The synergistic interactions among disease and the contextual social environment (i.e., SDoH) in which they occur can result in a syndemic. More specifically, a syndemic is described by the coming together of two or more health conditions (e.g., chronic illness and infectious disease) and their adverse interactions with each other and the SDoH that can provide the milieu for enhancing vulnerabilities, magnifying inequities, and worsening health outcomes for marginalized populations (14–16). A syndemic framework examines disease interactions and the contributions of structural, social, economic, and environmental factors that synergistically interact to contribute to adverse health outcomes for individuals and whole populations (16, 17). Singer first introduced the term syndemic in the 1990s when he described the interactions among substance abuse, violence, and AIDS (SAVA syndemic) (15). Singer identified the criteria necessary for a syndemic: (1) grouping of two or more health conditions or diseases in a population; (2) social and contextual factors that allow for the biological interactions to occur and for the development of adverse health outcomes, and (3) disease interactions that lead to negative outcomes (e.g., health, social, and behavioral) for the affected population and increases their health burden (15, 16). Other syndemics identified and studied by women researchers include the HIV, malnutrition, food insecurity syndemic and the violence, immigration, depression, type-2-diabetes, abuse syndemic (VIDDA syndemic) among Mexican women immigrants (15, 16). Syndemics are not restricted to communicable and chronic diseases and may be heightened by health inequality attributable to poverty, structural violence, and stigmatization (16). For example, research has demonstrated that children who encounter adverse experiences during childhood, such as living in a violent neighborhood or witnessing violence in their living environment are three times more likely as children who do not experience similar violence to be diagnosed with asthma. This synergistic relationship of living with fear, violence, and asthma are representative of a syndemic often observed in urban environments (16, 18).

To respond to the Women in Science Research Topic, we examined the contributions of female researchers to the COVID-19 syndemic. We examined GALE Biography, Historical Abstracts, and PubMed databases. The historical databases were reviewed with an emphasis on the time period: 1800-1918; 1919-1950 (WW1-WW2); and Post-WWII (1951-present). Two U.S. government reports featuring women and minority scientists were also utilized (19, 20). Searches were conducted from November 2021–January 2022.

For the GALE Biography and Historical Abstracts databases, we used the following search strings: [“public health” OR epidemiolog^*) AND (pioneer^* OR famous)]; and [“syndemic” AND (“women” OR “female”) AND (pioneer^* OR famous)], which identified 111 citations. We excluded citations if they did not focus: (a) on women's contributions; (b) on public health; or (c) on an English translation. Duplicate citations were excluded. A total of 23 citations resulted, highlighting women's significant contributions to public health in clinical, research, and policy/advocacy domains from the pre-Industrial Revolution period through the Post WW-II period.

For the PubMed database, using the search phrase, “syndemic and public health and female authors”, 69 articles were identified with 51 including the term “syndemic” in the abstract, title, or narrative of the article. Using the search phrase, “COVID-19 syndemic and public health and female authors”, 7 of the 51 published articles were identified. The articles in the PubMed database identified the long-standing SAVA syndemic and more recently the COVID-19 syndemic with the range of COVID-19 syndemic articles published between 2020 and 2021.

The historic literature review identified female health professionals' “pre-syndemic” contributions, which are often unrecognized in public health textbooks and curricula. The authors, who are both female, further note that this work provided a strong foundation upon which the essential public services of contemporary public health could be built. For example, female health professionals advanced the fields of public health nursing across the globe, contributed to our understanding of the zoonotic transmission that foreshadowed the contemporary One Health model, campaigned for gender-sensitive policies, established community clinics focusing on the overall wellness of the community, and expanded our scientific knowledge through research in fields such as bacteriology and immunology. The work of these women foreshadowed the need to address syndemics via a SDoH perspective.

The relationship between the SDoH and the COVID-19 syndemic is also evident in the results from the literature search which identified the following select global contributions from women health professionals:

Based on the work described above and prior research in this area, populations residing in environments with structural susceptibilities experience health adversities and syndemics to a greater extent than their less vulnerable counterparts which warrants a review of the contributory upstream determinants (e.g., social, economic, and political factors) (17).

Women researchers have proposed that the interactions between the COVID-19 syndemic and the SDoH engage in a bi-directional relationship (28). In this relationship, structural determinants (e.g., poverty, and violence); sociocultural determinants (e.g., lifestyle, family conflict, and support); socioeconomic determinants (e.g., employment and access to health care); and individual determinants (e.g., health behavior and self-efficacy) interact with each other. For example, if one is employed in a service industry as an hourly employee then they probably need to keep going to work due to the lack of sick time. If they do not work, they will not be paid which means they can't provide food and shelter for themselves or families. As a result, many of these people put themselves at risk of exposure to SARS-CoV-2 because the interactions of the SDoH with the COVID-19 syndemic removes their choice to prioritize their health (15, 17).

