Introduction

Coronavirus disease 2019 (COVID-19) was caused by the novel coronavirus SARS-CoV-2. It was first reported in Wuhan, China, in December 2019, and along the way it has emerged as a global pandemic [1]. According to officially published data from the World Health Organization (WHO), on September 6th 2023, a total of 770.437.327 confirmed cases and 6.956.900 deaths have been globally recorded [2]. The COVID-19 pandemic constituted a new public health challenge and has resulted in a number of negative health-related consequences, including increased mortality [3]. However, an accurate measurement of the number of deaths due to the COVID-19 pandemic is crucial for each country and region to understand the magnitude of the pandemic’s impact as well as assess the post pandemic period in order to inform appropriate public health policies.

Furthermore, reported deaths facilitate the quantification of the magnitude of the pandemic among different populations and allow for comparisons between countries and within regions over time [4]. However, associated mortality represents only a partial count of total deaths [5], whereas the reliability and validity of reported deaths varied greatly between the different countries given the variant methodologies used to define and count such events over time [6]. Consequently, excess mortality is a crucial measure for assessing the overall impact of the COVID-19 pandemic and associated public health measures.

Due to the above impact, the Coronavirus Disease 2019 has triggered tremendous interest in related statistics. Therefore, in April 2020, in cooperation with the National Statistical Institutes of the European Statistical System and the European Free Trade Association (EFTA), Eurostat set up a special data collection on weekly deaths, in order to support research and policy efforts related to the pandemic. National Statistical Institutes regularly and on a voluntary basis report data to Eurostat on weekly fatalities. The weekly deaths dataset that Eurostat publishes regularly is used to compute the monthly excess mortality indicators by mapping the deaths of each week to a full month [7].

Excess mortality is a term used in epidemiology and public health referring to the number of deaths from all causes occurring during a crisis, above and beyond what we would have expected to observe under “normal” conditions [8]. In the case of the COVID-19 pandemic, excess mortality is a more comprehensive measure of the total impact of the pandemic on mortality compared to the confirmed COVID-19 deaths alone. The excess mortality indicator, which is part of the European Statistical Recovery Dashboard, captures not only the confirmed deaths, but also COVID-19 deaths that were not correctly diagnosed and reported, as well as deaths from other causes that are attributable to the overall COVID-19 crisis and beyond [9]. Eurostat takes the number of people who died from any cause, in a given period, and compares it with a historical baseline calculated from data available between 20162019 that was not affected by the COVID-19 pandemic [7]. This indicator highlights the magnitude of the health crisis by providing a comparison of additional deaths among the European countries, allowing further analysis of the underlying causes. This approach estimates the impact of the COVID-19 crisis as well as the overall population mortality by including all deaths regardless of their cause [10].

According to information collected by Eurostat, the annual excess mortality for the European Union (EU) in 2020 was 11.7% higher than the 2016-2019 average, whilst in 2021 it was 14.0% higher. In 2022, the annual excess mortality for the EU was 11.2% higher than the 2016-2019 average. In June 2023, a month after the World Health Organization declared the end to the COVID-19 public-health emergency, excess mortality in the EU continued to rise with the EU rate reaching 2.5% (around 2,600 additional deaths compared to the average number of deaths for the same period in 2016-2019). Additionally, in June 2023, excess mortality continued to vary across the EU. Over half of the EU Member States recorded excess deaths. The most affected countries were Ireland, the Netherlands, Finland and Cyprus which had excess mortality rates between 13.3% and 14.4%. It is also worth mentioning that Cyprus was one of the EU Member States with the highest excess mortality rates during the pandemic (e.g., in 2022, Cyprus had the highest annual excess mortality reaching 26.4%). Moreover, in the first quarter of 2023 fourteen EU Member States recorded excess deaths, with the highest rates in Cyprus (10.8%) and the Netherlands (10.1%) [7].

