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Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread globally. However, the contribution of community versus household transmission to the overall risk of infection remains unclear. Methods: Between November 2021 and March 2022, we conducted an active case-finding study in an urban informal settlement with biweekly visits across 1174 households with 3364 residents. Individuals displaying coronavirus disease 2019 (COVID-19)-related symptoms were identified, interviewed along with household contacts, and defined as index and secondary cases based on reverse-transcription polymerase chain reaction (RT-PCR) and symptom onset. Results: In 61 households, we detected a total of 94 RT-PCR-positive cases. Of 69 sequenced samples, 67 cases (97.1%) were attributed to the Omicron BA.1* variant. Among 35 of their households, the secondary attack rate was 50.0% (95% confidence interval [CI], 37.0%-63.0%). Women (relative risk [RR], 1.6 [95% CI, .9-2.7]), older individuals (median difference, 15 [95% CI, 2-21] years), and those reporting symptoms (RR, 1.73 [95% CI, 1.0-3.0]) had a significantly increased risk for SARS-CoV-2 secondary infection. Genomic analysis revealed substantial acquisition of viruses from the community even among households with other SARS-CoV-2 infections. After excluding community acquisition, we estimated a household secondary attack rate of 24.2% (95% CI, 11.9%-40.9%). Conclusions: These findings underscore the ongoing risk of community acquisition of SARS-CoV-2 among households with current infections. The observed high attack rate necessitates swift booster vaccination, rapid testing availability, and therapeutic options to mitigate the severe outcomes of COVID-19.
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BACKGROUND: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment approach to change disease-causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. METHODS: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. RESULTS: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL-10 and IFN-γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis-challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. CONCLUSIONS: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre-clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis-induced allergy.
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Hipersensibilidade , Humanos , Camundongos , Animais , Modelos Animais de Doenças , Hipersensibilidade/terapia , Alérgenos , Inflamação , Citocinas , Dessensibilização Imunológica , Imunoglobulina ERESUMO
OBJECTIVE: Sufficient vitamin D (25-hydroxyvitamin D [25(OH)D]) serum levels are associated with decreased asthma symptoms. Our aim was to investigate associations between vitamin D and atopy, asthma, asthma severity, and asthma phenotypes in Brazilian teenagers. METHODS: This cross-sectional study involved 942 individuals (11-19 years old) engaged in an asthma cohort. The ISAAC questionnaire was employed to diagnosis asthma and asthma severity. Serum allergen-specific immunoglobulin E (sIgE) was measured by ImmunoCap and serum 25(OH)D was measured by ELISA. We calculated the correlation between sIgE and 25(OH)D. We used multivariate logistic regression analysis to assess associations of interest. RESULTS: We found that 25(OH)D deficiency was positively associated with atopy (OR 1.45, confidence interval [CI] 1.05-2.00) and high levels of this vitamin negatively correlated with sIgE to Dermatophagoides pteronyssinus (r = -0.11, p = 0.019). The average 25(OH)D serum level was 27.0 ± 9.5 ng/ml; 366 individuals (38.8%) had a sufficient level. There was no association between 25(OH)D and asthma, asthma severity or asthma phenotypes in the population. However, sex was a possible effect modifier of the association between vitamin D and asthma: insufficiency in asthmatic women (86%) was higher than in asthmatic men (42%), and there was an association between insufficient vitamin D levels and greater asthma risk only in women (OR = 3.06, 95% CI 1.16-8.07). CONCLUSION: We have shown that vitamin D deficiency was associated with greater risk of atopy in both sexes and vitamin D insufficiency was associated with asthma only in women. There was no association between vitamin D levels and asthma phenotypes or asthma severity.
