Applying Syndemic Theory to Acute Illness

The COVID-19 pandemic has laid bare deep geographic, racial, and economic inequities in the US and on a global level and has served as a reminder of the inseparable ties between biological and social processes in the health of individuals. This lesson is not specific to COVID-19 but rather has been at the heart of understanding mechanisms of chronic disease disparities such as HIV, diabetes, and tuberculosis for decades. Syndemic theory, which describes synergistically related, clustered epidemics that arise from harmful social conditions,¹ provides a helpful framework for understanding these complex relationships, and its application to clinical care, research, and health policy focused on acute illnesses can provide valuable insights.

Syndemic theory, with its roots in medical anthropology, has been revolutionary for progress in addressing other major public health challenges, but to date it has nearly exclusively been applied to chronic conditions. This is possibly due to its origins in describing community-level disparity patterns of HIV and to its historical application to conditions that have been more clearly understood to be related to modifiable behaviors such as substance use or diet. However, much benefit could be gained by the application of syndemic theory to acute conditions. This Viewpoint discusses 2 specific examples—sepsis and COVID-19—although other major acute medical conditions such as trauma, stroke, and acute coronary syndrome are similarly affected by a combination of community-specific medical and social forces that could be better understood and possibly better addressed through the use of syndemic frameworks.

Why Apply Syndemic Theory to Complex Systems?

Syndemic theory focuses on the adverse interactions between diseases and social conditions, specifically drawing attention to the mechanisms of these interactions. Identification of syndemic interactions allows for a new way of understanding the prevention and treatment of the involved conditions. For example, it may become clear that mortality from condition A cannot be reduced without addressing condition B, or condition B may be nearly completely prevented by adequately treating condition C. Syndemic frameworks have had an important role in informing the response to major public health challenges, such as the SAVA (substance abuse, violence, and AIDS) syndemic in urban US communities.^1,2 Using a syndemic framework, researchers identified subsets of patients infected with HIV who had poor outcomes not predicted by their viral characteristics but based on features of the other elements of the syndemic. For example, syndemic analysis demonstrated that high SAVA scores were associated with higher HIV viral loads and diminished effectiveness of antiretroviral treatment.^1,3 This insight directly informed a randomized clinical trial that demonstrated the reduction of HIV viral load among people who use illicit drugs and were enrolled in an abstinence-reinforcing treatment program.⁴

Applying Syndemic Theory to Acute Conditions

Acute conditions often serve as sentinel indicators of long-standing and complex relationships among the forces that influence an individual’s health. By providing a framework of disease-disease and social condition–disease interactions,¹ syndemic theory can improve understanding of acute health conditions within a specific population and could lead to key scientific advances in a way that isolated, condition-specific research has not.

Sepsis, a massive global health problem with nearly 50 million cases worldwide each year despite untold clinical, research, advocacy, education, and financial investments aimed to reduce its incidence, is an ideal acute health condition to which to apply a syndemic framework.⁵ Although sepsis is a challenge in nearly every location in the world, certain groups of people are at far higher risk than others. Sepsis risk in the US is predominantly driven by aging and multimorbidity, the coexistence of 2 or more chronic conditions. In the US, these risk factors are closely linked and geographically clustered. Despite a rich body of science on sepsis risk factors, most previous studies have focused on an individual’s personal health history, sociodemographic characteristics, or community features in isolation, without assessing the complex and spatially patterned relationships among them. This has been partly driven by data limitations, such that individual data sources are insufficient to evaluate all relevant risk factors in concert, as well as lack of a sufficient conceptual framework. This has led to little progress in reducing the incidence of sepsis in the US.

Sepsis, multimorbidity, aging, and low health care access and quality exist within a network of complex social and biological relationships, a pattern that is strongly suggestive of a syndemic. Deeper understanding of these relationships can improve understanding of the factors influencing individual sepsis risk. For example, the ability to better assess the sepsis risk profile of patients with multimorbidity and social risk factors before they acquire acute infection could lead to targeted sepsis prevention efforts such as intensive pneumococcal vaccination campaigns or enhanced research on ways to modify the relationship between environment and inflammatory response to acute infection.

COVID-19 is a second example of the potential usefulness of a syndemic framework with an acute health condition. Globally, the relationships between COVID-19, chronic comorbidities, and social conditions has led to the proposed consideration of some of these elements as part of a syndemic.⁶ As syndemics are, by nature, specific to local populations, it has become clear that racial and ethnic factors and racism are among the strongest driving social forces for COVID-19 disparities in the US. The relationship between racism and COVID-19 is multifaceted, and factors such as vaccine access, labor conditions, and exposure through employment in essential sectors and biological conditions such as obesity (which in turn has critical ties to social factors in the US) all have had key roles. Although these are only simplified examples from the complex systems that influence COVID-19 incidence, mortality, and morbidity in the US, they highlight the ways in which a syndemic approach to acute conditions such as COVID-19 may be helpful. For example, despite the remarkable rapid development of multiple highly effective vaccines against SARS-CoV-2, optimal societal benefit from the vaccines requires effectively understanding and addressing the causal mechanisms that influence delivery and uptake of the vaccine.

Syndemic Frameworks and the Way Forward for Acute Care Research and Health Policy

Use of a syndemic approach to acute medical conditions allows for critical improvements to the understanding of causality, disease prevention, and overall health. Acute health conditions exist within complex, community-specific, syndemic relationships. To leverage this insight and convert it into actionable improvements in the prevention and treatment of acute health conditions, medical and public health communities should employ the following steps:

1. Identify the fundamental social and biological conditions involved in the complex systems of acute illnesses within specific contexts of place and time. This will require linking multiple individual- and community-level data sources. Administrators of major health plans and state and federal government agencies will be essential in facilitating this type of data linkage and in fostering data access and collaboration. Clinicians have an important role in working with patients to identify the key social and biological processes affecting their patients’ health.

2. Evaluate key relationships between and among these conditions, including causal mechanisms and feedback loops, using community-informed research methods. Multilevel modeling is a well-established approach for the evaluation of syndemic relationships.⁷Agent-based modeling, a simulation model in which outcomes are determined by the local actions and interactions of agents within an environment, and geospatial analysis may be particularly helpful methods. Researchers and clinicians must collaborate across disciplines and traditionally siloed fields of medicine to assess important disease-disease interactions.

3. Investigate ways to shift the complex system of risk factors and forces that influence acute health conditions, and introduce new ways of thinking about prevention and intervention. These evaluations may reveal that prioritizing key elements of the system could have significant downstream effects on other components without having to address them all at once, with some elements essentially acting as levers or blockers. Through new research and community collaborations, it may become clear that a seemingly ineffective intervention tested in one population or with one outcome may actually be effective when tested in a different set of circumstances.

Syndemic frameworks can help identify or improve the efficacy and efficiency of new medical or policy intervention and can be powerful tools for social justice in health. It is time that researchers, clinicians, and health policy professionals focused on acute medical conditions embrace the complex systems within which they and patients exist and leverage a syndemic approach to improving the health of communities.