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AIMS AND OBJECTIVES: To study the effects of virtual reality (VR) on pain perception among a paediatric population while being vaccinated. We will also investigate the effects of VR on the fear experienced by children during the vaccination procedure, as well as parental satisfaction levels. BACKGROUND: Many studies, for example, in the fields of oncology, dermatology or plastic surgery, have described the benefits of using VR to reduce the perception of pain among paediatric populations. These results are encouraging, but their main limitations were the small sample sizes they included or their methodological design. DESIGN: This will be a randomised clinical trial. METHODS: SPIRIT guidelines were followed to report this protocol, and we will use the CONSORT and CONSORT-EHEALTH guidelines to report the randomised clinical trial. The sample will comprise 148 children aged 3-14 years who will come for vaccination at the Tres Forques Health Center. The participants will be randomly allocated into intervention group (VR; n = 74) or (the control group standard-of-care; n = 74) at a 1:1 ratio. The intervention group will view experiences with a VR headset as a distraction measure. The study variables will be the level of pain and fear perceived by the child during vaccination, parental satisfaction with the vaccination procedure, and sociodemographic and vaccination variables. RESULTS: The start of the study is planned for September 2020, and the results will be expected in September 2021. CONCLUSIONS: This study aims to identify what measures reduce pain and fear in children during vaccination, which in turn, can help to improve the degree of parental satisfaction with these procedures. RELEVANCE TO CLINICAL PRACTICE: Vaccination is an independent function of the nursing profession. Identifying which distraction measures reduce the perception of pain and fear in the paediatric population will not only improve children's experiences but will also improve the satisfaction of both parents and children, thus increasing the degree of compliance with the vaccination schedule.
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AIMS AND OBJECTIVES: To determine the effect of immersive virtual reality (VR) on perceived pain and fear in children during vaccination and parental satisfaction with the procedure. BACKGROUND: Virtual reality can reduce the perception of pain by children but only three studies have analysed its use during vaccination to date; these had small sample sizes and imperfect methodological designs. DESIGN: A randomised controlled clinical trial. METHODS: One hundred and sixty participants from the Tres Forques Health Center were randomly assigned to the intervention group (IG) (n = 82) in which distraction with immersive VR was used during the vaccination, while standard distraction techniques were used for the control group (n = 80). The primary outcome was pain (Wong-Baker FACES). Secondary outcomes included (Children's Fear Scale) and parental satisfaction with the vaccination procedure. Chi-squared tests were used for qualitative variables, relationships between quantitative variables were tested with Spearman correlations, and Mann-Whitney U- or Student t-tests were employed to assess the relationship between quantitative and qualitative variables. RESULTS: Compared to the controls, the children in the IG reported significantly less pain and fear, while parental satisfaction was significantly higher. Reported pain and fear did not differ according to the sex of the patient. Child age was not linked to fear but was related to pain: the younger the patient, the greater the pain they described. CONCLUSIONS: Immersive VR effectively controlled pain and fear in children during vaccination and increased parent satisfaction with the vaccination process. Patient sex did not influence the level of pain and fear but age did. RELEVANCE TO CLINICAL PRACTICE: Improving vaccination experiences can reduce perceived pain and fear in children and increase parent satisfaction, thereby enhancing vaccination schedule adherence and improving group immunity. REPORTING METHOD: The CONSORT Statement for non-pharmacological randomised clinical trials were followed.
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Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence is used to estimate the proportion of individuals within a population previously infected, to track viral transmission, and to monitor naturally and vaccine-induced immune protection. However, in sub-Saharan African settings, antibodies induced by higher exposure to pathogens may increase unspecific seroreactivity to SARS-CoV-2 antigens, resulting in false positive responses. To investigate the level and type of unspecific seroreactivitiy to SARS-CoV-2 in Africa, we measured immunoglobulin G (IgG), IgA, and IgM to a broad panel of antigens from different pathogens by Luminex in 602 plasma samples from African and European subjects differing in coronavirus disease 2019, malaria, and other exposures. Seroreactivity to SARS-CoV-2 antigens was higher in prepandemic African than in European samples and positively correlated with antibodies against human coronaviruses, helminths, protozoa, and especially Plasmodium falciparum. African subjects presented higher levels of autoantibodies, a surrogate of polyreactivity, which correlated with P. falciparum and SARS-CoV-2 antibodies. Finally, we found an improved sensitivity in the IgG assay in African samples when using urea as a chaotropic agent. In conclusion, our data suggest that polyreactive antibodies induced mostly by malaria are important mediators of the unspecific anti-SARS-CoV-2 responses, and that the use of dissociating agents in immunoassays could be useful for more accurate estimates of SARS-CoV-2 seroprevalence in African settings.
Subject(s)
Antibodies, Viral , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/epidemiology , Antibodies, Viral/blood , Seroepidemiologic Studies , SARS-CoV-2/immunology , Immunoglobulin G/blood , Adult , Male , Female , Middle Aged , Malaria/epidemiology , Malaria/immunology , Malaria/blood , Immunoglobulin M/blood , Young Adult , Aged , Adolescent , Europe/epidemiology , Immunoglobulin A/blood , Endemic Diseases , Africa/epidemiology , Africa South of the Sahara/epidemiologyABSTRACT
Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease affecting motor neurons. Pathological forms of Tar-DNA binding protein-43 (TDP-43), involving its mislocalisation to the cytoplasm and the formation of misfolded inclusions, are present in almost all ALS cases (97%), and ~ 50% cases of the related condition, frontotemporal dementia (FTD), highlighting its importance in neurodegeneration. Previous studies have shown that endoplasmic reticulum protein 57 (ERp57), a member of the protein disulphide isomerase (PDI) family of redox chaperones, is protective against ALS-linked mutant superoxide dismutase (SOD1) in neuronal cells and transgenic SOD1G93A mouse models. However, it remains unclear whether ERp57 is protective against pathological TDP-43 in ALS. Here, we demonstrate that ERp57 is protective against key features of TDP-43 pathology in neuronal cells. ERp57 inhibited the mislocalisation of TDP-43M337V from the nucleus to the cytoplasm. In addition, ERp57 inhibited the number of inclusions formed by ALS-associated variant TDP-43M337V and reduced the size of these inclusions. ERp57 was also protective against ER stress and induction of apoptosis. Furthermore, ERp57 modulated the steady-state expression levels of TDP-43. This study therefore demonstrates a novel mechanism of action of ERp57 in ALS. It also implies that ERp57 may have potential as a novel therapeutic target to prevent the TDP-43 pathology associated with neurodegeneration.
Subject(s)
Amyotrophic Lateral Sclerosis , DNA-Binding Proteins , Inclusion Bodies , Protein Disulfide-Isomerases , Protein Disulfide-Isomerases/genetics , Protein Disulfide-Isomerases/metabolism , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Humans , Inclusion Bodies/metabolism , Inclusion Bodies/genetics , Animals , Mice , Cell Nucleus/metabolism , Cytoplasm/metabolism , Neurons/metabolism , Neurons/drug effects , Superoxide Dismutase-1/genetics , MutationABSTRACT
Hexanucleotide repeat expansions (HREs) in the chromosome 9 open reading frame 72 (C9orf72) gene are the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both are debilitating neurodegenerative conditions affecting either motor neurons (ALS) in the brain and spinal cord or neurons in the frontal and/or temporal cortical lobes (FTD). HREs undergo repeat-associated non-ATG (RAN) translation on both sense and anti-sense strands, generating five distinct dipeptide repeat proteins (DPRs), poly-GA, -GR, -GP, -PA and -PR. Perturbed proteostasis is well-recognised in ALS pathogenesis, including processes affecting the endoplasmic reticulum (ER) and Golgi compartments. However, these mechanisms have not been well characterised for C9orf72-mediated ALS/FTD. In this study we demonstrate that C9orf72 DPRs polyGA, polyGR and polyGP (× 40 repeats) disrupt secretory protein transport from the ER to the Golgi apparatus in neuronal cells. Consistent with this finding, these DPRs also induce fragmentation of the Golgi apparatus, activate ER stress, and inhibit the formation of the omegasome, the precursor of the autophagosome that originates from ER membranes. We also demonstrate Golgi fragmentation in cells undergoing RAN translation that express polyGP. Furthermore, dysregulated ER-Golgi transport was confirmed in C9orf72 patient dermal fibroblasts. Evidence of aberrant ER-derived vesicles in spinal cord motor neurons from C9orf72 ALS patients compared to controls was also obtained. These data thus confirm that ER proteostasis and ER-Golgi transport is perturbed in C9orf72-ALS in the absence of protein over-expression. Hence this study identifies novel molecular mechanisms associated with the ER and Golgi compartments induced by the C9orf72 HRE.
