One year of COVID-19 pandemic: Case fatality ratio and infection fatality ratio. A systematic analysis of 219 countries and territories

Background. January 2021 marked one year since the start of COVID-19 pandemic: it is the time of intermediate conclusions. Objective. To evaluate CFR and IFR due to COVID-19 in various countries and territories, and to study if parameters of a population age affect CFR and IFR. Material and Methods. The databases of 219 countries were collected on the Worldometers, Index Mundi, Country Meters and World Bank websites. The processing of data was divided into two parts: the first part dealt with the calculation and analysis of CFR while the second, the calculation and analysis of IFR. Results. The calculations revealed that in 74 out of 219 countries, CFR was less than 1.00 %, in 69 countries it varied between 1.00 % and 2.00 %, and in 76 countries it was more than 2.00 %. The calculation of IFR revealed that in 183 countries, IFR was less than 1.00 %, in 22 countries IFR was between 1.00 % and 2.00 %, and only in 14 out of 219 countries IFR was more than 2.00 %. A correlation between IFR and parameters of a population age was found: the less median age and the percentage of 'aged' people – the less value of IFR, although, there was no correlation between parameters of a population age and CFR. Conclusion. The global health care system has gone through a year of serious trial caused by COVID-19 and appeared to have emerged victorious. In the majority of countries analyzed, the parameters of mortality due to COVID-19 were at a low level. So, there seems to be an objective basis for optimism and hope for an early end to the pandemic.


Introduction
Fatality rate. There are two most important characteristics of infectious diseases: the first is a case fatality ratio (CFR) and the second, an infection fatality ratio (IFR). Case fatality ratio is the proportion between the number of patients who died from COVID-19 and the number of confirmed cases of COVID-19, while Infection fatality ratio is the proportion between the number of patients who died from COVID-19 and the number of estimated cases infected with SARS-CoV-19 [1].
Case fatality ratio. In the first report provided by a group of experts from Imperial College London, there were 41 confirmed cases of COVID-19 with 2 deaths (17.01.20) [2], so, the CFR was 4.88 %. In the second report provided by the same group of experts, there were 440 confirmed cases with 9 deaths (22.01.20) [3]. Thus, the CFR was 2.05 %. In a study done by L.Liang, et al, (2020) the authors discussed a strange phenomenon of the current pandemic -"Why the Covid-19 mortality rate varies so greatly across countries, from over 16 % in France and Belgium to less than 0.1 % in Singapore and Qatar" [4]. In a recent study conducted in Malaysia, the authors also noted a wide variation of CFR worldwide and highlighted the low CFR in their country [5].
Infection fatality ratio. To calculate an IFR one needs to know the number of deaths from COVID-19, the total number of confirmed cases of the disease and the number of people who could be infected with the SARS-CoV-2 virus, yet suffered the disease asymptomatically or with minimal symptoms that did not attract the attention of the patient and doctors [1]. To identify the total number of infection prevalence, tests were carried out for the presence of the viral genome (Polymerase chain reaction), or for specific antibodies against SARS-CoV-2 virus (IgM and IgG). Due to the fact that polymerase chain reaction provided positive results for a limited time after infection, and specific antibodies were produced and circulated in the blood of an infected person only for several months [6,7], the percentage of seroprevalence would always be lower than the real one, and, therefore, IFR from COVID-19 would be always overestimated.
In the second report submitted by the aforementioned group of experts from Imperial College London dated January 22, 2020, there were 9 deaths, 440 confirmed cases, and the estimated number of infected people reached 4,000 [3]. Thus, the IFR was 0.23 %. According to a research conducted by M. Neil et al. (2020), the IFR was most likely to be in the range of 0.30-0.50 %, and it should not exceed 1.00 % [8]. In yet another study by A. Rostami, et al. (2020), covering the time from the start of the pandemic to August 14, 2020, the estimated number of all infected persons reached 263,565,606 people [9]. On the same day, according to data presented on the Worldometers website [10], there were 777,073 deaths from COVID-19, thus, the IFR was equal to 0.29 %.
In the article published by J. Ioannidis (2020), at the end of October 2020, worldwide, the number of infected people reached 10 %, and the IFR was between 0.15 % and 0.20 % [11].
Database. In this study, information on the number of reported deaths caused by COVID-19, reported cases of COVID-19, tests performed and population were collected on the Worldometers website. This site does not have investors, donors or grants that could influence the information published. The data published on the Worldometers website is compiled from over 5,000 sources, including official reports from the respective countries analyzed [10]. Information on the median age and percentage of the population aged 65 and above were obtained from the IndexMundi [12], Country Meters [13] and World Bank [14] websites.
The processing of data collected on January 22, 2021, was divided into two parts. The first involved calculating and analyzing CFR and the second, calculating and analyzing IFR. Based on the results obtained, corresponding graphs were prepared.

