Zika virus (ZIKV) is an emerging virus involved in recent outbreaks in Brazil. The association between the virus and Guillain-Barré syndrome (GBS) or congenital disorders has raised a worldwide concern. In this work, we investigated a rare Zika case, which was associated with GBS and spontaneous retained abortion. Using specific anti-ZIKV staining, the virus was identified in placenta (mainly in Hofbauer cells) and in several fetal tissues, such as brain, lungs, kidneys, skin and liver. Histological analyses of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema and necrosis in placenta, as well as tissue disorganization in the fetus. Increased cellularity (Hofbauer cells and TCD8+ lymphocytes), expression of local pro-inflammatory cytokines such as IFN-γ and TNF-α, and other markers, such as RANTES/CCL5 and VEGFR2, supported placental inflammation and dysfunction. The commitment of the maternal-fetal link in association with fetal damage gave rise to a discussion regarding the influence of the maternal immunity toward the fetal development. Findings presented in this work may help understanding the ZIKV immunopathogenesis under the rare contexts of spontaneous abortions in association with GBS.

During Schistosoma mansoni infection, there is morphological evidence of involvement of various hematopoietic growth factors, which cause eosinophil, neutrophil, megakaryocytic and erythroid extramedullary foci in the liver, lymph nodes and omental and mesenteric milky spots. While the eosinophil metaplasia in the periphery of hepatic granulomas roughly reproduced the intensity of the medullary eosinopoiesis, the neutrophil metaplasia, on the contrary, was more intense during the period of neutrophil depression in the bone marrow. This fact suggests that extramedullary hematopoietic foci are locally regulated, and amplify and/or compensate the systemic hematopoietic response during the infection.

A Síndrome de Bloch-Sulzberger (Incontinência Pigmentar) é uma genodermatose rara, que afeta, principalmente, o sexo feminino, pois costuma ser letal em pacientes do sexo masculino intraútero. Caracteriza-se, principalmente, pelas manifestações dermatológicas, podendo também apresentar anomalias dentárias, oftalmológicas e neurológicas. As lesões cutâneas apresentam 4 fases distintas: vesiculosa, verrucosa, pigmentar e atrófica; que podem seguir uma sequência irregular, havendo até sobreposição das mesmas

Background Neurological and other systemic complications occur in adults with severe COVID-19. Here we describe SARS-CoV-2 infection complicated by neuroinvasion in the post-mortem tissues of a child. Methods We performed a complete autopsy of a 14-month-old child who died of COVID-19 pneumonitis. Histological sections of multiple organs were stained with haematoxylin and eosin. Luxol fast blue staining for myelin and immunohistochemistry were performed in selected areas of the brain. The presence of SARS-CoV-2 was investigated by immunostaining with anti-spike protein antibody and by RT-qPCR. Findings Lesions included microthrombosis, pulmonary congestion, interstitial oedema, lymphocytic infiltrates, bronchiolar injury, collapsed alveolar spaces, cortical atrophy, and severe neuronal loss. SARS-CoV-2 staining was observed along the apical region of the choroid plexus (ChP) epithelium and in ependymal cells of the lateral ventricle, but was restricted to ChP capillaries and vessels in some regions. SARS-CoV-2 infection of brain tissue was confirmed by RT-qPCR in fragments of the ChP, lateral ventricle, and cortex. Interpretation Our results show multisystemic histopathological alterations caused by SARS-CoV-2 infection and contribute to knowledge regarding the course of fatal COVID-19 in children. Furthermore, our findings of ChP infection and viral neurotropism suggest that SARS-CoV-2 may invade the central nervous system by blood-cerebrospinal fluid barrier disruption. Funding Carlos Chagas Filho Foundation for Supporting Research in the State of Rio de Janeiro (FAPERJ); the National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES), in addition to intramural grants from D'Or Institute for Research and Education. Resumo Complicações sistêmicas e neurológicas foram descritas em adultos com COVID-19 grave. Neste trabalho, descrevemos a infecção por SARS-CoV-2, incluindo sua neuroinvasão, nos tecidos post-mortem de uma criança. Métodos Realizamos a autópsia completa de uma criança de 14 meses que morreu de pneumonite por COVID-19. Cortes histológicos de múltiplos órgãos foram corados com Hematoxilina e Eosina. A coloração de Luxol Fast Blue para mielina e imuno-histoquímica foram realizadas em áreas selecionadas do cérebro. A presença de SARS-CoV-2 foi investigada por imunomarcação com anticorpo anti-proteína spike e por RT-qPCR. Achados As lesões incluíram microtrombose, congestão pulmonar, edema intersticial, infiltrados linfocíticos, lesão bronquiolar, colapso dos espaços alveolares, atrofia cortical e perda neuronal grave. A presença de SARS-CoV-2 foi observada ao longo da região apical do epitélio do plexo coróide (PC) e nas células ependimárias do ventrículo...

