Environmental and structural factors associated with bacterial diversity in household dust across the Arizona-Sonora border.

We previously reported that asthma prevalence was higher in the United States (US) compared to Mexico (MX) (25.8% vs. 8.4%). This investigation assessed differences in microbial dust composition in relation to demographic and housing characteristics on both sides of the US-MX Border. Forty homes were recruited in the US and MX. Home visits collected floor dust and documented occupants' demographics, asthma prevalence, housing structure, and use characteristics. US households were more likely to have inhabitants who reported asthma when compared with MX households (30% vs. 5%) and had significantly different flooring types. The percentage of households on paved roads, with flushing toilets, with piped water and with air conditioning was higher in the US, while dust load was higher in MX. Significant differences exist between countries in the microbial composition of the floor dust. Dust from Mexican homes was enriched with Alishewanella, Paracoccus, Rheinheimera genera and Intrasporangiaceae family. A predictive metagenomics analysis identified 68 significantly differentially abundant functional pathways between US and MX. This study documented multiple structural, environmental, and demographic differences between homes in the US and MX that may contribute to significantly different microbial composition of dust observed in these two countries.

Novel chemical contaminants associated with thirdhand smoke in settled house dust.

Thirdhand smoke (THS) is the persistent and toxic residue from tobacco smoke in indoor environments. A comprehensive understanding of the chemical constituents of THS is necessary to assess the risks of long-term exposure and to establish reliable THS tracers. The objective of this study was to investigate compounds associated with THS through nontargeted analysis (NTA) of settled house dust samples from smokers' and non-smokers' homes, using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS). Compounds that were either only present in dust from smokers' homes or that had significantly larger abundance than in non-smokers' homes were termed qualified compounds. We identified 140 qualified compounds, and of these, 42 compounds were tentatively identified by searching matching mass spectra in NIST electron impact (EI) mass spectral library including 20 compounds confirmed with their authentic standards. Among the 42 compounds, 26 compounds were statistically more abundant (p < 0.10) in dust from homes of smokers; seven were tobacco-specific compounds, two of which (nornicotyrine, 3-ethenylpyridine) have not been reported before in house dust. Two compounds, tris (2-chloroethyl) phosphate (a toxic compound used as a flame retardant and reported in tobacco) and propanoic acid, 2-methyl-, 1-(1,1-dimethylethyl)-2-methyl-1,3-propanediyl ester (highly abundant and reported in exhaled air of smokers), were found in dust from all smokers' homes and in zero non-smokers' homes, making these potential THS tracers, possibly associated with recent smoking. Benzyl methyl ketone was significantly higher in dust in smokers' homes, and was previously reported not as a product of tobacco but rather as a form of methamphetamine. This compound was recently reported in mainstream tobacco smoke condensate through NTA as well. These identified potential tracers and chemical components of THS in this study can be further investigated for use in developing THS contamination and exposure assessments.

Studying full-shift inhalation exposures to volatile organic compounds (VOCs) among Latino workers in very small-sized beauty salons and auto repair shops.

Background: One in every 200 US jobs is in a beauty salon or auto repair shop, where workers are regularly exposed to volatile organic compounds (VOCs) that may cause a range of short- and long-term health issues. In these shops, Latino workers are overrepresented and lack culturally and linguistically appropriate industrial hygiene resources. This leaves a gap in knowledge on inhalation exposures to VOCs in this hard-to-reach and ubiquitous worker population. Objective: Our goal was to recruit hard-to-reach, predominantly Spanish-speaking workers in beauty salons and auto repair shops and monitor total VOC inhalation exposures for over entire work shifts, with minimal impact on workers, clients, and business. Methods: We developed and refined measurement and exposure assessment methods for personal and area full-shift VOC inhalation exposures. Results: With minimal participant loss, we measured over 500 h of real-time, personal VOC exposures and recorded activities and other exposure factors for 47 participants, while also documenting chemical inventories and quantifying indoor area concentrations of specific VOCs among 10 auto repair shops and 10 beauty salons. Conclusion: Lessons learned from our study can assist future studies of inhalation exposures in other hard-to-reach occupational populations.

Contamination of surfaces in children's homes with nicotine and the potent carcinogenic tobacco-specific nitrosamine NNK.