Case fatality ratio among COVID-19 patients in 219 countries
Objective. To study Case Fatality Ratio in 219 countries, 1 and to evaluate if parameters of a population age affect CFR. To increase the homogeneity of the main group of study, countries with death numbers of fewer than 50 were excluded from further analysis.
The main study group included 161 countries, with a total population of 7,529,891,314 people.
These countries had 97,225,719 confirmed cases of COVID-19 and 2,084,079 fatal cases due to the disease. For each country, the CFR was calculated by dividing the number of deaths by the number of confirmed cases.
Results. The overall case fatality ratio, derived by dividing the number of deaths (n=2,084,079) by the number of confirmed cases (n=97,225,719), was 2.14 %.

Conclusion.
The calculations done in this section showed that in 34 out of 159 countries, the case fatality ratio was less than 1.00%, in 58 countries it varied between 1.00% and 2.00%, and in 67 countries it was more than 2.00%. In 7 out of 159 countries, the CFR was less than 0.50%. Results. Since there were no fatal cases due to COVID-19 in 18 out of the 58 countries, CFR was 0.00 % (<0.50%). In the remaining 40 countries, CFR ranged from 0.05 % in Singapore to 10.00 % in Western Sahara, with an average CFR value of 1.57±2.09 %. In 22 out of 40 countries CFR was less than 1.00 %, in 11 countries CFR was between 1.00 % and 2.00 %, and in the remaining 7 countries, CFR was more than 2.00 %. In 13 out of 40 countries CFR was less than 0.50 %.
Conclusion. If the previous calculations done in section 1.2, and the CFRs of Mexico and Yemen were to be taken into account, then in 74 out of 219 countries, CFR was less than 1.00 %, in 69 countries CFR varied between 1.00 and 2.00 %, and in 76 countries, CFR was more than 2.00 %. In 38 out of 219 countries, CFR was less than 0.50 %.

Analysis of the effect of population age on CFR among COVID-19 patients
Background. According to the databases which dealt with population age [14], only one out of 11 countries with CFR>4.00 % -Bulgaria, was included in the list of the top 50 countries with the largest percentage of old adults.
Material and Methods. To study the effect of age on CFR, two parameters were used -median age of a population, and the percentage of 'aged' people who were 65 years and above [12][13][14]. 218 countries were divided into two groups: the first group consisted of 109 countries where CFR was less than a median value (Libya, CFR=1.54 %), while the second group consisted of the remaining 109 countries where CFR was more than the median value.
There were also comparisons of the same parameters in the group of countries with low, medium and high case fatality rates.
Results. In the first group of 109 countries, the average value of median age was 31.51±8.92 years, and aged people accounted for 9.84±6.57 % of the total population. In the second group of 109 countries, these parameters were 31.44±9.75 years and 10.14±6.68 %, respectively. There was no significant difference between analyzed parameters counted for both groups of countries (p>0.05).
In the group of 74 countries with CFR<1.00%, the average median age was 32.22±8.69 years, and aged people accounted for 9.85±6.29 % of the total population; in the group of 69 countries Results. The overall global CFR value was 2.22 %. The highest weekly CFR = 8.51% was calculated for the 6th week (Apr 12-18, 2020), and the lowest weekly CFR = 1.31% was calculated for the 34th week (Oct 25-31, 2020). Dynamics of the weekly CFR is illustrated in Figure 2. The highest daily CFR = 9.51 % was on Apr 17, 2020, and the lowest daily CFR = 1.07 % was on Oct 25, 2020.
Conclusion. The highest global weekly and daily CFR was in April, 2020, when clinical trials on the use of medicines for the treatment of COVID-19 were in the initial phase [16]. The lowest weekly and daily CFR was in October, 2020, when the majority of clinical trials had already been completed, and effective therapeutic protocols had been designed and recommended for worldwide application [16,17]. Further increase of the CFR globally and in some countries requires additional investigation. In the above graph, the X axis shows the number of each week, while the Y axis shows CFR (%).

