ABSTRACT
BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).
Subject(s)
Dengue Vaccines , Dengue Virus , Dengue , Vaccines, Attenuated , Adult , Child , Child, Preschool , Humans , Antibodies, Viral , Dengue/prevention & control , Dengue Vaccines/adverse effects , Dengue Vaccines/therapeutic use , Dengue Virus/immunology , Double-Blind Method , Vaccination , Vaccines , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/therapeutic use , Brazil , Vaccine Efficacy , Adolescent , Young Adult , Middle Aged , Follow-Up StudiesABSTRACT
The aim of this study is to investigate the inflammasome dysregulation in peripheral blood leukocytes of VEXAS patients. The constitutive and in vitro triggered activation of inflammasome in PBMC and neutrophils was analysed in two Brazilian patients with typical UBA1 mutations, and compared with heathy donors. Our findings highlight the constitutive activation of caspase-1 in VEXAS leukocytes, accompanied by increased plasma levels of IL-18. Furthermore, upon stimulation of isolated peripheral blood mononuclear cells (PBMC) and neutrophils, we observed not only the exhaustion of NLRP3 and NLRP1/CARD8 pathways in VEXAS PBMC but also a significant increase in NLRP3-mediated NETs release in VEXAS neutrophils. These findings support previous studies on the contribution of the inflammasome to VEXAS pathogenesis, identifying at least two profoundly affected pathways (NLRP3 and NLRP1/CARD8) in VEXAS peripheral blood.
ABSTRACT
Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.
Subject(s)
Chagas Disease , Parasites , Trypanosoma cruzi , Humans , Animals , Trypanosoma cruzi/genetics , Brazil/epidemiology , Parasitemia , Stroke Volume , Ventricular Function, Left , DNA , InflammationSubject(s)
Arthritis , Cysts , Lung Diseases, Interstitial , Humans , Child , Lung , Arthritis/diagnostic imagingABSTRACT
PROBLEM: Endometriosis exhibits several immune dysfunctions, including deficient natural killer (NK) cell cytotoxicity. MICA (MHC class I chain-related molecule A) is induced by biological stress and soluble MICA (sMICA) negatively modulates the expression of the activating receptor, NKG2D, reducing NK cells activities. We investigated the involvement of soluble MICA in NK cell-deficient activity in endometriosis. METHODS OF STUDY: sMICA levels (serum and peritoneal fluid-PF) were evaluated by ELISA. Circulating NK cell subsets quantification and its NKG2D receptor expression, NK cell cytotoxicity and CD107a, IFN-γ and IL-10 expressions by NK cells stimulated with K562 cells were determined by flow cytometry. RESULTS: We found higher sMICA levels (serum and PF) in endometriosis, especially in advanced and deep endometriosis. Endometriosis presented lower percentages of CD56dim CD16+ cytotoxic cells and impaired NK cell responses upon stimulation, resulting in lower CD107a and IFN-γ expressions, and deficient NK cell cytotoxicity. NK cell stimulation in the MICA-blocked condition (mimicking the effect of sMICA) showed decreased cytotoxicity in initial endometriosis stages and the emergence of a negative correlation between CD107a expression and sMICA levels. CONCLUSIONS: We suggest that soluble MICA is a potential player in endometriosis pathophysiology with involvement in disease progression and severity, contributing to NK cell impaired IFN-γ response and degranulation. NK cell compartment exhibits multiple perturbations, including quantitative deficiency and impaired cytotoxicity, contributing to inadequate elimination of ectopic endometrial tissue.
