Mortality Rates of the Spanish Flu and Coronavirus Disease 2019 in the Netherlands: A Historical Comparison

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has been called the deadliest disease event in history. In this study, we compared the cause-specific mortality rate of the Spanish flu (1918–1920) with that of COVID-19 (2020–2022) in the Netherlands. During the periods of exposure, about 50 000 people died of COVID-19 and 32 000 people of the Spanish flu. In absolute numbers, COVID-19 seems to be deadlier than Spanish flu. However, the crude mortality rates for COVID-19 and Spanish flu were 287 and 486 per 100 000 inhabitants, respectively. Comparing age-standardized mortality rates, there would have been 28 COVID-19– and 194 Spanish flu–related deaths in 1918–1920, or 214 Spanish flu– and 98 COVID-19–related deaths in 2020–2022 per 100 000 inhabitants per year. Thus, taking the population differences into account, the Spanish flu would have been deadlier than COVID-19.

In November 2022, the National Institute for Public Health (RIVM) declared the end of the coronavirus disease 2019 (COVID-19) epidemic in the Netherlands [1]. Although variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were still circulating in the Dutch population, virulence, symptoms, hospital admissions, and deaths had decreased significantly. Specific preventive or social measures were no longer considered necessary. During 2020–2022, COVID-19 was the most frequently occurring cause of death in the Netherlands [1]. COVID-19 was even called the deadliest disease event ever, a qualification previously given to what is commonly known as the “Spanish flu,” an infectious disease that raged a century earlier [2].

The Spanish flu (influenza A/H1N1) appeared in the Netherlands in July 1918. There were several outbreaks in rapid succession with a high mortality rate, followed by decreasing mortality rate and frequency of outbreaks [3, 4]. This epidemiological pattern resembles that of COVID-19 [5, 6]. Both pandemics hit the Netherlands with a huge impact on population and society. Mortality rate is a common measure for the severity of this impact. Therefore, we compared the cause-specific mortality rate of the Spanish flu with that of COVID-19 to answer the question: Which was actually a deadlier disease, the Spanish flu or COVID-19?

METHODS

In the current study, we compared the Spanish flu (1918–1920) with COVID-19 (2020–2022), using the absolute numbers of deaths and the crude as well as age-adjusted mortality rates in the Dutch population. Data on population by age and sex, mortality rate, and causes of death was obtained from the registries of Statistics Netherlands (CBS). CBS is a semigovernmental agency, collecting data on causes of death since 1901 [7]. For every deceased person in the Netherlands, there is a legal obligation for the attending physician to send a death certificate to CBS reporting ≥1 disease causing death. Death certificates are coded by CBS according to the prevailing version of the International Classification of Diseases (ICD), and tables of underlying causes of death are published monthly in times of epidemics or yearly as regular output.

The Spanish flu–related deaths were extracted from handwritten tabulations of causes of death by age and sex, archived by CBS, and available on demand. The COVID-19 deaths were extracted from files of coded death certificates with causes of death by age, sex, and month of death, available for research. Stored death records are anonymized (no name, address, etc) and not reducible to an individual person by cross-tabulation or otherwise. There were no living persons involved in this study, and according to Dutch Civil Law (article 7:458) no ethical approval is required for a secondary analysis on nonidentifiable data from deceased persons.

In this study, we identified cases by their corresponding ICD codes in the CBS cause-of-death registry. For counting deaths due to the Spanish flu (influenza A/H1N1), cases were found under the registered cause “influenza.” The excess mortality rate for “bronchopneumonia” and “croup pneumonia” (nowadays called lobar pneumonia) in 1918–1920 should also be attributed to influenza [8]. It is likely that when the cause of death was stated, (croup) pneumonia was an unspecified case of influenza. In addition, owing to the limited test technology and rapid development of the epidemic, death may have been attributed to the (presenting) secondary bacterial infection and not to the underlying influenza infection. Therefore, we defined the influenza-related mortality rate as the excess mortality rate of (croup) pneumonia in the years 1918–1920 together with the mortality rate for cases registered as “influenza.”

Deaths due to COVID-19 were identified by their corresponding ICD-10 codes (U07.1 and U07.2) in the CBS cause-of-death registry. During 2020–2022, CBS applied World Health Organization guidelines for coding COVID-19 on death certificates [9]. COVID-19 was assigned as an underlying cause of death when mentioned on part 1 of a death certificate by the certifying physician. Owing to the limited test capacity in 2020, the excess mortality rate for pneumonia in that year was attributed to SARS-CoV-2 for the same reasons and in the same way as mentioned for the Spanish flu. Thus, the COVID-19–related mortality rate was defined by cases with the disease as an underlying cause of death in 2020–2022 plus the excess mortality rate for pneumonia as an underlying cause of death in 2020.

The excess mortality rates for pneumonia in 2020 and for (croup) pneumonia in 1918–1920 were defined as the difference between the observed frequency of these causes of death in the particular period and the average number of deaths due to the disease in the 5 years preceding the start of the epidemic [10].

