ABSTRACT
Background: The emergence of new variants of SARS-CoV-2 has led to the administration of different booster vaccines to mitigate COVID-19. Vaccines with adenoviral vectors have been rarely associated with vaccine-induced immune thrombotic thrombocytopenia (VITT). Objectives: This study aimed to describe 15 cases of VITT after the third and fourth doses of the COVID-19 vaccine in Brazil. Methods: Cases were reported after all kinds of anti-SARS-CoV-2 booster vaccinations between October 17, 2021, and September 4, 2022. Results: Of the 26 suspected cases, 15 cases of VITT were analyzed. Of these, 10 were classified as definite VITT, 2 as probable, 1 as possible, and 2 as unlikely. The estimated frequency of definite, probable, or possible VITT was 0.33 cases per million. Cases were assigned to ChAdOx1 (13 cases), Ad26.COV2.S (1 case), and BNT162b2 (1 case). None of the patients received an adenoviral vaccine as a primary vaccination. The average age of participants was 34 years, and symptoms usually appeared 8 days after vaccination. Headache was the most common symptom, and cerebral veins were the most affected thrombotic site. The overall mortality risk was 53%. Anti-platelet factor 4 enzyme-linked immunosorbent assay serology was positive in 11 out of 15 patients (73.3%), negative in 2 (13.3%), and missing in 2 (13.3%). Conclusion: The study confirms that VITT is linked to the first exposure to adenoviral vector vaccines. Since January 2023, Brazil has recommended preferably COVID-19 messenger RNA vaccines for individuals aged 18 to 39 years. We suggest that, in the current disease scenario, COVID-19 adenovirus vaccines should not be the first choice for individuals aged <50 years who have not received a previous dose of this type of vaccine.
ABSTRACT
The present investigation comprised two independent observational arms to evaluate the influence of pre-existing flavivirus humoral immunity and the age-impact on 17DD-YF vaccination immunity. Flavivirus (YFV; DENV; ZIKV) serology and YF-specific cellular immunity was evaluated in 288 children/9Mths-4Yrs and 288 adults/18-49Yrs residents of areas without YFV circulation. Data demonstrated that flavivirus seropositivity at baseline was higher in Adults as compared to Children (26%;87%;67% vs 6%;13%;15%, respectively). The heterologous flavivirus seropositivity (DENV; ZIKV) did not impact the YF-specific cellular immune response at baseline. However, higher levels of NCD4, EMCD8, IFN-MCD8, NCD19 and nCMCD19 were observed in subjects with pre-existing YFV seropositivity. Primary vaccination of YFV-seronegative volunteers led to higher levels of YF-neutralizing antibodies in Adults as compared to Younger Children (9Mths-2Yrs). Although similar seropositivity rates observed amongst Children and Adults at D30-45, lower rates were observed in Younger Children (9Mths-2Yrs) at D365 (94%;95%;100% vs 87%;96%;99%, respectively). A progressive decline in antibody levels were reported at D365, being more expressive in Children as compared to Adults. All age-subgroups exhibited at D30-45 increased levels of eEfCD4, EMCD4, IFN-MCD8 and nCMCD19 together with a decrease of eEfCD8 and CMCD8. While an increase of EMCD8 were observed in all subgroups at D30-45, a declined duration at D365 was reported only in Younger Children (9Mths-2Yrs). Biomarker signatures further support that only Younger Children (9Mths-2Yrs) presented a progressive decline of EMCD8 at D365. Together, these findings demonstrated that regardless the similarities observed in YF-neutralizing antibodies, the age impacts the duration of cellular immune response to primary 17DD-YF vaccination.
Subject(s)
Yellow Fever Vaccine , Yellow Fever , Zika Virus Infection , Zika Virus , Adult , Antibodies, Neutralizing , Antibodies, Viral , Child , Humans , Immunity, Cellular , Vaccination , Yellow Fever/prevention & control , Yellow fever virusABSTRACT
A sobrevida em pacientes com câncer de mama tem aumentado nos últimos anos graças aos avanços no tratamento e na detecção precoce da doença. Com isso, desfechos intermediários e competitivos ao óbito pelo câncer de mama se tornaram desfechos importantes, a fim de evitar a piora da qualidade de vida, agravamento da doença e óbito por outras causas. Essa dissertação pretende avaliar a influência de fatores socioeconômicos, clínicos, anatomopatológicos e do tratamento na evolução clínica de mulheres com câncer primário de mama. A população de estudo é formada por pacientes do sexo feminino atendidas em um centro de referência em câncer no Rio de Janeiro no período de janeiro de 2003 a dezembro de 2005. O estudo foi dividido em dois artigos, em que o primeiro avaliou os efeitos dos fatores que se associam às diferentes causas de óbito em mulheres com câncer de mama utilizando modelos de riscos competitivos, e o segundo investigou os fatores associados a cada mudança na evolução clínica de mulheres com câncer de mama utilizando modelo multi-estado. No primeiro artigo foram analisadas 2753 mulheres e como desfechos óbito por câncer de mama e óbito não relacionado à doença. Idade avançada, raça/cor não branca, pior estadiamento e tabagismo foram associados à um maior risco de óbito por câncer de mama, enquanto que apenas a idade avançada foi associada à um maior risco de óbito por causa não relacionado à doença.
O segundo artigo analisou 2709 mulheres em relação à transição entre quatro estados: diagnóstico (s1), ativa/capaz de se cuidar (s2), incapaz de se cuidar (s3) e recidiva/metástase/óbito (s4). Fatores como idade avançada, raça/cor não branca, ausência de histórico familiar de câncer, neoplasias ductais e lobulares, bilateralidade do tumor e receptores hormonais negativos, independentemente do estadiamento clínico, foram associados à piora na capacidade funcional e ao agravamento da doença. Os resultados dessa dissertação evidenciam a importância da avaliação de desfechos intermediários e competitivos ao óbito por câncer de mama nos cuidados com as pacientes, para que sejam traçadas estratégias para aumento de sobrevida e melhora da qualidade de vida.
Survival in patients with breast cancer has increased in recent years due to advances in treatment and early detection of disease. Thus, intermediate and competitive outcomes to death by breast cancer have become important outcomes in order to avoid worsening the quality of life, worsening of disease and death from other causes. This dissertation aims to evaluate the influence of socioeconomic, clinical, pathological and treatment factors on clinical evolution in women with primary breast cancer. The study population consists of female patients with a primary diagnosis of breast cancer treated at a referral center for cancer in Rio de Janeiro enrolled from January 2003 to December 2005. The study was divided into two articles, in which the first evaluated the effects of factors that are associated with different causes of death in women with breast cancer using models of competing risks, and the second investigated the factors associated with each change in clinical evolution of women with breast cancer using multi-state model. In the first article were analyzed 2753 women and outcomes as death from breast cancer and death not related to disease. Older age, race / non-white, worse staging and smoking were associated with a higher risk of death from breast cancer, while only older age was associated with a higher risk of death from causes not related to disease.
The second article examined 2709 women in relation to the transition between four states: diagnosis (s1), active / able to take care of self (s2), unable to care of self (s3) and recurrence / metastasis / death (s4). Factors such as older age, race / non-white, no family history of cancer, ductal and lobular neoplasia, bilateral breast cancer and negative hormone receptor, regardless of clinical stage, were associated with worse Performance Status and the worsening of the disease. The results of this dissertation show the importance of the evaluation of intermediate and competitive outcomes to death from breast cancer in the care of the patients, so that strategies can be traced to increased survival and improved quality of life.
