Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study.

Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

O farmacêutico entre o trabalho prescrito e o real na Atenção Primária à Saúde / The pharmacist between prescribed and real work in Primary Health Care / El farmacéutico entre el trabajo prescrito y el real en la Atención Primaria de Salud

Resumo O trabalho do profissional farmacêutico na Atenção Primária à Saúde está em permanente construção. Este artigo analisa o trabalho realizado pelos farmacêuticos na gestão entre o que está prescrito e o que o real exige, na atenção primária do Distrito Federal. Trata-se de um estudo de caso, com triangulação na coleta e na análise dos dados, obtidos por meio de entrevistas e observação do trabalho de farmacêuticos de cinco Regiões de Saúde, resultando em três categorias: estrutura das farmácias; organização do trabalho; tempo e tarefas. O estudo evidencia que o farmacêutico tem sua atuação centrada nos seguintes grupos de ações: pausas; trabalho gerencial/logística; interrupção; atendimento aos usuários. As tarefas ligadas à assistência ao usuário são pontuais e esporádicas, com o foco da atuação nas gerenciais, sobretudo a logística. Apesar dos limites estruturais das farmácias, há elementos no contexto, revelados pelos farmacêuticos, que podem favorecer a ampliação das atividades técnico-assistenciais: a garantia do acesso aos medicamentos como princípio ético; as normativas; a postura de aprendizagem dos profissionais e de abertura para enfrentar o inusitado; a conexão com necessidades da equipe da Unidade Básica de Saúde; a ação coletiva dos farmacêuticos e a formação sobre cuidado farmacêutico.

Abstract The work of the pharmaceutical professional in Primary Health Care is under permanent construction. This article analyzes the work performed by pharmacists in managing what is prescribed and what is actually required in primary care in the Brazilian Federal District. This is a case study, with triangulation in the collection and analysis of data, obtained through interviews and observation of the work of pharmacists from five Health Regions, resulting in three categories: structure of pharmacies; work organization; time and tasks. The study shows that the pharmacist's performance is centered on the following groups of actions: breaks; managerial/logistics work; interruption; service to users. Tasks related to user assistance are punctual and sporadic, with the focus on management, especially logistics. Despite the structural limits of pharmacies, there are elements in the context that can favor the expansion of technical assistance activities: guaranteeing access to medicines as an ethical principle; the regulations; the learning attitude of professionals and openness to face the unusual; the connection with the needs of the Basic Health Unit team; the collective action of pharmacists and training on pharmaceutical care.

Resumen El trabajo del farmacéutico en la Atención Primaria de Salud está en permanente construcción. Este artículo analiza el trabajo que realizan los farmacéuticos en el manejo de lo prescrito y lo realmente requerido, en la atención primaria del Distrito Federal brasileño. Se trata de un estudio de caso, con triangulación en la recolección y el análisis de los datos, obtenidos a través de entrevistas y observación del trabajo de farmacéuticos de cinco Regiones de Salud, resultando en tres categorías: estructura de las farmacias; organización del trabajo; tiempo y tareas. El estudio muestra que el farmacéutico tiene su actuación centrada en los siguientes grupos de acciones: pausas; trabajo de gestión/logística; interrupción; servicio a los usuarios. Las tareas relacionadas con la atención al usuario son puntuales y esporádicas, con foco en las que son gestionadas, especialmente aquellas relacionadas con la logística. A pesar de los límites estructurales de las farmacias, existen elementos en el contexto que pueden favorecer la expansión de las actividades técnico-asistenciales: la garantía del acceso a los medicamentos como principio ético; las regulaciones; la postura de aprendizaje de los profesionales y de la apertura para enfrentar lo insólito; la conexión con las necesidades del equipo de la Unidad Básica de Salud; la acción colectiva de los farmacéuticos y la formación en atención farmacéutica.

Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection (PROUDEST Trial): Protocol for a Multicenter, Prospective Cohort Study.

