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1.
Front Immunol ; 15: 1399180, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707896

RESUMO

Primary humoral deficiency and secondary B-cell depletion may lead to prolonged Sars-Cov-2 infection due to a decreased viral clearance. Prolonged infection is mainly driven by the lack of anti-Sars-Cov-2 immunoglobulin (IVIg) especially in patients with no vaccine response. Anti-spike immunoglobulin can be provided by infusion of convalescent patients' plasma: recent studies highlighted that commercial immunoglobulin show high titers of neutralizing IgG. We conducted a single center retrospective cohort. We included 9 patients (6 males, median age 74 years old): one patient with X-linked agammaglobulinemia and 8 patients treated with rituximab (2 granulomatosis with polyangiitis, 1 neuromyelitis optica, 4 low grade B-cell lymphoma and 1 EBV post-transplant lymphoproliferative disorder). Mean serum globulin was 4 ± 1.6 g/L. 7/8 had received at least 3 doses of mRNA anti-Sars-Cov-2 vaccine (median 4) with no response (anti-Spike IgG 0 for 6 patients). In this specific population requiring oxygen therapy but no intensive care support, the administration of IVIg was well tolerated and provided a swift improvement of clinical status, a significant decrease of inflammation associated to the an improvement of radiological patterns. Our results suggest that immunoglobulin could be used as a salvage therapy as an alternative to convalescent plasma but highly stringent patient selection is required due to the worldwide shortage of IVIg.


Assuntos
COVID-19 , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas , SARS-CoV-2 , Humanos , Masculino , Idoso , Feminino , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , COVID-19/imunologia , COVID-19/terapia , SARS-CoV-2/imunologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Resultado do Tratamento , Imunização Passiva , Soroterapia para COVID-19 , Tratamento Farmacológico da COVID-19
2.
Allergy Asthma Proc ; 45(3): 180-185, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38755776

RESUMO

Background: The main treatment of common variable immunodeficiency (CVID) is to maintain immunoglobulin G (IgG) levels within the target range. However, trough IgG levels differ among patients with similar body mass index (BMI) and those receiving the same dose of immunoglobulin replacement therapy (IGRT). A crucial factor that underlies these differences is the presence of extensive bronchiectasis, which is associated with the immunoglobulin salvage pathway. Objective: We compared trough IgG levels in patients with CVID and with and in those without bronchiectasis who had received the same dose of IGRT for 2 years to determine the association of IgG level with infection frequency. Method: This retrospective cohort study included 61 patients with CVID, of whom 21 had bronchiectasis. We reviewed the electronic records for demographic variables, baseline immunoglobulin levels, mean trough IgG levels over 2 years, efficacy levels (trough IgG level - baseline IgG level), the time interval from treatment initiation to achieving the target trough IgG level (700 mg/dL), and the number of infections. Results: The median age of the patients was 39 years (IQR, 27-51), and 29 were women (47.5%). There were no significant differences between the groups in terms of age, age at diagnosis, delay in diagnosis, sex, BMI, IGRT type (subcutaneous or intravenous), and baseline immunoglobulin levels. Trough IgG and efficacy levels were lower (P < 0.001 and P = 0.016, respectively), the time required to achieve the target IgG level was longer in patients with bronchiectasis than in those without bronchiectasis, and this time interval was significantly associated with the infection frequency. Trough IgG and albumin levels were correlated (p = 0.007), with minor differences between the groups (p = 0.04). Conclusion: Bronchiectasis was significantly associated with a longer time to achieve the target IgG levels. These long-term differences between the patients with and those without bronchiectasis have significant clinical implications.


Assuntos
Bronquiectasia , Imunodeficiência de Variável Comum , Imunoglobulina G , Humanos , Bronquiectasia/imunologia , Feminino , Masculino , Imunodeficiência de Variável Comum/terapia , Imunodeficiência de Variável Comum/imunologia , Pessoa de Meia-Idade , Adulto , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Estudos Retrospectivos , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Imunização Passiva
3.
Clin Pharmacokinet ; 63(4): 497-509, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38427270