Subject(s)
Endometriosis , Female , Humans , Cell Degranulation , Killer Cells, Natural , Gene Expression , Disease Progression , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Histocompatibility Antigens Class I/metabolismABSTRACT
Hereditary angioedema (HAE) encompasses a group of diseases characterized by recurrent, genetically mediated angioedema associated with increased vascular permeability primarily due to bradykinin. The disease poses diagnostic challenges, leading to underdiagnosis and delayed therapy. Severe manifestations include laryngeal and intestinal angioedema, contributing to significant morbidity and mortality. If left undiagnosed, the estimated mortality rate of the disease ranges from 25% to 40% due to asphyxiation caused by laryngeal angioedema. There is a pressing need to enhance awareness of hereditary angioedema and its warning signs. The acronym "H4AE" may facilitate the memorization of these signs. This study comprehensively reviews clinical, laboratory, and physiopathological features of documented HAE subtypes. The study advocates for an improved HAE classification based on endotypes, building on the knowledge of angioedema pathophysiology. The proposed endotype classification of HAE offers a clear and applicable framework, encouraging advancements in disease understanding and classification.
ABSTRACT
Background: The Coronaviridae family comprises seven viruses known to infect humans, classified into alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1), which are considered endemic. Additionally, it includes SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome), and the novel coronavirus SARS-CoV-2, responsible for COVID-19. SARS-CoV-2 induces severe respiratory complications, particularly in the elderly, immunocompromised individuals and those with underlying diseases. An essential question since the onset of the COVID-19 pandemic has been to determine whether prior exposure to seasonal coronaviruses influences immunity or protection against SARS-CoV-2. Methods: In this study, we investigated a cohort of 47 couples (N=94), where one partner tested positive for SARS-CoV-2 infection via real-time PCR while the other remained negative. Plasma samples, collected at least 30 days post-PCR reaction, were assessed using indirect ELISA and competition assays to measure specific antibodies against the receptor-binding domain (RBD) portion of the Spike (S) protein from SARS-CoV-2, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1. Results: IgG antibody levels against the four endemic coronavirus RBD proteins were similar between the PCR-positive and PCR-negative individuals, suggesting that IgG against endemic coronavirus RBD regions was not associated with protection from infection. Moreover, we found no significant IgG antibody cross-reactivity between endemic coronaviruses and SARS-CoV-2 RBDs. Conclusions: Taken together, results suggest that anti-RBD antibodies induced by a previous infection with endemic HCoVs do not protect against acquisition of COVID-19 among exposed uninfected individuals.
Subject(s)
Antibodies, Viral , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Immunoglobulin G/immunology , Immunoglobulin G/blood , Male , Female , Antibodies, Viral/immunology , Antibodies, Viral/blood , Adult , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Coronavirus/immunology , Endemic Diseases , Cross Reactions/immunologyABSTRACT
Protective immunity to dengue virus (DENV) requires antibody response to all four serotypes. Systems vaccinology identifies a multi-OMICs pre-vaccination signature and mechanisms predictive of broad antibody responses after immunization with a tetravalent live attenuated DENV vaccine candidate (Butantan-DV/TV003). Anti-inflammatory pathways, including TGF-ß signaling expressed by CD68low monocytes, and the metabolites phosphatidylcholine (PC) and phosphatidylethanolamine (PE) positively correlate with broadly neutralizing antibody responses against DENV. In contrast, expression of pro-inflammatory pathways and cytokines (IFN and IL-1) in CD68hi monocytes and primary and secondary bile acids negatively correlates with broad DENV-specific antibody responses. Induction of TGF-ß and IFNs is done respectively by PC/PE and bile acids in CD68low and CD68hi monocytes. The inhibition of viral sensing by PC/PE-induced TGF-ß is confirmed in vitro. Our studies show that the balance between metabolites and the pro- or anti-inflammatory state of innate immune cells drives broad and protective B cell response to a live attenuated dengue vaccine.
Subject(s)
Antibodies, Viral , Dengue Vaccines , Dengue Virus , Dengue Vaccines/immunology , Humans , Dengue Virus/immunology , Antibodies, Viral/immunology , Dengue/immunology , Dengue/prevention & control , Dengue/virology , Monocytes/immunology , Monocytes/metabolism , Antibody Formation/immunology , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/immunology , Vaccination , Antibodies, Neutralizing/immunologyABSTRACT
Introduction: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported. Methods: In this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6-12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment. Results: SRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-α2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1ß serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.
ABSTRACT
Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, is a neglected disease affecting around 6 million people. About 30% of CD patients develop chronic Chagas disease cardiomyopathy (CCC), an inflammatory cardiomyopathy that occurs decades after the initial infection, while most infected patients (60%) remain asymptomatic in the so-called indeterminate form (IF). Death results from heart failure or arrhythmia in a subset of CCC patients. Myocardial fibrosis, inflammation, and mitochondrial dysfunction are involved in the arrhythmia substrate and triggering events. Survival in CCC is worse than in other cardiomyopathies, which may be linked to a Th1-T cell rich myocarditis with abundant interferon (IFN)-γ and tumor necrosis factor (TNF)-α, selectively lower levels of mitochondrial energy metabolism enzymes in the heart, and reduced levels of high-energy phosphate, indicating poor adenosine triphosphate (ATP) production. IFN-γ and TNF-α signaling, which are constitutively upregulated in CD patients, negatively affect mitochondrial function in cardiomyocytes, recapitulating findings in CCC heart tissue. Genetic studies such as whole-exome sequencing (WES) in nuclear families with multiple CCC/IF cases has disclosed rare heterozygous pathogenic variants in mitochondrial and inflammatory genes segregating in CCC cases. In this minireview, we summarized studies showing how IFN-γ and TNF-α affect cell energy generation, mitochondrial health, and redox homeostasis in cardiomyocytes, in addition to human CD and mitochondria. We hypothesize that cytokine-induced mitochondrial dysfunction in genetically predisposed patients may be the underlying cause of CCC severity and we believe this mechanism may have a bearing on other inflammatory cardiomyopathies.
Subject(s)
Cardiomyopathies , Chagas Cardiomyopathy , Chagas Disease , Mitochondrial Diseases , Humans , Tumor Necrosis Factor-alpha/metabolism , Chagas Cardiomyopathy/genetics , Chagas Cardiomyopathy/metabolism , Chagas Cardiomyopathy/pathology , Cardiomyopathies/etiology , Myocytes, Cardiac/metabolism , Inflammation , Arrhythmias, Cardiac , Chronic DiseaseABSTRACT
Monitoring U.S. Government-Supported Covid-19 Vaccine TrialsOperation Warp Speed was a partnership created to accelerate the development of Covid-19 vaccines. The National Institutes of Health oversaw one data and safety monitoring board to review/monitor all Operation Warp Speed trials. This article describes the challenges faced in monitoring these trials and provides ideas for future similar endeavors.
Subject(s)
COVID-19 Vaccines , COVID-19 , United States , Humans , Clinical Trials Data Monitoring Committees , National Institutes of Health (U.S.)ABSTRACT
Neste artigo de opinião, apresento uma breve história do desenvolvimento de vacinas, comentando sobre as formas clássicas de produção de vacinas utilizando o próprio agente infeccioso. Em seguida, abordo as vacinas virais, discutindo seus benefícios e dificuldades e a questão dos sorotipos virais, bem como as vacinas bacterianas e seu relativo sucesso. Apresento nossos estudos sobre doença cardíaca reumática e o desenvolvimento de uma vacina contra infecções estreptocócicas. Também discuto plataformas vacinais, especialmente os sucessos alcançados com vacinas de vetores virais não replicantes e, acima de tudo, o grande êxito das vacinas de RNA mensageiro (mRNA). As vacinas de mRNA tornaram-se possíveis somente após os avanços obtidos com a substituição de nucleotídeos que reduziam a ação da imunidade inata. Serão todas as vacinas desenvolvidas a partir de mRNA no futuro? Em seguida, abordo a questão das vias de administração de vacinas, seja por via subcutânea, intradérmica, intramuscular ou nasal. Exponho dados do meu laboratório sobre o desenvolvimento de uma vacina de instilação nasal que induziu uma resposta de proteção da mucosa, prevenindo a infecção e, consequentemente, a transmissão do SARS-CoV-2. Posteriormente, discuto quais vacinas futuras poderiam ser desenvolvidas para além das doenças infecciosas agudas. Por fim, discuto as vantagens do desenvolvimento de vacinas seguras, eficazes e de uso múltiplo, bem como a forma de torná-las acessíveis à população mundial, promovendo a equidade em saúde.
In this opinion article, I provide a brief history of vaccine development, commenting on the classic ways of producing vaccines using the infectious agent itself. I address viral vaccines, discussing their benefits and challenges and the issue of viral serotypes, as well as bacterial vaccines and their relative success. I present our studies on rheumatic heart disease and the development of a vaccine against streptococcal infection. I also discuss vaccine platforms, highlighting the success achieved with non-replicating viral vector-based vaccines and, especially, with messenger RNA (mRNA) vaccines. mRNA vaccines only became possible after the advances provided by the replacement of nucleotides that reduced the action of the innate immune system. Will all vaccines be made from mRNA in the future? Then, I address the issue of vaccine administration routes, whether subcutaneously, intradermally, intramuscularly, or intranasal. I present data from my laboratory on the development of an intranasal vaccine that induced a protective mucosal response, preventing infection and, consequently, the transmission of SARSCoV- 2. I discuss which future vaccines could be developed beyond acute infectious diseases. Finally, I discuss the advantages of developing safe, effective, multiple-use vaccines and how to make them accessible worldwide by promoting health equity.
Subject(s)
Humans , History, 21st CenturyABSTRACT
A incidência de anafilaxia pós-vacinal é um evento de saúde raro e carece de melhor detalhamento no Brasil. Neste estudo, objetivou-se descrever a incidência de anafilaxia como evento supostamente atribuído à vacinação e imunização (ESAVI) das vacinas do Programa Nacional de Imunizações (PNI).Foi realizado estudo retrospectivo com dados extraídos do sistema de notificação de ESAVI do PNI entre 01/2021 e 05/2023 com aceitação na Plataforma Brasil e aprovação ética. Foram identificados 84 casos encerrados com o descritor "anafilaxia" ou "choque anafilático" entre 290.101 eventos adversos notificados, concentrados principalmente nas regiões Sul e Sudeste. Crianças de 0 a 9 anos foram predominantemente afetadas, com maior incidência em mulheres e indivíduos brancos. A anafilaxia associou-se em números absolutos principalmente às vacinas COVID-19, destacando os fabricantes AstraZeneca/Fiocruz (vetor viral), Pfizer Comirnaty (RNAm) e CoronaVac (inativada), e a maior taxa de incidência foi com a vacina antirrábica (2,8 por milhão de doses aplicadas). A incidência global foi de 0,14/milhão de doses aplicadas. Entre os desfechos não foi relatado óbito. A subnotificação de casos é relevante e sublinha a importância de manter sistemas robustos de vigilância e manejo de reações alérgicas em programas de vacinação. Este estudo segue tendências mundiais da raridade da anafilaxia relacionada às vacinas. Os dados reforçam a segurança das vacinas COVID-19 e demais vacinas existentes no PNI, independente da demografia analisada.
Vaccine-related anaphylaxis is a rare health event, and its incidence requires further investigation in Brazil. The objective of this study was to describe the incidence of anaphylaxis as an event supposedly attributed to vaccination and immunization (ESAVI) associated with the Brazilian National Immunization Program (PNI). A retrospective study was conducted with data extracted from the PNI ESAVI notification system between January 2021 and May 2023, with ethical approval and registration in Plataforma Brasil. Among 290,101 adverse events reported, 84 cases closed with the descriptor "anaphylaxis" or "anaphylactic shock" were identified, mainly concentrated in the South and Southeast regions. Children aged 0 to 9 years were predominantly affected, with a higher incidence in women and white individuals. In absolute numbers, anaphylaxis was associated mainly with the AstraZeneca/Fiocruz (viral vector), Pfizer Comirnaty (mRNA), and CoronaVac (inactivated virus) COVID-19 vaccines, while the highest relative incidence was with the anti-rabies vaccine (2.8 cases per million doses administered). The overall incidence was 0.14 per million vaccine doses. No deaths were reported. Underreporting of vaccine-related anaphylaxis is relevant and highlights the importance of maintaining robust systems for surveillance and management of allergic reactions within vaccination programs. This study corroborates global trends in the rarity of vaccine-related anaphylaxis. The low incidence of this event, regardless of recipient demographics, provides further evidence of the safety of COVID-19 vaccines and other vaccines included in the PNI.
Subject(s)
HumansABSTRACT
Paciente do sexo feminino, com 63 anos de idade, portadora de mastocitose sistêmica há cerca de 20 anos, sendo agressiva há 10 anos. Crises quase diárias com manifestações do trato gastrointestinal e vasomotoras. Após diversas tentativas de tratamento, iniciou uso de midostaurina, um inibidor multiquinase. Depois de 6 meses de uso, observou-se bom controle dos sintomas, diminuição em quase 50% da triptase sérica e desaparecimento completo das lesões cutâneas.
A 63-year-old female presented with an approximately 20-year history of systemic mastocytosis, which had become aggressive over the past 10 years. She experienced almost daily episodes of gastrointestinal and vasomotor manifestations. After multiple treatment attempts, she was started on midostaurin, a multikinase inhibitor. At 6 months of therapy, satisfactory control of symptoms was achieved, with a nearly 50% reduction in serum tryptase and complete resolution of cutaneous lesions.
Subject(s)
Humans , Female , Middle Aged , Cyclin-Dependent Kinase Inhibitor Proteins , AnaphylaxisABSTRACT
Os distúrbios do olfato (DO) impactam de forma significativa na qualidade de vida dos indivíduos, e o conhecimento teórico a respeito do assunto deve ser de domínio dos alergologistas e imunologistas clínicos, possibilitando, assim, o seu diagnóstico e implementação de intervenções. Suas causas podem ser variadas, entre elas estão: rinite alérgica, rinossinusite crônica com ou sem pólipos, infecções de vias aéreas superiores, exposição a substâncias químicas, doenças neurológicas, drogas, traumas e o próprio envelhecimento. O olfato pode ser avaliado e mensurado através de testes com metodologias diferentes, cujo objetivo é avaliar parâmetros como a identificação de odores, limiar e discriminação olfativa. Esses testes são de fundamental importância para caracterizar objetivamente a queixa do paciente, como também avaliar o olfato antes e após determinada aplicação terapêutica. O tratamento das desordens olfativas é baseado em sua etiologia, portanto determinar a sua causa é indispensável para uma melhor eficácia no manejo. Entre as principais opções estão os corticoides tópicos, com impacto significativo nos pacientes com doença sinusal associada, treinamento olfatório e outras intervenções como ômega 3, vitamina A intranasal, e terapias que ainda requerem mais estudos.
Olfactory dysfunction significantly impacts quality of life, and allergists and clinical immunologists must be informed about it for diagnostic and interventional purposes. The causes are varied: allergic rhinitis, chronic rhinosinusitis with or without polyps, upper airway infections, exposure to chemicals, neurological diseases, drugs, trauma, and aging itself. Olfactory function can be evaluated and measured by several tests that use different methodologies to evaluate and identify odors, olfactory threshold, and olfactory discrimination. These tests are fundamental for objectively characterizing patient complaints and evaluating olfactory function before and after therapeutic interventions. Olfactory disorders are treated according to their etiology, so determining their cause is a major factor in treatment efficacy. The main options include topical corticosteroids, which have a significant impact on patients with sinus disease, olfactory training, other therapies (such as omega 3 and intranasal vitamin A), in addition to therapies that require further research.
Subject(s)
Humans , Fatty Acids, Omega-3 , COVID-19ABSTRACT
Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).
ABSTRACT
The severity of SARS-CoV2 infection, Covid19 disease, should account for the diversity of human individual immu-noinflammatory responses. Serum immunological markers during Covid19 illness may lead to individualized thera-peutics with better outcomes. Efficient treatment for Covid19 may require: 1) early disease detection, 2) combined drug therapy for 3) targeting the virus replication cycle, and 4) individualized drug treatment for specific immu-noinflammatory human profile responses administered in a 5) timely manner. Covid19 is unlikely to be the last emergent human disease with fast pandemic potential. Gathering knowledge on the individual human host profiles of immunoinflammatory responses is an opportunity that could lead us to understand individual differences in re-sponse to infection at the individual and population level, paving the way to faster, more efficient strategies to tack-le upcoming infectious diseases. This is a position paper based on an integrative non-exhaustive literature revision (AU)
A diversidade das respostas imunoinflamatórias individuais humanas muito provavelmente tem papel na gravidade da doença Covid19 causada pela infecção pelo vírus SARS-CoV2. Marcadores imunológicos séricos durante a Covid19 po-dem guiar a escolha de terapias individualizadas com melhores resultados. O tratamento eficiente para Covid19 pode exigir: 1) detecção precoce da doença, 2) terapia medicamentosa combinada com alvo ao 3) ciclo de replicação do ví-rus e 4) terapia anti-inflamatória individualizada para perfis de respostas imunoinflamatórias humanas, administradas em tempo hábil. É improvável que a Covid19 seja a última doença humana emergente com potencial de alastramento veloz pandêmico. Reunir conhecimento sobre perfis de respostas imunoinflamatórias individuais dos hospedeiros humanos é uma oportunidade ímpar que pode nos levar a entender as diferenças dessas respostas entre indivíduos, abrindo caminho para estratégias terapêuticas mais rápidas e eficientes no combate à futuras epidemias (AU)
Subject(s)
Treatment Outcome , Essay , Severe Acute Respiratory Syndrome , Cytokine Release Syndrome , COVID-19 Nucleic Acid Testing , COVID-19/therapy , ImmunityABSTRACT
Abstract Objectives The study describes a case series of hereditary angioedema with C1 Inhibitor Deficiency (C1INH-HAE) in order to corroborate six clinical warning signs "HAAAAE (H4AE)" to enable early identification of this disease. Methods The authors analyzed the C1INH-HAE cohort to analyze the clinical aspects of the present study's patients and corroborate the six clinical warning signs of the Hereditary Angioedema Brazilian Guidelines. Data regarding demographics, the onset of disease, time to diagnosis, frequency of attacks per year, organs involved, triggers, crisis duration and their outcomes, and disease treatment were collected. Then the authors developed an acronym, H4AE, to help healthcare professionals remember the warning signs. Results The authors included 98 patients in the study, with a mean age of 38.1 years, 67.3% being female, and 75.3% with a family history of HAE. HAE diagnosis was delayed, on average, 13.7 years after its initial manifestation. Exploratory laparotomy was reported by 26.9%, and orotracheal intubation by 21.3% of the present study's patients; 61.3% and 30.3% of them were admitted at least once in the hospital and in the intensive care unit, respectively. The authors constructed an acronym "H4AE" with the six warning signs of HAE: Hereditary, recurrent Angioedema, Abdominal pain, Absence of urticaria, Absence of response to antihistamines, Estrogen association. Conclusion C1INH-HAE is still underdiagnosed and associated with high morbidity. The study showed clinical features of this disease, corroborating the warning signs, which may be useful in raising awareness and improving the diagnosis of C1INH-HAE. The authors suggest the acronym "H4AE" to remind the warning signs.