To assure the health of populations experiencing these syndemics, the authors propose, based on female health professionals' contributions in this area, that significant reform of public health policy in the U.S. occurs that assures a basic standard of living where housing is affordable, a minimum wage allows for healthy food choices, and universal healthcare, as a few starting points. Such systemic change will take years but if the COVID-19 syndemic has taught us anything, it is that to survive the next pandemic, with the least amount of morbidity and mortality, will require starting with a healthy population and not the magnitude of widespread inequity that currently exists in the U.S.

Supplementary Table 1 highlights the myriad contributions of female health professionals to the pre-syndemic and COVID-19 syndemic domains.

Another area that warrants attention is the role of the exposome in syndemics. The exposome, coined by Wild in 2005 (29) is intended to complement the genome, and is defined as the exposure measures for an individual over their lifetime and how those exposures relate to the individual's health (30, 31). Exposures can include determinants in the form of the natural environment (e.g., air pollution and toxicants), built environment (e.g., greenspace and walkability) and social environment (e.g., neighborhood deprivation and lifestyle) (32, 33). These interactions have been shown to have negative effects on asthma, cardiovascular disease, diabetes, and hypertension which have been reported as co-morbidities for severe COVID-19 (32, 34–36).

The exposome may help to explain why some populations experience more serious cases of COVID-19 compared to other groups (37). Studies have shown that SARS-CoV-2 binds to a human angiotensin converting enzyme 2 (ACE2) receptor located on the epithelial cells of the lungs, blood vessels, brain, kidney, and intestines (38). Exposure to environmental toxins (e.g., air pollution), lifestyle behaviors (e.g., high fat diet), and underlying disease (e.g., diabetes) can affect the expression of ACE2 and possibly increase the severity of the SARS-CoV-2 infection (37). Therefore, it is possible that gene and environmental interactions could account for varying rates of COVID-19 susceptibility among different racial and ethnic groups (37–39).

Female scientists are also contributing directly to exposome research. For example, the Hercules project at Emory University was funded by the U.S. National Institute of Environmental Health Sciences in 2013 to support exposome research. Several women participated in discovering, implementing, and evaluating the application of the exposome concept to advance our understanding of how gene-environment interactions affect population health (40). For example, women researchers have also been studying how certain air pollutants may affect the brain and increase the risk for dementia. The study combines survey data with traffic-related air pollution data based on geographic location, enabling researchers to evaluate relationships between air pollutant mixtures and stages of cognitive decline.

Another female researcher has been developing a novel model to assess the effects of metal exposure on fetal lung development. The research examines whether pregnant women's exposure to heavy metals, such as cadmium and arsenic, interferes with fetal lung development. This study advances our understanding of how environmental exposures that occur prior to birth may contribute to pulmonary disease. Additional women researchers are examining the intersection of genomics, cultural competency, and health disparities, calling for the establishment of culturally competent systems of care (41).

Building on the work of female health professionals who have preceded them, the authors of the present study propose that in addition to a bi-directional relationship between SDoH and a syndemic, that there is potential for a bi-directional relationship between the exposome and a syndemic and a bi-directional relationship between the exposome and SDoH (Figure 1). For example, populations residing in overcrowded, poor quality housing that is zoned between an auto-body shop and a crematorium in an urban environment may be living with historical housing segregation practices. This population may work in a service occupation earning an hourly wage, may be exposed to air pollutants and toxicants via their living environment and the public transportation system that is necessary to attend work, and run errands. The local food source is a centralized convenience store which does not provide a reliable supply of fruits and vegetables at an affordable price. This population resides in a high crime neighborhood where the murder rate, gang violence, and illegal drug use are increasing. These SDOH-exposome interactions make one more susceptible to the COVID-19 syndemic due to the multitude of exposures encountered. In turn, these conditions contribute to an evolving syndemic hotspot of COVID-19, substance misuse, and toxic stress accelerating negative environmental exposures (e.g., medical waste, hypodermic needles, and increased carbon emissions) that act as force multipliers for the population's allostatic load (42).

The environment has been reported to be responsible for ~70–90% of chronic disease while one's genome is purported to be responsible for 10–30% of chronic disease (43). Thus, a review of the exposome may complement a syndemic mitigation approach that considers the SDoH, political, and economic factors that propagate biological and societal epidemics.