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BACKGROUND: The impact of thrombolytics directed towards different thrombus components regarding site of occlusion in combination with mechanical thrombectomy (MT) to achieve endovascular complete recanalization is unclear. METHODS: Retrospective analysis of a prospective database in two stroke centers. Intracranial thrombi retrieved by MT were analyzed using hematoxylin-eosin staining for fibrin and red blood cell proportions, and CD61 immunostaining for platelets proportion in thrombus (PLTPT) assessment. Thrombi composition, baseline variables, etiology, treatment features and occlusion location were analyzed. RESULTS: Overall, 221 patients completed the per protocol analysis and 110 cases achieved a final expanded Thrombolysis in Cerebral Infarction (eTICI) 3 (49%) of which 70 were MT (32%) by first pass effect (FPE). Thrombi from medium distal vessel occlusions had higher PLTPT compared with thrombi from proximal large vessel occlusions (68% vs 61%, P=0.026). In particular, middle cerebral artery M2-M3 segment thrombi had the highest PLTPT (70%), and basilar artery thrombi the lowest PLTPT (41%). After logistic regression analysis adjusted for occlusion location and intravenous fibrinolysis, lower baseline National Institutes of Health Stroke Scale score (adjusted OR (aOR) 0.95, 95% CI 0.913 to 0.998) and PLTPT (aOR 0.97, 95% CI 0.963 to 0.993) were independently associated with FPE. Fewer MT passes (aOR 0.67, 95% CI 0.538 to 0.842) and platelet poor thrombus (<62% PLTPT; aOR 2.39, 95% CI 1.288 to 4.440) were independently associated with final eTICI 3. CONCLUSIONS: Occlusion location might be a surrogate parameter for thrombus composition. Platelet poor clots and fewer MT passes were independently associated with complete endovascular recanalization. Clinical trials testing the benefits of combining selective intra-arterial platelet antagonists with MT to improve endovascular outcomes are warranted.
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Holographic lenses (HLs) are part of holographic optical elements (HOE), and are being applied to concentrate solar energy on a focal point or focal line. In this way, the concentrated energy can be converted into electrical or thermal energy by means of a photovoltaic cell or a thermal absorber tube. HLs are able to passively track the apparent motion of the sun with a high acceptance angle, allowing tracking motors to be replaced, thus reducing the cost of support structures. This article focuses on a review of the materials used in the recording of a holographic lens (HL) or multiple HLs in photovoltaic and/or concentrating solar collectors. This review shows that the use of photopolymers for the recording of HLs enables high-performance efficiency in physical systems designed for energy transformation, and presents some important elements to be taken into account for future designs, especially those related to the characteristics of the HL recording materials. Finally, the article outlines future recommendations, emphasizing potential research opportunities and challenges for researchers entering the field of HL-based concentrating solar photovoltaic and/or concentrating solar thermal collectors.
