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.
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 DERR1-10.2196/28925
Hybrid immunity, as a result of infection and vaccination to SARS-CoV-2, has been well studied in adults but limited evidence is available in children. We evaluated the antibody responses to primary SARS-CoV-2 infection among vaccinated and unvaccinated children aged ≥ 5 years. Methods: A longitudinal cohort study of children aged ≥ 5 was conducted during August 2021–August 2022, at sites in Arizona, Texas, Utah, and Florida. Children submitted weekly nasal swabs for PCR testing and provided sera 14–59 days after PCR-confirmed SARS-CoV-2 infection. Antibodies were measured by ELISA against the receptor-binding domain (RBD) and S2 domain of ancestral Spike (WA1), in addition to Omicron (BA.2) RBD, following infection in children, with and without prior monovalent ancestral mRNA COVID-19 vaccination. Results: Among the 257 participants aged 5 to 18 years, 166 (65%) had received at least two mRNA COVID-19 vaccine doses ≥ 14 days prior to infection. Of these, 53 occurred during Delta predominance, with 37 (70%) unvaccinated at the time of infection. The remaining 204 infections occurred during Omicron predominance, with 53 (26%) participants unvaccinated. After adjusting for weight, age, symptomatic infection, and gender, significantly higher mean RBD AUC values were observed among the vaccinated group compared to the unvaccinated group for both WA1 and Omicron (p < 0.0001). A smaller percentage of vaccinated children reported fever during illness, with 55 (33%) reporting fever compared to 44 (48%) unvaccinated children reporting fever (p = 0.021). Conclusions: Children with vaccine-induced immunity at the time of SARS-CoV-2 infection had higher antibody levels during convalescence and experienced less fever compared to unvaccinated children during infection.
Understanding the relative risk of SARS-CoV-2 infection across occupations can inform guidance to protect workers and communities. Less is known about infection risk for first responders and other essential workers than for health care personnel.
Objective
To compare the prevaccination incidence of SARS-CoV-2 infection among first responders and other essential workers with incidence among health care personnel.
Design, Setting, and Participants
This was a prospective cohort study of health care personnel, first responders, and other essential workers in Arizona from July 20, 2020, to March 14, 2021. Participants were seronegative at enrollment, had frequent direct contact with others at work, worked at least 20 hours per week, and submitted weekly nasal swab specimens for real-time reverse transcriptase polymerase chain reaction analysis. Data analyses were performed from April 19, 2021, to June 4, 2021.
Exposures
Occupation was the primary exposure of interest. Confounders assessed were sociodemographic characteristics, health status, community exposure, and work exposure.
Main Outcomes and Measures
Crude incidence of SARS-CoV-2 infection was defined as the sum of first positive SARS-CoV-2 infections in participants divided by person-weeks at risk. Negative binomial regression was used to model SARS-CoV-2 infection by occupation to estimate unadjusted and adjusted incidence rate ratios (IRRs). The least absolute shrinkage and selection operator (LASSO) method was used to generate a parsimonious multivariable model.
Results
The study cohort comprised 1766 Arizona workers (mean age [SD], 43.8 [11.1] years; 1093 [61.9%] female; 401 [22.7%] were Hispanic and 1530 [86.6%] were White individuals) of whom 44.2% were health care personnel, 22.4% first responders, and 33.4% other essential workers. The cohort was followed up for 23 393 person-weeks. Crude incidence of SARS-CoV-2 infection was 6.7, 13.2, and 7.4 per 1000 person-weeks at risk for health care personnel, first responders, and other essential workers, respectively. In unadjusted models, first responders had twice the incidence of infection as health care personnel (IRRs, 2.01; 95% CI, 1.44-2.79). While attenuated, this risk remained elevated in adjusted LASSO-optimized models (IRR, 1.60; 95% CI, 1.07-2.38). Risk of infection among other essential workers was no different than for health care personnel in unadjusted or adjusted models.
Conclusions and Relevance
This prospective cohort study found that first responders had a higher incidence of SARS-CoV-2 infection than health care personnel, even after adjusting for potential confounding factors. Given their frequent contact with each other and with the public and their high rates of SARS-CoV-2 infection, the safety challenges for first responders warrant greater public health attention and research.
Neuromotor dysfunction is a consistent finding in high-risk and archival studies of schizophrenia, but the sources of this dysfunction and its role in the developmental course of the disorder remain poorly understood. This study examined childhood motor predictors of adult psychiatric outcome in a birth cohort sample (72 patients with schizophrenia or schizoaffective disorder, 63 unaffected siblings, and 7,941 nonpsychiatric controls), evaluated prospectively with neurologic examinations at 8 months, 4 years, and 7 years of age. Deviance on motor coordination measures at 7 years was associated with both adult schizophrenia and unaffected sibling status, suggesting that a cofamilial (and perhaps genetic) factor underlies motor coordination deficits in schizophrenia. Unusual movements at ages 4 and 7 predicted adult schizophrenia but not unaffected sibling status, indicating that these deficits may be specific to those who will develop the clinical phenotype. None of the motor precursors were confined to patients with an early age at first treatment contact. Fetal hypoxia predicted unusual movements at 4 but not 7 years among the preschizophrenia subjects, suggesting neurodevelopmental dependence of its functional effects. Neither prenatal complications nor birth weight were associated with motor dysfunction in preschizophrenia subjects or their unaffected siblings at any age. Finally, preschizophrenia children did not show the expected developmental decline in unusual movements, perhaps reflecting aberrant functional maturation of cortical-subcortical pathways.
The BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine was recommended by CDC's Advisory Committee on Immunization Practices for persons aged 12-15 years (referred to as adolescents in this report) on May 12, 2021, and for children aged 5-11 years on November 2, 2021 (1-4). Real-world data on vaccine effectiveness (VE) in these age groups are needed, especially because when the B.1.1.529 (Omicron) variant became predominant in the United States in December 2021, early investigations of VE demonstrated a decline in protection against symptomatic infection for adolescents aged 12-15 years and adults* (5). The PROTECT† prospective cohort of 1,364 children and adolescents aged 5-15 years was tested weekly for SARS-CoV-2, irrespective of symptoms, and upon COVID-19-associated illness during July 25, 2021-February 12, 2022. Among unvaccinated participants (i.e., those who had received no COVID-19 vaccine doses) with any laboratory-confirmed SARS-CoV-2 infection, those with B.1.617.2 (Delta) variant infections were more likely to report COVID-19 symptoms (66%) than were those with Omicron infections (49%). Among fully vaccinated children aged 5-11 years, VE against any symptomatic and asymptomatic Omicron infection 14-82 days (the longest interval after dose 2 in this age group) after receipt of dose 2 of the Pfizer-BioNTech vaccine was 31% (95% CI = 9%-48%), adjusted for sociodemographic characteristics, health information, frequency of social contact, mask use, location, and local virus circulation. Among adolescents aged 12-15 years, adjusted VE 14-149 days after dose 2 was 87% (95% CI = 49%-97%) against symptomatic and asymptomatic Delta infection and 59% (95% CI = 22%-79%) against Omicron infection. Fully vaccinated participants with Omicron infection spent an average of one half day less sick in bed than did unvaccinated participants with Omicron infection. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.
BACKGROUND Firefighters are at 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 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+ year) firefighter multicenter prospective cohort study. METHODS The structure of the FFCCS includes a fire service oversight and planning board (OPB) to provide guidance and foster communication between researchers and fire organizations; a data coordinating center (DCC) overseeing survey data collection and data management; an exposure assessment center (EAC) working with quantitative exposure data to construct a firefighter job exposure matrix; and a biomarker analysis center (BAC), 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 utilizes a set of core and project-specific survey questions accompanied by collection of biological samples (blood and urine) for 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 (e.g. 1-2 years) after enrollment. FFCCS data collection and analysis have been developed to evaluate unique exposures for specific firefighter groups, cancer risks, and endpoints 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 (US). RESULTS FFCCS study protocol development was first funded by the US Federal Emergency Management Agency (FEMA) in 2016, with enrollment beginning in February of 2018. As of September 2024, >6,200 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 (WUI) 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 fire service community-engaged multicenter prospective cohort study. Study results are contributing to evaluation of exposures, effects, and preventive interventions across multiple sectors of the US fire service with broad implications nationally.
Importance Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance. Objective To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages. Design, Setting, and Participants A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase–polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 from December 14, 2020, to April 19, 2022, with follow-up until May 9, 2022, reported. Exposures SARS-CoV-2 lineage (origin strain, Delta variant, Omicron variant) and COVID-19 vaccination status. Main Outcomes and Measures Clinical outcomes included presence of symptoms, specific symptoms (including fever or chills), illness duration, and medical care seeking. Virologic outcomes included viral load by quantitative reverse transcriptase–polymerase chain reaction testing along with viral viability. Results Among 1199 participants with COVID-19 infection (714 [59.5%] women; median age, 41 years), 14.0% were infected with the origin strain, 24.0% with the Delta variant, and 62.0% with the Omicron variant. Participants vaccinated with the second vaccine dose 14 to 149 days before Delta infection were significantly less likely to be symptomatic compared with unvaccinated participants (21/27 [77.8%] vs 74/77 [96.1%]; OR, 0.13 [95% CI, 0-0.6]) and, when symptomatic, those vaccinated with the third dose 7 to 149 days before infection were significantly less likely to report fever or chills (5/13 [38.5%] vs 62/73 [84.9%]; OR, 0.07 [95% CI, 0.0-0.3]) and reported significantly fewer days of symptoms (10.2 vs 16.4; difference, −6.1 [95% CI, −11.8 to −0.4] days). Among those with Omicron infection, the risk of symptomatic infection did not differ significantly for the 2-dose vaccination status vs unvaccinated status and was significantly higher for the 3-dose recipients vs those who were unvaccinated (327/370 [88.4%] vs 85/107 [79.4%]; OR, 2.0 [95% CI, 1.1-3.5]). Among symptomatic Omicron infections, those vaccinated with the third dose 7 to 149 days before infection compared with those who were unvaccinated were significantly less likely to report fever or chills (160/311 [51.5%] vs 64/81 [79.0%]; OR, 0.25 [95% CI, 0.1-0.5]) or seek medical care (45/308 [14.6%] vs 20/81 [24.7%]; OR, 0.45 [95% CI, 0.2-0.9]). Participants with Delta and Omicron infections who received the second dose 14 to 149 days before infection had a significantly lower mean viral load compared with unvaccinated participants (3 vs 4.1 log 10 copies/μL; difference, −1.0 [95% CI, −1.7 to −0.2] for Delta and 2.8 vs 3.5 log 10 copies/μL, difference, −1.0 [95% CI, −1.7 to −0.3] for Omicron). Conclusions and Relevance In a cohort of US essential and frontline workers with SARS-CoV-2 infections, recent vaccination with 2 or 3 mRNA vaccine doses less than 150 days before infection with Delta or Omicron variants, compared with being unvaccinated, was associated with attenuated symptoms, duration of illness, medical care seeking, or viral load for some comparisons, although the precision and statistical significance of specific estimates varied.
