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2.
Lancet Rheumatol ; 6(6): e339-e351, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38734019

ABSTRACT

BACKGROUND: The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two COVID-19 vaccine doses, is not fully understood. The OCTAVE DUO trial aimed to determine the value of third vaccinations in a wide range of patients with primary and secondary immunodeficiencies. METHODS: OCTAVE-DUO was a prospective, open-label, multicentre, randomised, controlled, phase 3 trial investigating humoral and T-cell responses in patients who are immunocompromised following a third vaccine dose with BNT162b2 or mRNA-1273, and of NVX-CoV2373 for those with lymphoid malignancies. We recruited patients who were immunocompromised from 11 UK hospitals, aged at least 18 years, with previous sub-optimal responses to two doses of SARS-CoV-2 vaccine. Participants were randomly assigned 1:1 (1:1:1 for those with lymphoid malignancies), stratified by disease, previous vaccination type, and anti-spike antibody response following two doses. Individuals with lived experience of immune susceptibility were involved in the study design and implementation. The primary outcome was vaccine-specific immunity defined by anti-SARS-CoV-2 spike antibodies (Roche Diagnostics UK and Ireland, Burgess Hill, UK) and T-cell responses (Oxford Immunotec, Abingdon, UK) before and 21 days after the third vaccine dose analysed by a modified intention-to-treat analysis. The trial is registered with the ISRCTN registry, ISRCTN 15354495, and the EU Clinical Trials Register, EudraCT 2021-003632-87, and is complete. FINDINGS: Between Aug 4, 2021 and Mar 31, 2022, 804 participants across nine disease cohorts were randomly assigned to receive BNT162b2 (n=377), mRNA-1273 (n=374), or NVX-CoV2373 (n=53). 356 (45%) of 789 participants were women, 433 (55%) were men, and 659 (85%) of 775 were White. Anti-SARS-CoV-2 spike antibodies measured 21 days after the third vaccine dose were significantly higher than baseline pre-third dose titres in the modified intention-to-treat analysis (median 1384 arbitrary units [AU]/mL [IQR 4·3-7990·0] compared with median 11·5 AU/mL [0·4-63·1]; p<0·001). Of participants who were baseline low responders, 380 (90%) of 423 increased their antibody concentrations to more than 400 AU/mL. Conversely, 166 (54%) of 308 baseline non-responders had no response after the third dose. Detectable T-cell responses following the third vaccine dose were seen in 494 (80%) of 616 participants. There were 24 serious adverse events (BNT612b2 eight [33%] of 24, mRNA-1273 12 [50%], NVX-CoV2373 four [17%]), two (8%) of which were categorised as vaccine-related. There were seven deaths (1%) during the trial, none of which were vaccine-related. INTERPRETATION: A third vaccine dose improved the serological and T-cell response in the majority of patients who are immunocompromised. Individuals with chronic renal disease, lymphoid malignancy, on B-cell targeted therapies, or with no serological response after two vaccine doses are at higher risk of poor response to a third vaccine dose. FUNDING: Medical Research Council, Blood Cancer UK.


Subject(s)
BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Immunocompromised Host , Immunogenicity, Vaccine , SARS-CoV-2 , Humans , Female , Male , COVID-19/prevention & control , COVID-19/immunology , Middle Aged , Immunocompromised Host/immunology , SARS-CoV-2/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Aged , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , Antibodies, Viral/blood , Prospective Studies , Immunization, Secondary , 2019-nCoV Vaccine mRNA-1273/immunology , Adult , T-Lymphocytes/immunology , United Kingdom , ChAdOx1 nCoV-19/immunology
4.
Article in English | MEDLINE | ID: mdl-38656040

ABSTRACT

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.


