Comprehensive landscape of neutralizing antibody and cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF primary vaccination in adults.

The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV(D0)] and after vaccination (Day 30-45) [Primary Vaccinees, PV(D30-45)]. Data demonstrated high levels of neutralizing antibodies for PV(D30-45) leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV(D30-45), with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV(D30-45) as compared to NV(D0) (532vs398). Moreover, PV(D30-45) exhibited increased levels of Terminal Effector (CD45RA+CCR7-) CD4+ and CD8+ T-cells and Non-Classical memory B-cells (IgD+CD27+). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV(D30-45) further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.

Immune response induced by standard and fractional doses of 17DD yellow fever vaccine.

The re-emergence of yellow fever (YF) urged new mass vaccination campaigns and, in 2017, the World Health Organization approved the use of the fractional dose (FD) of the YF vaccine due to stock shortage. In an observational cross-sectional investigation, we have assessed viremia, antibodies, soluble mediators and effector and memory T and B-cells induced by primary vaccination of volunteers with FD and standard dose (SD). Similar viremia and levels of antibodies and soluble markers were induced early after immunization. However, a faster decrease in the latter was observed after SD. The FD led to a sustained expansion of helper T-cells and an increased expression of activation markers on T-cells early after vaccination. Although with different kinetics, expansion of plasma cells was induced upon SD and FD immunization. Integrative analysis reveals that FD induces a more complex network involving follicular helper T cells and B-cells than SD. Our findings substantiate that FD can replace SD inducing robust correlates of protective immune response against YF.

Factors associated with yellow fever vaccine failure: A systematic literature review.

INTRODUCTION: Considering that vaccination with yellow fever vaccine (YFV) is the most important method to prevent and control yellow fever (YF), this study synthesized evidence on factors associated with YFV failure. METHODS: A systematic review (SR) was performed in the PubMed, Cochrane CENTRAL, Embase, and LILACS databases up to November 2019. Observational and experimental analytical epidemiological studies that analyzed the failure of YFV were included. This review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and meta-Analyses. RESULTS: A total of 1,466 articles were identified after searching the databases of which 46 were included in the qualitative analysis after applying the elegibility criteria. Our findings indicated that YFV confers protective immunity in different age groups; when produced by different producers; when administered simultaneously with a range of other vaccines; when used as fractional doses and when used with prophylactic and immunosuppressive therapies. It failed to produce a protective response in some pregnant women, children under two years of age, children with Kwashiorkor and when long periods of time have passed after vaccination. For individuals with human immunodeficiency virus (HIV), the results were divergent. CONCLUSIONS: The results of this SR revealed the factors associated with the failure of the YFV, and the results can support recommendations on vaccination policies, support the safety of health professionals who work directly with immunization in the implementation of the vaccination schedule, in addition to guiding future research and enhance the credibility of YFV in the prevention of a serious disease such as YF.

Effect of vaccination against Covid-19 one year after its introduction in Brazil.

BACKGROUND: Worldwide, several efforts have been made to develop, distribute and administer safe and effective vaccines to reduce morbidity and mortality and control the Covid-19 pandemic. This study aimed to analyze the effect of vaccination against Covid-19, one year after its introduction in Brazil. METHODS: An ecological study that analyzed the general effect of vaccination against Covid-19 on disease morbidity and mortality indicators among the Brazilian population aged 18 years or older per epidemiological week (EW), comparing the pre and postvaccination period. Morbidity and mortality indicators were calculated from secondary databases (hospitalization rate, severity, case fatality rate and mortality) and vaccination coverage by age groups (18 to 59 years and 60 years or older). Morbimortality trends were estimated using the JoinPoint model and their association with vaccine coverage using the Poisson model. RESULTS: The average weekly percentage change (AWPC) of morbidity and mortality indicators reduced after the introduction of Covid-19 vaccination: hospitalization rate (from 15.3% to -6.0%), severity (from 0.4% to -0.2%), case fatality rate (from 0.3% to -0.2%) and mortality (from 20.5% to -4.3%). The following indicators were inversely associated with the increase in vaccine coverage against Covid-19: hospitalization (IRR: 0.974), mortality (IRR: 0.975) and lethality for people aged 60 years or older (IRR: 0.997). CONCLUSIONS: In spite of the three epidemic waves and the circulation of variants of concern, the general effect of vaccination against Covid-19 in reducing the trend of morbidity and mortality from the disease in Brazil was demonstrated. These findings contribute to a better understanding of the mass vaccination program against Covid-19 and may inform future public health policies.

Multisystem inflammatory syndrome in children: a cross-sectional study of cases and factors associated with deaths during the COVID-19 pandemic in Brazil, 2020. / Síndrome inflamatória multissistêmica pediátrica: estudo seccional dos casos e fatores associados aos óbitos durante a pandemia de COVID-19 no Brasil, 2020.

OBJECTIVE: To characterize the clinical-epidemiological profile of multisystem inflammatory syndrome in children temporally associated with COVID-19 (MIS-C), and to identify factors associated with MIS-C deaths in Brazil, 2020. METHODS: This was a cross-sectional study, using national MIS-C monitoring data. Logistical regression was performed to estimate crude and adjusted odds ratios (OR). RESULTS: Median case (n=652) age was 5 years, 57.1% were male, 52.0% were of brown race/skin color and 6.4% died. Likelihood of death was greater among those who presented O2 saturation <95% (ORa=4.35 - 95%CI 1.69;11.20) and altered urea results (ORa=5.18 - 95%CI 1.91;14.04); likelihood of death was lower when red skin blotches were not present (ORa=0.23 - 95%CI 0.09;0.62), when anticoagulants were used (ORa=0.32 - 95%CI 0.12;0.89) and when immunoglobulins were used (ORa=0.38 - 95%CI 0.15;1.01). CONCLUSION: Fatality ratios were higher among cases that presented O2 saturation <95% and altered urea results. Fatality ratios were lower among those with red skin blotches, and those who used immunoglobulins and anticoagulants.