Based on a wider literature search, we document an excess mortality being observed worldwide during the COVID-19 pandemic and beyond. Rossen, et al. showed that USA experienced substantial excess mortality in 2020 and 2021 related to the COVID-19 pandemic, which was higher than in Europe for nearly all age groups, with an additional 44.1 excess deaths per 100,000 person years overall from 2020-2021. During 2020-2021, the USA experienced 154.5 cumulative age-standardized excess all-cause deaths per 100,000 person years [11]. Another study estimated excess mortality from the COVID-19 pandemic in 191 countries and territories, and 252 sub-national units for selected countries. Although reported COVID-19 deaths between Jan 1, 2020, and Dec 31, 2021, totaled 5.94 million worldwide, they estimated that 18.2 million people died worldwide because of the COVID-19 pandemic (as measured by excess mortality) over that same period. The global all-age rate of excess mortality due to the COVID-19 pandemic was 120.3 deaths per 100,000 of the population, and excess mortality rate exceeded 300 deaths per 100,000 of the population specifically in 21 countries [12].

 We have previously reported on the general population mortality in Cyprus during the pandemic as compared over a sixyear period (2016-2021), having observed a substantial increase in population mortality in 2021 compared to 2020. Moreover, we found that, when excluding deaths reported as caused by COVID-19, we still documented significant residual increased mortality in the general population indicating that a significant portion of the worrying increase of 9.7% of all-cause mortality in 2021 was not explained completely by COVID-19 deaths [13].

Consequently, the aim of our present study was to examine possible excess mortality occurring in Cyprus over the past three years as compared to the average mortality observed during the pre-pandemic period.

Materials and Methods

In this study we performed exploratory data analysis with information obtained from publicly available official databases. Information on weekly reported all-cause mortality from Cyprus was downloaded from the European Statistical Office (Eurostat) as the official data reported by the Cyprus Ministry of Health [14]. Eurostat provides packaged information about the total deaths on a weekly basis for all European countries [16]. We selected the Eurostat database that provides the above mortality data in age groups based on 20-year intervals. In addition, we used publicly available data from the European Centre for Disease Prevention and Control (ECDC) on the numbers of COVID-19 related deaths and on vaccination records reported on a daily basis [15].

All datasets downloaded from the above two databases were transformed into monthly aggregated records by different age groups in order to maintain a global consistent period index reference for relevant comparisons. The resulting transformation outputs included total all-cause deaths, total COVID-19 deaths, and total SARS-CoV-2 vaccination doses for Cyprus by different age groups tabulated on a monthly basis.

Due to the variety of different time intervals used by different international official databases and scientists reporting from around the world, we decided to use the monthly basis format as deemed more appropriate for analyzing mortality data and vaccination records for Cyprus [17]. In addition, monthly grouped data are comparable to the report format used by Eurostat.

In order to compare the potential mortality deviation (excess deaths) before and after the COVID period, we calculated the average monthly mortality using the years 2016 to 2019. This selected reference time period was based on the same time period used by Eurostat [16]. Our data were converged based on the same protocol as defined by Eurostat on excess mortality, which was stated as the rate of additional deaths in a month compared to the average number of deaths over a baseline period (2016-2019) [7]. Quarterly grouped data were also used to generate specific graphs for representation purposes.

Monthly counts and percentage changes were used to compare mortality over time and between years. Cumulative curves were also employed to provide an unbiased methodological approach to graphically represent the evolution of mortality trend lines over time. This approach is particularly useful for highly fluctuated values at short time intervals such as the small numbers observed with the Cyprus monthly data.

Results

Trends of all-cause mortality is presented in both tabular and graphical forms as delineated below. In Table 1, we present the total number of deaths from all causes over the study period of 7 years (2016-2022) on a monthly basis. It is important to note that the first official SARS-CoV-2 cases were reported in Cyprus on March 10th, 2020 and the vaccination program started on Dec 27th, 2020. Subsequently, in Figure 1 we depict the total number of deaths from all causes presented on an annual basis as reported officially by the Ministry of Health to the Eurostat database. Using the reference line generated by the average mortality from years 2016 to 2019, we have identified significant excess mortality, which is clustered mostly in years 2021 and 2022.

Table 1: Total deaths by month and year in Cyprus (data from Eurostat).

Figure 1: Total deaths from all causes presented on a yearly basis. Data obtained from the Eurostat dataset for the period between 2016 to 2022. The reference average line was generated using mortality data from 2016 to 2019. The average line is used to assess deviation from the pre-COVID-19 period. The excess deaths are shown in red.

In Table 2, we describe the total number of deaths from all causes presented on a quarterly basis for each year including the total and mean weekly deaths and percentage change for each of the two consecutive years over the time period between 2016 and 2022. Similar representation of the data is given in Figure 2. The reference trend line in Figure 2 is generated using baseline mortality data from 2016 to 2019 (1474 deaths per quarter). This is used to assess deviation from the pre COVID-19 period by indicating excess deaths in red.