Subject(s)
Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Immunocompromised Host , Immunogenicity, Vaccine , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antibodies, Viral/blood , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , COVID-19/prevention & control , COVID-19/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Immunization, Secondary , Immunocompetence/immunology , Immunocompromised Host/immunology , Vaccines, Inactivated/immunology , Vaccines, Inactivated/administration & dosage
5.
Prensa méd. argent ; 110(1): 26-30, 20240000. fig
Article in Spanish | LILACS, BINACIS | ID: biblio-1552628

ABSTRACT

Nocardia es una bacteria grampositiva con amplia distribución en el medio ambiente. Puede producir variadas de infecciones. Si bien, las vías respiratorias son la principal puerta de entrada de Nocardia sp. ­y como consecuencia de lo mismo 50% de los pacientes posee compromiso pulmonar- las infecciones por Nocardia van desde infecciones de piel y partes blandas hasta abscesos cerebrales. La piel puede ser el órgano de afectación primaria y el primer signo clínico de infección o formar parte de una infección diseminada. La nocardiosis diseminada, es una grave enfermedad que involucra a dos sitios no contiguos de infección o el rescate del agente causal en hemocultivos. Afecta a pacientes debilitados con condiciones o con cierto grado de inmunodepresión; particularmente de inmunidad celular; como trasplantados de órganos sólido o hematopoyeticos, uso de corticoides, neoplasias, VIH, alcoholismo ­aunque se describen infecciones en pacientes inmunocompetentes­. El diagnóstico es dificultoso y la sospecha clínica es fundamental para el inicio de la terapéutica. Se describen dos casos de infecciones de piel y partes blandas ocasionadas por Nocardia; de evolución subaguda-cronica;. Una de ellas localizada: micetoma de pie, la segunda, una celulitis abdominal recurrente complicada con compromiso sistémico; en ambas estuvo presente la demora en el diagnóstico.


Nocardia is a gram-positive bacteria with wide distribution in the environment. It can cause a wide range of infections. Although the respiratory tract is the main entry point for Nocardia sp. ­ and as a consequence of the same, 50% of patients have lung involvement ­ nocardia infections range from skin and soft tissue infections to brain abscesses. The skin can be the primary organ of involvement and the first clinical sign of infection or be part of a disseminated infection, secondary to a primary pulmonary form. Disseminated nocardiosis is a serious disease that involves two non-contiguous sites of infection or the recovery of the causative agent in blood cultures. It commonly affects patients with weakened conditions or a certain degree of immunosuppression; particularly cellular immunity, such as solid or hematopoietic organ transplants, use of corticosteroids, neoplasms, HIV, alcoholism - although infections are described in immunocompetent patients. The diagnosis is difficult and clinical suspicion is essential for the initiation of therapy. Two cases of skin and soft tissue infections caused by Nocardia were described of subacute-chronic evolution. One of them localized: mycetoma of the foot, the second, a recurrent abdominal cellulites complicated with systemic involvement; Delay in diagnosis was present in both


Subject(s)
Humans , Female , Adult , Aged , Immunocompromised Host/immunology , Soft Tissue Infections/therapy , Nocardia Infections/diagnosis , Delayed Diagnosis
6.
Am J Transplant ; 24(6): 897-904, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38341028

ABSTRACT

In 2023, the Food and Drug Administration approved 2 recombinant subunit respiratory syncytial virus (RSV) vaccines based on prefusion RSV F glycoproteins for the prevention of RSV-associated lower respiratory tract disease. These vaccines were subsequently recommended for individuals ≥60 years of age using shared clinical decision-making by the Center for Disease Control and Prevention's Advisory Committee on Immunization Practices. The development, deployment, and uptake of respiratory virus vaccines are of particular importance for solid organ recipients who are at higher risk of infectious complications and poor clinical outcomes, including from RSV-associated lower respiratory tract disease, compared to patients without immunocompromise. This review aims to summarize what is currently known about the burden of RSV disease in solid organ transplantation, to describe the currently available tools to mitigate the risk, and to highlight considerations regarding the implementation of these vaccines before and after transplantation. We also explore areas of unmet need for organ transplant recipients including questions of RSV vaccine effectiveness and safety, inequities in disease and vaccine access based on race and socioeconomic status, and expansion of coverage to immunocompromised individuals below the age of 60 years.