Retrospective cohort of children and adolescents hospitalized by COVID-19 in Brazil from the beginning of the pandemic to August 1st, 2020. / Coorte retrospectiva de crianças e adolescentes hospitalizados por COVID-19 no Brasil do início da pandemia a 1º de agosto de 2020.

OBJECTIVES: To characterize the study population, estimating the in-hospital lethality rate by state and analysing associated factors with COVID-19-related deaths. METHODS: A retrospective cohort study was carried out of hospitalised children and adolescents diagnosed with COVID-19, confirmed by RT-PCR, whose outcome was death by COVID-19 or recovery, from 2020 March 1 to August 1. The data source was the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe in Brazilian acronym), where patients with Severe Acute Respiratory Syndrome (SARS) are notified. Children were defined as those between the ages of 0 and 11, and adolescents those between 12 and 18. A bi and multivariate analysis were performed using Poisson Regression with robust variance, with adjusted Relative Risk as the final association measure. RESULTS: A total of 4,930 cases were analysed; 2,553 (51.8%) were males, 2,335 (47.4%) were brown-skinned. The Federative Unit of Roraima presented the highest in-hospital case-fatality rate, with 68.8% (11/16). Multivariate analysis showed that belonging to the age group adolescent (RR = 1.59; 95%CI 1.12 - 2.25; p = 0.009), SARS-critical patient (RR = 4.56; 95%CI 2, 77 - 7.51; p < 0.001) and presenting immunological disorders (RR = 2.24; 95%CI 1.58 - 3.17; p < 0.001) as comorbidities were statistically associated factors with death by COVID-19. CONCLUSION: It was observed that adolescents, SARS-critical patients, and presence of immunological disorders were important factors associated with death. Active surveillance and differentiated care are recommended for patients with chronic diseases and special immunological conditions.

OBJETIVOS: Caracterizar a população do estudo, estimar a taxa de letalidade intra-hospitalar por estado e analisar fatores associados aos óbitos por COVID-19. MÉTODOS: Foi realizado estudo de coorte retrospectiva de crianças e adolescentes hospitalizados com diagnóstico de COVID-19 confirmado por transcrição reversa seguida de reação em cadeia da polimerase (RT-PCR), tendo como desfecho óbito por COVID-19 ou recuperação, entre 1º de março e 1º de agosto de 2020. A fonte de dados foi o Sistema de Informação de Vigilância Epidemiológica da Gripe (SIVEP-Gripe), ao qual são notificados pacientes internados com Síndrome Respiratória Aguda Grave (SRAG). Consideraram-se crianças os pacientes com idade entre 0 e 11 anos completos e adolescentes aqueles com idade entre 12 e 18 anos completos. Realizou-se análise bi e multivariável por meio de Regressão de Poisson com variância robusta, utilizando-se como medida de associação final o Risco Relativo ajustado (RRa). RESULTADOS: Dos 4.930 casos analisados, 2.553 (51,8%) eram do sexo masculino. A raça/cor autodeclarada parda foi a mais frequente, com 2.335 (47,4%). A unidade federativa de Roraima apresentou a maior taxa de letalidade intra-hospitalar, com 68,8% (n = 11/16). A análise multivariada mostrou que pertencer ao grupo etário adolescente (RR = 1,59; IC95% 1,12 - 2,25; p = 0,009), ter sido classificado como SRAG-crítico (RR = 4,56; IC95% 2,77 - 7,51; p < 0,001) e apresentar imunopatia (RR = 2,24; IC95% 1,58 - 3,17; p < 0,001) como comorbidade configuraram-se como fatores associados ao óbito pela COVID-19. CONCLUSÃO: Observou-se que ser adolescente, ter classificação de SRAG-crítico e imunopatia como comorbidade foram importantes fatores associados ao óbito. Recomenda-se vigilância ativa e cuidados diferenciados a portadores de doenças crônicas e condições imunológicas especiais.

CCL3, CCL5, IL-15, IL-1Ra and VEGF compose a reliable algorithm to discriminate classes of adverse events following 17DD-YF primary vaccination according to cause-specific definitions.

In the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI ("A1" class) from cases with other illnesses ("C" class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1ß, IL-6 and TNF-α were observed in YEL-AEFI ("A1" and "C" classes) as compared to primary vaccines without YEL-AEFI [PV(day 3-28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1ß, IL-15, IL-1Ra and G-CSF were found in "A1" as compared to "C" class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate "A1" from "C". Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify "A1" followed by VEGF as branch nodes to discriminate Wild Type YFV infection ("C(WT-YFV)") from cases with other illnesses ("C*"). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases.

Serum biomarker profile orchestrating the seroconversion status of patients with autoimmune diseases upon planned primary 17DD Yellow fever vaccination.

