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Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine. Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days. In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.

Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occupational firefighting. 200 urine samples from 100 firefighters collected at baseline and two to four hours post-fire were analyzed using untargeted liquid-chromatography and high-resolution mass spectrometry. Changes in metabolite abundance after a fire were estimated with fixed effects linear regression, with false discovery rate (FDR) adjustment. Partial least squares discriminant analysis (PLS-DA) was also used, and variable important projection (VIP) scores were extracted. Systemic changes were evaluated using pathway enrichment for highly discriminating metabolites. Metabolome-wide-association-study (MWAS) identified 268 metabolites associated with firefighting activity at FDR q < 0.05. Of these, 20 were annotated with high confidence, including the amino acids taurine, proline, and betaine; the indoles kynurenic acid and indole-3-acetic acid; the known uremic toxins trimethylamine n-oxide and hippuric acid; and the hormone 7a-hydroxytestosterone. Partial least squares discriminant analysis (PLS-DA) additionally implicated choline, cortisol, and other hormones. Significant pathways included metabolism of urea cycle/amino group, alanine and aspartate, aspartate and asparagine, vitamin b3 (nicotinate and nicotinamide), and arginine and proline. Firefighters show a broad metabolic response to fires, including altered excretion of indole compounds and uremic toxins. Implicated pathways and features, particularly uremic toxins, may be important regulators of firefighter’s increased risk for urinary tract cancers.

The extent to which semi-quantitative antibody levels confer protection against SARS-CoV-2 infection in populations with heterogenous immune histories is unclear. Two nested case-control studies were designed within the multisite HEROES/RECOVER prospective cohort of frontline workers to study the relationship between antibody levels and protection against first-time post-vaccination infection and reinfection with SARS-CoV-2 from December 2021 to January 2023. All participants submitted weekly nasal swabs for rRT-PCR testing and blood samples quarterly and following infection or vaccination. Cases of first-time post-vaccination infection following a third dose of monovalent (origin strain WA-1) mRNA vaccine (n = 613) and reinfection (n = 350) were 1:1 matched to controls based on timing of blood draw and other potential confounders. Conditional logistic regression models were fit to estimate infection risk reductions associated with 3-fold increases in end titers for receptor binding domain (RBD). In first-time post-vaccination and reinfection study samples, most were female (67%, 57%), non-Hispanic (82%, 68%), and without chronic conditions (65%, 65%). The odds of first-time post-vaccination infection were reduced by 21% (aOR = 0.79, 95% CI = [0.66–0.96]) for each 3-fold increase in RBD end titers. The odds of reinfection associated with a 3-fold increase in RBD end titers were reduced by 23% (aOR = 0.77, 95% CI = [0.65–0.92] for unvaccinated individuals and 58% (aOR = 0.42, 95% CI = [0.22–0.84]) for individuals with three mRNA vaccine doses following their first infection. Frontline workers with higher antibody levels following a third dose of mRNA COVID-19 vaccine were at reduced risk of SARS-CoV-2 during Omicron predominance. Among those with previous infections, the point estimates of risk reduction associated with antibody levels was greater for those with three vaccine doses compared to those who were unvaccinated.

In a cohort of essential workers in the United States previously infected with SARS-CoV-2, risk factors for reinfection included being unvaccinated, infrequent mask use, time since first infection, and being non-Hispanic Black. Protecting workers from reinfection requires a multipronged approach including up-to-date vaccination, mask use as recommended, and reduction in underlying health disparities.

Background Demands on health systems due to COVID-19 are substantial, but drivers of healthcare utilization are not well defined in non-severe SARS-CoV-2 infections. Among a prospective cohort of frontline workers from July 2020 to February 2023, we assessed predictors of healthcare utilization during SARS-CoV-2 infection. Methods Weekly specimens tested via real-time reverse transcriptase polymerase chain reaction analysis. Participants reported sociodemographic, health status information, and illness experience information. Primary outcome was healthcare utilization during SARS-CoV-2 infection. Predictors included sociodemographic characteristics, baseline health status, and measures of illness severity. Multivariable logistic regression was utilized to generate odds ratios for predictors of healthcare utilization. Results 1,923 SARS-CoV-2 infections (1,276 first infections and 647 reinfections from 4,208 participants): 1221 (63.5%) individuals were between 40 and 65 years old; 1115 (58.0%) were female; 449 (23.3%) were Hispanic and 1305 (67.9%) non-Hispanic White. 294 (15.3%) individuals sought medical care during first infection, 106 (5.5%) during reinfection. Sociodemographic and baseline health characteristics were not associated with healthcare utilization during infections from any variant for first infections, while age (OR 1.04, 95%CI 1.01–1.07) was during Omicron reinfection. In first infection, number of symptoms (OR 1.16, 95%CI 1.00-1.36 in Origin/Alpha, OR 1.12, 95%CI 1.00-1.49 in Delta, OR 1.09, 95%CI 1.01–1.16 in Omicron), number of days spent in bed (OR 1.13, 95%CI 1.02–1.33 in Origin/Alpha, OR 1.23, 95%CI 1.00-1.59 in Delta, OR 1.12, 95%CI 1.03–1.22 in Omicron), and illness duration (OR 1.01, 95%CI 1.00-1.04 in Origin/Alpha, OR 1.01, 95%CI 1.00-1.03 in Delta, OR 1.01, 95%CI 1.00-1.02 in Omicron) were related to healthcare utilization for all variants. Number of days in bed (OR 1.12, 95%CI 1.01–1.27), illness duration (OR 1.01, 95%CI 1.00-1.02), and hours of work missed (OR 2.24, 95%CI 1.11–4.74) were positively associated with healthcare utilization during Omicron reinfection. Conclusion The main factors associated with healthcare utilization for SARS-CoV-2 infection were symptom severity and duration. Practices and therapeutics aimed at decreasing these factors would be most helpful in easing the burden on health systems.

