the number of confirmed cases. The resulting number, however, does not represent the true case fatality rate and might be off by orders of magnitude [...]2019-Novel Coronavirus (2019-nCoV): estimating the case fatality rate – a word of caution - Battegay Manue et al., Swiss Med Wkly, February 7, 2020A precise estimate of the case fatality rate is therefore impossible at present.
Presented on this page:
The case fatality rate (CFR) represents the proportion of cases who eventually die from a disease.
Once an epidemic has ended, it is calculated with the formula: deaths / cases.
But while an epidemic is still ongoing, as it is the case with the current novel coronavirus outbreak, this formula is, at the very least, "naïve" and can be "misleading if, at the time of analysis, the outcome is unknown for a non negligible proportion of patients." [8]
In other words, current deaths belong to a total case figure of the past, not to the current case figure in which the outcome (recovery or death) of a proportion (the most recent cases) hasn't yet been determined.
The correct formula, therefore, would appear to be:
CFR = deaths at day.x / cases at day.x-{T}
(where T = average time period from case confirmation to death)
This would constitute a fair attempt to use values for cases and deaths belonging to the same group of patients.
One issue can be that of determining whether there is enough data to estimate T with any precision, but it is certainly not T = 0 (what is implicitly used when applying the formula current deaths / current cases to determine CFR during an ongoing outbreak).
Let's take, for example, the data at the end of February 8, 2020: 813 deaths (cumulative total) and 37,552 cases (cumulative total) worldwide.
If we use the formula (deaths / cases) we get:
813 / 37,552 = 2.2% CFR (flawed formula).
With a conservative estimate of T = 7 days as the average period from case confirmation to death, we would correct the above formula by using February 1 cumulative cases, which were 14,381, in the denominator:
Feb. 8 deaths / Feb. 1 cases = 813 / 14,381 = 5.7% CFR (correct formula, and estimating T=7).
T could be estimated by simply looking at the value of (current total deaths + current total recovered) and pair it with a case total in the past that has the same value. For the above formula, the matching dates would be January 26/27, providing an estimate for T of 12 to 13 days. This method of estimating T uses the same logic of the following method, and therefore will yield the same result.
An alternative method, which has the advantage of not having to estimate a variable, and that is mentioned in the American Journal of Epidemiology study cited previously as a simple method that nevertheless could work reasonably well if the hazards of death and recovery at any time t measured from admission to the hospital, conditional on an event occurring at time t, are proportional, would be to use the formula:
CFR = deaths / (deaths + recovered)
which, with the latest data available, would be equal to:
1,115 / (1,115 + 4,794) = 19% CFR (worldwide)
If we now exclude cases in mainland China, using current data on deaths and recovered cases, we get:
2 / (2 + 54) = 3.6% CFR (outside of mainland China)
The sample size above is extremely limited, but this discrepancy in mortality rates, if confirmed as the sample grows in size, could be explained with a higher case detection rate outside of China especially with respect to Wuhan, where priority had to be initially placed on severe and critical cases, given the ongoing emergency.
Unreported cases would have the effect of decreasing the denominator and inflating the CFR above its real value. For example, assuming 10,000 total unreported cases in Wuhan and adding them back to the formula, we would get a CFR of 7.0% (quite different from the CFR of 19% based strictly on confirmed cases).
Neil Ferguson, a public health expert at Imperial College in the UK, said his “best guess” was that there were 100,000 affected by the virus even though there were only 2,000 confirmed cases at the time. [11]
Without going that far, the possibility of a non negligible number of unreported cases in the initial stages of the crisis should be taken into account when trying to calculate the case fatally rate.
As the days go by and the city organized its efforts and built the infrastructure, the ability to detect and confirm cases improved. As of February 3, for example, the novel coronavirus nucleic acid testing capability of Wuhan had increased to 4,196 samples per day from an initial 200 samples.[10]
A significant discrepancy in case mortality rate can also be observed when comparing mortality rates as calculated and reported by China NHC: a CFR of 3.1% in the Hubei province (where Wuhan, with the vast majority of deaths is situated), and a CFR of 0.16% in other provinces (19 times less).
Finally, we shall remember that while the 2003 SARS epidemic was still ongoing, the World Health Organization (WHO) reported a fatality rate of 4% (or as low as 3%), whereas the final case fatality rate ended up being 9.6%.
Asked at a press conference on February 4 what the current mortality rate (or case fatality rate, CFR) is, an official with China NHC said that [7]:
The World Health Organization (WHO) had mentioned 2% as a mortality rate estimate in a press conference on Wednesday, January 29 [1][2] and again on February 10. However, on January 29 WHO specified that this is a very early and provisional estimate that may change. Surveillance is increasing, within China but also globally, but at the time:
A preliminary study published on The Lancet on January 24 [3] provides an early estimation of 3% for the overall case fatality rate. Below we show an extract (highlights added for the relevant data and observations):
A novel coronavirus outbreak of global health concern - Chen Wang et al., The Lancet. January 24, 2020Of the 41 patients in this cohort, 22 (55%) developed severe dyspnoea and 13 (32%) required admission to an intensive care unit, and six died.
Hence, the case-fatality proportion in this cohort is approximately 14.6%, and the overall case fatality proportion appears to be closer to 3%.
However, both of these estimates should be treated with great caution because not all patients have concluded their illness (ie, recovered or died) and the true number of infections and full disease spectrum are unknown.
Importantly, in emerging viral infection outbreaks the case-fatality ratio is often overestimated in the early stages because case detection is highly biased towards the more severe cases.
As further data on the spectrum of mild or asymptomatic infection becomes available, one case of which was documented by Chan and colleagues, the case-fatality ratio is likely to decrease.
Nevertheless, the 1918 influenza pandemic is estimated to have had a case-fatality ratio of less than 5% but had an enormous impact due to widespread transmission, so there is no room for complacency.
Fatality rate can also change as a virus can mutate, according to epidemiologists.
A study on 138 hospitalized patients with 2019-nCoV infection, published on February 7 on JAMA, found that 26% of patients required admission to the intensive care unit (ICU) and 4.3% died, but a number of patients were still hospitalized at the time. [9]
A previous study had found that, out of 41 admitted hospital patients, 13 (32%) patients were admitted to an ICU and six (15%) died.[5]
The Wang et al. February 7 study published on JAMA found that the median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days.[9]
Previously. the China National Health Commission reported the details of the first 17 deaths up to 24 pm 22 Jan 2020. A study of these cases found that the median days from first symptom to death were 14 (range 6-41) days, and tended to be shorter among people of 70 year old or above (11.5 [range 6-19] days) than those with ages below 70 year old (20 [range 10-41] days.[6]
The JANA study found that, among those discharged alive, the median hospital stay was 10 days. [9]
For comparison, the case fatality rate with seasonal flu in the United Stats is less than 0.1% (1 death per every 1,000 cases).
Mortality rate for SARS was 10%, and for MERS 34%.
| Virus | Death Rate |
|---|---|
|
Wuhan Novel Coronavirus (2019-nCoV) | 2%* |
|
SARS | 9.6% |
|
MERS | 34% |
|
Swine Flu | 0.02% |
*estimate