Subject(s)
Organ Transplantation , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Humans , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Vaccines/immunology , Respiratory Syncytial Virus, Human/immunology , Immunocompromised Host/immunology
7.
JAMA ; 331(9): 723-724, 2024 03 05.
Article in English | MEDLINE | ID: mdl-38353960

ABSTRACT

This Medical News story discusses a recent study that found people who are immunocompromised clear SARS-CoV-2 at varying rates.


Subject(s)
COVID-19 , Immunocompromised Host , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/virology , Immunocompromised Host/immunology , SARS-CoV-2/immunology , Viral Load/immunology
8.
Nature ; 626(8001): 1094-1101, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38383783

ABSTRACT

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks1-5, give rise to highly divergent lineages6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.


Subject(s)
COVID-19 , Health Surveys , Persistent Infection , SARS-CoV-2 , Humans , Amino Acid Substitution , Antibodies, Monoclonal/immunology , COVID-19/epidemiology , COVID-19/virology , Evolution, Molecular , Immunocompromised Host/immunology , Mutation , Persistent Infection/epidemiology , Persistent Infection/virology , Post-Acute COVID-19 Syndrome/epidemiology , Post-Acute COVID-19 Syndrome/virology , Prevalence , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2/chemistry , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Selection, Genetic , Self Report , Time Factors , Viral Load , Virus Replication
9.
An. pediatr. (2003. Ed. impr.) ; 99(6): 403-421, Dic. 2023. tab
Article in English, Spanish | IBECS | ID: ibc-228663

ABSTRACT

El número de personas con inmunodepresión está aumentando considerablemente debido a su mayor supervivencia y al empleo de nuevas terapias inmunosupresoras en diversas patologías crónicas. Se trata de un grupo heterogéneo de pacientes en los que la vacunación como arma preventiva supone uno de los pilares básicos de su bienestar, por su elevado riesgo a padecer infecciones. Este consenso, elaborado conjuntamente entre la Sociedad Española de Infectología Pediátrica (SEIP) y el Comité Asesor de Vacunas de la Asociación Española de Pediatría (CAV-AEP), aporta unas directrices para programar un calendario adaptado a cada paciente en situaciones especiales que incluye recomendaciones generales, vacunación en pacientes con trasplante de médula y trasplante de órgano sólido, vacunación en niños con errores innatos de la inmunidad, vacunación en el paciente oncológico, vacunación en pacientes con enfermedades crónicas o sistémicas y vacunación en niños viajeros inmunodeprimidos.(AU)


The number of people with immunosuppression is increasing considerably due to their greater survival and the use of new immunosuppressive treatments for various chronic diseases. This is a heterogeneous group of patients in whom vaccination as a preventive measure is one of the basic pillars of their wellbeing, given their increased risk of contracting infections. This consensus, developed jointly by the Sociedad Española de Infectología Pediátrica (Spanish Society of Pediatric Infectious Diseases) and the Advisory Committee on Vaccines of the Asociación Española de Pediatría (Spanish Association of Paediatrics), provides guidelines for the development of a personalised vaccination schedule for patients in special situations, including general recommendations and specific recommendations for vaccination of bone marrow and solid organ transplant recipients, children with inborn errors of immunity, oncologic patients, patients with chronic or systemic diseases and immunosuppressed travellers.(AU)


Subject(s)
Humans , Male , Female , Child , Adolescent , Infectious Disease Medicine , Vaccines , Immunocompromised Host/immunology , HIV/immunology , Immunosuppressive Agents/administration & dosage , Chronic Disease/prevention & control , Spain , Pediatrics , Consensus Development Conferences as Topic , Vaccination
10.
Viruses ; 15(2)2023 02 09.
Article in English | MEDLINE | ID: mdl-36851691