The present study aimed to investigate whether the serum biomarkers of immune response orchestrate the seroconversion status in patients with autoimmune diseases (AID) upon planned primary 17DD-YF vaccination. For this purpose a total of 161 individuals were enrolled in a prospective study, including patients with Rheumatoid Arthritis (RA = 38), Spondyloarthritis (SpA = 51), Systemic Lupus Erythematosus (SLE = 21) and Sjögren's Syndrome (SS = 30) along with a group of healthy controls (HC = 21). Analysis of plaque reduction neutralization test (PRNT) titers and seropositivity rates along with the 17DD-YF viremia and serum biomarkers were carried out at distinct time points (D0/D3-4/D5-6/D7/D14-28). The results demonstrated an overall lower PRNT titer and seropositivity rate (170 vs. 448; 77 vs. 95%) in AID as compared to HC, especially in SpA and SLE subgroups. No significant differences were observed in the viremia levels amongst groups. In general, a more prominent serum biomarker response was observed in AID as compared to HC, throughout the timeline kinetics. Remarkably, AID/PRNT(-) exhibited higher levels of several biomarkers at baseline as compared to AID/PRNT+. Moreover, while AID/PRNT(+) exhibited earlier increase in serum biomarkers at D3-4/D5-6, the AID/PRNT(-) displayed higher response at later time points (D7/D14-D28). Of note, a synchronic increase of IFN-γ at the peak of viremia (D5-6) was observed in HC and AID/PRNT(+) groups, whereas a later asynchronous IFN-γ response was reported for AID/PRNT(-) at D7. The biomarker profile tends to deflate at post-vaccination timeline, highlighting a putative immunomodulatory effect of live attenuated 17DD-YF vaccine in AID/PRNT(+), but not in AID/PRNT(-). Altogether these data suggested that inflammatory status prior vaccination, low IFN-γ at viremia peak and the occurrence of asynchronous biomarker storm after 17DD-YF vaccination may orchestrate the lack of neutralizing antibody response γ.

Retrospective cohort of children and adolescents hospitalized by COVID-19 in Brazil from the beginning of the pandemic to August 1st, 2020 / Coorte retrospectiva de crianças e adolescentes hospitalizados por COVID-19 no Brasil do início da pandemia a 1º de agosto de 2020

Objectives: To characterize the study population, estimating the in-hospital lethality rate by state and analysing associated factors with COVID-19-related deaths. Methods: a retrospective cohort study was carried out of hospitalised children and adolescents diagnosed with COVID-19, confirmed by RT-PCR, whose outcome was death by COVID-19 or recovery, from 2020 March 1 to August 1. The data source was the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe in Brazilian acronym), where patients with Severe Acute Respiratory Syndrome (SARS) are notified. Children were defined as those between the ages of 0 and 11, and adolescents those between 12 and 18. A bi and multivariate analysis were performed using Poisson Regression with robust variance, with adjusted Relative Risk as the final association measure. Results: A total of 4,930 cases were analysed; 2,553 (51.8%) were males, 2,335 (47.4%) were brown-skinned. The Federative Unit of Roraima presented the highest in-hospital case-fatality rate, with 68.8% (n=11/16). Multivariate analysis showed that belonging to the age group adolescent (RR = 1.59; 95% CI 1.12 - 2.25; p=0.009), SARS-critical patient (RR = 4.56; 95% CI 2, 77 - 7.51; p<0.001) and presenting immunological disorders (RR = 2.24; 95% CI 1.58 - 3.17; p<0.001) as comorbidities, were associated factors with death by COVID-19. Conclusion: it was observed that adolescents, SARS-critical patients, and presence of immunological disorders were important factors associated with death. Active surveillance and differentiated care are recommended for patients with chronic diseases and special immunological conditions.

Objetivos: Caracterizar a população do estudo, estimar a taxa de letalidade intra-hospitalar por estado e analisar fatores associados aos óbitos por COVID-19. Métodos: Foi realizado estudo de coorte retrospectiva de crianças e adolescentes hospitalizados com diagnóstico de COVID-19, confirmados por RT-PCR, tendo como desfecho óbito por COVID-19 ou recuperado, entre 1º de março a 1º de agosto de 2020. A fonte de dados foi Sistema de Informação de Vigilância Epidemiológica da Gripe (SIVEP-Gripe), onde são notificados pacientes internados com Síndrome Respiratória Aguda Grave (SRAG). Considerou-se crianças aqueles com idade entre 0 e 11 anos completos e adolescentes aqueles com idade entre 12 e 18 anos completos. Realizou-se análise bi e multivariável por meio de Regressão de Poisson com variância robusta, sendo utilizado como medida de associação final o Risco Relativo ajustado (RRa). Resultados: Dos 4.930 casos analisados, 2.553 (51,8%) eram do sexo masculino. A raça/cor autodeclarada parda foi a mais frequente com 2.335 (47,4%). A Unidade Federativa de Roraima apresentou a maior taxa de letalidade intra-hospitalar com 68,8% (n=11/16). Análise multivariada mostrou que pertencer ao grupo etário adolescente (RR= 1,59; IC95% 1,12 ­ 2,25; p=0,009), ter sido classificado como SRAG-crítico (RR= 4,56; IC95% 2,77 ­ 7,51; p<0,001) e apresentar imunopatia (RR= 2,24; IC95% 1,58 ­ 3,17; p<0,001) como comorbidade se configuraram como fatores associados ao óbito pela COVID-19. Conclusão: Observou-se que ser adolescente, ter classificação de SRAG-crítico e imunopatia como comorbidade foram importantes fatores associados ao óbito. Recomenda-se vigilância ativa e cuidados diferenciados a portadores de doenças crónicas e condições imunológicas especiais.

Síndrome inflamatória multissistêmica pediátrica: estudo seccional dos casos e fatores associados aos óbitos durante a pandemia de COVID-19 no Brasil, 2020 / Multisystem inflammatory syndrome in children: a cross-sectional study of cases and factors associated with deaths during the COVID-19 pandemic in Brazil, 2020

Objetivo: Caracterizar o perfil clínico-epidemiológico da síndrome inflamatória multissistêmica pediátrica temporalmente associada à COVID-19 (SIM-P) e identificar fatores associados aos óbitos de SIM-P no Brasil, 2020. Métodos: Estudo seccional, utilizando dados do monitoramento nacional da SIM-P. Empregou-se regressão logística para estimar razões de chances (OR, odds ratios ) brutas e ajustadas. Resultados: Os casos (n=652) apresentaram mediana de idade de 5 anos; 57,1% eram do sexo masculino e 52,0% de raça/cor da pele parda; 6,4% evoluíram a óbito. A chance de óbito foi significativamente maior nos que apresentaram saturação de O2<95% (ORa=4,35 - IC95% 1,69;11,20) e resultado alterado de ureia (ORa=5,18 - IC95% 1,91;14,04); e menor na ausência de manchas vermelhas pelo corpo (ORa=0,23 - IC95% 0,09;0,62), com uso de anticoagulantes (ORa=0,32 - IC95% 0,12;0,89) e imunoglobulinas (ORa=0,38 - IC95% 0,15;1,01). Conclusão: A letalidade foi maior entre casos que apresentaram saturação de O2<95% e ureia alterada; e menor nos que apresentaram manchas vermelhas, usaram imunoglobulinas e anticoagulantes.