BACKGROUND: Tobacco smoke exposure (TSE) through secondhand and thirdhand smoke is a modifiable risk factor that contributes to childhood morbidity. Limited research has assessed surface TSE pollution in children's environments as a potential source of thirdhand smoke exposure, and none have examined levels of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on surfaces. OBJECTIVE: This study measured surface NNK and nicotine in children's homes and associations with sociodemographics and parent-reported TSE behaviors. We assessed correlations of surface NNK and nicotine with dust NNK, dust nicotine, and child cotinine. METHODS: Home surface wipe NNK and nicotine data from 84 children who lived with smokers were analyzed. Tobit and simple linear regression analyses were conducted to assess associations of surface NNK and nicotine with child characteristics. Spearman's (ρ) correlations assessed the strength of associations between environmental markers and child cotinine. RESULTS: Nearly half (48.8%) of children's home surfaces had detectable NNK and 100% had detectable nicotine. The respective geometric means (GMs) of surface NNK and nicotine loadings were 14.0 ng/m2 and 16.4 µg/m2. Surface NNK positively correlated with surface nicotine (ρ = 0.54, p < 0.001) and dust NNK (ρ = 0.30, p = 0.020). Surface nicotine positively correlated with dust NNK (ρ = 0.42, p < 0.001) and dust nicotine (ρ = 0.24, p = 0.041). Children with household incomes ≤$15,000 had higher surface NNK levels (GM = 18.7 ng/m2, p = 0.017) compared to children with household incomes >$15,000 (GM = 7.1 ng/m2). Children with no home smoking bans had higher surface NNK (GM = 18.1 ng/m2, p = 0.020) and surface nicotine (GM = 17.7 µg/m2, p = 0.019) levels compared to children with smoking bans (GM = 7.5 ng/m2, 4.8 µg/m2, respectively). IMPACT: Although nicotine on surfaces is an established marker of thirdhand smoke pollution, other thirdhand smoke contaminants have not been measured on surfaces in the homes of children living with smokers. We provide evidence that the potent carcinogenic tobacco-specific nitrosamine NNK was detectable on surfaces in nearly half of children's homes, and nicotine was detectable on all surfaces. Surface NNK was positively correlated with surface nicotine and dust NNK. Detectable surface NNK levels were found in homes with indoor smoking bans, indicating the role of NNK as a persistent thirdhand smoke pollutant accumulating on surfaces as well as in dust.

Environmental and Structural Factors Associated with Bacterial Diversity in Household Dust Across the Arizona-Sonora Border.

We previously reported that asthma prevalence was higher in the United States (US) compared to Mexico (MX) (25.8% vs 8.4%). This investigation assessed differences in microbial dust composition in relation to demographic and housing characteristics on both sides of the US-MX Border. Forty homes were recruited in the US and MX. Home visits collected floor dust and documented occupants' demographics, asthma prevalence, and housing structure and use characteristics. US households were more likely to have inhabitants who reported asthma when compared with MX households (30% vs 5%) and had significantly different flooring types. The percentage of households on paved roads, with flushing toilets, with piped water and with air conditioning was higher in the US, while dust load was higher in MX. Significant differences exist between countries in the microbial composition of the floor dust. Dust from US homes was enriched with Geodermatophilus, whereas dust from Mexican homes was enriched with Alishewanella and Chryseomicrobium. A predictive metagenomics analysis identified 68 significantly differentially abundant functional pathways between US and MX. This study documented multiple structural, environmental, and demographic differences between homes in the US and MX that may contribute to significantly different microbial composition of dust observed in these two countries.

Changes and stability of hand nicotine levels in children of smokers: Associations with urinary biomarkers, reported child tobacco smoke exposure, and home smoking bans.

