Environmental Impacts on COVID-19: Mechanisms of Increased Susceptibility.

Background: Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in >554M cases and >6.3M deaths worldwide. The disease caused by SARS-CoV-2, COVID-19, has resulted in a broad range of clinical symptoms differing in severity. Initially, the elderly were identified as particularly susceptible to severe COVID-19, with children experiencing less severe disease. However, as new variants arise, the epidemiology of SARS-CoV-2 infection is changing, and the disease severity in children is increasing. While environmental impacts on COVID-19 have been described, the underlying mechanisms are poorly described. Objective: The Pacific Basin Consortium for Environment and Health (PBC) held meeting on September 16, 2021, to explore environmental impacts on infectious diseases, including COVID-19. Methods: The PBC is an international group of environmental scientists and those interested in health outcomes. The PBC met to present preliminary data and discuss the role of exposures to airborne pollutants in enhancing susceptibility to and severity of respiratory tract viral infections, including COVID-19. Findings: Analysis of the literature and data presented identified age as an important factor in vulnerability to air pollution and enhanced COVID-19 susceptibility and severity. Mechanisms involved in increasing severity of COVID-19 were discussed, and gaps in knowledge were identified. Conclusions: Exposure to particulate matter (PM) pollution enhanced morbidity and mortality to COVID-19 in a pediatric population associated with induction of oxidative stress. In addition, free radicals present on PM can induce rapid changes in the viral genome that can lead to vaccine escape, altered host susceptibility, and viral pathogenicity. Nutritional antioxidant supplements have been shown to reduce the severity of viral infections, inhibit the inflammatory cytokine storm, and boost host immunity and may be of benefit in combating COVID-19.

Adapting to Climate Change: Leveraging Systems-Focused Multidisciplinary Research to Promote Resilience.

Approximately 2000 official and potential Superfund sites are located within 25 miles of the East or Gulf coasts, many of which will be at risk of flooding as sea levels rise. More than 60 million people across the United States live within 3 miles of a Superfund site. Disentangling multifaceted environmental health problems compounded by climate change requires a multidisciplinary systems approach to inform better strategies to prevent or reduce exposures and protect human health. The purpose of this minireview is to present the National Institute of Environmental Health Sciences Superfund Research Program (SRP) as a useful model of how this systems approach can help overcome the challenges of climate change while providing flexibility to pivot to additional needs as they arise. It also highlights broad-ranging SRP-funded research and tools that can be used to promote health and resilience to climate change in diverse contexts.

Enhancing Data Integration, Interoperability, and Reuse to Address Complex and Emerging Environmental Health Problems.

Environmental health sciences (EHS) span many diverse disciplines. Within the EHS community, the National Institute of Environmental Health Sciences Superfund Research Program (SRP) funds multidisciplinary research aimed to address pressing and complex issues on how people are exposed to hazardous substances and their related health consequences with the goal of identifying strategies to reduce exposures and protect human health. While disentangling the interrelationships that contribute to environmental exposures and their effects on human health over the course of life remains difficult, advances in data science and data sharing offer a path forward to explore data across disciplines to reveal new insights. Multidisciplinary SRP-funded teams are well-positioned to examine how to best integrate EHS data across diverse research domains to address multifaceted environmental health problems. As such, SRP supported collaborative research projects designed to foster and enhance the interoperability and reuse of diverse and complex data streams. This perspective synthesizes those experiences as a landscape view of the challenges identified while working to increase the FAIR-ness (Findable, Accessible, Interoperable, and Reusable) of EHS data and opportunities to address them.

Understanding exposures and latent disease risk within the National Institute of Environmental Health Sciences Superfund Research Program.