RESUMO

BACKGROUND AND OBJECTIVE: During the COVID-19 pandemic, trials on convalescent plasma (ConvP) were performed without preceding dose-finding studies. This study aimed to assess potential protective dosing regimens by constructing a population pharmacokinetic (popPK) model describing anti-SARS-CoV-2 antibody titers following the administration of ConvP or hyperimmune globulins (COVIg). METHODS: Immunocompromised patients, testing negative for anti-SARS-CoV-2 spike antibodies despite vaccination, received a range of anti-SARS-CoV-2 antibodies in the form of COVIg or ConvP infusion. The popPK analysis was performed using NONMEM v7.4. Monte Carlo simulations were performed to assess potential COVIg and ConvP dosing regimens for prevention of COVID-19. RESULTS: Forty-four patients were enrolled, and data from 42 were used for constructing the popPK model. A two-compartment elimination model with mixed residual error best described the Nab-titers after administration. Inter-individual variation was associated to CL (44.3%), V1 (27.3%), and V2 (29.2%). Lean body weight and type of treatment (ConvP/COVIg) were associated with V1 and V2, respectively. Median elimination half-life was 20 days (interquartile range: 17-25 days). Simulations demonstrated that even monthly infusions of 600 mL of the ConvP or COVIg used in this trial would not achieve potentially protective serum antibody titers for > 90% of the time. However, as a result of hybrid immunity and/or repeated vaccination, plasma donors with extremely high antibody titers are now readily available, and a > 90% target attainment should be possible. CONCLUSION: The results of this study may inform future intervention studies on the prophylactic and therapeutic use of antiviral antibodies in the form of ConvP or COVIg. CLINICAL TRIAL REGISTRATION NUMBER: NL9379 (The Netherlands Trial Register).


Assuntos
Anticorpos Antivirais , Soroterapia para COVID-19 , COVID-19 , Imunização Passiva , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/sangue , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Imunização Passiva/métodos , Hospedeiro Imunocomprometido , Modelos Biológicos , Método de Monte Carlo
4.
Influenza Other Respir Viruses ; 18(3): e13272, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38501337

RESUMO

The emergence of SARS-CoV-2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with all monoclonal antibodies having lost any neutralization activity. We report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited from COVID-19 convalescent plasma (CCP). At Day 28, the overall survival was 76% (95% CI 67-86) with no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or autoimmune diseases. No safety concern was reported during the course of the study. These results showed that CCP is well tolerated and represents a treatment option for immunocompromised patients who remain highly impacted by the COVID19 epidemic.


Assuntos
COVID-19 , Humanos , COVID-19/terapia , Soroterapia para COVID-19 , SARS-CoV-2 , Imunização Passiva , Hospedeiro Imunocomprometido , Anticorpos Antivirais/uso terapêutico , Anticorpos Neutralizantes
5.
Ann Hematol ; 103(6): 2123-2131, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38436671

RESUMO

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.


Assuntos
Anticorpos Monoclonais Humanizados , COVID-19 , Neoplasias Hematológicas , SARS-CoV-2 , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/complicações , Idoso , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/complicações , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , SARS-CoV-2/imunologia , Adulto , Idoso de 80 Anos ou mais , Imunização Passiva , Anticorpos Antivirais/sangue , Infecções Irruptivas
6.
Sci Rep ; 14(1): 6072, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480826

RESUMO

Blood transfusions from convalescent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients could be used to treat patients with severe infections or immunocompromised patients. However, it is necessary to select the optimal donors to maximize the utilization of resources. In this study, we investigated the associations among body mass index (BMI), tobacco smoking, exercise frequency and duration, and alcohol consumption with the SARS-CoV-2 immunoglobulin-G (IgG) antibody titer levels with in the Chinese convalescent blood donor population. Here we show that BMI, smoking habits, and exercise frequency appear to be predictive factors for IgG levels in convalescent male blood donors. However, these variables were not observed as predictive of IgG levels in female convalescent blood donors. The findings could be used to optimize the screening for potential blood donors to treat immunocompromised or severely ill COVID-19 patients.