Standardization by age and sex was performed to compare the mortality rates of both epidemics in a population that had changed significantly over the past century. With direct standardization, the observed frequency of occurrence of a (in this case) cause of death in a particular age group of a population is applied to the same age group in another (reference) population. In this way, the occurrence of the cause of death for a population was calculated as if this population were structured in the same way as the reference population. As a result, an observed difference in mortality rate cannot be attributed to a difference in age structure. Since in this case there was no clear reference population, we projected the age-adjusted mortality rate of the Spanish flu to the time period of 2020–2022, and the age-adjusted mortality rate of COVID-19 to the time period of 1918–1920. The exposure times of 30 months for the Spanish flu and 35 months for COVID-19 were included in the calculations.

For the intended comparison, we will first describe the course of both epidemics in the Netherlands, then picture the difference in age structure of the exposed populations, and finally compare both epidemics by projections of the age-standardized mortality rate in the corresponding years.

RESULTS

The Spanish flu first hit the Netherlands in July 1918. The outbreak was characterized by 3 rapidly recurring mortality “waves” before an annual seasonal pattern emerged in 2021 (Figure 1).

The first case of COVID-19 was registered in the Netherlands on 6 February 2020, marking the start of an epidemic outbreak that would take a high toll over 2020–2022. According to CBS, there were 47 544 deaths with COVID-19 as an underlying cause of death. When the deaths from unspecified pneumonia in 2020 were added, 49 988 deaths could be attributed to COVID-19. The mortality pattern reflected the outbreaks of different SARS-CoV-2 variants in the Netherlands: the original (Wuhan) variant from March to November 2020, the Alpha (British) variant from December 2020 to June 2021, the Delta (Indian) variant from mid-2021 to January 2022, and the Omicron variant(s) from January 2022 to the present (Figure 2).

When comparing the mortality of the Spanish flu with that of COVID-19, differences between the exposed populations must be considered. In the Netherlands, on average, 6.6 million inhabitants were exposed to the Spanish flu and 17.5 million to COVID-19. The period of exposure was 35 months for COVID-19 and 30 months for the Spanish flu. In addition to differences in population size and exposure time, there was also a difference in age structure (Figure 3). In 1918–1920 there was a relatively young population, with only 6% of the population was >65 years old. In 2020–2022, 20% of the population was >65 years old.

Figure 4 shows the numbers of deaths due to the Spanish flu in 1918–1920 and to COVID-19 in 2020–2022. The highest number of COVID-19 deaths was observed in Dutch residents aged ≥65 years, while the Spanish flu mainly affected those aged <40 years.

The crude mortality rate, on average, was 287/100 000 inhabitants for COVID-19 (Table 1) and 486/100 000 for the Spanish flu (Table 2). Over a period of 35 months, there were, on average, 98 COVID-19 deaths per 100 000 inhabitants per year. Most deaths (>60%) occurred in inhabitants ≥80 years old (Table 1).

A projection of the age-specific death rates of COVID-19 onto the population of 1918–1920 resulted in 4653 (expected) deaths due to COVID-19. Over a period of 30 months, this came down to an average of 28 COVID-19 deaths per 100 000 inhabitants per year (Table 2).

Over a period of 30 months, there were on average 194 deaths due to the Spanish flu per 100 000 inhabitants per year (Table 2). The Spanish flu was characterized by a high mortality rate among young adults (aged 20–39 years). A projection of the age-specific death rates of the Spanish flu on the population of 2020–2022 resulted in 108 759 (expected) deaths. Over a period of 30 months, this came down to an average of 214 deaths due to the Spanish flu per 100 000 inhabitants per year (Table 1).

DISCUSSION

The Spanish flu and COVID-19 compete for the title of deadliest disease ever [2]. We compared the cause-specific mortality rate of the Spanish flu with that of COVID-19 in the Netherlands. Although in absolute number the deaths from COVID-19 (49 988) exceeded those from the Spanish flu (32 172), the crude mortality rate of Spanish flu (486/100 000 inhabitants) was higher than that of COVID-19 (287/100 000). Age standardized with the 1919–1920 population as the standard and corrected for the exposure time, the mortality rate of Spanish flu (194/100 000) was also higher than that of COVID-19 (28/100 000), and with the 2020–2022 population as the standard the mortality rate of Spanish flu (214/100 000) was also higher than that of COVID-19 (98/100 000).

The cause-specific mortality rate relies on the observation of death by a physician and the available knowledge of pathophysiology. There is a strong similarity between the pathophysiological mechanism of deaths caused by Spanish flu and COVID-19. Deaths from Spanish flu (influenza A/H1N1) were usually the result of a disease process, which began with a severe acute viral infection that spread along the respiratory tract and resulted in severe lung tissue damage. When the viral infection was followed by a secondary bacterial infection of the lungs, the patient died of severe respiratory failure [3, 4]. Such a secondary bacterial infection is still considered to be the pathophysiological mechanism of a serious influenza infection [5]. In addition, deaths from influenza in 1918 were made worse by progressive cyanosis and collapse caused by an underlying sepsis associated with the (secondary) bacterial infection and an excessive immune response (cytokine storm), as is observed in COVID-19 as well [11].

