key: cord-0983478-5xofcago
authors: Agrawal, Siddarth; Gołębiowska, Justyna; Bartoszewicz, Bartłomiej; Makuch, Sebastian; Mazur, Grzegorz
title: Clinical preventive services to reduce pandemic deaths
date: 2020-11-25
journal: Prev Med Rep
DOI: 10.1016/j.pmedr.2020.101249
sha: 8b0e2fcada3c6419b508a45e2d4bbcd6266884dd
doc_id: 983478
cord_uid: 5xofcago

The recent COVID-19 pandemic has highlighted inadequacies in both national and international preparedness. The outbreak has resulted in an overburdening and incapacitation of health systems worldwide, as well as numerous deaths of individuals with comorbidities. We have performed a simulation study to examine the effect of comorbidities and their prevention on the clinical outcome and mortality of patients during the COVID-19 pandemic. The data from past and present outbreaks indicate that individuals with comorbidities are significantly more susceptible to infections and yield poorer clinical outcomes. Our simulation study revealed that the prevention of morbidities like hypertension, diabetes, and cardiovascular disease bears an enormous potential to decrease the COVID-19 death toll. The accumulating evidence emphasizes our ability to reduce both the susceptibility of uninfected individuals to pathogenic factors, as well as the mortality of infected individuals during pandemics by adopting a more comprehensive approach to disease prevention. Higher utilization of clinical preventive services is critical to reduce pandemic deaths and increase our preparedness for future outbreaks.

Pandemics are outbreaks of infectious diseases that result in increased morbidity and mortality over a wide geographic area, that cause significant economic, social, and political disruption. Unfortunately, recent events, most notably the COVID-19 outbreak, have highlighted inadequacies in both national and international preparedness and response. Not only the government and state leaders face difficulties, but the problem also affects every citizen. Numerous civilians are forced to deal with panic, insecurity, misinformation, and doubt. To further advance our preparedness and ability to respond to infectious disease outbreaks, it is crucial to identify the most significant challenges facing policymakers, based on past evidence, existing data, and future predictions. In this paper, we present data showing health status as a potentially significant factor in pandemic preparedness.

Pandemics have occurred throughout history and appear to be increasing in frequency.

Leading experts have been declaring for years that another pandemic whose rate and severity will match those of the Spanish flu is a matter not of if but of when 1 . Evidence points out that the risk of outbreaks has grown over the past century 2, 3 . Numerous factors, such as population growth, urbanization, increased travel and interconnectedness, a higher requirement for animal protein, habitat loss, environmental changes, and growing interactions at the human-animal interface affect the risk of a pandemic event by increasing the likelihood of a spark event or the potential spread of a pathogen 4, 5 . Probabilistic modeling and analytical tools such as exceedance probability have shown that in any given year the probability of influenza pandemic is about 1% 6 . Data published by the Institute for Disease

Modeling shows that if a highly contagious and lethal airborne pathogen, like the 1918 influenza, appeared today, over 30 million people globally would die in just six months 7 .

Less than two decades into the century, the world has already witnessed numerous outbreaks of varying degrees of contagiousness and lethality (Table 1) . Currently, the world is struggling with the COVID-19 outbreak, in less than four months after the onset, the number of confirmed cases has reached almost two million and continues to rise. With the global population predicted to reach close to 10 billion by 2050, and with a steady increase in travel and trade, public health systems will have less time to identify and contain an infection before it spreads. However, the risk of pathogen spread is not only determined by the level of preparedness of a nation. The initiation and progression of an outbreak are influenced by pathogen-specific factors, in particular genetic adaptation and mode of transmission, as well as humanpopulation factors, such as the density of the population and the susceptibility to infection 11 .

It is well-established that factors that affect an individual's immune system, such as comorbid diseases and obesity, amplify transmission rates and increase morbidity and mortality [12] [13] [14] .

The susceptibility of uninfected individuals to the pathogenic factor is primarily determined by their health status. Thus, a good overall level of health of the population emerges as a critical way to prevent mass casualties and to avoid overburdening and incapacitating a health care system which may lead to a twofold increase in all-cause mortality during outbreaks 15 .

We propose that health status of a population is a factor that has not yet been incorporated into pandemic preparedness considerations.

The data from past and present outbreaks indicate that individuals with comorbidities are more susceptible to infections and yield poorer clinical outcomes. For instance, the 2019-nCoV infection is more likely to affect individuals with comorbidities and may result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome 16 During the H1N1 influenza pandemic, reports on risk factors showed that obesity and hypertension not only increased the risk of death (odds ratio (OR) 2.74 and 1.49, respectively) but also were significantly associated with the requirement for hospitalization, ICU care, and ventilator support 19 . Moreover, the risk of severe outcomes after hospitalization was highest among patients with diabetes (relative risk (RR) 2.2) and with preexisting heart disease (RR 2.1) 20 . Also, it was found that smokers were at significantly higher risk of mortality (OR 5.97) 21 . Similarly, during the outbreak of severe acute respiratory syndrome (SARS), the presence of comorbidities increased the mortality risk to RR 9.0, with heart disease (RR 9.2), and diabetes (RR 4.7) being the most critical comorbidities 22 . The presence of comorbidities in patients with the Middle East respiratory syndrome (MERS) was associated with the development of the severe disease. MERS patients with underlying diseases, such as obesity, diabetes, and cardiac disease, had around four times higher risk of mortality (RR 3.74) 23 .