Understanding the health effects of exposures when there is a lag between exposure and the onset of disease is an important and challenging topic in environmental health research. The National Institute of Environmental Health Sciences (NIEHS) Superfund Basic Research and Training Program (SRP) is a National Institutes of Health (NIH) grant program that uses a multidisciplinary approach to support biomedical and environmental science and engineering research. Because of the multidisciplinary nature of the program, SRP grantees are well-positioned to study exposure and latent disease risk across humans, animal models, and various life stages. SRP-funded scientists are working to address the challenge of connecting exposures that occur early in life and prior to conception with diseases that manifest much later, including developing new tools and approaches to predict how chemicals may affect long-term health. Here, we highlight research from the SRP focused on understanding the health effects of exposures with a lag between exposure and the onset of the disease as well as provide future directions for addressing knowledge gaps for this highly complex and challenging topic. Advancing the knowledge of latency to disease will require a multidisciplinary approach to research, the need for data sharing and integration, and new tools and computation approaches to make better predications about the timing of disease onset. A better understanding of exposures that may contribute to later-life diseases is essential to supporting the implementation of prevention and intervention strategies to reduce or modulate exposures to reduce disease burden.

E-Waste in Africa: A Serious Threat to the Health of Children.

Waste electronic and electrical equipment (e-waste) consists of used and discarded electrical and electronic items ranging from refrigerators to cell phones and printed circuit boards. It is frequently moved from developed countries to developing countries where it is dismantled for valuable metals in informal settings, resulting in significant human exposure to toxic substances. E-waste is a major concern in Africa, with large sites in Ghana and Nigeria where imported e-waste is dismantled under unsafe conditions. However, as in many developing countries, used electronic and electrical devices are imported in large quantities because they are in great demand and are less expensive than new ones. Many of these used products are irreparable and are discarded with other solid waste to local landfills. These items are then often scavenged for the purpose of extracting valuable metals by heating and burning, incubating in acids and other methods. These activities pose significant health risks to workers and residents in communities near recycling sites. E-waste burning and dismantling activities are frequently undertaken at e-waste sites, often in or near homes. As a result, children and people living in the surrounding areas are exposed, even if they are not directly involved in the recycling. While toxic substances are dangerous to individuals at any age, children are more vulnerable as they are going through important developmental processes, and some adverse health impacts may have long-term impacts. We review the e-waste situation in Africa with a focus on threats to children's health.

The interplay between environmental exposures and COVID-19 risks in the health of children.

BACKGROUND: An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution. OBJECTIVES: To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps. METHODS: An international group of researchers interested in children's environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps. DISCUSSION: Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a "dirty" environment in conveying protection - an example of the "hygiene hypothesis"; and what are the long term health effects of SARS-Cov-2 infection in early life. CONCLUSION: A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.

Greater than the sum of its parts: focusing SRP research through a systems approach lens.

The National Institute of Environmental Health Sciences Superfund Research Program (SRP) funds diverse transdisciplinary research to understand how hazardous substances contribute to disease. SRP research focuses on how to prevent these exposures by promoting problem-based, solution-oriented research. SRP's mandate areas encompasses broad biomedical and environmental science and engineering research efforts and, when combined with research translation, community engagement, training, and data science, offers broad expertise and unique perspectives directed at a specific big picture question. The purpose of this commentary is to adapt a systems approach concept to SRP research to accommodate the complexity of a scientific problem. The SRP believes a systems approach offers a framework to understand how scientists can work together to integrate diverse fields of research to prevent or understand environmentally-influenced human disease by addressing specific questions that are part of a larger perspective. Specifically, within the context of the SRP, a systems approach can elucidate the complex interactions between factors that contribute to or protect against environmental insults. Leveraging a systems approach can continue to advance SRP science while building the foundation for researchers to address difficult emerging environmental health problems.

Benefits of basic research from the Superfund Research Program.

The National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS) Hazardous Substances Basic Research and Training Program [Superfund Research Program (SRP)] funds transdisciplinary research projects spanning the biomedical and environmental sciences to address issues related to potentially hazardous substances. We used a case study approach to identify how SRP-funded basic biomedical research has had an impact on society. We examined how transdisciplinary research projects from the SRP have advanced knowledge and led to additional clinical, public health, policy, and economic benefits. SRP basic biomedical research findings have contributed to the body of knowledge and influenced a broad range of scientific disciplines. It has informed the development of policies and interventions to reduce exposure to environmental contaminants to improve public health. Research investments by the SRP have had a significant impact on science, health, and society. Documenting the benefits of these investments provides insight into how basic research is translated to real-world applications.