ABSTRACT

Human metapneumovirus (hMPV) is an important cause of respiratory disease in immunocompromised individuals, yet hMPV infection has not been modeled before in immunocompromised animals. In this work, cotton rats S. hispidus immunosuppressed by cyclophosphamide were infected with hMPV, and viral replication and pulmonary inflammation in these animals were compared to those in normal hMPV-infected S. hispidus. The efficacy of prophylactic and therapeutic administration of the anti-hMPV antibody MPV467 was also evaluated. Immunosuppressed animals had higher pulmonary and nasal titers of hMPV on day 5 post-infection compared to normal animals, and large amounts of hMPV were still present in the respiratory tract of immunosuppressed animals on days 7 and 9 post-infection, indicating prolonged viral replication. Immunosuppression was accompanied by reduced pulmonary histopathology in hMPV-infected cotton rats compared to normal animals; however, a delayed increase in pathology and pulmonary chemokine expression was seen in immunosuppressed cotton rats. Prophylactic and therapeutic MPV467 treatments protected both upper and lower respiratory tracts against hMPV infection. The lung pathology and pulmonary expression of IP-10 and MIP-1α mRNA were reduced by therapeutic MPV467 administration. These results indicate that immunosuppressed cotton rats represent a useful model for studying hMPV pathogenesis and for evaluating therapeutics that could alleviate hMPV-induced disease in immunocompromised subjects.


Subject(s)
Immunocompromised Host , Metapneumovirus , Paramyxoviridae Infections , Sigmodontinae , Animals , Humans , Chemokine CCL3 , Immunocompromised Host/immunology , Immunosuppression Therapy , Paramyxoviridae Infections/immunology , Paramyxoviridae Infections/virology , Sigmodontinae/immunology , Sigmodontinae/virology , Disease Models, Animal
11.
Int J Cancer ; 152(4): 705-712, 2023 02 15.
Article in English | MEDLINE | ID: mdl-35830214

ABSTRACT

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients have increased morbidity and mortality rates of COVID-19 due to immunosuppression associated with the disease and ongoing therapy. The same immune impairment accompanying CLL and MM also affects suboptimal vaccine response. The study assessed the effectiveness of the humoral and T cell-mediated immunity following mRNA COVID-19 vaccination (using either BNT162b2 or mRNA-1273) in short-term (2-5 weeks after second dose) and long-term follow-up (12 weeks after vaccination). Between March and August 2021, blood samples were obtained from 62 CLL and 60 MM patients from eight different hematology departments in Poland. Total anti-RBD antibodies were detected in 37% MM patients before vaccination, increased to 91% and 94% in short- and long-term follow-up, respectively. In CLL, serological responses were detectable in 21% of patients before vaccination and increased to 45% in the short-term and 71% in long-term observation. We detected a tendency to higher frequencies of specific CD8+ T cells against SARS-CoV-2 after vaccination compared to samples before vaccination in MM patients and no changes in frequencies of specific T cells in CLL patients. Our study provides novel insights into mRNA vaccination efficacy in immunocompromised MM and CLL patients, and our findings highlight that specific CD8+ T cells against SARS-CoV-2 might be induced by vaccination but do not correlate positively with serological responses.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , COVID-19 , Immunocompromised Host , Leukemia, Lymphocytic, Chronic, B-Cell , Multiple Myeloma , Humans , BNT162 Vaccine/immunology , COVID-19/prevention & control , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Multiple Myeloma/immunology , SARS-CoV-2 , Immunocompromised Host/immunology , 2019-nCoV Vaccine mRNA-1273/immunology
12.
Clin Microbiol Infect ; 29(2): 240-246, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36067943