Assuntos
COVID-19 , Humanos , Masculino , Feminino , SARS-CoV-2 , Doadores de Sangue , Estudos Transversais , Imunização Passiva , Soroterapia para COVID-19 , Anticorpos Antivirais , Imunoglobulina G , China
7.
Transfusion ; 64(3): 443-448, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38327238

RESUMO

BACKGROUND: Patients with severe B-cell depletion related to hematological malignancies or B-cell targeted therapy suffer from impaired antibody responses to SARS-CoV-2 and are at risk for prolonged COVID-19. In this population, COVID-19 convalescent plasma (CCP) may provide passive immunity, enhance immune response, and promote virus neutralization. This study evaluated outcomes of B-cell depleted patients with persistent COVID-19 treated with CCP. STUDY DESIGN AND METHODS: This analysis included all consecutive severely B-cell depleted patients with persistent COVID-19, receiving CCP at Rambam between 01.2022-02.2023. Persistent COVID-19 was defined as the presence of symptoms for ≥14 days in patients with negative SARS-CoV-2 nucleocapsid antibody test results. RESULTS: Twenty patients met inclusion criteria, 17 of whom had hematological malignancies, two suffered from rheumatoid arthritis and one had both. Twelve patients received anti-CD-20 treatment, one - CAR-T cells and three underwent stem cell transplantation. The median duration of COVID-19 symptoms was 27.5 days (range 14-97); 12 patients had mild-to-moderate COVID-19 and 8 had severe infection. Sixteen patients required hospitalization. The majority of patients received other COVID-19 therapies before CCP. Within a median of two days (range 1-16) post-infusion, 19/20 patients clinically improved. No CCP-associated adverse events were documented. COVID-19 symptoms recurred in 3 of the improved patients. Two patients died from COVID-19 on days 1 and 90 following the first CCP infusion. DISCUSSION: In severely B-cell depleted patients with persistent COVID-19, CCP is safe and associated with rapid clinical improvement. This subset of immunocompromised patients could particularly benefit from CCP administration.


Assuntos
COVID-19 , Neoplasias Hematológicas , Humanos , COVID-19/terapia , COVID-19/etiologia , SARS-CoV-2 , Soroterapia para COVID-19 , Imunização Passiva/métodos , Anticorpos Antivirais , Neoplasias Hematológicas/terapia
8.
Sci Rep ; 14(1): 988, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200046

RESUMO

Although graft T cells assist in engraftment, mediate antiviral immune-reconstitution, and cause graft-versus-host disease, graft size is not determined by T-cell content of the graft. The conventional method of graft size determination based on CD34+ cells with alemtuzumab serotherapy is associated with delayed immune reconstitution, contributing to an increased risk of viral infections and graft failure. Alemtuzumab, a long half-life anti-CD52 monoclonal antibody is a robust T-cell depleting serotherapy, and relatively spares memory-effector T cells compared to naïve T cells. We therefore hypothesized that graft size based on T-cell content in patients receiving peripheral blood stem cell graft with alemtuzumab serotherapy would facilitate immune-reconstitution without increasing the risk of graft-versus-host disease. We retrospectively analysed twenty-six consecutive patients with non-malignant disorders grafted using alemtuzumab serotherapy and capping of graft T cells to a maximum of 600 million/kg. The graft T-cell capping protocol resulted in early immune-reconstitution without increasing the risk of severe graft-versus-host disease. Graft T-cell content correlated with CD4+ T-cell reconstitution and acute graft-versus-host disease. The course of CMV viraemia was predictable without recurrence and associated with early T-cell recovery. No patient developed chronic graft-versus-host disease. Overall survival at one year was 100% and disease-free survival was 96% at a median of 899 days (range: 243-1562). Graft size determined by peripheral blood stem cell graft T-cell content in patients receiving alemtuzumab serotherapy for non-malignant disorders is safe and leads to early T-cell immune-reconstitution with excellent survival outcomes.


Assuntos
Doença Enxerto-Hospedeiro , Humanos , Alemtuzumab/uso terapêutico , Estudos Retrospectivos , Imunização Passiva , Tamanho Celular
10.
Microbiol Spectr ; 12(1): e0328623, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38009954

RESUMO

IMPORTANCE: This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.


Assuntos
COVID-19 , Humanos , COVID-19/terapia , Soroterapia para COVID-19 , Interleucina-6 , SARS-CoV-2 , Citocinas , Imunização Passiva
11.
Vet. zootec ; 31: 37-41, 2024.
Artigo em Português | LILACS, VETINDEX | ID: biblio-1552978