Infection fatality ratio among COVID-19 patients in 219 countries
Objective. Based on the estimated IFR values, all the countries analyzed were divided into 13 groups, as illustrated in Figure 3.

Conclusion.
The calculations done in this section showed that in 123 out of 141 countries, the IFR was below 1.00 %, in 16 countries IFR was between 1.00 and 2.00 %, and only in 2 countries IFR was above 2.00 %. In 101 out of 141 countries IFR was less than 0.50 %.

Estimation of IFR in the 78 countries excluded from the main study
As mentioned above, countries with fewer than 50 reported cases of deaths, countries without information on the number of tests performed, and countries where the number of tests performed exceeded the total population, were excluded from the IFR study group.

Methods and Results.
Considering that IFR is always less than CFR, we can estimate the highest possible value of IFR for the countries without information on the number of tests performed (n=13), and countries where the number of tests performed exceeded the total population (n=14). In 10 out of the 27 countries of this group, both CFR and IFR were less than 1.00%, in 5 countries, CFR and IFR were between 1.00% and 2.00%, and in 12 countries, both CFR and IFR were more than 2.00%. In 5 countries of this group CFR and IFR were less than 0.50%.
In 18 out of the 78 countries, there were no reported deaths due to COVID-19, so both CFR and IFR were 0.00%.
In the remaining 33 countries with fewer than 50 reported cases of deaths, IFR was calculated in a similar manner described in section 2.2. In 32 out of 33 countries IFR was less 1.00%, and in 1 country IFR was between 1.00% and 2.00%. In 30 out of 33 countries IFR was less than 0.50%.

Conclusion.
The calculations done in the section 2. Since some of the patients were tested more than once, the real IFR values could be lower than presented in the study.

Analysis of the effect of age on IFR among COVID-19 patients
Background. According to the database which dealt with population age, 17 out of 36 countries with IFR>1.00 % were included in the list of top 50 countries with the largest percentage of old adults [14].
Objective. To evaluate if parameters of a population age affect IFR.
Material and Methods. To study the effect of age on IFR, two parameters were used -median age and the percentage of 'aged' people [12][13][14]. 218 countries were divided into two groups: the first group consisted of 109 countries where IFR was less than a median value (Tunisia, IFR=0.208 %), and the second group consisted of the other 109 countries, where IFR value was more than the median value.
Results. In the first group of countries, the average value of median age was 27.06±8.05 years, and aged people were 7.00±4.88 % of the total population. In the second group, these parameters were 35.82±8.45 years and 12.93±6.82 %, respectively. There was a highly significant difference between analyzed parameters counted for both groups of countries: for median age p<0.05E-11 and for percent of aged people p<0.05E-10.
Conclusion. The calculations and analysis done in this section has revealed a correlation between IFR value and median age and percentage of aged people living in the analyzed countries: the younger population -the less value of IFR.

Discussion
In this study two main parameters of mortality from COVID-19 were estimated. As a result of the CFR calculation, countries were distributed from a minimum value of 0.17% in Qatar to a maximum value of 28.94% in Yemen. Likewise, based on IFR calculations, countries were distributed from a minimum value of 0.005% in Guinea to a maximum value of 2.575% in the United Kingdom. A correlation between the percentage of aged population and mortality was revealed only for IFR, but not for CFR. According to earlier publications, mortality due to COVID-19 depended on continents, countries, regions, patients' age, comorbidities, money spent on health care, therapeutic protocols used, etc. [4][5][18][19][20].

Conclusion
More than a year has passed since the COVID-19 pandemic was announced. The global health care system has gone through serious trials and seemed to have emerged victorious. Under the leadership of WHO, hundreds of clinical trials have been carried out [16], which have led to the development of effective therapeutic protocols with the application of well-known medicines used successfully for many years [17].
Current estimations of both CFR and IFR have led to the conclusion that the danger of the disease caused by the new SARS-CoV-2 virus was significantly less than expected at the time of its emergence [21]. About a third of the countries analyzed have emerged as leaders in the fight against COVID-19, as they have successfully brought the fatality rate to a minimal level. In these countries, every fatal case caused by the SARS-CoV-2 was treated as a tragic exception rather than a typical outcome of a new disease. Countries which have been successful in fighting this new disease should be emulated, especially by those countries where the fight against COVID-19 has not been so successful.
Thus, this study provides an objective basis for optimism and inspires a hope for an early end to the pandemic.
Disclosure Statement: The author declares there are no conflicts of interest in the submitted manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.