Sharing SRP data to reduce environmentally associated disease and promote transdisciplinary research.

The National Institute of Environmental Health Sciences (NIEHS) Superfund Basic Research and Training Program (SRP) funds a wide range of projects that span biomedical, environmental sciences, and engineering research and generate a wealth of data resulting from hypothesis-driven research projects. Combining or integrating these diverse data offers an opportunity to uncover new scientific connections that can be used to gain a more comprehensive understanding of the interplay between exposures and health. Integrating and reusing data generated from individual research projects within the program requires harmonization of data workflows, ensuring consistent and robust practices in data stewardship, and embracing data sharing from the onset of data collection and analysis. We describe opportunities to leverage data within the SRP and current SRP efforts to advance data sharing and reuse, including by developing an SRP dataset library and fostering data integration through Data Management and Analysis Cores. We also discuss opportunities to improve public health by identifying parallels in the data captured from health and engineering research, layering data streams for a more comprehensive picture of exposures and disease, and using existing SRP research infrastructure to facilitate and foster data sharing. Importantly, we point out that while the SRP is in a unique position to exploit these opportunities, they can be employed across environmental health research. SRP research teams, which comprise cross-disciplinary scientists focused on similar research questions, are well positioned to use data to leverage previous findings and accelerate the pace of research. Incorporating data streams from different disciplines addressing similar questions can provide a broader understanding and uncover the answers to complex and discrete research questions.

The Importance of Community Engagement and Research Translation within the NIEHS Superfund Research Program.

The National Institute of Environmental Health Sciences Superfund Research Program (SRP) funds university-based, solution-oriented research to understand how hazardous substances contribute to disease and how to prevent exposures to these hazardous substances. A unique aspect of the SRP is that, beyond the biomedical, environmental sciences, and engineering research projects, SRP-funded centers are required to include community engagement to build partnerships with affected communities and research translation to communicate and facilitate the use of research findings. The SRP views both as effective ways to inform and advance science for protection of public health. The purpose of community engagement within the centers is to ensure bidirectional communication between the researchers and the community, identify best practices and activities in community engagement for prevention and intervention activities, enhance knowledge, and support the needs of the communities impacted by hazardous waste sites. The SRP views research translation as communicating and facilitating the use of research findings emanating from the center in a manner most appropriate for their application and for the advancement of a center's research objectives. The SRP has a strong history of seeking opportunities to work with communities and stakeholders, by translating and sharing research findings in an impactful and informative manner with long-lasting benefits to improve public health.

Advancing science in rapidly changing environments: opportunities for the Central and Eastern European Conference on Health and the Environment to connect to other networks.

The Central and Eastern Europe region is faced with longstanding environmental health problems as well as emerging health threats from pollution caused by the region's recent period of rapid industrialization. As researchers in the region continue to work to address these problems, they could find unique approaches by increasing collaborations between biomedical and non-biomedical scientists and by more closely following the Superfund Research Program model of pursuing basic research, then connecting with stakeholders in the region to share and apply new knowledge. To build upon and leverage research in the region, researchers and stakeholders should work to formalize the bi-annual meeting of the Central and Eastern European Conference on Health and the Environment into a more cohesive organization and make efforts to connect to broader global networks that aim to spread research results and applications around the world. By taking these steps to connect to the broader world of environmental health research, the CEE region stakeholders can reduce pollution-related disease, minimize costs of hazardous waste remediation, and help grow the economy in their region.

Children's Environmental Health in South and Southeast Asia: Networking for Better Child Health Outcomes.

Children are particularly vulnerable to environmental hazards because they receive higher doses of pollutants in any given environment and often do not have equitable access to social protection mechanisms such as environmental and health care services. The World Health Organization established a global network of collaborating centres that address children's environmental health (CEH). The network developed a focus on low- and middle-income countries (LMICs) and is broadening its reach by conducting regional workshops for CEH.Objective: This paper reports on the outcomes of a workshop held in conjunction with the 17th International Conference (November 2017) of the Pacific Basin Consortium for Environment and Health, focused on the state of CEH in South and Southeast Asia as presented by seven countries from the region (India, Bangladesh, Nepal, Bhutan, Vietnam, Thailand, Sri Lanka).Workshop outcomes: Country reports presented at the meeting show a high degree of similarity with respect to the issues threatening the health of children. The most common problems are outdoor and household air pollution in addition to exposure to heavy metals, industrial chemicals, and pesticides. Many children still do not have adequate access to clean water and improved sanitation while infectious diseases remain a problem, especially for children living in poverty. Child labour is widely prevalent, generally without adequate training or personal protective equipment. The children now face the dual burden of undernutrition and stunting on the one hand and overnutrition and obesity on the other.Conclusion: It is evident that some countries in these regions are doing better than others in varying areas of CEH. By establishing and participating in regional networks, countries can learn from each other and harmonise their efforts to protect CEH so that all can benefit from closer interactions.

Pollution and children's health.

FINDINGS: The Lancet Commission on Pollution and Health found that pollution - air, water, soil, and chemical pollution - was responsible in 2016 for 940,000 deaths in children worldwide, two-thirds of them in children under the age of 5. Pollution is inequitably distributed, and the overwhelming majority of pollution-related deaths in children occurred in low- and middle-income countries (LMICs). Most were due to respiratory and gastrointestinal diseases caused by polluted air and water. Pollution is linked also to multiple non-communicable diseases (NCDs) in children including low birth weight, asthma, cancer and neurodevelopmental disorders, and these diseases are on the rise. The full impact of pollution, especially chemical pollution on the global burden of pediatric disease is not yet known, but almost certainly is undercounted because patterns of chemical exposure are not well charted and the potential toxicity of many chemical pollutants has not been characterized. The list of pediatric NCDs attributed to pollution will likely expand as the health effects of newer chemical pollutants are better defined and additional associations between pollution and disease are discovered. CONCLUSION: Pollution prevention presents a major, largely unexploited opportunity to improve children's health and prevent NCDs, especially in LMICs. Failure to incorporate pollution prevention into NCD control programs is a major missed opportunity for disease prevention.

Pollution and Global Health ­ An Agenda for Prevention.

SUMMARY: Pollution is a major, overlooked, global health threat that was responsible in 2015 for an estimated 9 million deaths and great economic losses. To end neglect of pollution and advance prevention of pollution-related disease, we formed the Lancet Commission on Pollution and Health. Despite recent gains in understanding of pollution and its health effects, this Commission noted that large gaps in knowledge remain. To close these gaps and guide prevention, the Commission made research recommendations and proposed creation of a Global Observatory on Pollution and Health. We posit that successful pollution research will be translational and based on transdisciplinary collaborations among exposure science, epidemiology, data science, engineering, health policy, and economics. We envision that the Global Observatory on Pollution and Health will be a multinational consortium based at Boston College and the Harvard T.H. Chan School of Public Health that will aggregate, geocode, and archive data on pollution and pollution-related disease; analyze these data to discern trends, geographic patterns, and opportunities for intervention; and make its findings available to policymakers, the media, and the global public to catalyze research, inform policy, and assist cities and countries to target pollution, track progress, and save lives. https://doi.org/10.1289/EHP3141.

The Curious Case of Cholangiocarcinoma: Opportunities for Environmental Health Scientists to Learn about a Complex Disease.

Deaths from complex, noncommunicable diseases such as cancer are predicted to continue to increase worldwide, with low- and middle-income countries bearing the brunt of the burden. This problem requires a concentrated global effort to avoid devastating losses of life as well as economic losses. Cholangiocarcinoma (CCA) is a readily studied model of complex, noncommunicable disease, but it receives little attention outside of the scientific community in Southeast Asia. Here, we bring attention to the opportunity to study CCA as a model to understand the role of multiple, complex factors in cancer. These factors include allostatic load, individual genetic susceptibility, and environmental exposures such as chemicals, diet, socioeconomic factors, and psychosocial stress. The study of CCA offers a unique opportunity to make novel observations that could advance progress in prevention and intervention approaches for prevalent diseases that involve complex, multifactorial interactions.