It is evident that the population's health status is a crucial determinant of mortality during outbreaks of infectious diseases.

To We propose the following set of assumptions for the simulation:

1. We assume that the probability of SARS-CoV-2 infection is equal for both patients with comorbidities and patients without comorbidities. We consider this assumption realistic because current preventive measures in the United States including social distancing and quarantine apply to both groups. We have decided to study the case of the United States in this simulation because of its large population, high percentage of patients with comorbidities and availability of reliable data for analysis.

2. We assume that case-fatality rates for patients with hypertension (6%), diabetes (7.3%), Table 2 . A limitation of the simulation study is that it does not take into consideration the occurrence of more than one comorbidity, nor the subtype (eg. diabetes type 1 or type 2) and the clinical stage of the disease. Based on our simulation, prevention of hypertension bears the highest potential to decrease the COVID-19 death toll -up to almost 12% if the population with hypertension is reduced by 30%. On the other hand, prevention of diabetes has the lowest potential to limit COVID-19

deaths of the three studied comorbidities -due both to relatively low risk ratio and prevalence of diabetes.

It is essential to mention that the results presented in this simulation also do not depend on the percentage of the population infected by the coronavirus. Of course, the higher the infected population, the higher the total mortality, and the higher the number of prevented deaths given the reduction of the prevalence of the particular comorbid disease.

At the time of this analysis, the actual risk ratios for COVID-19 for patients with hypertension, diabetes, or cardiovascular disease in the United States remain unknown. In order to study the sensitivity of presented simulation results to changes of implied risk ratios, we calculated the percentage of prevented COVID-19 deaths due to reduced prevalence of comorbid disease as a function of implied risk ratios based on two assumptions:

1. We assume that the probability of becoming infected by COVID-19 is equal for both patients with comorbidities and patients without comorbidities.

2. We assume that higher utilization of clinical preventive services will reduce the population suffering from analyzed comorbidities by at least one-fourth (25%) 27, 28 The results are shown in Figure 1 . Each curve represents the percentage of prevented COVID-19 deaths as a function of the implied risk ratio connected to each of the three studied comorbid diseases. Curves for cardiovascular disease (9% prevalence) and diabetes (13% prevalence) are relatively flat and seem almost linear-the potential for preventing COVID-19 deaths remains below 8% even for risk ratios as high as 4. The third curve corresponds to hypertension with a 45% prevalence in US adults and has a high potential of preventing COVID-19 deaths -above 5% even for risk ratios as low as 1.6.

It is worth pointing out that as long as assumption 1 holds (the probability of becoming infected by COVID-19 is equal for both patients with comorbidities and patients without comorbidities), the results presented above do not depend on the percentage of the population infected by the coronavirus, nor do they depend on the actual case-fatality rates for patients with and without comorbidities. This means that the prevention of diseases like hypertension, with a very high prevalence in the population, will yield significant reduction of mortality during future outbreaks of diseases like COVID-19, even if the actual risk ratios turn out to be moderately low.

Economic evaluations of preventive services show favorable cost-effectiveness of the majority of interventions intended to prevent or control morbidities at an early stage, in particular conditions that are responsible for a large share of the world's burden of diseases, such as diabetes, hypertension, and cardiovascular disease [29] [30] [31] [32] . In the face of damaging consequences of an outbreak on the economy and increasingly constrained resources, preventive activities emerge as a realistic way of achieving better health results.

It is estimated that 60% of adult Americans suffer from at least one chronic disease or condition, and over 40% have multiple morbidities 33 . By 2030, more than 80 million people alone in the United States will have at least three chronic diseases 34 . 

The recent COVID-19 pandemic has highlighted inadequacies in both national and international preparedness. Evidence points out that population health management emerges as a critical way to prevent mass casualties and to avoid overburdening and incapacitating a health care system during pandemics. Current models emphasize our ability to reduce the susceptibility of uninfected individuals to a pathogenic factor, as well as the mortality of infected individuals during pandemics by improving the population health status. In this paper, we have shown that higher utilization of clinical preventive services and a more comprehensive approach to prevention of morbidities like hypertension, diabetes, and cardiovascular diseases will yield significant reduction of mortality during future outbreaks, and substantially increase pandemic preparedness. Pandemic preparedness should take population health status and disease management into consideration.

SA conceived the idea, designed the study and wrote the manuscript. JG collected the data and wrote the manuscript. BB performed the simulation study, SM and GM reviewed and edited the manuscript. 

The authors declare no conflict of interests.

The authors confirm that the data supporting the findings of this study are available within the article.

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Figure 1. The percentage of prevented COVID-19 deaths as a function of Implied Risk Ratio  The prevention of comorbidities can reduce the COVID-19 death toll  Prevention of hypertension bears the highest potential to decrease COVID-19 deaths

Each curve represents the percentage of prevented COVID-19 deaths as a function of the implied risk ratio connected to each of the three studied comorbid diseases. Curves for cardiovascular disease (9% prevalence) and diabetes (13% prevalence) are relatively flat and seem almost linear-the potential for preventing COVID-19 deaths remains below 8% even for risk ratios as high as 4. The third curve corresponds to hypertension with a 45% prevalence in US adults and has a high potential of preventing COVID-19 deaths -above 5% even for risk ratios as low as 1.6. 

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: