Background: COVID-19 has spread worldwide since late 2019, with an unprecedented case count and death toll globally. Health care personnel (HCP), first responders, and other essential and frontline workers (OEWs) are at increased risk of SARS-CoV-2 infection because of frequent close contact with others. Objective: The Arizona Healthcare, Emergency Response, and Other Essential Workers Study (AZ HEROES) aims to examine the epidemiology of SARS-CoV-2 infection and COVID-19 illness among adults with high occupational exposure risk. Study objectives include estimating the incidence of SARS-CoV-2 infection in essential workers by symptom presentation and demographic factors, determining independent effects of occupational and community exposures on incidence of SARS-CoV-2 infection, establishing molecular and immunologic characteristics of SARS-CoV-2 infection in essential workers, describing the duration and patterns of real-time reverse transcription–polymerase chain reaction (rRT-PCR) positivity, and examining postvaccine immunologic response. Methods: Eligible participants include Arizona residents aged 18 to 85 years who work at least 20 hours per week in an occupation involving regular direct contact (ie, within 3 feet) with others. Recruitment goals are stratified by demographic characteristics (50% aged 40 years or older, 50% women, and 50% Hispanic or American Indian), by occupation (40% HCP, 30% first responders, and 30% OEWs), and by prior SARS-CoV-2 infection (with up to 50% seropositive at baseline). Information on sociodemographics, health and medical history, vaccination status, exposures to individuals with suspected or confirmed SARS-CoV-2 infection, use of personal protective equipment, and perceived risks are collected at enrollment and updated through quarterly surveys. Every week, participants complete active surveillance for COVID-like illness (CLI) and self-collect nasal swabs. Additional self-collected nasal swab and saliva specimens are collected in the event of CLI onset. Respiratory specimens are sent to Marshfield Laboratories and tested for SARS-CoV-2 by rRT-PCR assay. CLI symptoms and impact on work and productivity are followed through illness resolution. Serum specimens are collected every 3 months and additional sera are collected following incident rRT-PCR positivity and after each COVID-19 vaccine dose. Incidence of SARS-CoV-2 infections will be calculated by person-weeks at risk and compared by occupation and demographic characteristics as well as by seropositivity status and infection and vaccination history. Results: The AZ HEROES study was funded by the US Centers for Disease Control and Prevention. Enrollment began on July 27, 2020; as of May 1, 2021, a total of 3165 participants have been enrolled in the study. Enrollment is expected to continue through December 1, 2021, with data collection continuing through at least April 2022, contingent upon funding. Conclusions: AZ HEROES is unique in aiming to recruit a diverse sample of essential workers and to prospectively follow strata of SARS-CoV-2 seronegative and seropositive adults. Survey results combined with active surveillance data on exposure, CLI, weekly molecular diagnostic testing, and periodic serology will be used to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, assess the intensity and durability of immune responses to natural infection and COVID-19 vaccination, and contribute to the evaluation of COVID-19 vaccine effectiveness. International Registered Report Identifier (IRRID): DERR1-10.2196/28925

Background: Workers critical to emergency response and continuity of essential services during the COVID-19 pandemic are at a disproportionally high risk of SARS-CoV-2 infection. Prospective cohort studies are needed for enhancing the understanding of the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, identifying risk factors, assessing clinical outcomes, and determining the effectiveness of vaccination. Objective: The Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) prospective cohort study was designed to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, examine the risk factors for infection and clinical spectrum of illness, and assess the effectiveness of vaccination among essential workers. Methods: The RECOVER multisite network was initiated in August 2020 and aims to enroll 3000 health care personnel (HCP), first responders, and other essential and frontline workers (EFWs) at 6 US locations. Data on participant demographics, medical history, and vaccination history are collected at baseline and throughout the study. Active surveillance for the symptoms of COVID-19–like illness (CLI), access of medical care, and symptom duration is performed by text messages, emails, and direct participant or medical record reports. Participants self-collect a mid-turbinate nasal swab weekly, regardless of symptoms, and 2 additional respiratory specimens at the onset of CLI. Blood is collected upon enrollment, every 3 months, approximately 28 days after a reverse transcription polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infection, and 14 to 28 days after a dose of any COVID-19 vaccine. From February 2021, household members of RT-PCR–confirmed participants are self-collecting mid-turbinate nasal swabs daily for 10 days. Results: The study observation period began in August 2020 and is expected to continue through spring 2022. There are 2623 actively enrolled RECOVER participants, including 280 participants who have been found to be positive for SARS-CoV-2 by RT-PCR. Enrollment is ongoing at 3 of the 6 study sites. Conclusions: Data collected through the cohort are expected to provide important public health information for essential workers at high risk for occupational exposure to SARS-CoV-2 and allow early evaluation of COVID-19 vaccine effectiveness. International Registered Report Identifier (IRRID): DERR1-10.2196/31574