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Asma , Hipersensibilidade Imediata , Deficiência de Vitamina D , Masculino , Feminino , Humanos , Estudos Transversais , Brasil/epidemiologia , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Calcifediol , Hipersensibilidade Imediata/complicações , Hipersensibilidade Imediata/epidemiologia , Asma/complicações , Imunoglobulina E , VitaminasRESUMO
BACKGROUND: Allergen-specific immunotherapy (AIT) is the only clinical approach that can potentially cure some allergic diseases by inducing immunological tolerance. Dermatophagoides pteronyssinus is considered as the most important source of mite allergens worldwide, with high sensitization rates for the major allergens Der p 1, Der p 2 and Der p 23. The aim of this work is to generate a hypoallergenic hybrid molecule containing T-cell epitopes from these three major allergens. METHODS: The hybrid protein termed Der p 2231 containing T-cell epitopes was purified by affinity chromatography. The human IgE reactivity was verified by comparing those with the parental allergens. The hybrid was also characterized immunologically through an in vivo mice model. RESULTS: The hybrid rDer p 2231 stimulated in peripheral blood mononuclear cells (PBMCs) isolated from allergic patients with higher levels of IL- 2, IL-10, IL-15 and IFN-γ, as well as lower levels of IL-4, IL-5, IL-13, TNF-α and GM-CSF. The use of hybrid molecules as a therapeutic model in D. pteronyssinus allergic mice led to the reduction of IgE production and lower eosinophilic peroxidase activity in the airways. We found increased levels of IgG antibodies that blocked the IgE binding to the parental allergens in the serum of allergic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL-10 and IFN-γ and decreased the secretion of IL-4 and IL-5, when compared with parental allergens and D. pteronyssinus extract. CONCLUSIONS: rDer p 2231 has the potential to be used in AIT in patients co-sensitized with D. pteronyssinus major allergens, once it was able to reduce IgE production, inducing allergen-specific blocking antibodies, restoring and balancing Th1/Th2 immune responses, and inducing regulatory T-cells.
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Antígenos de Dermatophagoides , Epitopos de Linfócito T , Hipersensibilidade , Animais , Humanos , Camundongos , Alérgenos , Antígenos de Dermatophagoides/imunologia , Antígenos de Dermatophagoides/farmacologia , Antígenos de Dermatophagoides/uso terapêutico , Proteínas de Artrópodes , Dermatophagoides pteronyssinus , Epitopos de Linfócito T/química , Epitopos de Linfócito T/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Imunoglobulina E , Interleucina-10 , Interleucina-4 , Interleucina-5 , Leucócitos Mononucleares , Pyroglyphidae , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Imunoterapia/métodosRESUMO
BACKGROUND: The structural environment of urban slums, including physical, demographic, and socioeconomic attributes, renders inhabitants more vulnerable to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Yet, little is known about the specific determinants that contribute to high transmission within these communities. We therefore aimed to investigate SARS-CoV-2 seroprevalence in an urban slum in Brazil. METHODS AND FINDINGS: We performed a cross-sectional serosurvey of an established cohort of 2,041 urban slum residents from the city of Salvador, Brazil between November 2020 and February 2021, following the first Coronavirus Disease 2019 (COVID-19) pandemic wave in the country and during the onset of the second wave. The median age in this population was 29 years (interquartile range [IQR] 16 to 44); most participants reported their ethnicity as Black (51.5%) or Brown (41.7%), and 58.5% were female. The median size of participating households was 3 (IQR 2 to 4), with a median daily per capita income of 2.32 (IQR 0.33-5.15) US Dollars. The main outcome measure was presence of IgG against the SARS-CoV-2 spike protein. We implemented multilevel models with random intercepts for each household to estimate seroprevalence and associated risk factors, adjusting for the sensitivity and specificity of the assay, and the age and gender distribution of our study population. We identified high seroprevalence (47.9%, 95% confidence interval [CI] 44.2% to 52.1%), particularly among female residents (50.3% [95% CI 46.3% to 54.8%] versus 44.6% [95% CI 40.1% to 49.4%] among male residents, p < 0.01) and among children (54.4% [95% CI 49.6% to 59.3%] versus 45.4% [95% CI 41.5% to 49.7%] among adults, p < 0.01). Adults residing in households with children were more likely to be seropositive (48.6% [95% CI 44.8% to 52.3%] versus 40.7% [95% CI 37.2% to 44.3%], p < 0.01). Women who were unemployed and living below the poverty threshold (daily per capita household income <$1.25) were more likely to be seropositive compared to men with the same employment and income status (53.9% [95% CI 47.0% to 60.6%] versus 32.9% [95% CI 23.2% to 44.3%], p < 0.01). Participation in the study was voluntary, which may limit the generalizability of our findings. CONCLUSIONS: Prior to the peak of the second wave of the COVID-19 pandemic, cumulative incidence as assessed by serology approached 50% in a Brazilian urban slum population. In contrast to observations from industrialized countries, SARS-CoV-2 incidence was highest among children, as well as women living in extreme poverty. These findings emphasize the need for targeted interventions that provide safe environments for children and mitigate the structural risks posed by crowding and poverty for the most vulnerable residents of urban slum communities.
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COVID-19 , Adulto , Brasil/epidemiologia , COVID-19/epidemiologia , Criança , Estudos Transversais , Feminino , Humanos , Imunoglobulina G , Masculino , Pandemias , Áreas de Pobreza , SARS-CoV-2 , Estudos Soroepidemiológicos , Glicoproteína da Espícula de CoronavírusRESUMO
Reliable and scalable seroepidemiology methods are needed to estimate SARS-CoV-2 incidence and monitor the dynamics of population-level immunity as the pandemic evolves. We aimed to evaluate the reliability of SARS-CoV-2 normalized ELISA optical density (nOD) at a single dilution compared to titers derived from serial dilutions. We conducted serial serosurveys within a community-based cohort in Salvador, Brazil. Anti-S IgG ELISA (Euroimmun AG) was performed with 5 serial 3-fold dilutions of paired sera from 54 participants. Changes in nOD reliably predicted increases and decreases in titers (98.1% agreement, κ = 95.8%). Fitting the relationship between nOD and interpolated titers to a log-log curve yields highly accurate predictions of titers (r2 = 0.995) and changes in titers (r2 = 0.975), using only 1 to 2 dilutions. This approach can significantly reduce the time, labor and resources needed for large-scale serosurveys to ascertain population-level changes in exposure and immunity.
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COVID-19 , SARS-CoV-2 , Humanos , Reprodutibilidade dos Testes , Estudos Soroepidemiológicos , Anticorpos Antivirais , COVID-19/diagnóstico , Imunoglobulina GRESUMO
AIM: Molecular sensitization profile analyses of allergic individuals to the house dust mites (HDM) Blomia tropicalis and Dermatophagoides pteronyssinus from Brazil and Austria, in the attempt to comprehend the individual contribution of the molecular components in the diagnosis of HDM allergy. METHODOLOGY: These analyses were made using a new in vitro multiplex allergen assay which allows simultaneous measurement of specific IgE against the whole allergen extract as well its components. RESULTS AND CONCLUSION: The data showed that in Brazil the inclusion of the molecular components Blo t 5 and/or Blo t 21 major allergens and Blo t 2 can increase the sensitivity and specificity of the assay for the diagnosis of allergy to B. tropicalis, using matrix-based methodologies. Also we highlighted, for the first time, the importance of Blo t 2 analysis for a sensitive diagnosis, since some individuals were sensitized only to this molecular component. Regarding the sensitization profile of individuals sensitized to D. pteronyssinus, we point out the importance of analyzing the molecular components Der p23 and Der p 7, in addition to Der p 1 and Der p 2 for an accurate diagnosis based on matrices.