RESUMO

A colostragem é essencial para a saúde dos bezerros neonatos, uma vez que não há a transferência de imunidade através da placenta, ou seja, o contato inicial do organismo com anticorpos se dá através da primeira mamada, onde há transferência da imunidade passiva. Sendo assim, o objetivo do trabalho é revisar os benefícios da acidificação ou silagem do colostro para otimizar a conservação da dieta líquida em fazendas; analisar o impacto no desempenho de bezerros em comparação com o colostro tradicional refrigerado em aleitamentos convencionais. O volume ideal preconizado é, no mínimo, 10% do peso vivo do animal nas primeiras duas horas e mais 5% do peso vivo nas seis a oito horas seguintes a primeira ingestão, para que se obtenha um bom desenvolvimento durante o crescimento, caso contrário, a falta da administração do colostro nas primeiras horas de vida predispõe enfermidades, tais como pneumonia e diarreia, prejudicando assim a saúde e consequentemente o desempenho em relação a outros animais que receberam uma colostragem adequada. Problemas com a qualidade do colostro surgem devido ao armazenamento inadequado, especialmente em propriedades sem refrigeração. A falta de sistemas de congelamento resulta em administração de leite em temperatura ambiente por períodos prolongados, prejudicando assim a imunidade e nutrição dos bezerros durante a colostragem. Todavia, há alternativas para o problema tal como o fornecimento de silagem de colostro. Em alguns casos, o processo de acidificação demanda a adição de ácidos no leite, a fim de evitar o crescimento de microrganismos patogênicos. O principal aspecto positivo do leite acidificado é a manutenção em temperatura ambiente, ou seja, não há a necessidade de passar por processos de refrigeração.


Colostrum is essential for the health of newborn calves, since there is no transfer of immunity through the placenta, that is, the body's initial contact with antibodies occurs through the first feeding, where there is a transfer of passive immunity. Therefore, the objective of the work is to review the benefits of acidifying or colostrum silage to optimize the conservation of liquid diets on farms; analyze the impact on calf performance compared to traditional refrigerated colostrum in conventional sucklers. The recommended ideal volume is at least 10% of the animal's live weight in the first two hours and a further 5% of its live weight in the six to eight hours following the first ingestion, so that good development is achieved during growth, otherwise, the lack of colostrum administration in the first hours of life predisposes diseases, such as pneumonia and diarrhea, thus harming health and consequently performance in relation to other animals that received adequate colostrum. Problems with colostrum quality arise due to inadequate storage, especially in unrefrigerated properties. The lack of freezing systems results in milk being administered at room temperature for prolonged periods, thus damaging the calves immunity and nutrition during colostrum. However, there are alternatives to the problem such as the supply of colostrum silage. In some cases, the acidification process requires the addition of acids to the milk in order to prevent the growth of pathogenic microorganisms. The main positive aspect of acidified milk is that it remains at room temperature, that is, there is no need to undergo refrigeration processes.


El calostro es esencial para la salud de los terneros recién nacidos, ya que no existe transferencia de inmunidad a través de la placenta, es decir, el contacto inicial del cuerpo con los anticuerpos ocurre a través de la primera alimentación, donde existe una transferencia de inmunidad pasiva. Por lo tanto, el objetivo del trabajo es revisar los beneficios de acidificar o ensilar el calostro para optimizar la conservación de dietas líquidas en granjas; analizar el impacto en el rendimiento de los terneros en comparación con el calostro refrigerado tradicional en lechones convencionales. El volumen ideal recomendado es al menos el 10% del peso vivo del animal en las dos primeras horas y otro 5% de su peso vivo en las seis a ocho horas siguientes a la primera ingesta, para que se consiga un buen desarrollo durante el crecimiento, en caso contrario. la falta de administración de calostro en las primeras horas de vida predispone a enfermedades, como neumonía y diarrea, perjudicando la salud y consecuentemente el rendimiento en relación a otros animales que recibieron el calostro adecuado. Los problemas con la calidad del calostro surgen debido a un almacenamiento inadecuado, especialmente en propiedades no refrigeradas. La falta de sistemas de congelación provoca que la leche se administre a temperatura ambiente durante períodos prolongados, dañando así la inmunidad y la nutrición de los terneros durante el calostro. Sin embargo, existen alternativas al problema como el suministro de ensilaje de calostro. En algunos casos, el proceso de acidificación requiere la adición de ácidos a la leche para evitar el crecimiento de microorganismos patógenos. El principal aspecto positivo de la leche acidificada es que se mantiene a temperatura ambiente, es decir, no es necesario someterse a procesos de refrigeración.