BACKGROUND: Exposure to thirdhand smoke (THS) residue takes place through inhalation, ingestion, and dermal transfer. Hand nicotine levels have been proposed to measure THS pollution in the environment of children, but little is known about its variability and stability over time and correlates of change. OBJECTIVES: The goal was to determine the stability of hand nicotine in comparison to urinary biomarkers and to explore factors that influence changes in hand nicotine. METHODS: Data were collected from 0 to 11-year-old children (Mean age = 5.9) who lived with ≥1 tobacco smokers (N = 129). At a 6-week interval, we collected repeated measures of hand nicotine, four urinary biomarkers (cotinine, trans-3'-hydroxycotinine, nicotelline N-oxides, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), and parent-reported child tobacco smoke exposure (TSE). Dependent sample t-tests, correlations, and multivariable regression analyses were conducted to examine the changes in child TSE. RESULTS: Hand nicotine levels (r = 0.63, p < 0.001) showed similar correlations between repeated measures to urinary biomarkers (r = 0.58-0.71; p < 0.001). Different from urinary biomarkers, mean hand nicotine levels increased over time (t(113) = 3.37, p < 0.001) being significantly higher in children from homes without smoking bans at Time 2 (p = 0.016) compared to Time 1 (p = 0.003). Changes in hand nicotine correlated with changes in cotinine and trans-3'-hydroxycotinine (r = 0.30 and r = 0.19, respectively, p < 0.05). Children with home smoking bans at Time 1 and 2 showed significantly lower hand nicotine levels compared to children without home smoking bans. DISCUSSION: Findings indicate that hand nicotine levels provide additional insights into children's exposure to tobacco smoke pollutants than reported child TSE and urinary biomarkers. Changes in hand nicotine levels show that consistent home smoking bans in homes of children of smokers can lower THS exposure. Hand nicotine levels may be influenced by the environmental settings in which they are collected.

Characterization of the humoral and cellular immunity induced by a recombinant BCG vaccine for the respiratory syncytial virus in healthy adults.

Introduction: The human respiratory syncytial virus (hRSV) is responsible for most respiratory tract infections in infants. Even though currently there are no approved hRSV vaccines for newborns or infants, several candidates are being developed. rBCG-N-hRSV is a vaccine candidate previously shown to be safe in a phase I clinical trial in adults (clinicaltrials.gov identifier #NCT03213405). Here, secondary immunogenicity analyses were performed on these samples. Methods: PBMCs isolated from immunized volunteers were stimulated with hRSV or mycobacterial antigens to evaluate cytokines and cytotoxic T cell-derived molecules and the expansion of memory T cell subsets. Complement C1q binding and IgG subclass composition of serum antibodies were assessed. Results: Compared to levels detected prior to vaccination, perforin-, granzyme B-, and IFN-γ-producing PBMCs responding to stimulus increased after immunization, along with their effector memory response. N-hRSV- and mycobacterial-specific antibodies from rBCG-N-hRSV-immunized subjects bound C1q. Conclusion: Immunization with rBCG-N-hRSV induces cellular and humoral immune responses, supporting that rBCG-N-hRSV is immunogenic and safe in healthy individuals. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/, identifier NCT03213405.

Delivery platforms for broadly neutralizing antibodies.

PURPOSE OF REVIEW: Passive administration of broadly neutralizing antibodies (bNAbs) is being evaluated as a therapeutic approach to prevent or treat HIV infections. However, a number of challenges face the widespread implementation of passive transfer for HIV. To reduce the need of recurrent administrations of bNAbs, gene-based delivery approaches have been developed which overcome the limitations of passive transfer. RECENT FINDINGS: The use of DNA and mRNA for the delivery of bNAbs has made significant progress. DNA-encoded monoclonal antibodies (DMAbs) have shown great promise in animal models of disease and the underlying DNA-based technology is now being tested in vaccine trials for a variety of indications. The COVID-19 pandemic greatly accelerated the development of mRNA-based technology to induce protective immunity. These advances are now being successfully applied to the delivery of monoclonal antibodies using mRNA in animal models. Delivery of bNAbs using viral vectors, primarily adeno-associated virus (AAV), has shown great promise in preclinical animal models and more recently in human studies. Most recently, advances in genome editing techniques have led to engineering of monoclonal antibody expression from B cells. These efforts aim to turn B cells into a source of evolving antibodies that can improve through repeated exposure to the respective antigen. SUMMARY: The use of these different platforms for antibody delivery has been demonstrated across a wide range of animal models and disease indications, including HIV. Although each approach has unique strengths and weaknesses, additional advances in efficiency of gene delivery and reduced immunogenicity will be necessary to drive widespread implementation of these technologies. Considering the mounting clinical evidence of the potential of bNAbs for HIV treatment and prevention, overcoming the remaining technical challenges for gene-based bNAb delivery represents a relatively straightforward path towards practical interventions against HIV infection.