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BACKGROUND: The emergence of new SARS-CoV-2 variants and the waning of immunity raise concerns about vaccine effectiveness and protection against COVID-19. While antibody response has been shown to correlate with the risk of infection with the original variant and earlier variants of concern, the effectiveness of antibody-mediated protection against Omicron and the factors associated with protection remain uncertain. METHODS: We evaluated antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from Wuhan and variants of concern by Luminex and their role in preventing breakthrough infections 1 year after a third dose of mRNA vaccination, in a cohort of health care workers followed since the pandemic onset in Spain (N = 393). Data were analyzed in relation to COVID-19 history, demographic factors, comorbidities, vaccine doses, brand, and adverse events. RESULTS: Higher levels of anti-S IgG and IgA to Wuhan, Delta, and Omicron were associated with protection against vaccine breakthroughs (IgG against Omicron S antigen HR, 0.06, 95%CI, 0.26-0.01). Previous SARS-CoV-2 infection was positively associated with antibody levels and protection against breakthroughs, and a longer time since last infection was associated with lower protection. In addition, priming with BNT162b2 followed by mRNA-1273 booster was associated with higher antibody responses than homologous mRNA-1273 vaccination. CONCLUSIONS: Data show that IgG and IgA induced by vaccines against the original strain or by hybrid immunization are valid correlates of protection against Omicron BA.1 despite immune escape and support the benefits of heterologous vaccination regimens to enhance antibodies and the prioritization of booster vaccination in individuals without recent infections.
Subject(s)
COVID-19 , Humans , COVID-19/prevention & control , 2019-nCoV Vaccine mRNA-1273 , SARS-CoV-2 , BNT162 Vaccine , Breakthrough Infections , Vaccination , Immunoglobulin A , Immunoglobulin G , Antibodies, ViralABSTRACT
The RTS,S/AS02A malaria vaccine is based on the Plasmodium falciparum circumsporozoite protein (PfCSP), which is O-fucosylated on the sporozoite surface. We determined whether RTS,S/AS02A-induced immunoglobulin G (IgG) antibodies recognize vaccine-like nonfucosylated PfCSP better than native-like fucosylated PfCSP. Similar to previous vaccine trials, RTS,S/AS02A vaccination induced high anti-PfCSP IgG levels associated with malaria protection. IgG recognition of nonfucosylated and fucosylated PfCSP was equivalent, suggesting that PfCSP fucosylation does not affect antibody recognition. Clinical Trials Registration. NCT00197041.
Subject(s)
Malaria Vaccines , Malaria, Falciparum , Humans , Plasmodium falciparum , Malaria, Falciparum/prevention & control , Immunoglobulin G , Antibodies, Protozoan , Protozoan ProteinsABSTRACT
PURPOSE: Many patients with acute coronary syndrome experience problematic or altered sexual function. This aspect of the disease is frequently ignored or overlooked by the healthcare community even though it can strongly influence health-related patient quality of life (HRQoL). Thus, the aim of this study was to compare the effects of a specific cardiac rehabilitation programme focused on aerobic and neuromuscular strength-resistance training to those of a classic rehabilitation programme, both in terms of HRQoL and erectile dysfunction in patients with acute coronary syndrome. METHODS: This study reports both secondary and unregistered outcomes from a double-blinded, randomised, and controlled clinical trial. The proposed intervention was based on the completion of a 20-session (10-week) cardiac rehabilitation programme for patients with cardiovascular disease. The patient cohort had been diagnosed with acute coronary syndrome and was recruited at the Cardiology Service of a private tertiary hospital. The outcomes assessed in this study were HRQoL and erectile disfunction assessed at baseline, after the intervention, and at a 6-month follow-up. RESULTS: A total of 30 participants were randomly allocated to each study arm. The results of the two-way mixed ANOVAs showed significant group × time interactions for all the outcome measures (EQ-5D_index, p = 0.004; EQ-5D_VAS, p = 0.017; QLMI-Q, p ≤ 0.001; and IIEF-5, p = 0.001). CONCLUSION: The neuromuscular strength training programme was more effective than the classic strength training programme in terms of increasing the HRQoL and improving erectile dysfunction in patients following acute coronary syndrome, with differences still remaining between these groups at the 6-month follow-up.