BACKGROUND: A growing body of evidence suggests that SARS-COV-2 infection during pregnancy may affect maternal-fetal outcomes and possibly result in implications for the long-term development of SARS-CoV-2-exposed children. OBJECTIVE: The PROUDEST (Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection Study) is a multicenter, prospective cohort study designed to elucidate the repercussions of COVID-19 for the global health of mothers and their children. METHODS: The PROUDEST trial comprises 2 prospective, sequential substudies. The PREGNANT substudy will clinically assess the effects of SARS-CoV-2 infection on pregnancy, childbirth, and puerperium from a mechanistic standpoint to elucidate the pregnancy-related inflammatory and immunological phenomena underlying COVID-19. Pregnant women aged 18-40 years who have been exposed (proven with laboratory tests) to SARS-CoV-2 (group A; n=300) will be compared to control subjects with no laboratory evidence of in-pregnancy exposure to the virus (group B; n=300). Subjects exposed to other infections during pregnancy will be excluded. The BORN substudy is a long-term follow-up study that will assess the offspring of women who enrolled in the prior substudy. It will describe the effects of SARS-CoV-2 exposure during pregnancy on children's growth, neurodevelopment, and metabolism from birth up to 5 years of age. It includes two comparison groups; group A (exposed; n=300) comprises children born from SARS-CoV-2-exposed pregnancies, and group B (controls; n=300) comprises children born from nonexposed mothers. RESULTS: Recruitment began in July 2020, and as of January 2021, 260 pregnant women who were infected with SARS-CoV-2 during pregnancy and 160 newborns have been included in the study. Data analysis is scheduled to start after all data are collected. CONCLUSIONS: Upon completion of the study, we expect to have comprehensive data that will provide a better understanding of the effects of SARS-CoV-2 infection and related inflammatory and immunological processes on pregnancy, puerperium, and infancy. Our findings will inform clinical decisions regarding the care of SARS-CoV-2-exposed mothers and children and support the development of evidence-based public health policies. TRIAL REGISTRATION: Brazilian Register of Clinical Trials RBR65QXS2; https://ensaiosclinicos.gov.br/rg/RBR-65qxs2. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26477.

Molecular and Cellular Biomarkers of COVID-19 Prognosis: Protocol for the Prospective Cohort TARGET Study.

BACKGROUND: Since the beginning of the COVID-19 pandemic, the world's attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths. OBJECTIVE: In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19. METHODS: To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction-confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care. RESULTS: The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase. CONCLUSIONS: This study is original in terms of the different parameters analyzed in the same sample of patients with COVID-19. The project, which is currently in the data collection phase, was approved by the Brazilian Committee of Ethics in Human Research (CAAE 30846920.7.0000.0008). TRIAL REGISTRATION: Brazilian Registry of Clinical Trials RBR-62zdkk; https://ensaiosclinicos.gov.br/rg/RBR-62zdkk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24211.

Evidence for the presence of glutamatergic receptors in adult Schistosoma mansoni.

Several studies have suggested that L-glutamate is a putative neurotransmitter in helminths. The present study investigated the presence of non-N-methyl-D-aspartate (NMDA) ionotropic receptors for glutamate in four subcellular fractions from adult male Schistosoma mansoni. Low-affinity (K(d)=221+/-80 nM) binding sites for [3H]kainic acid (KA) were detected in the heterogeneous (P(1)) fraction, which contains pieces of unbroken worm tissues, tegument, nuclei, and some vesicles. This binding was inhibited by classical glutamatergic ligands in the following order of potency: KA>L-glutamate>alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)>quisqualate congruent with 6,7-dinitroquinoline-2,3-dione (DNQX). However, neither NMDA, a selective agonist for NMDA receptors, nor DL-threo-beta-hydroxyaspartate (THA) and 1-trans-pyrollidine-2-dicarboxylic acid (PDC), inhibitors of high-affinity glutamate transporters, modified [3H]KA binding to the P(1) fraction. In addition, no specific binding for 10nM [3H]AMPA was detected in any subcellular fraction from S. mansoni. These results suggested the presence of KA receptors in adult male worms. This is supported by the evidence that direct application of 10 microM KA to whole worms produced a corkscrew-like coiling of their bodies, modifying the motility of the worms. The KA-induced response, measured as a decrease of the body area, was time-dependent and reversible. PDC was ineffective at blocking the KA effects, indicating that KA does not depend on high-affinity glutamate transporters to reach its site of action. On the other hand, DNQX, the non-NMDA antagonist, was able to partially inhibit KA-induced responses. As a whole, the present data support the presence of a glutamatergic signaling pathway in this parasite.