In view of the misunderstanding of the CFR calculation in many published articles, we have, for the first time, established a method to calculate the instant CFR of COVID-19. This method resolved the problems of COVID-19 patients with uncertain outcomes and the time lag between the diagnosis and outcome. By using this new calculation, we determined and compared the CFRs of COVID-19 in Italy, Spain, France and Germany, which are the European countries where the epidemic was most severe. The results showed that the average CFR of COVID-19 was highest in France and lowest in Germany.
At present, the global epidemic of COVID-19 is still ongoing. Assessing the hazards of infectious diseases is a vital concern in epidemiology13. Generally, an accurate CFR of an infectious disease can be obtained after the epidemic is over on the basis of the number of total deaths and the number of total confirmed cases. However, the number of confirmed cases, deaths and cured cases are constantly changing14 during the epidemic.
Recently, some scientists reported the “CFR” of COVID-19 in their publications. However, we found that this crude CFR9,10 was mostly obtained by dividing the number of cumulative deaths by the number of cumulative confirmed cases, which would underestimate the real CFR of COVID-19. For example, Zhang extracted a total of 72,314 COVID-19 cases reported in China's Infectious Disease Information System15. There were a total of 1,023 deaths out of 44,672 confirmed cases for an overall CFR of 2.3%. While this may seem reasonable on the surface, the fact that there were still 38,909 hospitalized cases among the confirmed cases was ignored. The outcomes of these hospitalized patients remained uncertain. Some patients died a few days later. Therefore, this number of future deaths should be added to the dividend when calculating the CFR. In addition, Sun et al. reported that the CFR was 2.1% (361/17,205) 16 in China, which also misled the public as it was estimated by using the same calculation as Zhang et al. These results may represent a large deviation from reality. Interestingly, Yang et al. used a simple linear regression model to estimate the CFR of COVID-19 in mainland China17; the reported CFR was 2.10% (95% CI: 2.05–2.14%). However, at present, the outbreak has been basically controlled in China. Therefore, the CFR can be obtained by dividing the total deaths (4,644) by the total confirmed cases (84,451); the current estimated CFR in China is approximately 5.5%, which is obviously higher than expected in all above papers. Therefore, estimating the CFR is challenging18.
We assumed the CFR during the epidemic process to be a collection of many successive instant CFRs. We set the instant unit of the CFR as one day and calculated the daily CFR. The daily CFR was equal to the number of daily cumulative deaths being divided by the number of daily cumulative confirmed cases. The difference from the above calculation is that the two numbers in the equation (deaths and confirmed cases) occurred on the same estimated diagnosis date. The deaths (dividends) were not diagnosed as confirmed cases (divisors) on the calculation date. Instead, they were diagnosed as confirmed cases a period of time (death time) ago. Therefore, in the CFR equation, when the dividend was the number of daily cumulative deaths, the divisor should be the number of daily cumulative confirmed cases diagnosed on the same date when the deaths (in the dividend) were diagnosed as confirmed cases. We used this method to estimate the CFR (5.7%) of COVID-19 in China 11; the estimated CFR is close to its actual value (5.5%), supporting that this method is reliable.
COVID-19 is a topic of general concern to all humankind. Due to the differences in attention, medical facilities, public consciousness of self-protective measures, and economics, there are some differences in the epidemic situation in different countries. The number of confirmed cases/deaths/recovery cases is changing every day, so it is difficult to use a simple number or average number to show the mortality rate and CFR. Hence, we used the instant CFR approach to estimate the impact of the epidemic and changes in the hazards associated with COVID-19 in different European countries.
According to the different levels of the CFR in different places, we are able to determine the status of the COVID-19 situation in different countries. The CFR could be an important reference and indicator for real-time measurement of epidemic inside a country and even for comparison among different countries. Germany has shown the lowest CFR of COVID-19, demonstrating that Germany has provided the best medical facilities for COVID-19 among these four European countries. France has the highest average CFR (16.7%) and it has surpassed that in Italy (16.0%) after June, indicating that the French needs to take more stringent measures to control COVID-19. Meanwhile, France has maintained the highest instant CFR after stabilization (20.0%). Since late April, 2020, the instant CFR has stabilized at approximately 15% in Italy, and 20% in France, respectively, which means that the French and Italian people and government should pay more attention to the epidemic right now.
During the outbreak of severe acute respiratory syndrome (SARS) in 2003, a total of 8,422 SARS cases were reported in 32 countries and regions. The global death toll from SARS was 919, with a CFR of nearly 11% for SARS worldwide. However, the current total number of COVID-19 cases and deaths for now is far more than the respective reported numbers for SARS. The SARS epidemic was most severe in China (Beijing, Hong Kong) and some countries in Southeast Asia, while SARS epidemic in Europe was relatively mild, and SARS had no widespread impact in European countries. The number of SARS cases in Italy, Spain, France and Germany was 4, 1, 7, 9, respectively, out of which there was only 1 death (from France). As a comparison, as for June 18, 2020, the instant (average) CFR of COVID-19 was 14.4%~27.6% (16.0%), 2.2%~14.7% (11.0%), 8.2%~25.0% (16.7%) and 2.0%~10.5 (5.0%) in Italy, Spain, France and Germany, respectively. Obviously, the current status of the COVID-19 epidemic in Europe is much more serious than it was for SARS in 2003. We have also determined that the incidence rates and mortality rates of COVID-19 for the four European countries are significantly higher than those for SARS in 2003. It seems that even though COVID-19 was first seen in Wuhan, China, the situation of China is currently well controlled. However, the epidemic has had widespread transmission worldwide. Why is the epidemic of COVID-19 worse than that of SARS in Europe? The transmissibility of the SARS virus is not strong, so it has been limited to only some places. Since SARS had a strong lethality, it still showed a high CFR in the limited endemic areas. On the other hand, COVID-19 is highly contagious, and it has a stronger ability to spread among people, so the whole world has been affected.
The number of confirmed cases and the number of deaths in Europe are still rising. Our study developed a new method of estimating the CFR of COVID-19. Then, we compared the CFRs of COVID-19 in four European countries and found that, as for July 9, 2020, the average CFR of COVID-19 was highest in France and lowest in Germany. Since late April 2020, the CFR has stabilized at approximately 15%, 20% and 5% in Italy, France and Germany, respectively. Since early June, 2020, the CFR in Spain has stabilized at approximately 11%. This more accurate way is established to calculate the CFR may provide a basis for the prevention and control of infectious diseases.