Subject(s)
Acute Coronary Syndrome , Cardiac Rehabilitation , Erectile Dysfunction , Resistance Training , Sexual Dysfunction, Physiological , Male , Humans , Quality of Life/psychology , Resistance Training/methodsABSTRACT
Amyotrophic lateral sclerosis (ALS) is a severely debilitating neurodegenerative condition that is part of the same disease spectrum as frontotemporal dementia (FTD). Mutations in the CCNF gene, encoding cyclin F, are present in both sporadic and familial ALS and FTD. However, the pathophysiological mechanisms underlying neurodegeneration remain unclear. Proper functioning of the endoplasmic reticulum (ER) and Golgi apparatus compartments is essential for normal physiological activities and to maintain cellular viability. Here, we demonstrate that ALS/FTD-associated variant cyclin FS621G inhibits secretory protein transport from the ER to Golgi apparatus, by a mechanism involving dysregulation of COPII vesicles at ER exit sites. Consistent with this finding, cyclin FS621G also induces fragmentation of the Golgi apparatus and activates ER stress, ER-associated degradation, and apoptosis. Induction of Golgi fragmentation and ER stress were confirmed with a second ALS/FTD variant cyclin FS195R, and in cortical primary neurons. Hence, this study provides novel insights into pathogenic mechanisms associated with ALS/FTD-variant cyclin F, involving perturbations to both secretory protein trafficking and ER-Golgi homeostasis.
Subject(s)
Amyotrophic Lateral Sclerosis , Frontotemporal Dementia , Humans , Amyotrophic Lateral Sclerosis/metabolism , Frontotemporal Dementia/genetics , Frontotemporal Dementia/metabolism , Endoplasmic Reticulum-Associated Degradation , Endoplasmic Reticulum/metabolism , Golgi Apparatus/metabolism , Mutation , Cyclins/metabolismABSTRACT
We use a hybrid superconductor-semiconductor transmon device to perform spectroscopy of a quantum dot Josephson junction tuned to be in a spin-1/2 ground state with an unpaired quasiparticle. Because of spin-orbit coupling, we resolve two flux-sensitive branches in the transmon spectrum, depending on the spin of the quasiparticle. A finite magnetic field shifts the two branches in energy, favoring one spin state and resulting in the anomalous Josephson effect. We demonstrate the excitation of the direct spin-flip transition using all-electrical control. Manipulation and control of the spin-flip transition enable the future implementation of charging energy protected Andreev spin qubits.
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In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study (N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP142, and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood.
Subject(s)
Malaria, Falciparum , Malaria , Child , Infant , Infant, Newborn , Humans , Child, Preschool , Female , Pregnancy , Plasmodium falciparum , Cohort Studies , Burkina Faso/epidemiology , Maternal Exposure , Placenta , Antibodies, Protozoan , Malaria/epidemiology , Immunoglobulin G , Antigens, ProtozoanABSTRACT
OBJECTIVE: To investigate the specific and combined effects of personal concentrations of some per- and polyfluoroalkyl substances (PFAS), other persistent organic pollutants (POPs), and chemical elements -measured in individuals' blood several years before the pandemic- on the development of SARS-CoV-2 infection and COVID-19 disease in the general population. METHODS: We conducted a prospective cohort study in 240 individuals from the general population of Barcelona. PFAS, other POPs, and chemical elements were measured in plasma, serum, and whole blood samples, respectively, collected in 2016-2017. PFAS were analyzed by liquid chromatography-triple quadrupole mass spectrometry. SARS-CoV-2 infection was detected by rRT-PCR in nasopharyngeal swabs and/or antibody serology in blood samples collected in 2020-2021. RESULTS: No individual PFAS nor their mixtures were significantly associated with SARS-CoV-2 seropositivity or COVID-19 disease. Previously identified mixtures of POPs and elements (Porta et al., 2023) remained significantly associated with seropositivity and COVID-19 when adjusted for PFAS (all OR > 4 or p < 0.05). Nine chemicals comprised mixtures associated with COVID-19: thallium, ruthenium, lead, benzo[b]fluoranthene, DDD, other DDT-related compounds, manganese, tantalum, and aluminium. And nine chemicals comprised the mixtures more consistently associated with SARS-CoV-2 seropositivity: thallium, ruthenium, lead, benzo[b]fluoranthene, DDD, gold, and (protectively) selenium, indium, and iron. CONCLUSIONS: The PFAS studied were not associated with SARS-CoV-2 seropositivity or COVID-19. The results confirm the associations between personal blood concentrations of some POPs and chemical elements and the risk of COVID-19 and SARS-CoV-2 infection in what remains the only prospective and population-based cohort study on the topic. Mixtures of POPs and chemical elements may contribute to explain the heterogeneity in the risks of SARS-CoV-2 infection and COVID-19 in the general population.