Assuntos
Animais , Bovinos , Imunização Passiva/veterinária , Colostro , Leite/química , Animais Recém-Nascidos/crescimento & desenvolvimento
12.
Ter Arkh ; 95(8): 722-729, 2023 Oct 11.
Artigo em Russo | MEDLINE | ID: mdl-38158913

RESUMO

On July 3, 2023, an interdisciplinary Council of Experts "The burden of COVID-19 in a heterogeneous population of immunocompromised patients - post-pandemic realities" was held in Moscow with leading experts in pulmonology, rheumatology, hematology, oncology, nephrology, allergology-immunology, transplantation, and infectious diseases. The aim of the meeting was to discuss the current clinical and epidemiologic situation related to COVID-19, the relevance of disease prevention strategies for high-risk patients. The experts addressed the following issues: 1) the disease burden of COVID-19 in 2023 for patients with immunodeficiency in different therapeutic areas; 2) the place of passive immunization with monoclonal antibodies as a method of COVID-19 prophylaxis among immunocompromised patients; 3) prerequisites for the inclusion of passive immunization of immunocompromised patients into routine clinical practice.


Assuntos
COVID-19 , Reumatologia , Humanos , COVID-19/epidemiologia , Imunização Passiva , Hospedeiro Imunocomprometido , Atenção à Saúde
13.
J Transl Med ; 21(1): 693, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794448

RESUMO

Antibody technology is widely used in the fields of biomedical and clinical therapies. Nonetheless, the complex in vitro expression of recombinant proteins, long production cycles, and harsh storage conditions have limited their applications in medicine, especially in clinical therapies. Recently, this dilemma has been overcome to a certain extent by the development of mRNA delivery systems, in which antibody-encoding mRNAs are enclosed in nanomaterials and delivered to the body. On entering the cytoplasm, the mRNAs immediately bind to ribosomes and undergo translation and post-translational modifications. This process produces monoclonal or bispecific antibodies that act directly on the patient. Additionally, it eliminates the cumbersome process of in vitro protein expression and extends the half-life of short-lived proteins, which significantly reduces the cost and duration of antibody production. This review focuses on the benefits and drawbacks of mRNA antibodies compared with the traditional in vitro expressed antibodies. In addition, it elucidates the progress of mRNA antibodies in the prevention of infectious diseases and oncology therapy.


Assuntos
Anticorpos Biespecíficos , Imunização Passiva , Humanos , RNA Mensageiro/genética , Preparações Farmacêuticas , Anticorpos Biespecíficos/uso terapêutico , Proteínas Recombinantes , Imunoterapia
14.
Blood Cancer Discov ; 4(6): 427-429, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37769160

RESUMO

SUMMARY: Lancman and colleagues find that infection risk in patients treated with anti-BCMA bispecific antibodies for relapsed/refractory multiple myeloma is associated with severe immunoglobulin deficiency and may be mitigated by immunoglobulin replacement therapy. The study has implications for managing infection risk and raises questions about the optimal duration of treatment with these potent, novel immunotherapies. See related article by Lancman et al., p. 440 (4) .


Assuntos
Anticorpos Biespecíficos , Mieloma Múltiplo , Humanos , Anticorpos Biespecíficos/uso terapêutico , Imunoterapia , Imunização Passiva , Antígeno de Maturação de Linfócitos B
15.
Toxins (Basel) ; 15(7)2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37505731

RESUMO

Humans have faced poisonous animals since the most ancient times. It is recognized that certain animals, like specific plants, produce toxic substances that can be lethal, but that can also have therapeutic or psychoactive effects. The use of the term "venom", which initially designated a poison, remedy, or magic drug, is now confined to animal poisons delivered by biting. Following Louis Pasteur's work on pathogenic microorganisms, it was hypothesized that venoms could be related to bacterial toxins and that the process of pathogenicity attenuation could be applied to venoms for the prevention and treatment of envenomation. Cesaire Phisalix and Gabriel Bertrand from the National Museum of Natural History as well as Albert Calmette from the Institut Pasteur in Paris were pioneers in the development of antivenomous serotherapy. Gaston Ramon refined the process of venom attenuation for the immunization of horses using a formalin treatment method that was successful for diphtheria and tetanus toxins. This paved the way for the production of antivenomous sera at the Institut Pasteur, as well as for research on venom constituents and the characterization of their biological activities. The specific activities of certain venom components, such as those involved in blood coagulation or the regulation of chloride ion channels, raises the possibility of developing novel therapeutic drugs that could serve as anticoagulants or as a treatment for cystic fibrosis, for example. Scientists of the Institut Pasteur of Paris have significantly contributed to the study of snake venoms, a topic that is reported in this review.