Policy-relevant differences between secondhand and thirdhand smoke: strengthening protections from involuntary exposure to tobacco smoke pollutants.

Starting in the 1970s, individuals, businesses and the public have increasingly benefited from policies prohibiting smoking indoors, saving thousands of lives and billions of dollars in healthcare expenditures. Smokefree policies to protect against secondhand smoke exposure, however, do not fully protect the public from the persistent and toxic chemical residues from tobacco smoke (also known as thirdhand smoke) that linger in indoor environments for years after smoking stops. Nor do these policies address the economic costs that individuals, businesses and the public bear in their attempts to remediate this toxic residue. We discuss policy-relevant differences between secondhand smoke and thirdhand smoke exposure: persistent pollutant reservoirs, pollutant transport, routes of exposure, the time gap between initial cause and effect, and remediation and disposal. We examine four policy considerations to better protect the public from involuntary exposure to tobacco smoke pollutants from all sources. We call for (a) redefining smokefree as free of tobacco smoke pollutants from secondhand and thirdhand smoke; (b) eliminating exemptions to comprehensive smoking bans; (c) identifying indoor environments with significant thirdhand smoke reservoirs; and (d) remediating thirdhand smoke. We use the case of California as an example of how secondhand smoke-protective laws may be strengthened to encompass thirdhand smoke protections. The health risks and economic costs of thirdhand smoke require that smokefree policies, environmental protections, real estate and rental disclosure policies, tenant protections, and consumer protection laws be strengthened to ensure that the public is fully protected from and informed about the risks of thirdhand smoke exposure.

Remediation of Thirdhand Tobacco Smoke with Ozone: Probing Deep Reservoirs in Carpets.

We assessed the efficacy of ozonation as an indoor remediation strategy by evaluating how a carpet serves as a sink and long-term source of thirdhand tobacco smoke (THS) while protecting contaminants absorbed in deep reservoirs by scavenging ozone. Specimens from unused carpet that was exposed to smoke in the lab ("fresh THS") and contaminated carpets retrieved from smokers' homes ("aged THS") were treated with 1000 ppb ozone in bench-scale tests. Nicotine was partially removed from fresh THS specimens by volatilization and oxidation, but it was not significantly eliminated from aged THS samples. By contrast, most of the 24 polycyclic aromatic hydrocarbons detected in both samples were partially removed by ozone. One of the home-aged carpets was installed in an 18 m3 room-sized chamber, where its nicotine emission rate was 950 ng day-1 m-2. In a typical home, such daily emissions could amount to a non-negligible fraction of the nicotine released by smoking one cigarette. The operation of a commercial ozone generator for a total duration of 156 min, reaching concentrations up to 10,000 ppb, did not significantly reduce the carpet nicotine loading (26-122 mg m-2). Ozone reacted primarily with carpet fibers, rather than with THS, leading to short-term emissions of aldehydes and aerosol particles. Hence, by being absorbed deeply into carpet fibers, THS constituents can be partially shielded from ozonation.

Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults.

BACKGROUND: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. METHODS: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. FINDINGS: Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p < 0.0001; Geometric mean titer p = 0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4+ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4+ T lymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found. INTERPRETATION: Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4+T cell response may confer protection against the Omicron variant. FUNDING: The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy.

What a mix! Volatile organic compounds and worker exposure in small business beauty salons in Tucson, Arizona.

Introduction: Small business beauty salons have volatile organic compounds (VOCs) in their workplace air. VOCs are present as ingredients in beauty or hair products. They may also form because of chemical reactions, where thermal-styling elements accelerate the volatilization of these compounds. Uncertainties remain about the relationship between air pollutant concentrations and the variety of beauty salon activities in a work shift. Investigating these associations can help determine high-risk services, associated products, and at-risk workers. Methods: In this exploratory study, female community health workers recruited beauty salons from target zip codes in predominately Latino neighborhoods, including primarily Spanish-speaking small businesses. We collected salon chemical inventories, business characteristics, and participant activity logs to understand how chemicals and activities influence the total and specific VOC concentrations. We sampled personal total VOCs and specific VOCs from the same shop during the participant work shift. We also measured personal total VOCs for four work shifts per shop. Results: A linear mixed effects model of log VOCs on the fixed effect of activity and the random effects of salon and shift within the salon showed that the variance between salons explains over half (55%) of the total variance and is 4.1 times bigger than for shifts within salons. Summa canisters detected 31 specific VOCs, and hazard scores ranged between 0 and 4.3. 2-Propanol (isopropyl alcohol) was the only VOC detected in all shifts of all salons. Discussion: In this study, differences in VOC measurements were primarily between salons. These differences may result from differences in ventilation, services rendered, and product lines applied.

Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial.

Background: The development of vaccines to control the coronavirus disease 2019 (COVID-19) pandemic progression is a worldwide priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. Methods: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac separated by 2 (0-14 schedule) or 4 weeks (0-28 schedule); 2302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. Results: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern (VOCs) between schedules. Stimulation of peripheral blood mononuclear cells (PBMCs) with Mega pools of Peptides (MPs) induced the secretion of interferon (IFN)-γ and the expression of activation induced markers in CD4+ T cells for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-γ secretion. Conclusions: Immunization with CoronaVac in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. Funding: Ministry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. Clinical trial number: NCT04651790.

SARS-CoV-2 vaccine booster in solid organ transplant recipients previously immunised with inactivated versus mRNA vaccines: A prospective cohort study.

Background: Solid-organ transplant (SOT) recipients have worse COVID-19 outcomes than general population and effective immunisation in these patients is essential but more difficult to reach. We aimed to determine the immunogenicity of an mRNA SARS-CoV-2 vaccine booster in SOT recipients previously immunised with either inactivated or homologous SARS-CoV-2 mRNA vaccine. Methods: Prospective cohort study of SOT recipients under medical care at Red de Salud UC-CHRISTUS, Chile, previously vaccinated with either CoronaVac or BNT162b2. All participants received a BNT162b2 vaccine booster. The primary study end point was anti-SARS-CoV-2 total IgG antibodies (TAb) seropositivity at 8-12 weeks (56-84 days) post booster. Secondary end points included neutralising antibodies (NAb) and specific T-cell responses. Findings: A total of 140 (50% kidney, 38% liver, 6% heart) SOT recipients (mean age 54 [13.6] years; 64 [46%] women) were included. Of them, 62 had homologous (three doses of BNT162b2) and 78 heterologous vaccine schedules (two doses of CoronaVac followed by BNT162b2 booster). Boosters were received at a median of 21.3 weeks after primary vaccination. The proportion achieving TAb seropositivity (82.3% vs 65.4%, P = 0.035) and NAb positivity (77.4% vs 55.1%, P = 0.007) were higher for the homologous versus the heterologous group. On the other hand, the number of IFN-γ and IL-2 secreting SARS-CoV-2-specific T-cells did not differ significantly between groups. Interpretation: This cohort study shows that homologous mRNA vaccine priming plus boosting in SOT recipients, reaches a significantly higher humoral immune response than inactivated SARS-CoV-2 vaccine priming followed by heterologous mRNA booster. Funding: School of Medicine, UC-Chile and ANID.ClinicalTrials.gov ID: NCT05124509.

A Booster Dose of CoronaVac Increases Neutralizing Antibodies and T Cells that Recognize Delta and Omicron Variants of Concern.

CoronaVac is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization (WHO). Previous studies reported increased levels of neutralizing antibodies and specific T cells 2 and 4 weeks after two doses of CoronaVac; these levels were significantly reduced at 6 to 8 months after the two doses. Here, we report the effect of a booster dose of CoronaVac on the anti-SARS-CoV-2 immune response generated against the variants of concern (VOCs), Delta and Omicron, in adults participating in a phase III clinical trial in Chile. Volunteers immunized with two doses of CoronaVac in a 4-week interval received a booster dose of the same vaccine between 24 and 30 weeks after the second dose. Neutralization capacities and T cell activation against VOCs Delta and Omicron were assessed 4 weeks after the booster dose. We observed a significant increase in neutralizing antibodies 4 weeks after the booster dose. We also observed a rise in anti-SARS-CoV-2-specific CD4+ T cells over time, and these cells reached a peak 4 weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2-specific T cells induced by the booster showed activity against VOCs Delta and Omicron. Our results show that a booster dose of CoronaVac increases adults' humoral and cellular anti-SARS-CoV-2 immune responses. In addition, immunity induced by a booster dose of CoronaVac is active against VOCs, suggesting adequate protection. IMPORTANCE CoronaVac is an inactivated vaccine against SARS-CoV-2 that has been approved by WHO for emergency use. Phase III clinical trials are in progress in several countries, including China, Brazil, Turkey, and Chile, and have shown safety and immunogenicity after two doses of the vaccine. This report characterizes immune responses induced by two doses of CoronaVac followed by a booster dose 5 months after the second dose in healthy Chilean adults. The data reported here show that a booster dose increased the immune responses against SARS-CoV-2, enhancing levels of neutralizing antibodies against the ancestral strain and VOCs. Similarly, anti-SARS-CoV-2 CD4+ T cell responses were increased following the booster dose. In contrast, levels of gamma interferon secretion and T cell activation against the VOCs Delta and Omicron were not significantly different from those for the ancestral strain. Therefore, a third dose of CoronaVac in a homologous vaccination schedule improves its immunogenicity in healthy volunteers.