Objetivo: Caracterizar el perfil clínico-epidemiológico de los casos por síndrome inflamatorio multisistémico pediátrico asociado temporalmente a la COVID-19 (SIM-PedS) e identificar factores asociados a los óbitos por SIM-PedS en Brasil, 2020. Métodos: Estudio transversal basado en datos del monitoreo nacional de la SIM-PedS, Brasil, 2020. Se utilizó regresión logística para estimar razones de probabilidades brutas y ajustadas (OR, odds ratio). Resultados: Los casos (n=652) presentaron edad mediana de 5 años, 57,1% eran hombres, 52,0% de raza/color pardo y 6,4% falleció. La probabilidad de muerte fue significativamente mayor entre aquellos con saturación de O2<95% (ORa=4,35 - IC95%1,69;11,20) y resultado alterado de urea (ORa=5,18 - IC95% 1,91;14,04); menor en ausencia de manchas rojas como erupción (ORa=0,23 - IC95% 0,09;0,62), con uso de anticoagulantes (ORa=0,32 - IC95% 0,12;0,89) e inmunoglobulinas (ORa=0,38 - IC95%0,15;1,01). Conclusión: La letalidad fue mayor entre casos que presentaron saturación de O2<95% y urea alterada, y menor entre aquellos con manchas rojas, que usaron inmunoglobulinas y anticoagulantes.

Objective: To characterize the clinical-epidemiological profile of multisystem inflammatory syndrome in children temporally associated with COVID-19 (MIS-C), and to identify factors associated with MIS-C deaths in Brazil, 2020. Methods: This was a cross-sectional study, using national MIS-C monitoring data. Logistical regression was performed to estimate crude and adjusted odds ratios (OR). Results: Median case (n=652) age was 5 years, 57.1% were male, 52.0% were of brown race/skin color and 6.4% died. Likelihood of death was greater among those who presented O2 saturation <95% (ORa=4.35 - 95%CI 1.69;11.20) and altered urea results (ORa=5.18 - 95%CI 1.91;14.04); likelihood of death was lower when red skin blotches were not present (ORa=0.23 - 95%CI 0.09;0.62), when anticoagulants were used (ORa=0.32 - 95%CI 0.12;0.89) and when immunoglobulins were used (ORa=0.38 - 95%CI 0.15;1.01). Conclusion: Fatality ratios were higher among cases that presented O2 saturation <95% and altered urea results. Fatality ratios were lower among those with red skin blotches, and those who used immunoglobulins and anticoagulants.

Description of COVID-19 hospitalized health worker cases in the first nine weeks of the pandemic, Brazil, 2020. / Descrição dos casos hospitalizados pela COVID-19 em profissionais de saúde nas primeiras nove semanas da pandemia, Brasil, 2020.

OBJECTIVE: To describe COVID-19 hospitalized health worker cases in Brazil. METHODS: This was a descriptive case series study; it included cases that became ill between February 21st and April 15th, 2020 registered on the Influenza Surveillance Information System (SIVEP-Gripe, acronym in Portuguese). RESULTS: Of the 184 cases, 110 (59.8%) were female and median age was 44 years (min-max: 23-85); 89 (48.4%) were nursing professionals and 50 (27.2%) were doctors. Ninety-two (50.0%) presented comorbidity, with heart disease predominating (n=37; 40.2%). Of the 112 professionals with a record of case progression, 85 (75.9%) were cured and 27 (24.1%) died, 18 of whom were male. CONCLUSION: The profile of COVID-19 hospitalized health workers is similar to that of the general population with regard to age and comorbidities, but different in relation to sex. The most affected areas were nursing and medicine.

Planned Yellow Fever Primary Vaccination Is Safe and Immunogenic in Patients With Autoimmune Diseases: A Prospective Non-interventional Study.

Yellow Fever (YF) vaccination is suggested to induce a large number of adverse events (AE) and suboptimal responses in patients with autoimmune diseases (AID); however, there have been no studies on 17DD-YF primary vaccination performance in patients with AID. This prospective non-interventional study conducted between March and July, 2017 assessed the safety and immunogenicity of planned 17DD-YF primary vaccination in patients with AID. Adult patients with AID (both sexes) were enrolled, along with healthy controls, at a single hospital (Vitória, Brazil). Included patients were referred for planned vaccination by a rheumatologist; in remission, or with low disease activity; and had low level immunosuppression or the attending physician advised interruption of immunosuppression for safety reasons. The occurrence of AE, neutralizing antibody kinetics, seropositivity rates, and 17DD-YF viremia were evaluated at various time points (day 0 (D0), D3, D4, D5, D6, D14, and D28). Individuals evaluated (n = 278), including patients with rheumatoid arthritis (RA; 79), spondyloarthritis (SpA; 59), systemic sclerosis (8), systemic lupus erythematosus (SLE; 27), primary Sjögren's syndrome (SS; 54), and healthy controls (HC; 51). Only mild AE were reported. The frequency of local and systemic AE in patients with AID and HC did not differ significantly (8 vs. 10% and 21 vs. 32%; p = 1.00 and 0.18, respectively). Patients with AID presented late seroconversion profiles according to kinetic timelines of the plaque reduction neutralization test (PRNT). PRNT-determined virus titers (copies/mL) [181 (95% confidence interval (CI), 144-228) vs. 440 (95% CI, 291-665), p = 0.004] and seropositivity rate (78 vs. 96%, p = 0.01) were lower in patients with AID after 28 days, particularly those with SpA (73%) and SLE (73%), relative to HC. The YF viremia peak (RNAnemia) was 5-6 days after vaccination in all groups. In conclusion, consistent seroconversion rates were observed in patients with AID and our findings support that planned 17DD-YF primary vaccination is safe and immunogenic in patients with AID.

Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil.

The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. The R0 value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4-5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.

Description of COVID-19 hospitalized health workers in the first nine weeks of the pandemic, Brazil, 2020 / Descripción de casos hospitalizados de COVID-19 en profesionales de la salud en las primeras nueve semanas de la pandemia, Brasil, 2020 / Descrição dos casos hospitalizados pela COVID-19 em profissionais de saúde nas primeiras nove semanas da pandemia, Brasil, 2020

Objective. Describing the COVID-19 hospitalization in health professionals in Brazil. Methods. Serial cases descriptive study; we included the cases with illness between February 21st and April 15th, 2020; registered in Flu Surveillance Information System (SIVEP-Gripe, in Brazilian acronym). Results. From the 184 (1.76%) cases, 110 (59.8%) were female, with a median age of 44 years (min-max: 23-85). Of the 184, 89 (48.4%) are nursing professionals and 50 (27.2%) are doctors. Still, 92 (50.0%) presented comorbidity, with heart disease predominating (n = 37; 40.2%). Of the 112 professionals with a record of evolution, 85 (75.9%) were cured and 27 (24.1%) died, 18 (66.7%) of whom were male. Conclusion. The profile descripted is similar to the population's in age and comorbidities, but different in relation to sex. The most affected areas were nursing and medicine.

Objetivo. Descrever os casos hospitalizados pela COVID-19 em profissionais de saúde no Brasil. Métodos. Estudo descritivo de tipo Série de Casos; foram incluídos aqueles com adoecimento entre 21 de fevereiro e 15 de abril de 2020, registrados no Sistema de Informação de Vigilância da Gripe (SIVEP-Gripe). Resultados. Dos 184 casos, 110 (59,8%) eram do sexo feminino, com mediana de idade de 44 anos (mínima-máxima: 23-85), 89 (48,4%) eram profissionais da enfermagem e 50 (27,2%) médicos. Ainda, 92 (50,0%) apresentavam comorbidade, predominando cardiopatias (n=37; 40,2%). Dos 112 profissionais com registro de evolução, 85 (75,9%) alcançaram cura e 27 (24,1%) foram a óbito, 18 destes do sexo masculino. Conclusão. O perfil dos profissionais de saúde hospitalizados por COVID-19 é semelhante ao da população quanto à idade e comorbidades; porém, diferente quanto ao sexo. As áreas profissionais mais acometidas foram a Enfermagem e a Medicina.

Descrição dos casos hospitalizados pela COVID-19 em profissionais de saúde nas primeiras nove semanas da pandemia, Brasil, 2020 / Descripción de los casos hospitalizados por COVID-19 en profesionales de salud en las primeras nueve semanas de la pandemia, Brasil, 2020 / Description of COVID-19 hospitalized health worker cases in the first nine weeks of the pandemic, Brazil, 2020

Objetivo: Descrever os casos hospitalizados pela COVID-19 em profissionais de saúde no Brasil. Métodos: Estudo descritivo de tipo série de casos; foram incluídos aqueles com adoecimento entre 21 de fevereiro e 15 de abril de 2020, registrados no Sistema de Informação de Vigilância da Gripe (SIVEP-Gripe). Resultados: Dos 184 casos, 110 (59,8%) eram do sexo feminino, com mediana de idade de 44 anos (mínima-máxima: 23-85); 89 (48,4%) eram profissionais da enfermagem e 50 (27,2%) eram médicos. Ainda, 92 (50,0%) apresentavam comorbidade, predominando cardiopatias (n=37; 40,2%). Dos 112 profissionais com registro de evolução, 85 (75,9%) alcançaram cura e 27 (24,1%) foram a óbito, 18 destes do sexo masculino. Conclusão: O perfil dos profissionais de saúde hospitalizados por COVID-19 é semelhante ao da população quanto à idade e comorbidades; porém, diferente quanto ao sexo. As áreas profissionais mais acometidas foram a enfermagem e a medicina.

Objetivo: Describir los casos hospitalizados por COVID-19 en profesionales de salud, en Brasil. Métodos: Estudio descriptivo del tipo serie de casos; se incluyeron aquellos que enfermaron entre el 21 de febrero y el 15 de abril de 2020, registrados en el Sistema de Información de Vigilancia de la Gripe (SIVEP-Gripe). Resultados: De los 184 (1,76%) casos 110 (59,8%) eran del sexo femenino, con promedio de edad de 44 años (mínima-máxima: 23-85), 89 (48,4%) eran profesionales de enfermería y 50 (27,2%) médicos. Además, 92 (50,0%) presentaron comorbilidad, predominando las cardiopatías (n=37; 40,2%). De los 112 profesionales con un historial de evolución, 85 (75,9%) fueron curados y 27 (24,1%) murieron, 18 de los cuales era de sexo masculino. Conclusión: El perfil de los hospitalizados por COVID-19 es similar al de la población en edad y comorbilidades, aunque diferente con relación a sexo. Las áreas más afectadas fueron la enfermería y la medicina.