Assuntos
Venenos , Toxinas Biológicas , Animais , Cavalos , Imunização , Imunização Passiva , Venenos de Serpentes
16.
Vox Sang ; 118(9): 794-797, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37489640

RESUMO

BACKGROUND AND OBJECTIVES: COVID-19 convalescent plasma (CCP) has retained potency and clinical efficacy against SARS-CoV-2 and is currently of utmost value for seronegative immunocompromised patients. Since most of the effect is due to the vaccine boost of infection-elicited antibodies, there is a theoretical concern that the frequency of suitable donors is declining. MATERIALS AND METHODS: In this single-institution serosurvey, we screened 599 consecutive donors attending our area in two different seasons (300 in November 2022 and 299 in February 2023) using the Abbott Alinity® anti-Spike immunoglobulin G assay. RESULTS: More than 80% of random donors qualify according to the FDA criteria for high-titre CCP (>4350 AU/mL), with a stable trend. CONCLUSION: Despite reduced anti-Spike vaccine boost deployment in the general population, we have shown here that high-titre CCP units are easier than ever to procure. This finding also has implications for the derivation of standard immunoglobulins, which are finally approaching the potency of hyperimmune serum and could soon represent an alternative to CCP.


Assuntos
COVID-19 , Vacinas Anticâncer , Humanos , Doadores de Sangue , COVID-19/terapia , Soroterapia para COVID-19 , SARS-CoV-2 , Itália , Imunoglobulina G , Anticorpos Antivirais/uso terapêutico , Imunização Passiva , Anticorpos Neutralizantes
17.
Clin Lymphoma Myeloma Leuk ; 23(10): 719-732, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37353432

RESUMO

Secondary antibody deficiency (SAD) is a subtype of secondary immunodeficiency characterized by low serum antibody concentrations (hypogammaglobulinemia) or poor antibody function. SAD is common in patients with multiple myeloma (MM) due to underlying disease pathophysiology and treatment-related immune system effects. Patients with SAD are more susceptible to infections and infection-related morbidity and mortality. With therapeutic advancements improving MM disease control and survival, it is increasingly important to recognize and treat the often-overlooked concurrent immunodeficiency present in patients with MM. The aims of this review are to define SAD and its consequences in MM, increase SAD awareness, and provide recommendations for SAD management. Based on expert panel discussions at a standalone meeting and supportive literature, several recommendations were made. Firstly, all patients with MM should be suspected to have SAD regardless of serum antibody concentrations. Patients should be evaluated for immunodeficiency at MM diagnosis and stratified into management categories based on their individualized risk of SAD and infection. Infection-prevention strategy education, early infection reporting, and anti-infective prophylaxis are key. We recommend prophylactic antibiotics or immunoglobulin replacement therapy (IgRT) should be considered in patients with severe hypogammaglobulinemia associated with a recurrent or persistent infection. To ensure an individualized and efficient treatment approach is utilized, patient's immunoglobin G concentration and infection burden should be closely monitored throughout treatment. Patient choice regarding route and IgRT treatment is also key in reducing treatment burden. Together, these recommendations and proposed management algorithms can be used to aid physician decision-making to improve patient outcomes.


Assuntos
Agamaglobulinemia , Síndromes de Imunodeficiência , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Agamaglobulinemia/terapia , Síndromes de Imunodeficiência/tratamento farmacológico , Imunização Passiva , Anticorpos/uso terapêutico
18.
J Hematol Oncol ; 16(1): 32, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37005697

RESUMO

Only few studies have analyzed the efficacy of tixagevimab/cilgavimab to prevent severe Coronavirus disease 2019 (COVID-19) and related complications in hematologic malignancies (HM) patients. Here, we report cases of breakthrough COVID-19 after prophylactic tixagevimab/cilgavimab from the EPICOVIDEHA registry). We identified 47 patients that had received prophylaxis with tixagevimab/cilgavimab in the EPICOVIDEHA registry. Lymphoproliferative disorders (44/47, 93.6%) were the main underlying HM. SARS-CoV-2 strains were genotyped in 7 (14.9%) cases only, and all belonged to the omicron variant. Forty (85.1%) patients had received vaccinations prior to tixagevimab/cilgavimab, the majority of them with at least two doses. Eleven (23.4%) patients had a mild SARS-CoV-2 infection, 21 (44.7%) a moderate infection, while 8 (17.0%) had severe infection and 2 (4.3%) critical. Thirty-six (76.6%) patients were treated, either with monoclonal antibodies, antivirals, corticosteroids, or with combination schemes. Overall, 10 (21.3%) were admitted to a hospital. Among these, two (4.3%) were transferred to intensive care unit and one (2.1%) of them died. Our data seem to show that the use of tixagevimab/cilgavimab may lead to a COVID-19 severity reduction in HM patients; however, further studies should incorporate further HM patients to confirm the best drug administration strategies in immunocompromised patients.