Deaths from COVID-19 are attributed to a severe pneumonia leading to acute respiratory failure (acute respiratory distress syndrome). The virus (SARS-CoV-2) binds to angiotensin-converting enzyme 2 receptors present in the epithelial cells of the lung tissue and penetrates the host cell via a so-called spike protein on the virus [11, 12]. The viral pneumonia is accompanied by extensive destruction of lung tissue underlying the acute respiratory distress syndrome or may be complicated by a secondary bacterial pneumonia, as was the case with Spanish flu. Angiotensin-converting enzyme 2 receptors are not restricted to the lungs. They are also present in the endothelial cells of blood vessels, the tissue that lines the intestines, and other organ cells [12]. Thus, general organ failure is also observed as direct cause of death in severe SARS-CoV-2 infection.

The deadliness of COVID-19 and influenza does not depend on the pathophysiology of death alone. Apart from the similarities in pathophysiological mechanisms, there is a difference in origin, viral characteristics, and vulnerability of age groups (Table 3). For reasons yet unknown, many young adults died of the Spanish flu in 1918–1920, while in 2020–2022 it was mainly a large group of vulnerable elderly people who died of COVID-19 [13]. Thus, the deadliness of the epidemics differed for different age groups.

Regarding the “deadliness” of an epidemic, not only the cause-specific mortality rate but also the overall mortality rate should be considered as well. In the period 1918–1920, the overall mortality rate varied between 1.1% and 1.8%, while in 2020–2022, it varied between 0.81% and 0.98% [14]. This difference in overall mortality rates can be explained by the difference in healthcare with its preventive measures and therapeutic options. In 1918–1920 there was no vaccination against influenza virus, and there were no antibiotics to treat the secondary bacterial infection. The population therefore had to rely on an immunity that was developed in elderly persons who survived previous 19th-century influenza epidemics, such as the Russian flu of 1890, and was not yet present in young people.

A vaccine against the SARS-CoV-2 virus was developed quickly. Vaccination campaigns started in December 2020. Medications (antibiotics, anticoagulants, and corticosteroids) and intensive care units were also available to treat serious complications of the infection. So, taking the overall mortality rate into account, the Spanish flu appeared to be deadlier than COVID-19 against the background of a large difference in healthcare systems.

A strong point of the current study is the cause-specific approach and an overview over the COVID-19 pandemic in the Netherlands, which lasted from February 2020 to December 2022. Other studies trying to compare Spanish flu and COVID-19 dated before 2022 and therefore could not include the whole pandemic period. The cause-specific approach was chosen from a medical point of view—that is, death attributed to Spanish flu or COVID-19 by physicians as reported on death certificates. We did not consider the excess overall mortality rate, which is sometimes considered the gold standard for the impact of an epidemic on society from a health policy point of view [15]. Excess mortality rate is associated with an underlying epidemic, but association is not causation. Many other factors intervene. With Spanish flu, the first World War, for instance, also caused an increase in mortality rate, and with COVID-19 it was not possible to explain the excess deaths completely by COVID-19 deaths [14]. Delays in treatment and social isolation were proposed as explanations [14], which could be considered indirect effects of the circulating virus and not direct causation of death by the virus.

Studying a shift in causes of death was also not our scope. A limitation of a cause-specific approach is the validity of the diagnosis reported on a death certificate [16]. For both COVID-19 and the historical records of Spanish flu, there were no estimates of validity available. We included cases of (broncho)pneumonia in the period of exposure, as this might have been misclassified a cause of death against a background of absent test facilities or biased clinical judgments. The excess mortality rates of bronchopneumonia points at underregistration of COVID-19 or Spanish flu. However, CBS reports about 1.4 times more deaths due to COVID-19 than the RIVM registration of mandatory reported infectious diseases [17]. An explanation is lacking, and there is a difference in coverage (CBS included all deaths, and RIVM ,reported cases), but we might consider the estimate of the cause-of-death registration rather high.

In conclusion, was the Spanish flu deadlier than COVID-19? The answer depends on the perspective taken. In absolute numbers COVID-19 seems to be deadlier. The Spanish flu killed approximately 32 000 people, while 50 000 died of COVID-19. However, the crude mortality rate of Spanish flu (486/100 000) is higher than that of COVID-19 (287/100 000). With the 2020–2022 population as standard, the age-adjusted mortality rate of Spanish flu (214/100 000) was more than twice that of COVID-19 (98/100 000), and with the 1918–1920 population as the standard, the age-adjusted mortality rate of Spanish flu (194/100 000) was >6 times that of COVID-19 (28/100 000). Thus, accounting for differences in the populations, the Spanish flu was deadlier than COVID-19 in the Netherlands.

Notes

Disclaimer. The opinions expressed in this article are of the authors and do not necessarily represent the views of Statistics Netherlands (CBS).

References

Author notes