COVID-19 convalescent plasma composition and immunological effects in severe patients.

Convalescent plasma (CP) has emerged as a treatment for COVID-19. However, the composition and mechanism of action are not fully known. Therefore, we undertook a two-phase controlled study in which, first the immunological and metabolomic status of recovered and severe patients were evaluated. Secondly, the 28-day effect of CP on the immune response in severe patients was assessed. Nineteen recovered COVID-19 patients, 18 hospitalized patients with severe disease, and 16 pre-pandemic controls were included. Patients with severe disease were treated with CP transfusion and standard therapy (i.e., plasma recipients, n = 9) or standard therapy alone (n = 9). Clinical and biological assessments were done on day 0 and during follow-up on days 4, 7, 14, and 28. Clinical parameters, viral load, total immunoglobulin (Ig) G and IgA anti-S1-SARS-CoV-2 antibodies, neutralizing antibodies (NAbs), autoantibodies, cytokines, T and B cells, and metabolomic and lipidomic profiles were examined. Total IgG and IgA anti-S1-SARS-CoV-2 antibodies were key factors for CP selection and correlated with NAbs. In severe COVID-19 patients, mostly interleukin (IL)-6 (P = <0.0001), IL-10 (P = <0.0001), IP-10 (P = <0.0001), fatty acyls and glycerophospholipids were higher than in recovered patients. Latent autoimmunity and anti-IFN-α antibodies were observed in both recovered and severe patients. COVID-19 CP induced an early but transient cytokine profile modification and increases IgG anti-S1-SARS-CoV-2 antibodies. At day 28 post-transfusion, a decrease in activated, effector and effector memory CD4+ (P < 0.05) and activated and effector CD8+ (P < 0.01) T cells and naïve B cells (P = 0.001), and an increase in non-classical memory B cells (P=<0.0001) and central memory CD4+ T cells (P = 0.0252) were observed. Moreover, IL-6/IFN-γ (P = 0.0089) and IL-6/IL-10 (P = 0.0180) ratios decreased in plasma recipients compared to those who received standard therapy alone. These results may have therapeutic implications and justify further post-COVID-19 studies.

Systematic review of preclinical studies on the neutrophil-mediated immune response to air pollutants, 1980-2020.

Preclinical evidence about the neutrophil-mediated response in exposure to air pollutants is scattered and heterogeneous. This has prevented the consolidation of this research field around relevant models that could advance towards clinical research. The purpose of this study was to systematic review the studies of the neutrophils response to air pollutants, following the recommendations of the Cochrane Collaboration and the PRISMA guide, through 54 search strategies in nine databases. We include 234 studies (in vitro, and in vivo), being more frequent using primary neutrophils, Balb/C and C57BL6/J mice, and Sprague-Dawley and Wistar rats. The most frequent readouts were cell counts, cytokines and histopathology. The temporal analysis showed that in the last decade, the use of mice with histopathological and cytokine measurement have predominated. This systematic review has shown that study of the neutrophils response to air pollutants started 40 years ago, and composed of 100 different preclinical models, 10 pollutants, and 11 immunological outcomes. Mechanisms of neutrophils-mediated immunopathology include cellular activation, ROS production, and proinflammatory effects, leading to cell-death, oxidative stress, and inflammatory infiltrates in lungs. This research will allow consolidating the research efforts in this field, optimizing the study of causal processes, and facilitating the advance to clinical studies.

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World's Population.