Firefighters are exposed to carcinogens and have elevated cancer rates. We hypothesized that occupational exposures in firefighters would lead to DNA methylation changes associated with activation of cancer pathways and increased cancer risk. To address this hypothesis, we collected peripheral blood samples from 45 incumbent and 41 new recruit non-smoking male firefighters and analyzed the samples for DNA methylation using an Illumina Methylation EPIC 850k chip. Adjusting for age and ethnicity, we performed: 1) genome-wide differential methylation analysis; 2) genome-wide prediction for firefighter status (incumbent or new recruit) and years of service; and 3) Ingenuity Pathway Analysis (IPA). Four CpGs, including three in the YIPF6, MPST, and PCED1B genes, demonstrated above 1.5-fold statistically significant differential methylation after Bonferroni correction. Genome-wide methylation predicted with high accuracy incumbent and new recruit status as well as years of service among incumbent firefighters. Using IPA, the top pathways with more than 5 gene members annotated from differentially methylated probes included Sirtuin signaling pathway, p53 signaling, and 5' AMP-activated protein kinase (AMPK) signaling. These DNA methylation findings suggest potential cellular mechanisms associated with increased cancer risk in firefighters.

Background Firefighters have frequent exposure to carcinogens and an increased risk of cancer. Wildland-urban interface (WUI) fires, which involve both structures and undeveloped wildland fuels, pose unique challenges to the health of firefighters. However, the extent of health risks associated with these fires remains underexplored. Objectives This study aims to identify altered urine metabolites and metabolic processes among male firefighters that were associated with WUI fires as compared with municipal structure fires (MSF). Methods Untargeted metabolomic profiling was applied to pre-exposure (baseline) and postfire urine samples collected from firefighters responding to WUI and MSF fires. Differential analysis was conducted by fitting linear mixed effects regression models on preprocessed ion intensity and exposure status while adjusting for demographic covariates. Differential metabolites by post-exposure status were identified using a false discovery rate (FDR) threshold of < 0.05. Pathway analysis was performed to identify pathways that were significantly perturbed at a Bonferroni adjusted p-value < 0.05 level. We conducted differential and pathway analyses in both the WUI and MSF cohorts and compared the two fire types in terms of the number of differentially expressed metabolites and patterns of metabolic pathway enrichment. Results Eighty-five firefighters contributed paired baseline and post-fire samples from WUI events, and 98 firefighters contributed paired baseline and post-fire samples from MSF events. We performed metabolic profiling on baseline and postfire urine samples from WUI and MSF using four modes: HILIC(-), HILIC(+), C18(-), and C18(+) and identified metabolites against an in-house library. We identified 244, 297, 320, and 266 level-1 metabolites from the four respective modes. In the statistical analysis, the main model identified a total of 176 differential metabolites from WUI fires. For MSF, the model identified a total of 652 differential metabolites from the four respective modes. Most metabolites with significant changes after a WUI fire also changed significantly after an MSF event. Two metabolic pathways were significantly enriched after WUI fires, while 7 pathways were significantly enriched after MSF exposure and 2 pathways overlapped between the two types of fires. Conclusion Fire exposure induces numerous metabolic perturbations in firefighters responding to WUI fires, potentially contributing to their elevated cancer risk. Although individual metabolites changed in a similar fashion across both WUI and MSF, MSF were associated with an increased number of metabolite changes and some of the enriched pathways differed between exposures to WUI fires vs. MSF. These findings suggest that WUI and MSF exposures may share common biological responses while also posing unique health risks to firefighters.

Background Evidence from previous studies suggests that women firefighters have greater risk of some adverse reproductive outcomes. The purpose of this study was to investigate whether women firefighters had greater risk of miscarriage compared to non-firefighters and whether there were occupational factors associated with risk of miscarriage among firefighters. Methods We studied pregnancies in the United States fire service using data from the Health and Wellness of Women Firefighters Study ( n  = 3181). We compared the prevalence of miscarriage among firefighters to published rates among non-firefighters using age-standardized prevalence ratios. We used generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs) between occupational factors (employment (career/volunteer), wildland firefighter status (wildland or wildland-urban-interface/structural), shift schedule, fire/rescue calls at pregnancy start) and risk of miscarriage, adjusted for age at pregnancy, education, gravidity, BMI, and smoking. We evaluated if associations varied by age at pregnancy or employment. Results Among 1074 firefighters and 1864 total pregnancies, 404 pregnancies resulted in miscarriages (22%). Among most recent pregnancies, 138 resulted in miscarriage (13%). Compared to a study of US nurses, firefighters had 2.33 times greater age-standardized prevalence of miscarriage (95% CI 1.96–2.75). Overall, we observed that volunteer firefighters had an increased risk of miscarriage which varied by wildland status (interaction p -value< 0.01). Among structural firefighters, volunteer firefighters had 1.42 times the risk of miscarriage (95% CI 1.11–1.80) compared to career firefighters. Among wildland/wildland-urban-interface firefighters, volunteer firefighters had 2.53 times the risk of miscarriage (95% CI 1.35–4.78) compared to career firefighters. Conclusions Age-standardized miscarriage prevalence among firefighters may be greater than non-firefighters and there may be variation in risk of miscarriage by fire service role. Further research is needed to clarify these associations to inform policy and decision-making.

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.

Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb)] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE) cell model we found that both micromolar (3.9 μM) and submicromolar (0.8 μM) arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl) Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-). We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway.