ABSTRACT
Os efeitos generalizados exercidos pela pandemia da doença do Coronavírus 2019 (COVID-19) obrigaram governos e instituições de saúde mundiais a deslocar recursos para a contenção da crise sanitária e a desenvolver métodos para reduzi-los. As vacinas foram elencadas como principal método para conter a pandemia, com mais de um bilhão de doses administradas em todo o mundo. Entre as vacinas produzidas até o momento para combate ao vírus causador, SARS-CoV-2, estão as vacinas de vetores de adenovírus da Oxford-AstraZeneca (AZD1222) e a da Johnson & Johnson (Ad26.COV2.S). Após a implementação da vacinação em massa da população mundial, relatou-se um distúrbio pró-trombótico extremamente raro associado a ambas vacinas com trombocitopenia concomitante e desenvolvimento de anticorpos antiplaquetários fator 4 (anti-PF4). Esta desordem foi denominada inicialmente como Síndrome da Trombose com Trombocitopenia (STT) e posteriormente como Trombose Trombocitopênica Imune induzida por Vacina (TTIV). Os primeiros casos de trombose relacionados à vacinação para o SARS-CoV-2 começaram a ser reportados no final de fevereiro de 2021. Os relatos levaram à abertura de uma investigação pelas Agências do Reino Unido de Regulação de Produtos de Saúde e Medicina (MHRA) e Europeia de Medicina (EMA), as quais anunciaram em 11 de março de 2021 que não havia uma associação identificada. Entretanto, três grupos de cientistas da Noruega, Alemanha e Reino Unido reportaram, na semana seguinte, um caso de trombose localizada no seio venoso cerebral com trombocitopenia e anticorpos antiplaquetários fator 4 em um indivíduo que havia recebido a vacina da Oxford-AstraZeneca. Após maiores investigações, em 7 de abril de 2021, MHRA e EMA anunciaram a nova Síndrome de Trombose com Trombocitopenia e anticorpos antiplaquetários fator 4. Em 11 de novembro de 2021, houve a elaboração de uma definição de caso para STT, realizada pelo Brighton Collaboration, a qual engloba 5 critérios: (1) evidência de trombocitopenia sem exposição recente à heparina; (2) presença de trombose ou tromboembolismo confirmado por exame de imagem, procedimento cirúrgico, exame patológico ou dor de cabeça persistente com elevação de D-dímero (sugerindo trombose de seio venoso cerebral); (3) sintomas clínicos de trombose (Quadro 1); (4) exames de imagem e achados laboratoriais que confirmem o diagnóstico de trombose ou tromboembolismo; (5) achados laboratoriais que confirmem o diagnóstico de anticorpos de ativação plaquetária mediados por trombose, como enzima-imunoensaio (EIA) positivo para anti-PF4 e teste funcional positivo de ativação plaquetária com adição de PF4.
Subject(s)
Humans , Thrombocytopenia/chemically induced , Thrombosis/chemically induced , Adenovirus Vaccines/adverse effects , COVID-19/prevention & control , Syndrome , Thrombocytopenia/diagnosis , Thrombosis/drug therapyABSTRACT
Se describe la situación global de las infecciones por SARS-CoV-2 y los cuadros clínicos de COVID-19. Se presentan datos epidemiológicos de Centro América y de Guatemala, para ejemplificar algunos factores de riesgo de infección y morbilidad. Se revisa la función y estructura del sistema respiratorio, sus mecanismos de defensa innata -captura y remoción de agentes extraños, reconocimiento e inactivación de agentes potencialmente nocivos, reparación del daño y prevención de futuras incursiones por agentes identificados-, los de defensa adaptativa en las vías respiratorias y el microbioma. Se describen los tejidos linfoides nasal y bronquio-alveolar y la contribución de citoquinas, células especializadas y anticuerpos del tipo IgA secretoria a la protección antiviral, a la respuesta inflamatoria asociada a la infección y a la reparación del daño tisular. Se discuten las interacciones de SARS-CoV-2 con los mecanismos de defensa. Se presentan consideraciones para las medidas preventivas de infecciones, incluyendo la aplicación de vacunas, y para evitar enfermedad severa.
The global situation of SARS-CoV-2 infections and the clinical picture of COVID-19 are described. Epidemiological data from Central America and Guatemala are presented to exemplify some risk factors for infection and morbidity. The function and structure of the respiratory system and its innate defense mechanisms - capture and removal of foreign agents, recognition and inactivation of potentially harmful agents, repair of damage, and prevention of future incursions by identified agents are reviewed, as are those of the adaptive defense in the airways and of the respiratory microbiome. The nasal and bronchioalveolar lymphoid tissues are described. The contributions of cytokines, of specialized cells and of secretory IgA-type antibodies to antiviral protection, to the inflammatory response associated with infection, and to the repair of tissue damage are explained. SARS-CoV-2 interactions with defense mechanisms are discussed. Considerations are presented for the preventive measures of infections, including the application of vaccines, and those designed to avoid severe disease.
Subject(s)
Humans , Respiratory System , SARS-CoV-2 , COVID-19/prevention & control , Antiviral Agents , Morbidity , Defense Mechanisms , Adenovirus Vaccines , AntibodiesABSTRACT
The major immunogenic protein capsid (Cap) of porcine circovirus type 2 (PCV2) is critical to induce neutralizing antibodies and protective immune response against PCV2 infection. This study was conducted to investigate the immune response of recombinant adenovirus expressing PCV2b Cap and C-terminal domain of Yersinia pseudotuberculosis invasin (Cap-InvC) fusion protein in pigs. The recombinant adenovirus rAd-Cap-InvC, rAd-Cap and rAd were generated and used to immunize pigs. The phosphate-buffered saline was used as negative control. The specific antibodies levels in rAd-Cap-InvC and ZJ/C-strain vaccine groups were higher than that of rAd-Cap group (p < 0.05), and the neutralization antibody titer in rAd-Cap-InvC group was significantly higher than those of other groups during 21–42 days post-immunization (DPI). Moreover, lymphocyte proliferative level, interferon-γ and interleukin-13 levels in rAd-Cap-InvC group were increased compared to rAd-Cap group (p < 0.05). After virulent challenge, viruses were not detected from the blood samples in rAd-Cap-InvC and ZJ/C-strain vaccine groups after 49 DPI. And the respiratory symptom, rectal temperature, lung lesion and lymph node lesion were minimal and similar in the ZJ/C-strain and rAd-Cap-InVC groups. In conclusion, our results demonstrated that rAd-Cap-InvC was more efficiently to stimulate the production of antibody and protect pigs from PCV2 infection. We inferred that InvC is a good candidate gene for further development and application of PCV2 genetic engineering vaccine.
Subject(s)
Adenoviridae , Adenovirus Vaccines , Antibodies , Antibodies, Neutralizing , Capsid , Capsid Proteins , Circovirus , Genetic Engineering , Immunization , Interleukin-13 , Lung , Lymph Nodes , Lymphocytes , Swine , Yersinia pseudotuberculosisABSTRACT
Abstract Human adenovirus species F (HAdV-F) type 40 and 41 are commonly associated with acute diarrheal disease (ADD) across the world. Despite being the largest state in southeastern Brazil and having the second largest number of inhabitants, there is no information in the State of Minas Gerais regarding the role of HAdV-F in the etiology of ADD. This study was performed to determine the prevalence, to verify the epidemiological aspects of infection, and to characterize the strains of human adenoviruses (HAdV) detected. A total of 377 diarrheal fecal samples were obtained between January 2007 and August 2011 from inpatient and outpatient children of age ranging from 0 to 12 years. All samples were previously tested for rotavirus, norovirus, and astrovirus, and 314 of 377 were negative. The viral DNA was extracted, amplified using the polymerase chain reaction and the HAdV-positive samples were sequenced and phylogenetically analyzed. Statistical analyses were performed using the Chi-square test (p < 0.05), considering two conditions: the total of samples tested (377) and the total of negative samples for the remaining viruses tested (314). The overall prevalence of HAdV was 12.47% (47/377); and in 76.60% (36/47) of the positive samples, this virus was the only infectious agent detected. The phylogenetic analysis of partial sequences of 32 positive samples revealed that they all clustered with the HAdV-F type 41. The statistical analysis showed that there was no correlation between the onset of the HAdV infection and the origin of the samples (inpatients or outpatients) in the two conditions tested: the total of samples tested (p = 0.598) and the total of negative samples for the remaining viruses tested (p = 0.614). There was a significant association in the occurrence of infection in children aged 0–12 months for the condition 1 (p = 0.030) as well as condition 2 (p = 0.019). The occurrence of infections due to HAdV did not coincide with a pattern of seasonal distribution. These data indicate the significant involvement of HAdV-F type 41 in the etiology of ADD in Minas Gerais, which demonstrates the importance of other viral agents in the development of the disease after the introduction of rotavirus vaccine immunization.