Hand nicotine as an independent marker of thirdhand smoke pollution in children's environments.

BACKGROUND: Hand nicotine (HN) levels measure children's exposure to tobacco smoke pollutants from thirdhand and secondhand smoke. HN is associated with urinary and salivary cotinine, but the associations of HN with other tobacco smoke exposure (TSE) markers remain unknown. OBJECTIVES: We compared levels of HN and four urinary TSE biomarkers: cotinine, trans-3'-hydroxycotinine (3HC), nicotelline N-oxides, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and children's sociodemographic and TSE patterns. We also examined if HN is a plausible pathway for children's exposure to active smoking. METHODS: Data were collected from 175 non-smoking patients (Mean (SD) age = 5.4 (3.4) years) who lived with ≥1 cigarette smoker(s). HN and TSE biomarker levels were determined using LC-MS/MS. Multivariate and multivariable regression analyses were conducted to examine associations between TSE markers and parent-reported measures, controlling for sociodemographics. RESULTS: Of the five markers of TSE, cotinine (R2 = 0.221; p = 0.003) and HN (R2 = 0.247; p = 0.001) showed the strongest overall associations. Of the five markers, only cotinine showed significantly higher levels among Black children (ß^=0.307,p<0.05) independent of age, reported exposure, and home smoking bans. Cotinine (ß^=0.010,p<0.05), NNAL (ß^=0.012,p<0.05), and HN (ß^=0.011,p<0.05) showed significant positive associations with reported exposure independent of race, age, and home smoking bans. NNAL (ß^=-0.285,p<0.05) and HN (ß^=-0.336,p<0.05), but not cotinine, 3HC, and N-oxides, showed significantly lower levels among children who lived in homes with smoking bans. Child age, hand surface area, home smoking ban, and reported exposure independently accounted for 21 % of the variance in HN levels (p = 0.002). HN accounted for 30 % of the variance in cotinine independent of child race and child age. DISCUSSION: HN levels were associated with modifiable tobacco-related behaviors and shows promise as a marker of sources of THS pollution in a child's environment not captured by measurement of urinary cotinine alone. HN levels provide additional information about TSE, complementing other biomarkers when assessing children's overall TSE.

Safety and Non-Inferiority Evaluation of Two Immunization Schedules with an Inactivated SARS-CoV-2 Vaccine in Adults: A Randomized Clinical Trial.

Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac®, an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity, preventing severe COVID-19 cases. We investigate the safety and non-inferiority of two immunization schedules of CoronaVac® in a non-inferiority trial in healthy adults. A total of 2302 healthy adults were enrolled at 8 centers in Chile and randomly assigned to two vaccination schedules, receiving two doses with either 14 or 28 days between each. The primary safety and efficacy endpoints were solicited adverse events (AEs) within 7 days of each dose, and comparing the number of cases of SARS-CoV-2 infection 14 days after the second dose between the schedules, respectively. The most frequent local AE was pain at the injection site, which was less frequent in participants aged ≥60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. Most AEs were mild and transient. There were no significant differences for local and systemic AEs between schedules. A total of 58 COVID-19 cases were confirmed, and all but 2 of them were mild. No differences were observed in the proportion of COVID-19 cases between schedules. CoronaVac® is safe, especially in ≥60-year-old participants. Both schedules protected against COVID-19 hospitalization.