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BACKGROUND: Ambient air pollution has been associated with COVID-19 disease severity and antibody response induced by infection. OBJECTIVES: We examined the association between long-term exposure to air pollution and vaccine-induced antibody response. METHODS: This study was nested in an ongoing population-based cohort, COVICAT, the GCAT-Genomes for Life cohort, in Catalonia, Spain, with multiple follow-ups. We drew blood samples in 2021 from 1,090 participants of 2,404 who provided samples in 2020, and we included 927 participants in this analysis. We measured immunoglobulin M (IgM), IgG, and IgA antibodies against five viral-target antigens, including receptor-binding domain (RBD), spike-protein (S), and segment spike-protein (S2) triggered by vaccines available in Spain. We estimated prepandemic (2018-2019) exposure to fine particulate matter [PM ≤2.5µm in aerodynamic diameter (PM2.5)], nitrogen dioxide (NO2), black carbon (BC), and ozone (O3) using Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) models. We adjusted estimates for individual- and area-level covariates, time since vaccination, and vaccine doses and type and stratified by infection status. We used generalized additive models to explore the relationship between air pollution and antibodies according to days since vaccination. RESULTS: Among vaccinated persons not infected by SARS-CoV-2 (n=632), higher prepandemic air pollution levels were associated with a lower vaccine antibody response for IgM (1 month post vaccination) and IgG. Percentage change in geometric mean IgG levels per interquartile range of PM2.5 (1.7 µg/m3) were -8.1 (95% CI: -15.9, 0.4) for RBD, -9.9 (-16.2, -3.1) for S, and -8.4 (-13.5, -3.0) for S2. We observed a similar pattern for NO2 and BC and an inverse pattern for O3. Differences in IgG levels by air pollution levels persisted with time since vaccination. We did not observe an association of air pollution with vaccine antibody response among participants with prior infection (n=295). DISCUSSION: Exposure to air pollution was associated with lower COVID-19 vaccine antibody response. The implications of this association on the risk of breakthrough infections require further investigation. https://doi.org/10.1289/EHP11989.
Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Humans , Air Pollutants/analysis , COVID-19 Vaccines , Spain , Antibody Formation , Environmental Exposure/analysis , SARS-CoV-2 , Air Pollution/analysis , Particulate Matter/analysis , Nitrogen Dioxide/analysis , Immunoglobulin G/analysisABSTRACT
The characterization of the antibody response to SARS-CoV-2 and its determinants are key for the understanding of COVID-19. The identification of vulnerable populations to the infection and to its socioeconomic impact is indispensable for inclusive policies. We conducted an age-stratified cross-sectional community-based seroprevalence survey between June 12th and 19th 2020-during the easing of lockdown-in Cizur, Spain. We quantified IgG, IgM and IgA levels against SARS-CoV-2 spike and its receptor-binding domain in a sample of 728 randomly selected, voluntarily registered inhabitants. We estimated a 7.9% seroprevalence in the general population, with the lowest seroprevalence among children under ten (n = 3/142, 2.1%) and the highest among adolescents (11-20 years old, n = 18/159, 11.3%). We found a heterogeneous immune-response profile across participants regarding isotype/antigen-specific seropositivity, although levels generally correlated. Those with technical education level were the most financially affected. Fifty-five percent had visited a supermarket and 43% a sanitary centre since mid-February 2020. When comparing by gender, men had left the household more frequently. In conclusion, few days after strict lockdown, the burden of SARS-CoV-2 infection was the lowest in children under 10. The findings also suggest that a wider isotype-antigen panel confers higher sensitivity. Finally, the economic impact biases should be considered when designing public health measures.
Subject(s)
COVID-19 , Adolescent , Child , Male , Humans , Young Adult , Adult , COVID-19/epidemiology , SARS-CoV-2 , Spain/epidemiology , Cross-Sectional Studies , Seroepidemiologic Studies , Communicable Disease Control , Educational Status , Immunoglobulin Isotypes , Antibodies, ViralABSTRACT
BACKGROUND: There is wide, largely unexplained heterogeneity in immunological and clinical responses to SARS-CoV-2 infection. Numerous environmental chemicals, such as persistent organic pollutants (POPs) and chemical elements (including some metals, essential trace elements, rare earth elements, and minority elements), are immunomodulatory and cause a range of adverse clinical events. There are no prospective studies on the effects of such substances on the incidence of SARS-CoV-2 infection and COVID-19. OBJECTIVE: To investigate the influence of blood concentrations of POPs and elements measured several years before the pandemic on the development of SARS-CoV-2 infection and COVID-19 in individuals from the general population. METHODS: We conducted a prospective cohort study in 154 individuals from the general population of Barcelona. POPs and elements were measured in blood samples collected in 2016-2017. SARS-CoV-2 infection was detected by rRT-PCR in nasopharyngeal swabs and/or by antibody serology using eighteen isotype-antigen combinations measured in blood samples collected in 2020-2021. We analyzed the associations between concentrations of the contaminants and SARS-CoV-2 infection and development of COVID-19, taking into account personal habits and living conditions during the pandemic. RESULTS: Several historically prevalent POPs, as well as arsenic, cadmium, mercury, and zinc, were not associated with COVID-19, nor with SARS-CoV-2 infection. However, DDE (adjusted OR = 5.0 [95% CI: 1.2-21]), lead (3.9 [1.0-15]), thallium (3.4 [1.0-11]), and ruthenium (5.0 [1.8-14]) were associated with COVID-19, as were tantalum, benzo(b)fluoranthene, DDD, and manganese. Thallium (3.8 [1.6-8.9]), and ruthenium (2.9 [1.3-6.7]) were associated with SARS-CoV-2 infection, and so were lead, gold, and (protectively) iron and selenium. We identified mixtures of up to five substances from several chemical groups, with all substances independently associated to the outcomes. CONCLUSIONS: Our results provide the first prospective and population-based evidence of an association between individual concentrations of some contaminants and COVID-19 and SARS-CoV-2 infection. POPs and elements may contribute to explain the heterogeneity in the development of SARS-CoV-2 infection and COVID-19 in the general population. If the associations are confirmed as causal, means are available to mitigate the corresponding risks.
Subject(s)
COVID-19 , Environmental Pollutants , Ruthenium , Humans , COVID-19/epidemiology , Persistent Organic Pollutants , SARS-CoV-2 , Prospective Studies , ThalliumABSTRACT
Tabletop X-ray spectroscopy measurements at the carbon K-edge complemented by ab initio calculations are used to investigate the influence of the bromine atom on the carbon core-valence transitions in the bromobenzene cation (BrBz+). The electronic ground state of the cation is prepared by resonance-enhanced two-photon ionization of neutral bromobenzene (BrBz) and probed by X-rays produced by high-harmonic generation (HHG). Replacing one of the hydrogen atoms in benzene with a bromine atom shifts the transition from the 1sC* orbital of the carbon atom (C*) bonded to bromine by â¼1 eV to higher energy in the X-ray spectrum compared to the other carbon atoms (C). Moreover, in BrBz+, the X-ray spectrum is dominated by two relatively intense transitions, 1sCâπ* and 1sC*âσ*(C*-Br), where the second transition is enhanced relative to the neutral BrBz. In addition, a doublet peak shape for these two transitions is observed in the experiment. The 1sCâπ* doublet peak shape arises due to the spin coupling of the unpaired electron in the partially vacant π orbital (from ionization) with the two other unpaired electrons resulting from the transition from the 1sC core orbital to the fully vacant π* orbitals. The 1sC*âσ* doublet peak shape results from several transitions involving σ* and vibrational C*-Br mode activations following the UV ionization, which demonstrates the impact of the C*-Br bond length on the core-valence transition as well as on the relaxation geometry of BrBz+.