Objective: To describe COVID-19 hospitalized health worker cases in Brazil. Methods: This was a descriptive case series study; it included cases that became ill between February 21st and April 15th, 2020 registered on the Influenza Surveillance Information System (SIVEP-Gripe, acronym in Portuguese). Results: Of the 184 cases, 110 (59.8%) were female and median age was 44 years (min-max: 23-85); 89 (48.4%) were nursing professionals and 50 (27.2%) were doctors. Ninety-two (50.0%) presented comorbidity, with heart disease predominating (n=37; 40.2%). Of the 112 professionals with a record of case progression, 85 (75.9%) were cured and 27 (24.1%) died, 18 of whom were male. Conclusion: The profile of COVID-19 hospitalized health workers is similar to that of the general population with regard to age and comorbidities, but different in relation to sex. The most affected areas were nursing and medicine.

[Anaphylaxis related to measles, mumps, and rubella vaccine in Santa Catarina State, Brazil, 2014 and 2015]. / Anafilaxia relacionada à vacina sarampo, caxumba e rubéola, Santa Catarina, Brasil, 2014 e 2015.

The study aimed to describe cases and verify the frequency of anaphylaxis related to measles, mumps, and rubella (MMR) vaccine produced by manufacturer A and to assess associated risk factors. This was a case-control study (1:4) in Santa Catarina State, Brazil, from July 14, 2014, to January 12, 2015, in children from one year to less than five years of age, vaccinated with MMR and reported with anaphylaxis, while the controls were without anaphylaxis. The measure of association was odds ratio (OR) with 95% confidence interval (95%CI), using the chi-square and Fisher's exact tests. Anaphylaxis rates were calculated per doses distributed/administered. Fifteen cases and 60 controls were interviewed in 12 municipalities (counties). Anaphylaxis rates were 2.46 and 5.05 cases per 100,000 doses distributed and administered, respectively. Among the cases of anaphylaxis, eight (53.4%) were males, and among the controls, 36 (60%), with p = 0.64. The bivariate analysis of anaphylaxis and cow's milk protein allergy (CMPA) showed OR = 51.62, with p = 0.00002 and 95%CI: 5.59-476.11. The variables family food allergy, breastfeeding, previous post-vaccine adverse event (PVAE), and simultaneous vaccination were not statistically significant (p = 0.48; p = 1.00; p = 0.49; p = 0.61). Anaphylaxis rates per doses distributed/administered exceeded 1/100,000 doses administered (expected rate). Anaphylaxis and CMPA showed a statistically significant association. No statistically significant associations were found with simultaneous vaccination, breastfeeding, family food allergy, or history of PVAE. RECOMMENDATIONS: the manufacturer should specify the product's components in the package insert, and children with a history of CMPA should not be vaccinated with this vaccine.

Os objetivos consistiram em descrever os casos e verificar a frequência de anafilaxia relacionada à vacina sarampo, caxumba e rubéola (SCR) do produtor A, bem como avaliar os possíveis fatores de risco associados. Estudo de caso-controle (1:4), em Santa Catarina, Brasil, de 14 de julho de 2014 a 12 de janeiro de 2015, em crianças de um a menores de cinco anos, vacinadas com SCR e notificadas com anafilaxia, sendo os controles sem anafilaxia. Utilizou-se, como medida de associação, odds ratio (OR) com intervalo de 95% de confiança (IC95%) e os testes qui-quadrado e exato de Fisher. Calcularam-se taxas de anafilaxia por doses distribuídas/aplicadas. Entrevistaram-se 15 casos e 60 controles, em 12 municípios. As taxas de anafilaxia foram 2,46 e 5,05 por doses distribuídas e aplicadas, respectivamente. Dentre os casos de anafilaxia, oito (53,4%) eram do sexo masculino, e dentre os controles, 36 (60%), com p = 0,64. Na análise bivariada referente à anafilaxia e alergia à proteína do leite de vaca (APLV), verificou-se OR = 51,62, com p = 0,00002 e IC95%: 5,59-476,11. As variáveis alergia alimentar familiar, aleitamento materno, evento adverso pós-vacinação (EAPV) anterior e vacinação simultânea não foram estatisticamente significativas (p = 0,48; p = 1,00; p = 0,49; p = 0,61). Taxas de anafilaxia por doses distribuídas/aplicadas ficaram acima de 1/100 mil doses aplicadas (taxa esperada). Anafilaxia e APLV apresentaram associação estatisticamente significativa. Não foram encontradas associações estatísticas referentes à vacinação simultânea, aleitamento materno, alergia alimentar familiar e EAPV anterior. Recomendou-se ao produtor informar na bula todos os componentes do produto e que crianças com história pregressa de APLV não sejam vacinadas com essa vacina.

Los objetivos consistieron en describir los casos y verificar la frecuencia de anafilaxia, relacionada con la vacuna del sarampión, paperas y rubeola (SCR) del productor A, así como evaluar los posibles factores de riesgo asociados. Estudio de caso-control (1:4), en Santa Catarina, Brasil, de 14 de julio de 2014 a 12 de enero de 2015, en niños de uno a menores de cinco años, vacunadas con SCR y notificadas con anafilaxia, siendo los controles sin anafilaxia. Se utilizó, como medida de asociación, odds ratio (OR) con un intervalo de 95% de confianza (IC95%) y los testes chi-cuadrado y exacto de Fisher. Se calcularon las tasas de anafilaxia por dosis distribuidas/aplicadas. Se entrevistaron 15 casos y 60 controles, en 12 municipios. Las tasas de anafilaxia fueron 2,46 y 5,05 por dosis distribuidas y aplicadas, respectivamente. Entre los casos de anafilaxia, ocho (53,4%) eran del sexo masculino, y entre los controles, 36 (60%), con p = 0,64. En el análisis bivariado referente a la anafilaxia y alergia a la proteína de leche de vaca (APLV), se verificó OR = 51,62, con p = 0,00002 e IC95%: 5,59-476,11. Las variables alergia alimentaria familiar, lactancia materna , evento adverso pos-vacunación (EAPV) anterior y vacunación simultánea no fueron estadísticamente significativas (p = 0,48; p = 1,00; p = 0,49; p = 0,61). Tasas de anafilaxia por dosis distribuidas/aplicadas se situaron encima de 1/100.000 dosis aplicadas (tasa esperada). Anafilaxia y APLV presentaron una asociación estadísticamente significativa. No fueron encontradas asociaciones estadísticas referentes a la vacunación simultánea, lactancia materna, alergia alimentaria familiar y EAPV anterior. Se recomendó al productor informar en el prospecto sobre todos los componentes del producto, y que los niños con historial anterior de APLV no sean vacunados con esa vacuna.