Assuntos
COVID-19 , Neoplasias Hematológicas , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Anticorpos Monoclonais , Imunização Passiva , Sistema de Registros
19.
Front Immunol ; 14: 1143870, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006290

RESUMO

Background: Herpes simplex viruses (HSV) cause ubiquitous human infections. For vaccine development, knowledge concerning correlates of protection is essential. Therefore, we investigated (I) if humans are in principle capable producing cell-to-cell spread inhibiting antibodies against HSV and (II) whether this capacity is associated with a reduced HSV-1 reactivation risk. Methods: We established a high-throughput HSV-1-ΔgE-GFP reporter virus-based assay and evaluated 2,496 human plasma samples for HSV-1 glycoprotein E (gE) independent cell-to-cell spread inhibiting antibodies. Subsequently, we conducted a retrospective survey among the blood donors to analyze the correlation between the presence of cell-to-cell spread inhibiting antibodies in plasma and the frequency of HSV reactivations. Results: In total, 128 of the 2,496 blood donors (5.1%) exhibited high levels of HSV-1 gE independent cell-to-cell spread inhibiting antibodies in the plasma. None of the 147 HSV-1 seronegative plasmas exhibited partial or complete cell-to-cell spread inhibition, demonstrating the specificity of our assay. Individuals with cell-to-cell spread inhibiting antibodies showed a significantly lower frequency of HSV reactivations compared to subjects without sufficient levels of such antibodies. Conclusion: This study contains two important findings: (I) upon natural HSV infection, some humans produce cell-to-cell spread inhibiting antibodies and (II) such antibodies correlate with protection against recurrent HSV-1. Moreover, these elite neutralizers may provide promising material for immunoglobulin therapy and information for the design of a protective vaccine against HSV-1.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Humanos , Estudos Retrospectivos , Proteínas do Envelope Viral , Imunização Passiva , Anticorpos Bloqueadores
20.
Viruses ; 15(3)2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36992465

RESUMO

Patients receiving treatment with B-cell-depleting monoclonal antibodies, such as anti-CD20 monoclonal antibodies, such as rituximab and obinutuzumab, either for hematological disease or another diagnosis, such as a rheumatological disease, are at an increased risk for medical complications and mortality from COVID-19. Since inconsistencies persist regarding the use of convalescent plasma (CP), especially in the vulnerable patient population that has received previous treatment with B-cell-depleting monoclonal antibodies, further studies should be performed in thisdirection. The aim of the present study was to describe the characteristics of patients with previous use of B-cell-depleting monoclonal antibodies and describe the potential beneficial effects of CP use in terms of mortality, ICU admission and disease relapse. In this retrospective cohort study, 39 patients with previous use of B-cell-depleting monoclonal antibodies hospitalized in the COVID-19 department of a tertiary hospital in Greece were recorded and evaluated. The mean age was 66.3 years and 51.3% were male. Regarding treatment for COVID-19, remdesivir was used in 89.7%, corticosteroids in 94.9% and CP in 53.8%. In-hospital mortality was 15.4%. Patients who died were more likely to need ICU admission and also had a trend towards a longer hospital stay, even though the last did not reach statistical significance. Patients treated with CP had a lower re-admission rate for COVID-19 after discharge. Further studies should be performed to identify the role of CP in patients with treatment with B-cell-depleting monoclonal antibodies suffering from COVID-19.


Assuntos
COVID-19 , Humanos , Masculino , Idoso , Feminino , COVID-19/terapia , COVID-19/etiologia , SARS-CoV-2 , Estudos Retrospectivos , Imunização Passiva/efeitos adversos , Soroterapia para COVID-19 , Anticorpos Monoclonais/uso terapêutico
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