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The ability of antibodies to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important correlate of protection. For routine evaluation of protection, however, a simple and cost-efficient anti-SARS-CoV-2 serological assay predictive of serum neutralizing activity is needed. We analyzed clinical epidemiological data and blood samples from two cohorts of health care workers in Barcelona and Munich to compare several immunological readouts for evaluating antibody levels that could be surrogates of neutralizing activity. We measured IgG levels against SARS-CoV-2 spike protein (S), its S2 subunit, the S1 receptor binding domain (RBD), and the full length and C terminus of nucleocapsid (N) protein by Luminex, and against RBD by enzyme-linked immunosorbent assay (ELISA), and assessed those as predictors of plasma surrogate-neutralizing activity measured by a flow cytometry assay. In addition, we determined the clinical and demographic factors affecting plasma surrogate-neutralizing capacity. Both cohorts showed a high positive correlation between IgG levels to S antigen, especially to RBD, and the levels of plasma surrogate-neutralizing activity, suggesting RBD IgG as a good correlate of plasma neutralizing activity. Symptomatic infection, with symptoms such as loss of taste, dyspnea, rigors, fever and fatigue, was positively associated with anti-RBD IgG positivity by ELISA and Luminex, and with plasma surrogate-neutralizing activity. Our serological assays allow for the prediction of serum neutralization activity without the cost, hazards, time, and expertise needed for surrogate or conventional neutralization assays. Once a cutoff is established, these relatively simple high-throughput antibody assays will provide a fast and cost-effective method of assessing levels of protection from SARS-CoV-2 infection. IMPORTANCE Neutralizing antibody titers are the best correlate of protection against SARS-CoV-2. However, current tests to measure plasma or serum neutralizing activity do not allow high-throughput screening at the population level. Serological tests could be an alternative if they are proved to be good predictors of plasma neutralizing activity. In this study, we analyzed the SARS-CoV-2 serological profiles of two cohorts of health care workers by applying Luminex and ELISA in-house serological assays. Correlations of both serological tests were assessed between them and with a flow cytometry assay to determine plasma surrogate-neutralizing activity. Both assays showed a high positive correlation between IgG levels to S antigens, especially RBD, and the levels of plasma surrogate-neutralizing activity. This result suggests IgG to RBD as a good correlate of plasma surrogate-neutralizing activity and indicates that serology of IgG to RBD could be used to assess levels of protection from SARS-CoV-2 infection.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Antibodies, Neutralizing , Health Personnel , Immunoglobulin G , Antibodies, ViralABSTRACT
Rationale: The identification of novel molecules associated with asthma may provide insights into the mechanisms of disease and their potential clinical implications. Objectives: To conduct a screening of circulating proteins in childhood asthma and to study proteins that emerged from human studies in a mouse model of asthma. Methods: We included 2,264 children from eight birth cohorts from the Mechanisms of the Development of ALLergy project and the Tucson Children's Respiratory Study. In cross-sectional analyses, we tested 46 circulating proteins for association with asthma in the selection stage and carried significant signals forward to a validation and replication stage. As CK (creatine kinase) was the only protein consistently associated with asthma, we also compared whole blood CK gene expression between subjects with and without asthma (n = 249) and used a house dust mite (HDM)-challenged mouse model to gain insights into CK lung expression and its role in the resolution of asthma phenotypes. Measurements and Main Results: As compared with the lowest CK tertile, children in the highest tertile had significantly lower odds for asthma in selection (adjusted odds ratio, 95% confidence interval: 0.31; 0.15-0.65; P = 0.002), validation (0.63; 0.42-0.95; P = 0.03), and replication (0.40; 0.16-0.97; P = 0.04) stages. Both cytosolic CK forms (CKM and CKB) were underexpressed in blood from asthmatics compared with control subjects (P = 0.01 and 0.006, respectively). In the lungs of HDM-challenged mice, Ckb expression was reduced, and after the HDM challenge, a CKB inhibitor blocked the resolution of airway hyperresponsiveness and reduction of airway mucin. Conclusions: Circulating concentrations and gene expression of CK are inversely associated with childhood asthma. Mouse models support a possible direct involvement of CK in asthma protection via inhibition of airway hyperresponsiveness and reduction of airway mucin.