ABSTRACT

OBJECTIVES: To monitor the early emergence of genetic mutations related to reduced susceptibility to monoclonal anti-body (mAb)-based treatment in immunocompromised patients with long-term viral excretion using whole-genome sequencing at a tertiary university hospital in Barcelona, Spain. METHODS: Serial severe acute respiratory syndrome coronavirus 2-positive samples (mid-December 2021-mid-March 2022) from eight immunosuppressed, fully vaccinated patients (for solid-organ transplantation or haematologic malignancies) with long-term viral excretion despite undergoing mAb therapy (sotrovimab) for coronavirus disease 2019 were selected. Whole-genome sequencing was performed following the ARTIC, version 4.1, protocol on the MiSeq platform. Mutations in the coding sequence of the spike protein with a frequency of ≥5% were studied. RESULTS: A total of 37 samples from the studied cases were analysed. All the cases, except one, were confirmed to have the Omicron variant BA.1; one had Delta (AY.100). Thirty-four different mutations were detected within the receptor-binding domain of the spike protein in 62.5% of patients, eight of which were not lineage related and located in the sotrovimab target epitope (P337L, E340D, E340R, E340K, E340V, E340Q, R346T and K356T). Except for P337L, all changes showed a significant increase in frequency or fixation after the administration of sotrovimab. Some of them have been associated with either reduced susceptibility to mAb therapy, such as those at position 340, or the acquisition of a new glycosylation site (346 and 356 positions). CONCLUSIONS: This study highlights the importance of monitoring for early in vivo selection of mutations associated with reduced susceptibility to mAb therapy, especially in immunocompromised patients receiving anti-viral drugs, whose immune response is not able to control viral replication, resulting in long-term viral shedding, and those receiving selective evolution pressure. Virologic surveillance of genetically resistant viruses to available anti-viral therapies is considered a priority for both patients and the community.


Subject(s)
COVID-19 , Drug Resistance, Viral , Immunocompromised Host , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Virus Shedding , Humans , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/genetics , COVID-19/immunology , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Drug Resistance, Viral/genetics , Immunocompromised Host/immunology , Virus Shedding/genetics , Virus Shedding/immunology
13.
O.F.I.L ; 33(4)2023. tab, graf
Article in Spanish | IBECS | ID: ibc-230072

ABSTRACT

Introducción: En la temporada 2020-2021 se realizaron campañas mayores de vacunación antigripal, primordialmente en pacientes inmunocomprometidos y sus convivientes. Objetivos: Principal: determinar el impacto de la pandemia COVID-19 en la tasa de vacunación antigripal en la temporada 2020-2021 en pacientes con patologías con carácter inmunosupresor, pacientes pertenecientes a grupos de riesgo y las personas convivientes. Secundarios: porcentaje de vacunas administradas, incidencia de infección del virus de la gripe y la influencia del Servicio de Farmacia sobre la decisión de los pacientes a vacunarse. Metodología: Estudio observacional, prospectivo, de ocho meses de duración, realizado en un hospital comarcal de 125 camas, en pacientes con patologías con carácter inmunosupresor y pacientes que solicitaban la vacunación y estaban incluidos en los grupos de riesgo. Resultados: En la campaña de vacunación 2020-2021 hubo un aumento de pacientes vacunados en un 44,1% (89) con respecto a la vacunación 2019-2020. En el 2019-2020 el 5,3% (6/113) presentaron cuadro de gripe y de los que no recibieron la vacuna el 7,9% (7/89). En la campaña 2020-2021 ningún paciente presentó cuadro de gripe, el 56,4% (114/202) de los pacientes refirieron que fueron influenciados por el servicio de farmacia para vacunarse. Conclusiones: La pandemia por COVID-19 aumentó las tasas de vacunación antigripal en la temporada 2020-2021 ayudando a disminuir la mortalidad en pacientes que sufrieron la enfermedad por la COVID-19. El Servicio de Farmacia influyó positivamente en la tasa de vacunación. (AU)


Introduction: In the 2020-2021 season larger vaccination campaigns were carried out, primarily in immunocompromised patients and their partners. Objectives: Primary end point: determine the impact of the COVID-19 pandemic on the influenza vaccination rate in the 2020-2021 season, in patients with immunosuppressive pathologies, people living with risk groups and patients who requested it and belonged to risk groups. Secondary end point: percentage of vaccines administered, incidence of influenza virus infection and the influence of the Pharmacy Service on the decision of patients to be vaccinated. Methodology: An eight-month prospective, observational study conducted in a 125-bed regional hospital in patients with immunosuppressive pathologies and patients who requested vaccination and were included in risk groups. Results: In the 2020-2021 vaccination campaign, there was an increase in vaccinated patients by 44.1% (89 patients) compared to the 2019-2020 vaccination. In 2019-2020 5.3% (6/113) presented flu symptoms and of those who did not receive the vaccine 7.9% (7/89). In the 2020-2021 campaign, no patient had flu symptoms, 56.4% (114/202) of the patients reported that their decision to get vaccinated was because it was offered at the hospital pharmacy. Conclusions: The COVID-19 pandemic increased flu vaccination rates in the 2020-2021 season, causing lower mortality in patients who suffered from the COVID-19 disease. The Pharmacy Service positively influenced the vaccination rate. (AU)


Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , /prevention & control , Immunization Programs , Influenza Vaccines/supply & distribution , Immunocompromised Host/immunology , Prospective Studies , Risk Groups , Pandemics , Pharmacies/supply & distribution , Influenza, Human , Spain/epidemiology
14.
Arch. pediatr. Urug ; 94(1): e205, 2023. tab
Article in Spanish | LILACS, UY-BNMED, BNUY | ID: biblio-1439316

ABSTRACT

Introducción: las infecciones fúngicas invasivas (IFI) son un problema de salud en creciente aumento. Objetivo: describir las características epidemiológicas, microbiológicas y clínicas de los menores de 15 años con IFI hospitalizados en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell entre 2010- 2019. Metodología: estudio retrospectivo, mediante revisión de historias clínicas. Variables: edad, sexo, comorbilidades, factores de riesgo, clínica, patógenos, tratamiento y evolución. Resultados: se registraron 26 casos de IFI en 23 niños. La mediana de edad fue 8 años, de sexo femenino 17, con comorbilidades 17: infección por VIH 5, enfermedad hematooncológica 4. Todos presentaban factores de riesgo para IFI. Las manifestaciones clínicas de sospecha fueron: fiebre en 19, síntomas neurológicos 11, respiratorios 9, gastrointestinales 6, urinarios 2, sepsis/shock en 3. Los agentes identificados fueron: Candida spp en 14, Cryptococcus neoformans complex 8 y Aspergillus fumigatus complex 4. Tratamiento: se indicó fluconazol en 15, asociado a anfotericina B 11. Todas las infecciones por candida fueron sensibles a los azoles. Fallecieron 7 niños, la mediana de edad fue 1 año. En 4 se identificó Candida spp, Aspergillus fumigatus complex 2 y Cryptococcus neoformans complex 1. Conclusiones: las IFI son poco frecuentes, afectan en su mayoría a niños inmunocomprometidos asociando elevada mortalidad. El diagnóstico requiere alto índice de sospecha. Candida spp y Cryptococcus spp fueron los agentes más involucrados. El inicio precoz del tratamiento acorde a la susceptibilidad disponible se asocia a menor mortalidad.


Summary: Introduction: invasive fungal infections (IFI) are an increasing health problem. Objective: describe the epidemiological, microbiological and clinical characteristics of children under 15 years of age with IFI hospitalized at the Pereira Rossell Hospital Center between 2010-2019. Methodology: retrospective study, review of medical records. Variables: age, sex, comorbidities, risk factors, symptoms, pathogens, treatment and evolution. Results: 26 cases of IFI were recorded involving 23 children. Median age 8 years, female 17, comorbidities 17, HIV infection 5, hematological-oncological disease 4. All with risk factors. Suspicion symptoms: fever 19, neurological symptoms 11, respiratory 9, gastrointestinal 6, urinary 2, sepsis / shock 3. Identified agents: Candida spp 14, Cryptococcus neoformans complex 8 and Aspergillus fumigatus complex 4. Treatment: fluconazole 15, associated with amphotericin B 11. All candida infections were sensitive to azoles. 7 died, median age 1 year. In 4, Candida spp was isolated, Aspergillus fumigatus complex in 2 and Cryptococcus neoformans complex in 1. Conclusions: IFI are rare, mostly affecting immunocompromised children, associated with high mortality. The diagnosis requires a high index of suspicion. Candida spp and Cryptococcus spp were the most involved agents. Early treatment according to available susceptibility is associated with lower mortality.