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Genetic and epigenetic factors are considered to be critical for host-parasite interactions. There are limited data on the role of such factors during human infections with Ascaris lumbricoides. Here, we describe the potential role of genetic factors as determinants of the Th2 immune response to A. lumbricoides in Brazilian children. Stool samples were collected from the children to detect A. lumbricoides by microscopy and peripheral blood leukocytes (PBLs) were cultured in whole blood cultures for detection of cytokines (IL-5, IL-10, and IL-13) in vitro. Levels of anti-A. lumbricoides IgE and IgG4 were measured in plasma. DNA was extracted from PBLs and genotyped using Illumina 2.5 Human Omni Beadchip. Candidate genes associated with A. lumbricoides responses were identified and SNVs in these selected genes associated with the Th2 immune response to A. lumbricoides. Haplotype, gene expression, and epigenetic analyses were done to identify potential associations with Th2 immune responses. GWAS on samples from 1,189 children identified WSB1 as a candidate gene, and IL-21R was selected as a biologically relevant linked gene for further analysis. Variants in WSB1 and IL21R were associated with markers of Th2 immune responses: increased A. lumbricoides-specific IgE and IL-5/IL-13 by PBLs from infected compared to uninfected individuals. In infected children, WSB1 but not IL21R gene expression was suppressed and increased methylation was observed in the WSB1 promoter region. This is the first study to show an association between genetic variants in WSB1 and IL21R and Th2 immune responses during A. lumbricoides infections in children. WSB1/IL21R pathways could provide a potential target for the treatment of Th2-mediated diseases.
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Ascaríase/imunologia , Ascaris lumbricoides/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Receptores de Interleucina-21/genética , Células Th2/imunologia , Animais , Brasil , Células Cultivadas , Criança , Citocinas/metabolismo , Metilação de DNA , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Imunidade Celular , Masculino , Regiões Promotoras Genéticas/genéticaRESUMO
BACKGROUND: There is growing concern about individuals reported to suffer repeat COVID-19 disease episodes, these in a small number of cases characterised as de novo infections with distinct sequences, indicative of insufficient protective immunity even in the short term. METHODS: Observational case series and case-control studies reporting 33 cases of recurrent, symptomatic, qRT-PCR positive COVID-19. Recurrent disease was defined as symptomatic recurrence after symptom-free clinical recovery, with release from isolation >14 days from the beginning of symptoms confirmed by qRT-PCR. The case control study-design compared this group of patients with a control group of 62 patients randomly selected from the same COVID-19 database. RESULTS: Of 33 recurrent COVID-19 patients, 26 were female and 30 were HCW. Mean time to recurrence was 50.5 days which was associated with being a HCW (OR 36.4 (p <0.0001)), and blood type A (OR 4.8 (pâ¯=â¯0.002)). SARS-CoV-2 antibodies were signifcantly lower in recurrent patients after initial COVID-19 (2.4⯱â¯0.610; p<0.0001) and after recurrence (6.4⯱â¯11.34; pâ¯=â¯0.007). Virus genome sequencing identified reinfection by a different isolate in one patient. CONCLUSIONS: This is the first detailed case series showing COVID-19 recurrence with qRT-PCR positivity. For one individual detection of phylogenetically distinct genomic sequences in the first and second episodes confirmed bona fide renfection, but in most cases the data do not formally distinguish between reinfection and re-emergence of a chronic infection reservoir. These episodes were significantly associated with reduced Ab response during initial disease and argue the need for ongoing vigilance without an assumption of protection after a first episode.
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COVID-19 , Pessoal de Saúde , Reinfecção , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
An 11-year-old male mixed-breed cat, with exclusively indoor life, presented 3 cough episodes after the owners tested positive by RT-PCR for SARS-CoV-2. The house is inhabited by 5 people (3 adults and 2 children), and 2 of the adults have shown mild symptoms associated with throat discomfort. The cat was vaccinated, had no history of any previous disease, and tested negative for feline coronavirus (FCoV), feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV). Rectal sample collected from the cat was positive for SARS-CoV-2 by RT-PCR. Viral genome sequences recovered from human and cat samples showed an average 99.4% sequence identity. This is the first report of genome sequences of SARS-CoV-2 recovered from a cat and its owner in Latin America.