Multi-Omics Profiling for Health.

The world has witnessed a steady rise in both non-infectious and infectious chronic diseases, prompting a cross-disciplinary approach to understand and treating disease. Current medical care focuses on treating people after they become patients rather than preventing illness, leading to high costs in treating chronic and late-stage diseases. Additionally, a "one-size-fits all" approach to health care does not take into account individual differences in genetics, environment, or lifestyle factors, decreasing the number of people benefiting from interventions. Rapid advances in omics technologies and progress in computational capabilities have led to the development of multi-omics deep phenotyping, which profiles the interaction of multiple levels of biology over time and empowers precision health approaches. This review highlights current and emerging multi-omics modalities for precision health and discusses applications in the following areas: genetic variation, cardio-metabolic diseases, cancer, infectious diseases, organ transplantation, pregnancy, and longevity/aging. We will briefly discuss the potential of multi-omics approaches in disentangling host-microbe and host-environmental interactions. We will touch on emerging areas of electronic health record and clinical imaging integration with muti-omics for precision health. Finally, we will briefly discuss the challenges in the clinical implementation of multi-omics and its future prospects.

Acne exacerbation: the role of exposome factors and current trends in maintenance therapy

At the present stage, acne is considered as a multifactorial dermatosis, in the formation of which a significant role is played by genetically determined hyperandrogenism and impaired secretion of the sebaceous glands, as well as changes in the skin microbiome. It is known that the risk of occurrence and severity of the disease are significantly influenced by various environmental components, which are commonly called exposure factors. This article provides an analysis of studies on the influence of the most common exposure factors on the pathogenesis and clinical course of acne: diet, skin care, stress, novel coronavirus infection (COVID-19), environmental pollution and climatic conditions. It has been shown that these factors affect the main components of the skin barrier, affect the microbiota and immune reactivity, which subsequently leads to the activation of the leading pathological mechanisms of acne formation. Considering the variety of factors that provoke the disease, emphasis is placed on the need for proper skin care and pathogenetically substantiated therapy in a maintenance regimen with the appointment of topical retinoids and azelaic acid. Due to anti-inflammatory and comedonolytic effects, as well as inhibition of the growth of Cutibacterium acne, these active ingredients provide a complex effect on the main pathogenetic links of the disease. The article presents our own clinical observations of patients with acne, who underwent complex therapy and prevention of exacerbations with the use of Adaklin and Azix-Derm. It was noted that these drugs are effective both in the complex treatment and in the prevention of exacerbations in patients with mild to moderate acne, while the therapy is well tolerated by patients the resulting adverse events are reversible, easily corrected with moisturizing agents and do not require discontinuation of drugs. © 2022, Remedium Group Ltd. All rights reserved.

Socioexposomics of COVID-19 across New Jersey: a comparison of geostatistical and machine learning approaches.

BACKGROUND: Disparities in adverse COVID-19 health outcomes have been associated with multiple social and environmental stressors. However, research is needed to evaluate the consistency and efficiency of methods for studying these associations at local scales. OBJECTIVE: To assess socioexposomic associations with COVID-19 outcomes across New Jersey and evaluate consistency of findings from multiple modeling approaches. METHODS: We retrieved data for COVID-19 cases and deaths for the 565 municipalities of New Jersey up to the end of the first phase of the pandemic, and calculated mortality rates with and without long-term-care (LTC) facility deaths. We considered 84 spatially heterogeneous environmental, demographic and socioeconomic factors from publicly available databases, including air pollution, proximity to industrial sites/facilities, transportation-related noise, occupation and commuting, neighborhood and housing characteristics, age structure, racial/ethnic composition, poverty, etc. Six geostatistical models (Poisson/Negative-Binomial regression, Poison/Negative-Binomial mixed effect model, Poisson/Negative-Binomial Bersag-York-Mollie spatial model) and two Machine Learning (ML) methods (Random Forest, Extreme Gradient Boosting) were implemented to assess association patterns. The Shapley effects plot was established for explainable ML and change of support validation was introduced to compare performances of different approaches. RESULTS: We found robust positive associations of COVID-19 mortality with historic exposures to NO2, population density, percentage of minority and below high school education, and other social and environmental factors. Exclusion of LTC deaths does not significantly affect correlations for most factors but findings can be substantially influenced by model structures and assumptions. The best performing geostatistical models involved flexible structures representing data variations. ML methods captured association patterns consistent with the best performing geostatistical models, and furthermore detected consistent nonlinear associations not captured by geostatistical models. SIGNIFICANCE: The findings of this work improve the understanding of how social and environmental disparities impacted COVID-19 outcomes across New Jersey.

Identifying environmental risk factors for post-acute sequelae of SARS-CoV-2 infection: An EHR-based cohort study from the recover program.

Post-acute sequelae of SARS-CoV-2 infection (PASC) affects a wide range of organ systems among a large proportion of patients with SARS-CoV-2 infection. Although studies have identified a broad set of patient-level risk factors for PASC, little is known about the association between "exposome"-the totality of environmental exposures and the risk of PASC. Using electronic health data of patients with COVID-19 from two large clinical research networks in New York City and Florida, we identified environmental risk factors for 23 PASC symptoms and conditions from nearly 200 exposome factors. The three domains of exposome include natural environment, built environment, and social environment. We conducted a two-phase environment-wide association study. In Phase 1, we ran a mixed effects logistic regression with 5-digit ZIP Code tabulation area (ZCTA5) random intercepts for each PASC outcome and each exposome factor, adjusting for a comprehensive set of patient-level confounders. In Phase 2, we ran a mixed effects logistic regression for each PASC outcome including all significant (false positive discovery adjusted p-value < 0.05) exposome characteristics identified from Phase I and adjusting for confounders. We identified air toxicants (e.g., methyl methacrylate), particulate matter (PM2.5) compositions (e.g., ammonium), neighborhood deprivation, and built environment (e.g., food access) that were associated with increased risk of PASC conditions related to nervous, blood, circulatory, endocrine, and other organ systems. Specific environmental risk factors for each PASC condition and symptom were different across the New York City area and Florida. Future research is warranted to extend the analyses to other regions and examine more granular exposome characteristics to inform public health efforts to help patients recover from SARS-CoV-2 infection.

Acne exacerbation: the role of exposome factors and current trends in maintenance therapy

At the present stage, acne is considered as a multifactorial dermatosis, in the formation of which a significant role is played by genetically determined hyperandrogenism and impaired secretion of the sebaceous glands, as well as changes in the skin microbiome. It is known that the risk of occurrence and severity of the disease are significantly influenced by various environmental components, which are commonly called exposure factors. This article provides an analysis of studies on the influence of the most common exposure factors on the pathogenesis and clinical course of acne: diet, skin care, stress, novel coronavirus infection (COVID-19), environmental pollution and climatic conditions. It has been shown that these factors affect the main components of the skin barrier, affect the microbiota and immune reactivity, which subsequently leads to the activation of the leading pathological mechanisms of acne formation. Considering the variety of factors that provoke the disease, emphasis is placed on the need for proper skin care and pathogenetically substantiated therapy in a maintenance regimen with the appointment of topical retinoids and azelaic acid. Due to anti-inflammatory and comedonolytic effects, as well as inhibition of the growth of Cutibacterium acne, these active ingredients provide a complex effect on the main pathogenetic links of the disease. The article presents our own clinical observations of patients with acne, who underwent complex therapy and prevention of exacerbations with the use of Adaklin and Azix-Derm. It was noted that these drugs are effective both in the complex treatment and in the prevention of exacerbations in patients with mild to moderate acne, while the therapy is well tolerated by patients the resulting adverse events are reversible, easily corrected with moisturizing agents and do not require discontinuation of drugs. © 2022, Remedium Group Ltd. All rights reserved.

Impact of air pollution on ischemic heart disease: Evidence, mechanisms, clinical perspectives.

Ambient air pollution, and especially particulate matter (PM) air pollution <2.5 µm in diameter (PM2.5), has clearly emerged as an important yet often overlooked risk factor for atherosclerosis and ischemic heart disease (IHD). In this review, we examine the available evidence demonstrating how acute and chronic PM2.5 exposure clinically translates into a heightened coronary atherosclerotic burden and an increased risk of acute ischemic coronary events. Moreover, we provide insights into the pathophysiologic mechanisms underlying PM2.5-mediated atherosclerosis, focusing on the specific biological mechanism through which PM2.5 exerts its detrimental effects. Further, we discuss about the possible mechanisms that explain the recent findings reporting a strong association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, increased PM2.5 exposure, and morbidity and mortality from IHD. We also address the possible mitigation strategies that should be implemented to reduce the impact of PM2.5 on cardiovascular morbidity and mortality, and underscoring the strong need of clinical trials demonstrating the efficacy of specific interventions (including both PM2.5 reduction and/or specific drugs) in reducing the incidence of IHD. Finally, we introduce the emerging concept of the exposome, highlighting the close relationship between PM2.5 and other environmental exposures (i.e.: traffic noise and climate change) in terms of common underlying pathophysiologic mechanisms and possible mitigation strategies.

A Randomized, Controlled Clinical Trial of a Dermocosmetic Containing Vichy Volcanic Mineralizing Water and Probiotic Fractions in Subjects with Rosacea Associated with Erythema and Sensitive Skin and Wearing Protective Masks.

Purpose: Rosacea is a common facial dermatosis, with flares induced by exposome factors. M89PF containing Vichy mineralizing water, probiotic fractions, hyaluronic acid, niacinamide and tocopherol repairs the skin barrier and reinforces skin defences against exposome factors. This study assessed the benefit of M89PF in subjects with rosacea associated with erythema and sensitive skin during the Covid-19 pandemic using protective face masks. Methods: M89PF was compared to usual skin care in a randomized, split-face study, for 30 days in subjects with rosacea associated with erythema and sensitive skin. Clinical evaluations included erythema, desquamation, skin tightness, dryness, burning sensation, itching, stinging, stinging test, and local tolerability. Instrument evaluations included erythema, skin hydration and TEWL. Subject satisfaction was also assessed. Results: Erythema significantly improved with M89PF at both time points (p<0.01 at D15, and p<0.001 at D30). Skin sensitivity assessed by the skin stinging test improved significantly (p<0.01) with M89PF at D30, compared to baseline and usual skin care. Skin erythema, tightness, dryness, hydration and TEWL significantly improved (p≤0.05) with M89PF at D15 and D30, versus baseline and the untreated side. Subjects were highly satisfied with M89PF at D15 and D30. Tolerance was very good in all subjects. Conclusion: In subjects with rosacea, M89PF significantly reduces erythema, skin tightness, dryness and TEWL, and improves skin hydration and skin sensitivity, even when using protective masks. M89PF is well tolerated and received high satisfaction ratings. ClinicalTrialsgov No: NCT05562661.

Population-wide measures due to the COVID-19 pandemic and exposome changes in the general population of Cyprus in March-May 2020.

Non-pharmacological interventions (e.g., stay-at-home orders, school closures, physical distancing) implemented during the COVID-19 pandemic are expected to have modified routines and lifestyles, eventually impacting key exposome parameters, including, among others, physical activity, diet and cleaning habits. The objectives were to describe the exposomic profile of the general Cypriot population and compliance to the population-wide measures implemented during March-May 2020 to lower the risk of SARS-CoV-2 transmission, and to simulate the population-wide measures' effect on social contacts and SARS-CoV-2 spread. A survey was conducted in March-May 2020 capturing different exposome parameters, e.g., individual characteristics, lifestyle/habits, time spent and contacts at home/work/elsewhere. We described the exposome parameters and their correlations. In an exposome-wide association analysis, we used the number of hours spent at home as an indicator of compliance to the measures. We generated synthetic human proximity networks, before and during the measures using the dynamic-[Formula: see text]1 model and simulated SARS-CoV-2 transmission (i.e., to identify possible places where higher transmission/number of cases could originate from) on the networks with a dynamic Susceptible-Exposed-Infectious-Recovered model. Overall, 594 respondents were included in the analysis (mean age 45.7 years, > 50% in very good health and communicating daily with friends/family via phone/online). The median number of contacts at home and at work decreased during the measures (from 3 to 2 and from 12 to 0, respectively) and the hours spent at home increased, indicating compliance with the measures. Increased time spent at home during the measures was associated with time spent at work before the measures (ß= -0.87, 95% CI [-1.21,-0.53]) as well as with being retired vs employed (ß= 2.32, 95% CI [1.70, 2.93]). The temporal network analysis indicated that most cases originated at work, while the synthetic human proximity networks adequately reproduced the observed SARS-CoV-2 spread. Exposome approaches (i.e., holistic characterization of the spatiotemporal variation of multiple exposures) would aid the comprehensive description of population-wide measures' impact and explore how behaviors and networks may shape SARS-CoV-2 transmission.

Comprehensive profiling of the human viral exposome in households containing an at-risk child with mitochondrial disease during the 2020-2021 COVID-19 pandemic.

BACKGROUND: Viral infection is a major cause of morbidity in children with mitochondrial disease (MtD). As a result, families with children with MtD are highly adherent to risk mitigation behaviours (RMBs) advised by the Centers for Disease Control and Prevention during the COVID-19 pandemic that can modulate infection risk. METHODS: Deep serologic phenotyping of viral infections was performed via home-based sampling by combining SARS-CoV-2 serologic testing and phage display immunoprecipitation and sequencing. Samples were collected approximately 1 year apart (October 2020 to April 2021 and October 2021 to March 2022) on households containing a child with MtD. RESULTS: In contrast to our first collection in 2020-2021, SARS-CoV-2 antibody profiles for all participants in 2021-2022 were marked by greater isotype diversity and the appearance of neutralizing antibodies. Besides SARS-CoV-2, households (N = 15) were exposed to >38 different respiratory and gastrointestinal viruses during the study, averaging five viral infections per child with MtD. Regarding clinical outcomes, children with MtD (N = 17) experienced 34 episodes of illness resulting in 6 hospitalizations, with some children experiencing multiple episodes. Neurologic events following illness were recorded in five patients. Infections were identified via clinical testing in only seven cases. Viral exposome profiles were consistent with clinical testing and even identified infections not captured by clinical testing. CONCLUSIONS: Despite reported adherence to RMBs during the COVID-19 pandemic by families with a child with MtD, viral infection was pervasive. Not all infections resulted in illness in the child with MtD, suggesting that some were subclinical or asymptomatic. However, selected children with MtD did experience neurologic events. Our studies emphasize that viral infections are inexorable, emphasizing the need for further understanding of host-pathogen interactions through broad serologic surveillance.

Assuring Healthy Populations During the COVID-19 Pandemic: Recognizing Women's Contributions in Addressing Syndemic Interactions.

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. Populations residing in environments with structural susceptibilities experience health disparities and syndemics to a greater extent than their less vulnerable counterparts. The interactions among the social determinants of health (SDoH) and the COVID-19 pandemic have had different results for marginalized populations and have worsened health outcomes for many in this synergistic pandemic. Also, the exposome, the exposure measures for an individual over their lifetime and how those exposures relate to the individual's health, may help to explain why some populations experience more serious cases of COVID-19 compared to other groups. The purpose of this perspective is to: (1) examine the relationship between the syndemic model and the SDoH-exposome; (2) highlight, via specific examples, the contributions of female health professionals to SDoH and the COVID-19 syndemic in response to the Women in Science Research Topic, and (3) propose health policy to address syndemic-exposome interactions to help mitigate or prevent public health challenges. By investing in policies that assure health for all populations, the investments could pay dividends in the form of a less severe syndemic next time since we are starting from a place of health and not disease. Lastly, due to the magnification of underlying societal inequities laid bare during the COVID-19 syndemic, we support the expansion of the disease-focused syndemic model to include societal syndemics, such as systemic racism.

The Role of Exposomes in the Pathophysiology of Autoimmune Diseases II: Pathogens.

In our continuing examination of the role of exposomes in autoimmune disease, we use this review to focus on pathogens. Infections are major contributors to the pathophysiology of autoimmune diseases through various mechanisms, foremost being molecular mimicry, when the structural similarity between the pathogen and a human tissue antigen leads to autoimmune reactivity and even autoimmune disease. The three best examples of this are oral pathogens, SARS-CoV-2, and the herpesviruses. Oral pathogens reach the gut, disturb the microbiota, increase gut permeability, cause local inflammation, and generate autoantigens, leading to systemic inflammation, multiple autoimmune reactivities, and systemic autoimmunity. The COVID-19 pandemic put the spotlight on SARS-CoV-2, which has been called "the autoimmune virus." We explore in detail the evidence supporting this. We also describe how viruses, in particular herpesviruses, have a role in the induction of many different autoimmune diseases, detailing the various mechanisms involved. Lastly, we discuss the microbiome and the beneficial microbiota that populate it. We look at the role of the gut microbiome in autoimmune disorders, because of its role in regulating the immune system. Dysbiosis of the microbiota in the gut microbiome can lead to multiple autoimmune disorders. We conclude that understanding the precise roles and relationships shared by all these factors that comprise the exposome and identifying early events and root causes of these disorders can help us to develop more targeted therapeutic protocols for the management of this worldwide epidemic of autoimmunity.

Assessment of indoor and outdoor air quality in primary schools of Cyprus during the COVID-19 pandemic measures in May-July 2021.

Combined pollutant effects from indoor and outdoor sources on children's health, while being at school have not been holistically tackled. The aim of the School Temperature and Environmental Pollutants Study (STEPS) was to perform a school population representative assessment of indoor air quality (IAQ) in primary schools of densely and intermediate populated areas of Cyprus (n = 42). The study took place during May-July 2021 when a school-specific COVID-19 protocol was in place. Questionnaire-based characteristics of schools/classrooms were collected along with 24/48-h long IAQ monitoring of air temperature, relative humidity (RH), particulate matter (PM), carbon dioxide (CO2) and volatile organic compounds (VOCs), using low-cost sensors. Mixed effect models assessed the IAQ determinants during school hours. Indoor PM, temperature, RH and VOCs increased with progressing school periods in the day, while indoor CO2 decreased. Indoor RH and CO2 were negatively associated with % open windows, while indoor PM2.5 was positively associated. Most of school time (85%), indoor air temperature exceeded the recommended upper limit (27 °C), while a third of indoor PM2.5 (24-h) measurements exceeded 15 µg/m3. The interplay of clean indoor air with adequate ventilation and adaptation to heat stress in schools is important and its comprehensive characterization requires holistic methodological approaches and tools.

Evaluating predictive relationships between wristbands and urine for assessment of personal PAH exposure.

During events like the COVID-19 pandemic or a disaster, researchers may need to switch from collecting biological samples to personal exposure samplers that are easy and safe to transport and wear, such as silicone wristbands. Previous studies have demonstrated significant correlations between urine biomarker concentrations and chemical levels in wristbands. We build upon those studies and use a novel combination of descriptive statistics and supervised statistical learning to evaluate the relationship between polycyclic aromatic hydrocarbon (PAH) concentrations in silicone wristbands and hydroxy-PAH (OH-PAH) concentrations in urine. In New York City, 109 participants in a longitudinal birth cohort wore one wristband for 48 h and provided a spot urine sample at the end of the 48-hour period during their third trimester of pregnancy. We compared four PAHs with the corresponding seven OH-PAHs using descriptive statistics, a linear regression model, and a linear discriminant analysis model. Five of the seven PAH and OH-PAH pairs had significant correlations (Pearson's r = 0.35-0.64, p ≤ 0.003) and significant chi-square tests of independence for exposure categories (p ≤ 0.009). For these five comparisons, the observed PAH or OH-PAH concentration could predict the other concentration within a factor of 1.47 for 50-80% of the measurements (depending on the pair). Prediction accuracies for high exposure categories were at least 1.5 times higher compared to accuracies based on random chance. These results demonstrate that wristbands and urine provide similar PAH exposure assessment information, which is critical for environmental health researchers looking for the flexibility to switch between biological sample and wristband collection.

Earth Dreams: Reimagining ARPA for Health of People, Places and Planet.

Bold new approaches are urgently needed to overcome global health challenges. The proposed Advanced Research Projects Agency for Health (ARPA-H) is intended to provide rapid health breakthroughs. While new technologies for earlier disease detection and more effective treatment are critical, we urge equal attention be given to the wider (physical, emotional, social, political, and economic) environmental ecosystems driving the non-communicable disease (NCD) crisis in the first place. This requires an integrated, cross-sectoral vision that spans the interwoven connections affecting health across the scales of people, places, and planet. This wider "exposome" perspective considers biopsychosocial factors that promote resilience and reduce vulnerabilities of individuals and communities over time-the many variables driving health disparities. Since life course health is strongly determined by early life environments, early interventions should be prioritized as a matter of effectiveness and social justice. Here, we explore the origins of the Advanced Research Project Agency and point to its potential to build integrated solutions, with wisdom and ethical value systems as a compass. Since the planned ARPA-H is anticipated to spawn international collaborations, the imagined concept is of relevance to a broad audience of researchers. With appropriate input, the quest for health equity through personalized, precision medicine while deconstructing unacceptable structural inequities may be accelerated.

Exposomes and metabolic health through a physical activity lens: a narrative review.

In this narrative review, we provide an overview of the role of physical activity as part of differing exposomes (our combined non-genetic exposures from conception onwards) and environmental influences on metabolic health. We discuss 'beneficial' exposomes (green/natural outdoor spaces, sun exposure, healthy diets and features of built environments) that could synergise with physical activity to prevent metabolic dysfunction, particularly that related to lifestyle diseases of obesity, type 2 diabetes and metabolic syndrome. Physical activity may also reduce the capacity of some adverse exposomes, specifically those with significant levels of air pollution, to contribute towards metabolic dysfunction. Other exposomes, such as those experienced during pandemics (including COVID-19), potentially limit opportunities for physical activity, and there may be unexpected combined effects of physical activity with other infections (e.g. adenovirus-36) on metabolic health. Finally, we discuss how environments could be better optimised to create exposomes that promote the health benefits of physical activity and likely future directions of this research field.

An external exposome-wide association study of COVID-19 mortality in the United States.

The risk factors for severe COVID-19 beyond older age and certain underlying health conditions are largely unknown. Recent studies suggested that long-term environmental exposures may be important determinants of severe COVID-19. However, very few environmental factors have been studied, often separately, without considering the totality of the external environment (i.e., the external exposome). We conducted an external exposome-wide association study (ExWAS) using the nationwide county-level COVID-19 mortality data in the contiguous US. A total of 337 variables characterizing the external exposome from 8 data sources were integrated, harmonized, and spatiotemporally linked to each county. A two-phase procedure was used: (1) in Phase 1, a random 50:50 split divided the data into a discovery set and a replication set, and associations between COVID-19 mortality and individual factors were examined using mixed-effect negative binomial regression models, with multiple comparisons addressed, and (2) in Phase 2, a multivariable regression model including all variables that are significant from both the discovery and replication sets in Phase 1 was fitted. A total of 13 and 22 variables were significant in the discovery and replication sets in Phase 1, respectively. All the 4 variables that were significant in both sets in Phase 1 remained statistically significant in Phase 2, including two air toxicants (i.e., nitrogen dioxide or NO2, and benzidine), one vacant land measure, and one food environment measure. This is the first external exposome study of COVID-19 mortality. It confirmed some of the previously reported environmental factors associated with COVID-19 mortality, but also generated unexpected predictors that may warrant more focused evaluation.

Exposome changes in primary school children following the wide population non-pharmacological interventions implemented due to COVID-19 in Cyprus: A national survey.

BACKGROUND: Non-pharmacological interventions (NPI), including lockdowns, have been used to address the COVID-19 pandemic. We describe changes in the environment and lifestyle of school children in Cyprus before the lockdown and during school re-opening, and assess compliance to NPI, using the exposome concept. METHODS: During June 2020, parents completed an online questionnaire about their children's lifestyle/behaviours for two periods; school re-opening (May 21-June 26) following the population-wide lockdown, and the school period before lockdown (before March). FINDINGS: Responses were received for 1509 children from over 180 primary schools. More than 72% of children complied with most NPI measures; however, only 48% decreased the number of vulnerable contacts at home. Sugary food consumption was higher in the post-lockdown period with 37% and 26% of the children eating sugary items daily and 4-6 times/week, compared to 33% and 19%, respectively, for the pre-lockdown period (p<0.001). Children's physical activity decreased compared to pre-lockdown (p<0.001), while screen time increased in the post-lockdown period, with 25% of children spending 4-7 hours/day in front of screens vs. 10% in the pre-lockdown period (p<0.001). About half of the children washed their hands with soap 4-7 times/day post-lockdown vs. 30% in the pre-lockdown period (p<0.001). INTERPRETATION: This national survey showed a high degree of compliance to NPI measures among school children. Furthermore, the exposome profile of children may be affected in the months following NPI measures due to alterations in diet, physical activity, sedentary behaviour, and hand hygiene habits. FUNDING: Partial funding by the EXPOSOGAS project, H2020 Research and Innovation Programme (grant #810995).

Exposome-based public health interventions for infectious diseases in urban settings.