The first fatal case caused by the new genome type 7i is described in an 8-month-old boy requiring long-term respiratory support who developed Reye's syndrome, acute respiratory distress, and bronchiolitis obliterans with fatal evolution. Adenovirus was detected in nasopharyngeal secretions and was persistently positive during hospitalization. IgM and IgG adenovirus antibody titers measured in serum by enzyme-linked immunoassay (EIA) were 1:32 and 1:800, respectively. Serum interleukins (IL) and interferons (IFN) measured by EIA were as follows: IL-2, 110 pg/ml; IL-6, 300 pg/ml; IL-8, 7,000 pg/ml; TNF-alpha, 35 pg/ml, IL-1 and IL-4 undetectable, IFN-alpha 2,200 pg/ml, and IFN-gamma 700 pg/ml. Virologic studies showed that adenovirus isolated belonged to subgenus B, and digestion of viral DNA with Bam HI, Sma I, Bgl II, and Hind III identified the isolate as belonging to genome type 7i. Autopsy showed bronchiolitis obliterans with diffuse alveolar damage and perivenular fatty degeneration with polymorphonuclear infiltrates in the periportal spaces. The difficulty in obtaining adequate oxygenation with minimization of iatrogenic oxygen injury is discussed.

Immunotherapy can revolutionize anti-cancer therapy if specific targets are available.

Coronavirus disease 2019 (COVID-19) was initially characterized as a respiratory illness. Neurological manifestations were reported mostly in severely affected patients. Routes for brain infection and the presence of virus particles in situ have not been well described, raising controversy about how the virus causes neurological symptoms. Here, we report the autopsy findings of a 1-year old infant with COVID-19. In addition to pneumonitis, meningitis and multiple organ damage related to thrombosis, a previous encephalopathy may have contributed to additional cerebral damage. SARS-CoV-2 infected the choroid plexus, ventricles, and cerebral cortex. This is the first evidence of SARS-CoV-2 detection in an infant post-mortem brain.

Immunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated by protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis of Variable gene Expressions in Numerous tissues) that automatizes the systematic and fast identification of CSG-encoded peptides highly affine to Major Histocompatibility Complexes (MHC) starting from transcriptome data. We applied RAVEN to a dataset assembled from 2,678 simultaneously normalized gene expression microarrays comprising 50 tumor entities, with a focus on oligo-mutated pediatric cancers, and 71 normal tissue types. RAVEN performed a transcriptome-wide scan in each cancer entity for gender-specific CSGs, and identified several established CSGs, but also many novel candidates potentially suitable for targeting multiple cancer types. The specific expression of the most promising CSGs was validated in cancer cell lines and in a comprehensive tissue-microarray. Subsequently, RAVEN identified likely immunogenic CSG-encoded peptides by predicting their affinity to MHCs and excluded sequence identity to abundantly expressed proteins by interrogating the UniProt protein-database. The predicted affinity of selected peptides was validated in T2-cell peptide-binding assays in which many showed binding-kinetics like a very immunogenic influenza control peptide. Collectively, we provide an exquisitely curated catalogue of cancer-specific and highly MHC-affine peptides across 50 cancer types, and a freely available software (https://github.com/JSGerke/RAVENsoftware) to easily apply our algorithm to any gene expression dataset. We anticipate that our peptide libraries and software constitute a rich resource to advance anti-cancer immunotherapy.