Fifty ~20-amino acid (aa)-long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus' main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing ß-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRß1* (HLA-DRß1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRß1* molecules), predicted to cover 77.5% to 83.1% of the world's population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

Immune characterization of a Colombian family cluster with SARS-CoV-2 infection. / Caracterización inmunológica de un grupo familiar colombiano con infección por SARS-CoV-2

INTRODUCTION: Immunological markers have been described during COVID-19 and persist after recovery. These immune markers are associated with clinical features among SARSCoV-2 infected individuals. Nevertheless, studies reporting a comprehensive analysis of the immune changes occurring during SARS-CoV-2 infection are still limited. OBJECTIVE: To evaluate the production of proinflammatory cytokines, the antibody response, and the phenotype and function of NK cells and T cells in a Colombian family cluster with SARS-CoV-2 infection. MATERIALS AND METHODS: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. The frequency, phenotype, and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with spike/RdRp peptides) were assessed by flow cytometry. Anti-SARS-CoV-2 antibodies were determined using indirect immunofluorescence and plaque reduction neutralization assay. RESULTS: During COVID-19, we observed a high proinflammatory-cytokine production and a reduced CD56bright-NK cell and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by high IL-10 production. However, during recovery, we observed a bifunctional response characterized by the co-expression of CD107a and granzyme B or perforin. CONCLUSION: Although the proinflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and to guide future immunotherapy strategies.

Introducción. Se han descrito diferentes marcadores inmunológicos durante la COVID-19, los cuales persisten incluso después de la convalecencia y se asocian con los estadios clínicos de la infección. Sin embargo, aún son pocos los estudios orientados al análisis exhaustivo de las alteraciones del sistema inmunológico en el curso de la infección. Objetivo. Evaluar la producción de citocinas proinflamatorias, la reacción de anticuerpos, y el fenotipo y la función de las células NK y los linfocitos T en una familia colombiana con infección por SARS-CoV-2. Materiales y métodos. Se evaluaron las citocinas proinflamatorias mediante RT-PCR y ELISA; la frecuencia, el fenotipo y la función de las células NK (en cocultivos con células K562) y linfocitos T CD8+ (estimulados con péptidos spike/RdRp) mediante citometría de flujo, y los anticuerpos anti-SARS-CoV-2, mediante inmunofluorescencia indirecta y prueba de neutralización por reducción de placa. Resultados. Durante la COVID-19 hubo una producción elevada de citocinas proinflamatorias, con disminución de las células NK CD56bright y reacción citotóxica. Comparados con los controles sanos, los individuos infectados presentaron con gran frecuencia linfocitos T CD8+ disfuncionales CD38+HLA-DR-. Además, en los linfocitos T CD8+ estimulados con péptidos virales, predominó una reacción monofuncional con gran producción de IL-10 durante la fase aguda y una reacción bifuncional caracterizada por la coexpresión de CD107a y granzima B o perforina durante la convalecencia. Conclusión. Aunque la reacción inflamatoria caracteriza la infección por SARS-CoV-2, hay otras alteraciones fenotípicas y funcionales en células NK y linfocitos T CD8+ que podrían asociarse con la progresión de la infección. Se requieren estudios adicionales para entender estas alteraciones y guiar futuras estrategias de inmunoterapia.

Cutaneous endometriosis: Presentation of 33 cases and literature review.

OBJECTIVE: Cutaneous endometriosis is a rare condition that usually affects the abdominal wall in women with a history of open abdominal surgery. It has a characteristic clinical picture of a mass and pain associated with menstruation. The diagnosis is difficult on being an uncommon and little known condition. Once there is suspicion, a correct anamnesis and examination is usually sufficient. The treatment is normally surgery. STUDY DESIGN: The study included all women identified with a diagnosis of cutaneous endometriosis over a period of 20 years. The variables collected and analysed included, age, surgical history, gynaecology history, symptoms, time period between surgery and consultation, specialist consulted, location, size, tests performed, treatment, and recurrence. RESULTS: A total of 33 women were identified, with a mean age of 35.4 ±â€¯2.33 years. A surgical history was found in 31 (93%) of 33 women. The main symptom was abdominal mass (96%), followed by period pain (51%), and non-period pain (42%). The initial diagnosis was correct in 15 (45%) of 33 women, and after performing further tests it was correct in 23 (69%) of 33 women. The main additional test was fine needle aspiration (FNA) in 24 (72%) of 33 patients. Surgery was performed on 30 (90%) of 33 women, with 8 (24%) women requiring a prosthesis. There was a recurrence of cutaneous endometriosis in 3 (9%) women. CONCLUSION: Although it is a rare disease, its association with gynaecological surgery, and in particular caesarean section, means that there should be more awareness of this condition. Its diagnosis may be complicated due to lack of knowledge, when a proper examination and anamnesis can give us the key.

