Distinct Immune Phenotypes and Cytokine Profiles in Children with Differing Severity of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is usually mild and self-limited in children. However, a few Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections in children may progress to severe disease with respiratory distress or can result in a multisystem inflammatory syndrome (MIS-C) associated with COVID-19. The immune mechanisms for these differential clinical outcomes are largely unknown. METHODS: A prospective cohort study was performed to analyze the laboratory parameters, antibody response, immune phenotypes and cytokine profiles of 51 children with different clinical presentations of COVID-19. RESULTS: We found that the absolute lymphocyte counts gradually decreased with disease severity. Furthermore, SARS-CoV-2 IgG levels in the acute phase and convalescence were not significantly different in patients with different disease severity. A decrease in CD3 + , CD4 + and CD8 + T cells was observed as disease severity increased. Both CD4 + and CD8 + T cells were activated in children with COVID-19, but no difference in the percentage of HLADR + -expressing cells was detected across the severity groups. In contrast, MIS-C patients exhibited augmented exhausted effector memory CD8 + T cells. Interestingly, the cytokine profile in sera of moderate/severe and MIS-C patients revealed an increase in anti-inflammatory IL-1RA and a suppression of tumor necrosis factor-α, RANTES, eotaxin and PDGF-BB. MIS-C patients also exhibited augmented IL-1ß. CONCLUSIONS: We report distinct immune profiles dependent on severity in pediatric COVID-19 patients. Further investigation in a larger population will help unravel the immune mechanisms underlying pediatric COVID-19.

Immune Monitoring of Patients With Primary Immune Regulation Disorders Unravels Higher Frequencies of Follicular T Cells With Different Profiles That Associate With Alterations in B Cell Subsets.

Primary immune regulation disorders lead to autoimmunity, allergy and inflammatory conditions due to defects in the immune homeostasis affecting different T, B and NK cell subsets. To improve our understanding of these conditions, in this work we analyzed the T and B cell compartments of 15 PID patients with dysregulation, including 3 patients with STAT1 GOF mutation, 7 patients with CVID with dysregulation, 3 patients with mutations in CTLA4, 1 patient with CD25 mutation and 1 patient with STAT5b mutation and compared them with healthy donors and with CVID patients without dysregulation. CD4+ and CD8+ T cells from the patients exhibited a significant decreased frequency of naïve and regulatory T cells with increased frequencies of activated cells, central memory CD4+ T cells, effector memory CD8+ T cells and terminal effector CD8+ T cells. Patients also exhibited a significantly increased frequency of circulating CD4+ follicular helper T cells, with altered frequencies of cTfh cell subsets. Such cTfh cells were skewed toward cTfh1 cells in STAT1 GOF, CTLA4, and CVID patients, while the STAT5b deficient patient presented a skew toward cTfh17 cells. These alterations confirmed the existence of an imbalance in the cTfh1/cTfh17 ratio in these diseases. In addition, we unraveled a marked dysregulation in the B cell compartment, characterized by a prevalence of transitional and naïve B cells in STAT1 GOF and CVID patients, and of switched-memory B cells and plasmablast cells in the STAT5b deficient patient. Moreover, we observed a significant positive correlation between the frequencies cTfh17 cells and switched-memory B cells and between the frequency of switched-memory B cells and the serum IgG. Therefore, primary immunodeficiencies with dysregulation are characterized by a skew toward an activated/memory phenotype within the CD4+ and CD8+ T cell compartment, accompanied by abnormal frequencies of Tregs, cTfh, and their cTfh1 and cTfh17 subsets that likely impact on B cell help for antibody production, which likely contributes to their autoimmune and inflammatory conditions. Therefore, assessment of these alterations by flow cytometry constitutes a simple and straightforward manner to improve diagnosis of these complex clinical entities that may impact early diagnosis and patients' treatment. Also, our findings unravel phenotypic alterations that might be associated, at least in part, with some of the clinical manifestations observed in these patients.