Introdução: as infecções fúngicas invasivas (IFI) são um problema de saúde crescente. Objetivo: descrever as características epidemiológicas, microbiológicas e clínicas de crianças menores de 15 anos com IFI internadas no Centro Hospitalar Pereira Rossell entre 2010 e 2019. Metodologia: estudo retrospectivo, revisão de prontuários. Variáveis: idade, sexo, comorbidades, fatores de risco, sintomas, patógenos, tratamento e evolução. Resultados: foram registrados 26 casos de IFI em 23 crianças. Idade mediana 8 anos, sexo feminino 17, comorbidades 17, infecção por HIV 5, doença hemato-oncológica 4. Todos com fatores de risco. Suspeita clínica: febre 19, sintomas neurológicos 11, respiratórios 9, gastrointestinais 6, urinários 2, sepse/choque 3. Agentes identificados: Candida spp 14, Cryptococcus neoformans complexo 8 e Aspergillus fumigatus complexo 4. Tratamento: fluconazol 15, associado à anfotericina B 11. Todas as infecções por cândida foram sensíveis aos azóis. 7 morreram, idade média de 1 ano. Em 4 das crianças Cândida spp foi isolada, Aspergillus fumigatus complexo em 2 e Cryptococcus neoformans complexo em 1. Conclusões: IFIs são raras, afetando principalmente crianças imunocomprometidas, associadas a alta mortalidade. O diagnóstico requer alto índice de suspeita. Cândida spp e Cryptococcus spp são os agentes mais envolvidos. O tratamento precoce de acordo com a suscetibilidade disponível está associado a menor mortalidade.


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Invasive Fungal Infections/drug therapy , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Aspergillus fumigatus , Comorbidity , Fluconazole/therapeutic use , Child, Hospitalized , Amphotericin B/therapeutic use , Retrospective Studies , Risk Factors , Immunocompromised Host/immunology , Cryptococcosis/diagnosis , Cryptococcosis/drug therapy , Cryptococcus neoformans , Candidiasis, Invasive/diagnosis , Candidiasis, Invasive/drug therapy , Voriconazole/therapeutic use , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/mortality , Caspofungin/therapeutic use , Antifungal Agents/therapeutic use
15.
An. Fac. Cienc. Méd. (Asunción) ; 55(3): 58-63, 20221115.
Article in Spanish | LILACS | ID: biblio-1401553

ABSTRACT

Introducción: La tuberculosis representa la novena causa de muerte en todo el mundo. La infección latente puede reactivarse por situaciones que comprometan la inmunidad del huésped. La tuberculosis pulmonar es la manifestación más frecuente en pacientes inmunodeprimidos. La baciloscopia es la herramienta primaria en el diagnóstico de la tuberculosis pulmonar activa. Objetivos: Determinar la frecuencia de tuberculosis pulmonar con baciloscopia positiva en pacientes inmunocomprometidos que acuden al Servicio de Neumología del Hospital de Clínicas durante el periodo 2018 a 2019. Materiales y métodos: Diseño observacional, descriptivo, transversal, retrospectivo, muestreo no probabilístico de casos consecutivos. Se realizó la revisión de fichas clínicas de pacientes internados en la Cátedra de Neumología del Hospital de Clínicas (2018-2019), registrados en la estadística del servicio. Para el procesamiento y análisis de datos fue utilizada una planilla electrónica precodificada de Microsoft Excel. Resultados: Del total de historias clínicas de pacientes dentro de la población estudiada (n=34), en el 68% de los casos el diagnóstico se estableció mediante baciloscopia, el 65% de ellos con hallazgo tres cruces (+++). Conclusión: La frecuencia de baciloscopia positiva en inmunocomprometidos determinada fue elevada. Aunque se está disminuyendo su uso, es importante seguir practicando este estudio a todos los inmunocomprometidos con síntomas respiratorios debido a su bajo costo y practicidad.