Trends in net survival from ovarian cancer in six European Latin countries: results from the SUDCAN population-based study.

European Latin countries have some similarities in their health systems. It is thus interesting to look at their differences in cancer survival (here, ovarian cancer) through monitoring of specific indicators of quality care. The aim of this SUDCAN collaborative study was to compare the trends in 1 and 5-year net survival from ovarian cancer and the trends in the excess mortality rates between six European Latin countries (Belgium, France, Italy, Portugal, Spain and Switzerland). The data were extracted from the EUROCARE-5 database. First, the net survival was studied over the 2000-2004 period using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. The results are reported from 1992 to 2004 in France, Italy, Spain and Switzerland, and from 2000 to 2004 in Belgium and Portugal. The analyses were carried out using a flexible excess rate modelling. Over the period 2000-2004, there were slight differences in the 5-year age-standardized net survivals from ovarian cancer; they ranged from 36% in Spain to 42% in Belgium. Net survival was much higher in young than in old age groups, but this difference was more marked in Spain and less marked in France. Between 1992 and 2004, the net survival increased in all countries, mainly in young and middle-aged women. However, the differences in 5-year net survival between these countries were larger in 2004 than in 1992. Slight differences were observed in survival from ovarian cancer between the six European Latin countries. A considerable improvement in survival was observed in all countries, especially in young and middle-aged women. This study highlights the need for further monitoring of ovarian cancer outcomes.

Immune characterization of a Colombian family cluster with SARS-CoV-2 infection / Caracterización inmunológica de un grupo familiar colombiano con infección por SARS-CoV-2

Abstract | Introduction: Immunological markers have been described during COVID-19 and persist after recovery. These immune markers are associated with clinical features among SARS- CoV-2 infected individuals. Nevertheless, studies reporting a comprehensive analysis of the immune changes occurring during SARS-CoV-2 infection are still limited. Objective: To evaluate the production of proinflammatory cytokines, the antibody response, and the phenotype and function of NK cells and T cells in a Colombian family cluster with SARS-CoV-2 infection. Materials and methods: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. The frequency, phenotype, and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with spike/RdRp peptides) were assessed by flow cytometry. Anti-SARS-CoV-2 antibodies were determined using indirect immunofluorescence and plaque reduction neutralization assay. Results: During COVID-19, we observed a high proinflammatory-cytokine production and a reduced CD56bright-NK cell and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by high IL-10 production. However, during recovery, we observed a bifunctional response characterized by the co-expression of CD107a and granzyme B or perforin. Conclusion: Although the proinflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and to guide future immunotherapy strategies.

Resumen | Introducción. Se han descrito diferentes marcadores inmunológicos durante la COVID-19, los cuales persisten incluso después de la convalecencia y se asocian con los estadios clínicos de la infección. Sin embargo, aún son pocos los estudios orientados al análisis exhaustivo de las alteraciones del sistema inmunológico en el curso de la infección. Objetivo. Evaluar la producción de citocinas proinflamatorias, la reacción de anticuerpos, y el fenotipo y la función de las células NK y los linfocitos T en una familia colombiana con infección por SARS-CoV-2. Materiales y métodos. Se evaluaron las citocinas proinflamatorias mediante RT-PCR y ELISA; la frecuencia, el fenotipo y la función de las células NK (en cocultivos con células K562) y linfocitos T CD8+ (estimulados con péptidos spike/RdRp) mediante citometría de flujo, y los anticuerpos anti-SARS-CoV-2, mediante inmunofluorescencia indirecta y prueba de neutralización por reducción de placa. Resultados. Durante la COVID-19 hubo una producción elevada de citocinas proinflamatorias, con disminución de las células NK CD56 bright y reacción citotóxica. Comparados con los controles sanos, los individuos infectados presentaron con gran frecuencia linfocitos T CD8+ disfuncionales CD38+HLA-DR-. Además, en los linfocitos T CD8+ estimulados con péptidos virales, predominó una reacción monofuncional con gran producción de IL-10 durante la fase aguda y una reacción bifuncional caracterizada por la coexpresión de CD107a y granzima B o perforina durante la convalecencia. Conclusión. Aunque la reacción inflamatoria caracteriza la infección por SARS-CoV-2, hay otras alteraciones fenotípicas y funcionales en células NK y linfocitos T CD8+ que podrían asociarse con la progresión de la infección. Se requieren estudios adicionales para entender estas alteraciones y guiar futuras estrategias de inmunoterapia.