Anafilaxia relacionada à vacina sarampo, caxumba e rubéola, Santa Catarina, Brasil, 2014 e 2015 / Anaphylaxis related to measles, mumps, and rubella vaccine in Santa Catarina State, Brazil, 2014 and 2015 / Anafilaxia relacionada a la vacuna sarampión, paperas y rubeola, Santa Catarina, Brasil, 2014 y 2015

Resumo: Os objetivos consistiram em descrever os casos e verificar a frequência de anafilaxia relacionada à vacina sarampo, caxumba e rubéola (SCR) do produtor A, bem como avaliar os possíveis fatores de risco associados. Estudo de caso-controle (1:4), em Santa Catarina, Brasil, de 14 de julho de 2014 a 12 de janeiro de 2015, em crianças de um a menores de cinco anos, vacinadas com SCR e notificadas com anafilaxia, sendo os controles sem anafilaxia. Utilizou-se, como medida de associação, odds ratio (OR) com intervalo de 95% de confiança (IC95%) e os testes qui-quadrado e exato de Fisher. Calcularam-se taxas de anafilaxia por doses distribuídas/aplicadas. Entrevistaram-se 15 casos e 60 controles, em 12 municípios. As taxas de anafilaxia foram 2,46 e 5,05 por doses distribuídas e aplicadas, respectivamente. Dentre os casos de anafilaxia, oito (53,4%) eram do sexo masculino, e dentre os controles, 36 (60%), com p = 0,64. Na análise bivariada referente à anafilaxia e alergia à proteína do leite de vaca (APLV), verificou-se OR = 51,62, com p = 0,00002 e IC95%: 5,59-476,11. As variáveis alergia alimentar familiar, aleitamento materno, evento adverso pós-vacinação (EAPV) anterior e vacinação simultânea não foram estatisticamente significativas (p = 0,48; p = 1,00; p = 0,49; p = 0,61). Taxas de anafilaxia por doses distribuídas/aplicadas ficaram acima de 1/100 mil doses aplicadas (taxa esperada). Anafilaxia e APLV apresentaram associação estatisticamente significativa. Não foram encontradas associações estatísticas referentes à vacinação simultânea, aleitamento materno, alergia alimentar familiar e EAPV anterior. Recomendou-se ao produtor informar na bula todos os componentes do produto e que crianças com história pregressa de APLV não sejam vacinadas com essa vacina.

Abstract: The study aimed to describe cases and verify the frequency of anaphylaxis related to measles, mumps, and rubella (MMR) vaccine produced by manufacturer A and to assess associated risk factors. This was a case-control study (1:4) in Santa Catarina State, Brazil, from July 14, 2014, to January 12, 2015, in children from one year to less than five years of age, vaccinated with MMR and reported with anaphylaxis, while the controls were without anaphylaxis. The measure of association was odds ratio (OR) with 95% confidence interval (95%CI), using the chi-square and Fisher's exact tests. Anaphylaxis rates were calculated per doses distributed/administered. Fifteen cases and 60 controls were interviewed in 12 municipalities (counties). Anaphylaxis rates were 2.46 and 5.05 cases per 100,000 doses distributed and administered, respectively. Among the cases of anaphylaxis, eight (53.4%) were males, and among the controls, 36 (60%), with p = 0.64. The bivariate analysis of anaphylaxis and cow's milk protein allergy (CMPA) showed OR = 51.62, with p = 0.00002 and 95%CI: 5.59-476.11. The variables family food allergy, breastfeeding, previous post-vaccine adverse event (PVAE), and simultaneous vaccination were not statistically significant (p = 0.48; p = 1.00; p = 0.49; p = 0.61). Anaphylaxis rates per doses distributed/administered exceeded 1/100,000 doses administered (expected rate). Anaphylaxis and CMPA showed a statistically significant association. No statistically significant associations were found with simultaneous vaccination, breastfeeding, family food allergy, or history of PVAE. Recommendations: the manufacturer should specify the product's components in the package insert, and children with a history of CMPA should not be vaccinated with this vaccine.

Resumen: Los objetivos consistieron en describir los casos y verificar la frecuencia de anafilaxia, relacionada con la vacuna del sarampión, paperas y rubeola (SCR) del productor A, así como evaluar los posibles factores de riesgo asociados. Estudio de caso-control (1:4), en Santa Catarina, Brasil, de 14 de julio de 2014 a 12 de enero de 2015, en niños de uno a menores de cinco años, vacunadas con SCR y notificadas con anafilaxia, siendo los controles sin anafilaxia. Se utilizó, como medida de asociación, odds ratio (OR) con un intervalo de 95% de confianza (IC95%) y los testes chi-cuadrado y exacto de Fisher. Se calcularon las tasas de anafilaxia por dosis distribuidas/aplicadas. Se entrevistaron 15 casos y 60 controles, en 12 municipios. Las tasas de anafilaxia fueron 2,46 y 5,05 por dosis distribuidas y aplicadas, respectivamente. Entre los casos de anafilaxia, ocho (53,4%) eran del sexo masculino, y entre los controles, 36 (60%), con p = 0,64. En el análisis bivariado referente a la anafilaxia y alergia a la proteína de leche de vaca (APLV), se verificó OR = 51,62, con p = 0,00002 e IC95%: 5,59-476,11. Las variables alergia alimentaria familiar, lactancia materna , evento adverso pos-vacunación (EAPV) anterior y vacunación simultánea no fueron estadísticamente significativas (p = 0,48; p = 1,00; p = 0,49; p = 0,61). Tasas de anafilaxia por dosis distribuidas/aplicadas se situaron encima de 1/100.000 dosis aplicadas (tasa esperada). Anafilaxia y APLV presentaron una asociación estadísticamente significativa. No fueron encontradas asociaciones estadísticas referentes a la vacunación simultánea, lactancia materna, alergia alimentaria familiar y EAPV anterior. Se recomendó al productor informar en el prospecto sobre todos los componentes del producto, y que los niños con historial anterior de APLV no sean vacunados con esa vacuna.