The COVID-19 pandemic placed public health measures against infectious diseases at the core of global health challenges, especially in cities where more than half of the global population lives. SARS-CoV-2 is an exposure agent recently added to the network of exposures that comprise the human exposome, i.e. the totality of all environmental exposures throughout one's lifetime. At the same time, the application of measures to tackle SARS-CoV-2 transmission leads to changes in the exposome components and in characteristics of urban environments that define the urban exposome, a complementary concept to the human exposome, which focuses on monitoring urban health. This work highlights the use of a comprehensive systems-based approach of the exposome for better capturing the population-wide and individual-level variability in SARS-CoV-2 spread and its associated urban and individual exposures towards improved guidance and response. Population characteristics, the built environment and spatiotemporal features of city infrastructure, as well as individual characteristics/parameters, socioeconomic status, occupation and biological susceptibility need to be simultaneously considered when deploying non-pharmacological public health measures. Integrating individual and population characteristics, as well as urban-specific parameters is the prerequisite in urban exposome studies. Applications of the exposome approach in cities/towns could facilitate assessment of health disparities and better identification of vulnerable populations, as framed by multiple environmental, urban design and planning co-exposures. Exposome-based applications in epidemics control and response include the implementation of exposomic tools that have been quite mature in non-communicable disease research, ranging from biomonitoring and surveillance to sensors and modeling. Therefore, the exposome can be a novel tool in risk assessment and management during epidemics and other major public health events. This is a unique opportunity for the research community to exploit the exposome concept and its tools in upgrading and further developing site-specific public health measures in cities.

Exposome and Immunity Training: How Pathogen Exposure Order Influences Innate Immune Cell Lineage Commitment and Function.

Immune memory is a defining characteristic of adaptive immunity, but recent work has shown that the activation of innate immunity can also improve responsiveness in subsequent exposures. This has been coined "trained immunity" and diverges with the perception that the innate immune system is primitive, non-specific, and reacts to novel and recurrent antigen exposures similarly. The "exposome" is the cumulative exposures (diet, exercise, environmental exposure, vaccination, genetics, etc.) an individual has experienced and provides a mechanism for the establishment of immune training or immunotolerance. It is becoming increasingly clear that trained immunity constitutes a delicate balance between the dose, duration, and order of exposures. Upon innate stimuli, trained immunity or tolerance is shaped by epigenetic and metabolic changes that alter hematopoietic stem cell lineage commitment and responses to infection. Due to the immunomodulatory role of the exposome, understanding innate immune training is critical for understanding why some individuals exhibit protective phenotypes while closely related individuals may experience immunotolerant effects (e.g., the order of exposure can result in completely divergent immune responses). Research on the exposome and trained immunity may be leveraged to identify key factors for improving vaccination development, altering inflammatory disease development, and introducing potential new prophylactic treatments, especially for diseases such as COVID-19, which is currently a major health issue for the world. Furthermore, continued exposome research may prevent many deleterious effects caused by immunotolerance that frequently result in host morbidity or mortality.

Susceptibility to COVID-19 in populations with health disparities: Posited involvement of mitochondrial disorder, socioeconomic stress, and pollutants.

SARS-CoV-2 is a novel betacoronavirus that has caused the global health crisis known as COVID-19. The implications of mitochondrial dysfunction with COVID-19 are discussed as well as deregulated mitochondria and inter-organelle functions as a posited comorbidity enhancing detrimental outcomes. Many environmental chemicals (ECs) and endocrine-disrupting chemicals can do damage to mitochondria and cause mitochondrial dysfunction. During infection, SARS-CoV-2 via its binding target ACE2 and TMPRSS2 can disrupt mitochondrial function. Viral genomic RNA and structural proteins may also affect the normal function of the mitochondria-endoplasmic reticulum-Golgi apparatus. Drugs considered for treatment of COVID-19 should consider effects on organelles including mitochondria functions. Mitochondrial self-balance and clearance via mitophagy are important in SARS-CoV-2 infection, which indicate monitoring and protection of mitochondria against SARS-CoV-2 are important. Mitochondrial metabolomic analysis may provide new indicators of COVID-19 prognosis. A better understanding of the role of mitochondria during SARS-CoV-2 infection may help to improve intervention therapies and better protect mitochondrial disease patients from pathogens as well as people living with poor nutrition and elevated levels of socioeconomic stress and ECs.