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

The occupation of firefighting is classified as a Group 1 carcinogen. Increased cancer risk among firefighters may be partly attributable to increased occupational exposure to a range of chemicals, including per- and polyfluoroalkyl substances (PFAS). Some PFAS are known and suspect human carcinogens. Investigating epigenetic response to these PFAS exposures in firefighters may help to identify biological pathways of specific cancers, and previously unidentified health outcomes that are associated with PFAS. We therefore investigated the associations of serum PFAS concentrations with miRNA expression in firefighters. Serum samples collected from 303 firefighters from 6 sites across the USA were analyzed for 9 PFAS along with miRNA expression. Covariate-adjusted linear regression was used to estimate associations between log PFAS and miRNA expression, with false discovery rate (FDR) set to 0.05 for significance, and an exploratory cutoff of FDR q < 0.20. Gene set enrichment analysis (GSEA) was performed using miRTarBase's miRWalk pathways. Age, race-ethnicity, BMI, fire department, and sex were controlled for in all models. At FDR<0.05, the linear isomer of perfluorooctane sulfonic acid (PFOS) was inversely associated with miR-128-1-5p expression (Beta = -0.146, 95 % CI -0.216, -0.076). At a relaxed FDR of 0.20, we observed inverse associations for the sum of branched isomers of PFOS (Sm-PFOS) with 5 miRNAs (let-7d-5p, let-7a-5p, miR-423-5p, let-7b-5p, miR-629-5p). Several pathways were enriched for multiple PFAS, including those correlated with certain cancers, blood diseases, thyroid disorders, autoimmune disorders, and neurological outcomes. Some PFAS in firefighters were found to be associated with alteration of miRNA consistent with increased risk for a range of chronic diseases.

Background: Firefighters are at an increased risk of cancer and other health conditions compared with the general population. However, the specific exposures and mechanisms contributing to these risks are not fully understood. This information is critical to formulate and test protective interventions. Objective: The purpose of the Fire Fighter Cancer Cohort Study (FFCCS) is to conduct community-engaged research with the fire service to advance the evaluation and reduction of firefighter exposures, along with understanding and mitigating effects leading to an increased risk of cancer and other health conditions. This involves establishing a long-term (>30 years) firefighter multicenter prospective cohort study. Methods: The structure of the FFCCS includes a fire service oversight and planning board to provide guidance and foster communication between researchers and fire organizations; a data coordinating center overseeing survey data collection and data management; an exposure assessment center working with quantitative exposure data to construct a firefighter job exposure matrix; and a biomarker analysis center, including a biorepository. Together, the centers evaluate the association between firefighter exposures and toxic health effects. Firefighter research liaisons are involved in all phases of the research. The FFCCS research design primarily uses a set of core and project-specific survey questions accompanied by a collection of biological samples (blood and urine) for the analysis of biomarkers of exposure and effect. Data and samples are collected upon entry into the study, with subsequent collection after eligible exposures, and at intervals (eg, 1-2 years) after enrollment. FFCCS data collection and analysis have been developed to evaluate unique exposures for specific firefighter groups; cancer risks; and end points in addition to cancer, such as reproductive outcomes. Recruitment is carried out with coordination from partnering fire departments and eligible participants, including active career and volunteer firefighters in the United States. Results: The FFCCS protocol development was first funded by the US Federal Emergency Management Agency in 2016, with enrollment beginning in February 2018. As of September 2024, >6200 participants from >275 departments across 31 states have enrolled, including recruit and incumbent firefighters. Biological samples have been analyzed for measures of exposure and effect. Specific groups enrolled in the FFCCS include career and volunteer structural firefighters, women firefighters, trainers, fire investigators, wildland firefighters, firefighters responding to wildland-urban interface fires, and airport firefighters. Peer-reviewed published results include measurement of exposures and the toxic effects of firefighting exposure. Whenever possible, research results are provided back to individual participants. Conclusions: The FFCCS is a unique, community-engaged, multicenter prospective cohort study focused on the fire service. Study results contribute to the evaluation of exposures, effects, and preventive interventions across multiple sectors of the US fire service, with broad implications nationally. International Registered Report Identifier (IRRID): DERR1-10.2196/70522

Objective: The aim of the study is to examine associations between years of firefighting service and eight chronological age-adjusted measures of blood leukocyte epigenetic age acceleration: Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length. Methods: The study used a repeated measures analysis of data from 379 incumbent firefighters from eight career departments and 100 recruit firefighters from two of the departments, across the United States. Results: Incumbent firefighters had on average greater epigenetic age acceleration compared with recruit firefighters, potentially due to the cumulative effect of occupational exposures. However, among incumbent firefighters, additional years of service were associated with epigenetic age deceleration, particularly for GrimAge, a strong predictor of mortality. Conclusions: Long-term studies with more specific occupational exposure classification are needed to better understand the relationship between years of service and aging biomarkers.