[Perception of medical emergencies in a private pediatric hospital]. / Percepción de urgencias médicas en un hospital pediátrico privado.

BACKGROUND: The aim of this study was to determine if the care of child patients on admission, coincides with perception of real urgency on the part of parents with that of the doctor and not because of perceived worry in the family (perceived emergencies). METHODS: All the care given in the emergency department, from January 1st 2009 to December 31st 2010, was analyzed. A real urgency was determined by consensus on the conditions of the child. Sociodemographic of real urgency conditions were compared against those perceived. RESULTS: 8,888 consultations were given, of which 2,024 (22.7 %) met criteria for real urgency. The main causes of real urgency were infectious diseases were followed by accidents and poisoning. Of real emergencies 17 (1 %) eventually required intensive management. Factors associated with real urgency were age, non-infectious disease, occurring between Monday to Friday, during the morning shift and in the winter months. CONCLUSIONS: The frequency of care for real urgency was low compared to that reported in other pediatric centers. Restructuring of pre-consultation services for the implementation of optimal patient classification before going to emergency helps greatly to optimize the use of the emergency department, deriving the patients in true need sooner.

Introducción: el objetivo de este trabajo es conocer si la atención de los niños enfermos a su ingreso, coincide con percepción de urgencia real de parte de los padres con la del médico y no por la inquietud percibida en los familiares (urgencias sentidas). Métodos: se analizaron todas las atenciones otorgadas en el servicio de urgencias, del 1 enero del 2009 al 31 diciembre del 2010. Se determinó una urgencia real por consenso según las condiciones del menor. Se compararon las condiciones sociodemográficas de la urgencias reales contra las sentidas. Resultados: se otorgaron 8888 consultas, de las cuales 2024 (22.7 %) cumplieron criterios de urgencias reales. Las principales causas de urgencias reales fueron los procesos infecciosos seguidos de accidentes e intoxicaciones. De las urgencias reales 17 (1 %) requirieron finalmente manejo intensivo. Los factores asociados con una urgencia real fueron: la edad, enfermedades no infecciosas, ocurrencia entre el lunes a viernes, en el turno matutino y en los meses de invierno. Conclusiones: La frecuencia de atención de urgencias reales fue baja para lo informado en otros centros pediátricos. La restructuración de los servicios de preconsulta para la aplicación de una clasificación óptima de pacientes antes de pasar a urgencias ayudaría en gran medida al aprovechamiento máximo del servicio de urgencias, derivando desde antes la entrada de pacientes que realmente lo ameritan.

Genitourinary infections and their association with preterm labor.

Genitourinary tract infections are one cause of preterm delivery. Prematurity is one of the leading causes of perinatal mortality in the United States. Uterine contractions may be induced by cytokines and prostaglandins, which are released by microorganisms. Asymptomatic bacteriuria, gonococcal cervicitis and bacterial vaginosis are strongly associated with preterm delivery. The role of Chlamydia trachomatis, Trichomonas vaginalis and Ureaplasma urealyticum is less clear. By adopting a rational approach to the diagnosis and treatment of genitourinary infections, family physicians can substantially decrease a patient's risk of preterm delivery.