Table 2: Mortality in Cyprus by quarter including total and mean weekly deaths and percentage change for each of the two consecutive years over the time period 2016-2022.

Figure 2: Total deaths from all causes presented on a quarterly basis. Data obtained from the Eurostat dataset for the period between 2016 to 2022. The reference average line generated using mortality data from 2016 to 2019 (1474 deaths per quarter) is used to assess deviation being characterised as pre-COVID-19 period. The excess deaths are shown in red.

In Figure 3 we present the total SARS-CoV-2 vaccination doses submitted on a monthly basis in Cyprus. Two peaks have been identified, in May 2021 with 348,394 doses and in December 2021 with 203,927 doses. In cumulative terms, at the time of the first vaccinations peak event, 42% of the total Cyprus population received their first vaccination dose and increased to 71% at the time of the second peak event. The population estimate is obtained from ECDC based on the total population of 904,705 people in the Republic of Cyprus, excluding the Turkish occupied area. The number of cumulative excess deaths is increasing from December 2021 and continues thereafter.

Figure 3: We present the total SARS-CoV-2 vaccination doses submitted on a monthly basis in Cyprus. Two peaks have been identified in May 2021 and December 2021. The peaks correspond to the percentage of people receiving their first vaccination dose, which was 42% and 71% of the total Cyprus population, respectively. The population estimate is from ECDC based on the total population of 904,705 people in the Republic of Cyprus, excluding the Turkish occupied area. In the graph, we recognise that after each vaccination peak, a high-rate trend is followed on the cumulative curve of excess deaths. In July 2021, we observe a delay of three months from the vaccination peak to high-rate trend impact on deaths, while the worse performance is presented in the second vaccination peak, in December 2021 with a higher rate trend and without a delay impact signature. However, as this is a cumulative curve, we realise that the investigated period of 2021-2022 presents a significant increased amount of 2,624 all-caused deaths above the average of period 2016-2019.

In Figure 4 we delineate the mortality deviation from the average trend of years 2016-2019 as outlined in parallel to important key dates indicating the first COVID-19 case reported in Cyprus on March 10th 2020, the initiation of the vaccination campaign on December 27^th 2020 and the identified peaks of total vaccination doses delivered in May and December of 2021, respectively [15]. The overall curve represents the cumulative excess total deaths from all causes in Cyprus. We note that during the period between the start of SARS-CoV-2 epidemic in Cyprus and the start of the vaccination campaign, the mortality deviation is very low compared to the vaccination period that followed, which appears to increase during the vaccination period.

Figure 4: The mortality deviation from the average trend of years 2016 – 2019 is presented in the graph along with important key dates indicating the first COVID-19 cases reported in Cyprus on March 10^th 2020, the start of the vaccination campaign on December 27^th 2020 and the two identified peaks of total vaccination doses delivered in May and December of 2021, respectively. The overall curve represents the cumulative excess total deaths from all causes in Cyprus. We note that during the period between the start of SARS-CoV-2 epidemic in Cyprus and the start of the vaccination campaign, the mortality deviation is very low compared to the vaccination period that followed, which appears to increase drastically during the vaccination period and thereafter. The cumulative curve also suggests that the proposed assessment method of mortality trend can provide an unbiased result. Therefore, we are able to identify that the critical increased mortality occurring after December 2020 has led to about 3000 excess deaths within the years 2021-2022.

Finally, in Figure 5 we present the cumulative mortality for different age groups (below and above age 40). We note the improved quality of data trends assessment by using the cumulative method in mortality studies. Cumulative excess deaths although are documented among people below age 40, they remain inconclusive in Figure 5A. However, significant cumulative excess deaths are noted for people above age 40 in all age groups starting in the first quarter of 2021 and continuing thereafter (Figure 5B).

Figure 5 (A and B): In this figure we compare the cumulative mortality for different age groups (below and above age 40). We recognize the improved quality of data trends assessment by using the cumulative method in mortality studies. Cumulative excess deaths although are documented among people below age 40, they remain inconclusive in section A. However, significant cumulative excess deaths are noted for people above age 40 in all age groups starting in the first quarter of 2021 and continuing thereafter (section B).