Cineterapia y adicciones: el cine como herramienta de la terapia en pacientes con adicciones. Un estudio piloto / Cinematherapy and addictions: using cinema as tool for therapy in patients with addictions. A pilot study

El objetivo principal del presente estudio piloto fue evaluar la eficacia del cine como herramienta de la terapia en pacientes con adicciones, utilizando una intervención de tres sesiones de cineterapia. Se utilizó un enfoque cuantitativo, con un diseño de caso cuasi experimental u observacional. Se aplicaron los cuestionarios antes de la intervención y al finalizar cada sesión, para controlar los cambios producidos. Participaron 6 personas pertenecientes al grupo ambulatorio de un programa de rehabilitación por adicciones, en la ciudad de Godoy Cruz, Mendoza. Las variables evaluadas fueron el afrontamiento y los estadios de cambio, a través de los cuestionarios University of Rhode Island Change Assessment (URICA) e Inventario de Respuestas de Afrontamiento para Adultos (CRI-A). Los resultados obtenidos mostraron modificaciones en los estilos de afrontamiento a lo largo del proceso de cineterapia. No se observaron diferencias significativas respecto a los avances en los estadios de cambio

The main aim of the present study was to evaluate the efficacy of cinema as a therapy tool in patients with addictions, by means of three sessions of cinema therapy intervention. A quantitative approach was used, with a quasi-experimental or observational design. The questionnaires were applied before the intervention and at the end of each session, to control the changes produced. The sample consisted of 6 subjects (n = 6) adults of both sexes, belonging to the ambulatory group of a rehabilitation program for addictions, in the city of Godoy Cruz, Mendoza. The variables evaluated were coping strategies and the stages of change, through the questionnaires known as University of Rhode Island Change Assessment (URICA) and Inventory of Coping Responses for Adults (CRI-A). The results obtained showed modifications in the coping strategies throughout the cinematherapy process. No significant differences were observed with respect to the progress made in the stages of change

Melanoma amelanótico primario de vagina: reporte de un caso y revisión de la literatura / Primary amelanotic melanoma of the vagina: a case report and literature review

Objetivo: revisar el diagnóstico clínico, histológico e inmunohistoquímico; las alternativas terapéuticas y los factores que influyen en el pronóstico del melanoma amelanocítico de vagina. Materiales y métodos: se presenta el caso de una paciente de 49 años que consultó por masa vaginal de 8 cm en pared anterior de vagina, nacarada y con fondo necrótico a la Unidad de Patología Cervical y Colposcopia del Hospital de Engativá, institución de segundo nivel de complejidad que atiende pacientes de nivel socioeconómico bajo afiliados al régimen de seguridad pública. Se realizó resección amplia de la lesión. La patología quirúrgica informó melanoma fusocelular y epiteloide maligno. Se realizó una búsqueda sistemática usando las palabras clave: melanoma primario y vagina en las bases de datos Medline vía PubMed, Cochrane y Ebsco. Resultados: se encontraron 489 artículos de los cuales 31 estaban relacionados directamente con el tema, de estos se seleccionaron diez que correspondieron a nueve reportes de caso y a una revisión del tema. El diagnóstico clínico no es fácil. Las proteínas HMB45 y S100 son de gran utilidad en su identificación. La respuesta al tratamiento quirúrgico, la radioterapia y la quimioterapia es pobre. El pronóstico depende de la ploidía, la amelanosis y el índice mitótico. Conclusiones: el melanoma primario de vagina es una neoplasia rara y de mal pronóstico. Hace parte del grupo de melanomas de mucosa que tienen un origen y comportamiento biológico diferente al cutáneo. Tiene tendencia a la diseminación hematógena rápida y a recaídas locales. El tratamiento se basa en cirugía conservadora, radioterapia, quimioterapia y terapia biológica; sin embargo, su eficacia es limitada.

Objective: reviewing clinical, histological and immunohistochemical diagnosis, therapeutic alternatives and factors influencing prognosis for amelanotic melanoma of the vagina. Materials and methods: this article presents the case of a 49yearold patient who consulted the Engativá Hospital’s Cervical Pathology and Colposcopy Unit due to an 8 cm diameter necrotic pearlywhite vaginal mass on the anterior vaginal wall. The hospital is a secondary level complexity institution dealing with low socioeconomic level patients affiliated to the public (subsidized) social security (health) system. A broad resection was made of the lesion. Surgical pathology revealed epithelioid fusocellular malignant melanoma. A systematic literature search was made using the following key words: primary melanoma and vagina in Medline databases via Pub Med, Cochrane and Ebsco. Results: 31 of the 489 articles found were directly related to the topic; 10 new case reports and a review were selected. Clinical diagnosis is not easy; HMB45 and S100 proteins are extremely useful in identifying it.Response to surgical treatment, radiotherapy and chemotherapy is poor. Prognosis depends on ploidy, amelanosis and mitotic index. Conclusions: primary melanoma of the vagina is a rare neoplasm and has a poor prognosis. It forms part of a group of mucosal melanoma having an origin and biological behavior different to that of cutaneous melanoma. It tends to have rapid hematogenous dissemination and local relapses. Treatment is based on conservative surgery, radiotherapy, chemotherapy and biological therapy; however, its effectiveness is limited.