Descrição dos primeiros casos de febre pelo vírus Zika investigados em municípios da região Nordeste do Brasil, 2015 / Descripción de los primeros casos de fiebre por el virus Zika investigados en los municipios de la región noreste de Brasil, 2015 / Description of the first cases of Zika virus fever investigated in municipalities of the Brazilian Northeastern Region, 2015

OBJETIVO: Confirmar a circulação do vírus Zika e descartar outros agentes etiológicos em surto ocorrido no Rio Grande do Norte (RN), Maranhão (MA) e Paraíba (PB), em maio/2015. MÉTODOS: estudo descritivo de série de casos com residentes em Natal-RN, Barra do Corda-MA, São Luís-MA e João Pessoa-PB, 20 em cada estado, com exantema e ausência de febre ou febre baixa e um dos seguintes sinais/sintomas, hiperemia conjuntival, artralgia ou edema de membros; realizou-se RT-PCR/isolamento para Zika, enterovírus e vírus respiratórios, e sorologias (dengue, rubéola e parvovírus B19). RESULTADOS: os principais sintomas foram exantema (n=60), prurido (n=54) e artralgia (n=47); 51 indivíduos não apresentaram febre; identificou-se vírus Zika em 18 casos (12 na PB, quatro no MA e dois no RN) e anticorpos para dengue em 14. CONCLUSÃO: os sintomas foram compatíveis com febre pelo vírus Zika; houve confirmação laboratorial de Zika e dengue.

OBJETIVOS: confirmar la circulación del virus Zika y descartar otros agentes etiológicos en el brote ocurrido en Rio Grande do Norte (RN), Maranhão (MA) y Paraíba (PB), en mayo/2015. MÉTODOS: estudio descriptivo de serie de casos con residentes de Natal-RN, Barra do Corda-MA, São Luís-MA y João Pessoa-PB, 20 en cada estado, con exantema y ausencia de fiebre o fiebre baja y uno de los siguientes signos/síntomas, hiperemia conjuntival, artralgia o edema de miembros; se realizaron RT-PCR/aislamiento para Zika, enterovirus y virus respiratorios y serologías (dengue, rubéola y parvovirus B19). RESULTADOS: los principales síntomas fueron exantema (n=60), prurito (n=54) y artralgia (n=47); 51 individuos no presentaron fiebre, se identificó virus Zika en 18 casos (12 en PB, cuatro en MA y dos en RN) y anticuerpos para dengue en 14. CONCLUSIÓN: Los síntomas fueron compatibles con fiebre por el virus Zika; hubo confirmación por laboratorio de Zika y dengue.

OBJECTIVE: to confirm Zika virus circulation and discard other etiological agents in an outbreak occurred in the states of Rio Grande do Norte, Maranhão and Paraíba, in May, 2015. METHODS: this is a case series descriptive study with residents in Natal-RN, Barra do Corda-MA, São Luis-MA and João Pessoa-PB, with 20 cases in each state, presenting rash, absent or mild fever and one of the following signs/symptoms: conjunctival hyperemia, arthralgia or limb edema; RT-PCR/isolation tests for Zika, enterovirus and respiratory viruses, and serology tests (dengue, rubella and parvovirus B19) were performed. RESULTS: the main symptoms were rash (n=60), pruritus (n=54), and arthralgia (n=47); 51 individuals did not present fever; Zika virus was identified in 18 cases (12 in Paraíba, four in Maranhão and two in Rio Grande do Norte), and antibodies to dengue, in 14 cases. CONCLUSION: the symptoms were consistent with Zika virus fever; there was laboratory confirmation for Zika and dengue.

Description of the first cases of Zika virus fever investigated in municipalities of the Brazilian Northeastern Region, 2015. / Descrição dos primeiros casos de febre pelo vírus Zika investigados em municípios da região Nordeste do Brasil, 2015.

OBJECTIVE: to confirm Zika virus circulation and discard other etiological agents in an outbreak occurred in the states of Rio Grande do Norte, Maranhão and Paraíba, in May, 2015. METHODS: this is a case series descriptive study with residents in Natal-RN, Barra do Corda-MA, São Luis-MA and João Pessoa-PB, with 20 cases in each state, presenting rash, absent or mild fever and one of the following signs/symptoms: conjunctival hyperemia, arthralgia or limb edema; RT-PCR/isolation tests for Zika, enterovirus and respiratory viruses, and serology tests (dengue, rubella and parvovirus B19) were performed. RESULTS: the main symptoms were rash (n=60), pruritus (n=54), and arthralgia (n=47); 51 individuals did not present fever; Zika virus was identified in 18 cases (12 in Paraíba, four in Maranhão and two in Rio Grande do Norte), and antibodies to dengue, in 14 cases. CONCLUSION: the symptoms were consistent with Zika virus fever; there was laboratory confirmation for Zika and dengue.