Introduction: Tuberculosis represents the ninth leading cause of death worldwide. Latent infection can be reactivated by situations that compromise host immunity. Pulmonary tuberculosis is the most frequent manifestation in immunocompromised patients. Smear microscopy is the primary tool in the diagnosis of active pulmonary tuberculosis. Objectives: To determine the frequency of smear-positive pulmonary tuberculosis in immunocompromised patients attending the Pneumology Service of the Hospital de Clínicas during the period 2018 to 2019. Materials and methods: Observational, descriptive, cross-sectional, retrospective, non-probabilistic sampling of consecutive cases. A review of clinical records of patients admitted to the Department of Pneumology of the Hospital de Clínicas (2018-2019), registered in the statistics department of the service, was performed. A pre-coded Microsoft Excel spreadsheet was used for data processing and analysis. Results: Of the total patient medical records within the studied population (n=34), in 68% of the cases the diagnosis was established by smear microscopy, 65% of them with finding three crosses (+++). Conclusion: The frequency of positive smear microscopy in immunocompromised patients was high. Although its use is decreasing, it is important to continue performing this study in all immunocompromised patients with respiratory symptoms due to its low cost and practicality.


Subject(s)
Tuberculosis , Tuberculosis, Pulmonary , Patients , Immunocompromised Host/immunology
18.
Mol Med ; 28(1): 20, 2022 02 08.
Article in English | MEDLINE | ID: mdl-35135470

ABSTRACT

Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C+ NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021-000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1 .


Subject(s)
BNT162 Vaccine/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Immunocompromised Host/immunology , Killer Cells, Natural/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Viral/immunology , BNT162 Vaccine/administration & dosage , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Female , Flow Cytometry , Humans , Killer Cells, Natural/metabolism , Lymphocyte Count , Male , Middle Aged , NK Cell Lectin-Like Receptor Subfamily C/immunology , NK Cell Lectin-Like Receptor Subfamily C/metabolism , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Pandemics/prevention & control , SARS-CoV-2/physiology , Vaccination/methods , Vaccination/statistics & numerical data , Young Adult
19.
Life Sci Alliance ; 5(6)2022 06.
Article in English | MEDLINE | ID: mdl-35169017

ABSTRACT

SARS-CoV-2 vaccination has proven effective in inducing an immune response in healthy individuals and is progressively us allowing to overcome the pandemic. Recent evidence has shown that response to vaccination in some vulnerable patients may be diminished, and it has been proposed a booster dose. We tested the kinetic of development of serum antibodies to the SARS-CoV-2 Spike protein, their neutralizing capacity, the CD4 and CD8 IFN-γ T-cell response in 328 subjects, including 131 immunocompromised individuals (cancer, rheumatologic, and hemodialysis patients), 160 health-care workers (HCW) and 37 subjects older than 75 yr, after vaccination with two or three doses of mRNA vaccines. We stratified the patients according to the type of treatment. We found that immunocompromised patients, depending on the type of treatment, poorly respond to SARS-CoV-2 mRNA vaccines. However, an additional booster dose of vaccine induced a good immune response in almost all of the patients except those receiving anti-CD20 antibody. Similarly to HCW, previously infected and vaccinated immunocompromised individuals demonstrate a stronger SARS-CoV-2-specific immune response than those who are vaccinated without prior infection.


Subject(s)
COVID-19 Vaccines/immunology , Immunocompromised Host/immunology , T-Lymphocytes/immunology , 2019-nCoV Vaccine mRNA-1273/immunology , Aged , Antibodies, Neutralizing/immunology , B-Lymphocytes/immunology , BNT162 Vaccine/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Humans , Immunization, Secondary , Middle Aged , Neoplasms/immunology , Renal Dialysis
20.
Cell Host Microbe ; 30(2): 154-162.e5, 2022 02 09.
Article in English | MEDLINE | ID: mdl-35120605

ABSTRACT

Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from ancestral virus in a person with advanced HIV disease in South Africa; this person was infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, but it evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, it also showed extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion that SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, and this has implications for vaccine breakthrough and reinfections.


Subject(s)
Antibodies, Neutralizing/blood , BNT162 Vaccine/immunology , HIV Infections/pathology , Immune Evasion/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adult , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Cell Line , Chlorocebus aethiops , Female , HIV-1/immunology , Humans , Immunocompromised Host/immunology , Neutralization Tests , SARS-CoV-2/isolation & purification , South Africa , Vaccination , Vaccine Efficacy , Vero Cells
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