Assessing the Economic and Societal Benefits of SRP-Funded Research.

BACKGROUND: The National Institute of Environmental Health Sciences (NIEHS) Superfund Basic Research and Training Program (SRP) funds a wide range of transdisciplinary research projects spanning the biomedical and environmental sciences and engineering, supporting and promoting the application of that research to solving real-world problems. OBJECTIVES: We used a case study approach to identify the economic and societal benefits of SRP-funded research, focusing on the use of potentially hazardous substance remediation and site monitoring tools. We also identified successes and challenges involved in translating SRP grantees' research findings and advances into application. DISCUSSION: We identified remediation and detection research projects supported by the SRP with the most potential for economic and societal benefits and selected 36 for analysis. To examine the benefits of these applied technologies, we interviewed 28 SRP-supported researchers and 41 partners. Five case studies emerged with the most complete information on cost savings-total savings estimated at >$100 million. Our analysis identified added societal benefits such as creation of small businesses, land and water reuse, sustainable technologies, exposure reduction, and university-industry partnerships. CONCLUSIONS: Research funded by the SRP has yielded significant cost savings while providing additional societal benefits. https://doi.org/10.1289/EHP3534.

The role of nutrition in influencing mechanisms involved in environmentally mediated diseases.

Human exposure to environmental contaminants such as persistent chlorinated organics, heavy metals, pesticides, phthalates, flame retardants, electronic waste and airborne pollutants around the world, and especially in Southeast Asian regions, are significant and require urgent attention. Given this widespread contamination and abundance of such toxins as persistent organic pollutants (POPs) in the ecosystem, it is unlikely that remediation alone will be sufficient to address the health impacts associated with this exposure. Furthermore, we must assume that the impact on health of some of these contaminants results in populations with extraordinary vulnerabilities to disease risks. Further exacerbating risk; infectious diseases, poverty and malnutrition are common in the Southeast Asian regions of the world. Thus, exploring preventive measures of environmental exposure and disease risk through new paradigms of environmental toxicology, optimal and/or healthful nutrition and health is essential. For example, folic acid supplementation can lower blood arsenic levels, and plant-derived bioactive nutrients can lower cardiovascular and cancer risks linked to pollutant exposure. Data also indicate that diets enriched with bioactive food components such as polyphenols and omega-3 polyunsaturated fatty acids can prevent or decrease toxicant-induced inflammation. Thus, consuming healthy diets that exhibit high levels of antioxidant and anti-inflammatory properties, is a meaningful way to reduce the vulnerability to non-communicable diseases linked to environmental toxic insults. This nutritional paradigm in environmental toxicology requires further study in order to improve our understanding of the relationship between nutrition or other lifestyle modifications and toxicant-induced diseases. Understanding mechanistic relationships between nutritional modulation of environmental toxicants and susceptibility to disease development are important for both cumulative risk assessment and the design and implementation of future public health programs and behavioral interventions.

The National Institute of Environmental Health Sciences Superfund Research Program: a model for multidisciplinary training of the next generation of environmental health scientists.

The National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program (SRP) funds university-based, multidisciplinary research on human health and environmental science and engineering with the central goals to understand how hazardous substances contribute to disease and how to prevent exposures to these environmental chemicals. This multi-disciplinary approach allows early career scientists (e.g. graduate students and postdoctoral researchers) to gain experience in problem-based, solution-oriented research and to conduct research in a highly collaborative environment. Training the next generation of environmental health scientists has been an important part of the SRP since its inception. In addition to basic research, the SRP has grown to include support of broader training experiences such as those in research translation and community engagement activities that provide opportunities to give new scientists many of the skills they will need to be successful in their field of research. Looking to the future, the SRP will continue to evolve its training component by tracking and analyzing outcomes from its trainees by using tools such as the NIEHS CareerTrac database system, by increasing opportunities for trainees interested in research that goes beyond US boundaries, and in the areas of bioinformatics and data integration. These opportunities will give them the skills needed to be competitive and successful no matter which employment sector they choose to enter after they have completed their training experience.