ABSTRACT
A urticária aquagênica é uma forma rara de urticária crônica induzida (UCInd) desencadeada por um estímulo específico. A patogênese não é totalmente compreendida, mas os sintomas se iniciam minutos após a exposição cutânea à água, independentemente de sua temperatura, e as urticas têm o padrão foliculocêntricas. O diagnóstico é confirmado através do teste de provocação, e o tratamento de primeira linha são os anti-histamínicos de segunda geração. Neste artigo, relatamos um caso de urticária aquagênica e fazemos uma breve revisão da literatura sobre o tema.
Aquagenic urticaria is a rare form of chronic inducible urticaria (CIndU) triggered by a specific stimulus. Pathogenesis is not fully understood, but symptoms appear minutes after cutaneous exposure to water, regardless of temperature, and wheals have a folliculocentric pattern. The diagnosis of CIndU is confirmed by provocation testing using established protocols, and first-line treatment is second-generation antihistamines. In this article, we report a case of aquagenic urticaria and provide a brief review of the relevant literature.
Subject(s)
Humans , Female , Young Adult , Water , Histamine H1 Antagonists, Non-Sedating , Chronic Urticaria , Signs and Symptoms , Therapeutics , Skin Tests , Diagnosis , Histamine AntagonistsABSTRACT
Introdução: Os sintomas gerados pela urticária crônica (UC) afetam significativamente a qualidade de vida dos pacientes, e o estresse pode ser um fator de exacerbação. Isso se torna ainda mais importante no atual cenário de pandemia da doença causada pelo coronavírus (COVID-19). Diante da impossibilidade de manter a mesma quantidade de consultas presenciais, surgiu a necessidade de saber como estariam os pacientes com UC: se apresentariam exacerbação da doença de base caso se infectassem com o SARS-CoV-2, se a UC predisporia os pacientes a um quadro mais grave de COVID-19, e se o estresse emocional a que os pacientes estariam sujeitos exacerbaria sua doença de base. Métodos: Trata-se de um estudo observacional retrospectivo com dados coletados através do registro das informações coletadas de pacientes com UC durante remarcação de suas consultas, através de ligações telefônicas. Resultados: Foram incluídos 140 pacientes no estudo, no período de 29/04/2020 a 15/07/2020. O estresse emocional estava presente em 80 pacientes (57,1%), sendo que destes, 30% relataram piora da urticária. A obesidade foi a outra comorbidade mais relatada pelos pacientes com UC (35%). Dos 22 pacientes que procuraram o Pronto-Socorro, 9 (40,9%) foram investigados. Destes, 5 (55,6%) realizaram investigação específica para COVID-19. Conclusões: Durante a pandemia da COVID-19, os nossos pacientes com UC se encontraram mais estressados emocionalmente, e isso foi um fator associado à piora da urticária. A obesidade, no nosso grupo de pacientes, foi muito prevalente.
Introduction: Chronic urticaria (CU) symptoms significantly affect patient quality of life, and stress can be an exacerbating factor. This becomes even more important in the current pandemic setting of the novel coronavirus disease 2019 (COVID-19). Given the impossibility of maintaining the same schedule of in-person medical appointments, there was a need to know how patients with CU would behave: if they would have an exacerbation of the underlying disease if they became infected with SARS-CoV-2, if CU would predispose patients to a more severe form of COVID- 19, and if emotional stress would exacerbate their underlying disease. Methods: This is a retrospective observational study of data collected from records of patients with CU when their medical appointments were rescheduled via telephone call. Results: One hundred and forty patients were included in the study from 4/29/2020 to 7/15/2020. Stress was present in 80 patients (57.1%), of which 30% reported worsening of urticaria. Obesity was the most reported comorbidity in patients with CU (35%). Of the 22 patients who sought emergency care, 9 (40.9%) were investigated. Of these, 5 (55.6%) underwent specific investigation for COVID-19. Conclusions: During the COVID-19 pandemic, our CU patients were found to be more emotionally stressed, and this factor was associated with worsening of urticaria. Obesity, in our group of patients, was very prevalent.