BCG-Based Vaccines Elicit Antigen-Specific Adaptive and Trained Immunity against SARS-CoV-2 and Andes orthohantavirus.

Background:Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a live attenuated vaccine mainly administered to newborns and used for over 100 years to prevent the disease caused by Mycobacterium tuberculosis (M. tb). This vaccine can induce immune response polarization towards a Th1 profile, which is desired for counteracting M. tb, other mycobacteria, and unrelated intracellular pathogens. The vaccine BCG has been used as a vector to express recombinant proteins and has been shown to protect against several diseases, particularly respiratory viruses. Methods: BCG was used to develop recombinant vaccines expressing either the Nucleoprotein from SARS-CoV-2 or Andes orthohantavirus. Mice were immunized with these vaccines with the aim of evaluating the safety and immunogenicity parameters. Results: Immunization with two doses of 1 × 108 CFU or one dose of 1 × 105 CFU of these BCGs was safe in mice. A statistically significant cellular immune response was induced by both formulations, characterized as the activation of CD4+ and CD8+ T cells. Stimulation with unrelated antigens resulted in increased expression of activation markers by T cells and secretion of IL-2 and IFN-γ, while increased secretion of IL-6 was found for both recombinant vaccines; all of these parameters related to a trained immunity profile. The humoral immune response elicited by both vaccines was modest, but further exposure to antigens could increase this response. Conclusions: The BCG vaccine is a promising platform for developing vaccines against different pathogens, inducing a marked antigen-specific immune response.

A booster dose of an inactivated SARS-CoV-2 vaccine increases neutralizing antibodies and T cells that recognize Delta and Omicron variants of concern.

Background: CoronaVac ® is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization. Previous studies reported increased levels of neutralizing antibodies and specific T cells two- and four-weeks after two doses of CoronaVac ® , but the levels of neutralizing antibodies are reduced at six to eight months after two doses. Here we report the effect of a booster dose of CoronaVac ® on the anti-SARS-CoV-2 immune response generated against variants of concern (VOC) Delta and Omicron in adults participating in a phase 3 clinical trial in Chile. Methods: Volunteers immunized with two doses of CoronaVac ® in a four-week interval received a booster dose of the same vaccine between twenty-four and thirty weeks after the 2nd dose. Four weeks after the booster dose, neutralizing antibodies and T cell responses were measured. Neutralization capacities and T cell activation against VOC Delta and Omicron were detected at four weeks after the booster dose. Findings: We observed a significant increase in neutralizing antibodies at four weeks after the booster dose. We also observed an increase in CD4 + T cells numbers over time, reaching a peak at four weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2 specific T cells induced by the booster showed activity against VOC Delta and Omicron. Interpretation: Our results show that a booster dose of CoronaVac ® increases the anti-SARS-CoV-2 humoral and cellular immune responses in adults. Immunity induced by a booster dose of CoronaVac ® is active against VOC, suggesting an effective protection.

Sampling Low Air Pollution Concentrations at a Neighborhood Scale in a Desert U.S. Metropolis with Volatile Weather Patterns.

BACKGROUND: Neighborhood-scale air pollution sampling methods have been used in a range of settings but not in low air pollution airsheds with extreme weather events such as volatile precipitation patterns and extreme summer heat and aridity-all of which will become increasingly common with climate change. The desert U.S. metropolis of Tucson, AZ, has historically low air pollution and a climate marked by volatile weather, presenting a unique opportunity. METHODS: We adapted neighborhood-scale air pollution sampling methods to measure ambient NO2, NOx, and PM2.5 and PM10 in Tucson, AZ. RESULTS: The air pollution concentrations in this location were well below regulatory guidelines and those of other locations using the same methods. While NO2 and NOx were reliably measured, PM2.5 measurements were moderately correlated with those from a collocated reference monitor (r = 0.41, p = 0.13), potentially because of a combination of differences in inlet heights, oversampling of acutely high PM2.5 events, and/or pump operation beyond temperature specifications. CONCLUSION: As the climate changes, sampling methods should be reevaluated for accuracy and precision, especially those that do not operate continuously. This is even more critical for low-pollution airsheds, as studies on low air pollution concentrations will help determine how such ambient exposures relate to health outcomes.