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1.
Microbiol Spectr ; 10(1): e0256021, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35196802

RESUMO

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring frequent adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28-day mortality or alter levels of specific antibody responses before and after CIP infusion. In a single-arm phase II study, patients >18 years-old with respiratory symptoms with confirmed COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 h of admission. Levels of SARS-CoV-2 detected by PCR in the respiratory tract and circulating anti-SARS-CoV-2 antibody titers were sequentially measured before and after CIP transfusion. Twenty-nine patients were transfused high titer CIP and 48 contemporaneous comparable controls were identified. All classes of antibodies to the three SARS-CoV-2 target proteins were significantly increased at days 7 and 14 post-transfusion compared with baseline (P < 0.01). Anti-nucleocapsid IgA levels were reduced at day 28, suggesting that the initial rise may have been due to the contribution of CIP. The groups were well-balanced, without statistically significant differences in demographics or co-morbidities or use of remdesivir or dexamethasone. In participants transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). IMPORTANCE Transfusion of high-titer CIP to non-critically ill patients early after admission with COVID-19 respiratory disease was associated with significantly increased anti-SARS-CoV-2 specific antibodies (compared to baseline) and a non-significant reduction in ICU transfer and death (compared to controls). This prospective phase II trial provides a suggestion that the antiviral effects of CIP from early in the COVID-19 pandemic may delay progression to critical illness and death in specific patient populations. This study informs the optimal timing and potential population of use for CIP in COVID-19, particularly in settings without access to other interventions, or in planning for future coronavirus pandemics.


Assuntos
Anticorpos Antivirais/administração & dosagem , COVID-19/imunologia , COVID-19/terapia , Estado Terminal/terapia , Plasma/imunologia , SARS-CoV-2/imunologia , Idoso , COVID-19/mortalidade , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2/genética
3.
J Clin Immunol ; 42(2): 253-265, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34893946

RESUMO

Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding.


Assuntos
COVID-19/imunologia , COVID-19/terapia , Plasma/imunologia , Doenças da Imunodeficiência Primária/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Criança , Feminino , Humanos , Imunização Passiva/métodos , Masculino , Pessoa de Meia-Idade , Eliminação de Partículas Virais/imunologia , Adulto Jovem
4.
J Clin Immunol ; 42(2): 232-239, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34767118

RESUMO

PURPOSE: To study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment. METHODS: Sera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 Abs by ELISA and a pseudo virus-based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion. RESULTS: IFN-α2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract. CONCLUSIONS: IFN-α2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.


Assuntos
Autoanticorpos/imunologia , COVID-19/imunologia , COVID-19/terapia , Interferon alfa-2/imunologia , Plasma/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antivirais/imunologia , Transfusão de Componentes Sanguíneos/métodos , Estado Terminal , Feminino , Humanos , Imunização Passiva/métodos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia
5.
Nat Commun ; 12(1): 6853, 2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824251

RESUMO

Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient's pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/terapia , Imunidade , Imunização Passiva/métodos , Plasma/imunologia , Anticorpos Neutralizantes/imunologia , Doadores de Sangue , Humanos , Imunidade Humoral , Nucleocapsídeo/imunologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/imunologia
6.
Front Immunol ; 12: 633323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790190

RESUMO

Background: Convalescent plasma therapy is expected to be a promising alternative to supportive therapy during the SARS-CoV-2 pandemic outbreak. Altered immune response in repetitive convalescent plasma donors has not been widely studied. This case series was reported to analyze the patterns of immune responses and the factors that might influence them in repetitive convalescent plasma donors and increase awareness of COVID-19 survivors to donate their convalescent plasma. Cases Illustration: There were five repetitive donors who were eligible as convalescent plasma donor requirements. It was found two donors who showed increment of anti-SARS-CoV-2 IgG level after donation and two others who showed persistent anti-SARS-CoV-2 IgG level more than two months after recovered. Discussion: There was a difference in immune response in survivors who have the probability of being exposed to same antigens with survivors who did not, where the group of survivors who are at risk of exposure to antigens after recovery could trigger anamnestic immune response that can increase antiSARS-CoV-2 IgG levels. The other factor that influence the prolongation of anti-SARS-CoV-2 IgG levels are the possibility of neutralizing antibodies in plasma upregulation. Conclusion: Immunological phenomenon in SARS-CoV-2, both in survivors and convalescent plasma donors, have not been widely observed and studied. From the case series discussed above, it can be concluded that convalescent plasma donation does not yet have strong evidence of decreasing levels of specific antibodies against SARS-CoV-2 and plasmapheresis procedure is safe to be done without reducing the protective effect of donor antibody post-plasma donation.


Assuntos
COVID-19/imunologia , COVID-19/terapia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Plasma/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/imunologia , Doadores de Sangue , Convalescença , Feminino , Humanos , Imunização Passiva , Indonésia , Masculino , Pessoa de Meia-Idade
7.
mBio ; 12(6): e0297521, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34781736

RESUMO

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484, and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and variants of concern (VOCs), including B.1.1.7 (alpha), P.1 (gamma), and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting that different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to the first pandemic wave of prototype SARS-CoV-2 possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern. IMPORTANCE We describe the binding and neutralization properties of a new set of human monoclonal antibodies derived from memory B cells of 10 coronavirus disease 2019 (COVID-19) convalescent donors in the first pandemic wave of prototype SARS-CoV-2. There were 12 antibodies targeting distinct epitopes on spike, including two sites on the RBD and one on the N-terminal domain (NTD), that displayed cross-neutralization of VOCs, for which distinct antibody targets could neutralize discrete variants. This work underlines that natural infection by SARS-CoV-2 induces effective cross-neutralization against only some VOCs and supports the need for COVID-19 vaccination for robust induction of neutralizing antibodies targeting multiple epitopes of the spike protein to combat the current SARS-CoV-2 VOCs and any others that might emerge in the future.


Assuntos
Anticorpos Antivirais/sangue , Anticorpos Amplamente Neutralizantes/sangue , COVID-19/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , Convalescença , Epitopos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Pandemias , Plasma/imunologia , Ligação Proteica , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
8.
Clin Immunol ; 232: 108871, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34619377

RESUMO

Despite the burgeoning field of coronavirus disease-19 (COVID-19) research, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibodies remains unclear. This study validated two high-throughput immunological methods for use as surrogate live virus neutralisation assays and employed them to examine the half-life of SARS-CoV-2 neutralising antibodies in convalescent plasma donations made by 42 repeat donors between April and September 2020. SARS-CoV-2 neutralising antibody titres decreased over time but typically remained above the methods' diagnostic cut-offs. Using this longitudinal data, the average half-life of SARS-CoV-2 neutralising antibodies was determined to be 20.4 days. SARS-CoV-2 neutralising antibody titres appear to persist in the majority of donors for several months. Whether these titres confer protection against re-infection requires further study and is of particular relevance as COVID-19 vaccines become widely available.


Assuntos
Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/metabolismo , COVID-19/metabolismo , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Doadores de Sangue , COVID-19/imunologia , COVID-19/terapia , Feminino , Meia-Vida , Humanos , Imunização Passiva , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Plasma/imunologia , Plasma/metabolismo , SARS-CoV-2/imunologia , Adulto Jovem
9.
PLoS Pathog ; 17(9): e1009958, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34559854

RESUMO

Cross-reactive epitopes (CREs) are similar epitopes on viruses that are recognized or neutralized by same antibodies. The S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated. Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses. In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined. These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize. As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2. Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2 pseudoviruses. Collectively, our observations suggest that human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile.


Assuntos
Anticorpos Amplamente Neutralizantes/imunologia , Anticorpos Anti-HIV/imunologia , HIV-1/imunologia , SARS-CoV-2/imunologia , Anticorpos Monoclonais/imunologia , COVID-19/imunologia , Reações Cruzadas/imunologia , Humanos , Plasma/imunologia
10.
Nat Commun ; 12(1): 4864, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381030

RESUMO

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.


Assuntos
COVID-19/terapia , Plasma/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos , Variação Antigênica , Doadores de Sangue , COVID-19/mortalidade , Feminino , Humanos , Imunização Passiva/mortalidade , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
11.
Viruses ; 13(7)2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201767

RESUMO

We summarize here in vitro evidences of efficacy for convalescent plasma, currently approved vaccines and monoclonal antibodies against SARS-CoV-2 variants of concern (VOC: B.1.1.7, B.1.351, P.1, and B.1.617.2), variants of interest (VOI: B.1.427/B.1.429, P.2, B.1.525, P.3, B.1.526, and B.1.671.1), and other strains (B.1.1.298 and B.1.258delta). While waiting from real world clinical efficacy, these data provide guidance for the treating physician.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/sangue , Plasma/imunologia , SARS-CoV-2/imunologia , Vacinas Virais/imunologia , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Neutralizantes/imunologia , COVID-19/terapia , Humanos , Imunização Passiva/normas , Técnicas In Vitro , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus/imunologia
12.
Transfusion ; 61 Suppl 1: S119-S130, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269465

RESUMO

BACKGROUND: Hemorrhage is a leading cause of preventable death in civilian and military trauma. Freeze-dried plasma is promising for hemostatic resuscitation in remote prehospital settings, given its potential benefits in reducing blood loss and mortality, long storage at ambient temperatures, high portability, and rapid reconstitution for transfusion in austere environments. Here we assess the ex vivo characteristics of a novel Terumo's freeze-dried plasma product (TFDP). STUDY DESIGN AND METHODS: Rotational thromboelastometry (ROTEM) tests (INTEM, EXTEM, and FIBTEM) were conducted on plasma samples at 37°C with a ROTEM delta-machine using standard reagents and procedures. The following samples were analyzed: pooled plasma to produce TFDP, TFDP reconstituted, and stored immediately at -80°C, reconstituted TFDP stored at 4°C for 24 h and room temperature (RT) for 4 h before freezing at -80°C. Analysis of plasma concentrations of selected cytokines, chemokines, and vascular molecules was performed using a multiplex immunoassay system. One-way ANOVA with post hoc tests assessed differences in hemostatic and inflammatory properties. RESULTS: No significant differences in ROTEM variables (coagulation time [CT], clot formation time, α-angle, maximum clot firmness, and lysis index 30) between the TFDP-producing plasma and reconstituted TFDP samples were observed. Compared to control plasma, reconstituted TFDP stored at 4°C for 24 h or RT for 4 h showed a longer INTEM CT. Levels of immuno-inflammatory mediators were similar between frozen plasma and TFDP. CONCLUSIONS: TFDP is equivalent to frozen plasma with respect to global hemostatic and immuno-inflammatory mediator profiles. Further investigations of TFDP in trauma-induced coagulopathy models and bleeding patients are warranted.


Assuntos
Preservação de Sangue , Liofilização , Plasma/imunologia , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Humanos , Inflamação/imunologia
13.
J Clin Apher ; 36(4): 628-633, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33950554

RESUMO

BACKGROUND: Criteria for selection of FFP blood type has not been clearly established and use of group AB plasma is preferred by numerous transplantation protocols. AIMS: This study assesses the safety and efficacy of alternative group A or B plasma in ABO incompatible solid organ transplantation. MATERIALS & METHODS: Alternative use of group A or B plasma (incompatible plasma) was inevitable during the shortage of group AB plasma. Experience from select number of patients during the period of extreme group AB plasma shortage is described. RESULTS: The result of alternative use of group A or B plasma was within expectation, showing effective reduction of isoagglutinin titers for pre-operative desensitization and efficacy for treatment of post-operative patients. No immediate hemolytic transfusion reaction was reported. DISCUSSION: While validation in a larger cohort of patients is necessary, our limited experience have shown satisfactory clinical outcomes without adverse events. CONCLUSIONS: Use of incompatible group A or B plasma is a viable option when group AB plasma is limited.


Assuntos
Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos/terapia , Troca Plasmática/métodos , Transplante/métodos , Aglutininas/química , Bancos de Sangue/provisão & distribuição , Sobrevivência de Enxerto , Hemólise , Humanos , Transplante de Rim/efeitos adversos , Segurança do Paciente , Plasma/imunologia , Plasmaferese , Reação Transfusional , Resultado do Tratamento
14.
Chem Biol Interact ; 344: 109497, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33991505

RESUMO

Extracellular vesicles like exosomes are important therapeutic tactics for treating COVID -19. By utilizing convalescent plasma derived exosomes (CPExo) from COVID-19 recovered persistence could accelerate the treatment strategies in the current state of affairs. Adequate literature has shown that administering the exosome to the in vivo system could be beneficial and could target the pathogens in an effective and precise manner. In this hypothesis we highlight the CPExo instead of convalescent plasma (CP), perhaps to dispense of exosomes are gratified and it's more effectively acquired immune response conferral through antibodies. COVID-19 convalescent plasma has billions of exosomes and it has aptitudes to carry molecular constituents like proteins, lipids, RNA and DNA, etc. Moreover, exosomes are capable of recognizing antigens with adequate sensitivity and specificity. Many of these derivatives could trigger an immune modulation into the cells and act as an epigenetic inheritor response to target pathogens through RNAs. COIVID-19 resistance activated plasma-derived exosomes are either responsible for the effects of plasma beyond the contained immune antibodies or could be inhibitory. The proposed hypothesis suggests that preselecting the plasma-derived antibodies and RNAs merged exosomes would be an optimized therapeutic tactic for COVID-19 patients. We suggest that, the CPExo has a multi-potential effect for treatment efficacy by acting as immunotherapeutic, drug carrier, and diagnostic target with noncoding genetic materials as a biomarker.


Assuntos
COVID-19/imunologia , COVID-19/terapia , Exossomos/imunologia , Plasma/imunologia , Imunidade Adaptativa/imunologia , Anticorpos/imunologia , Antígenos/imunologia , DNA/imunologia , Humanos , Imunização Passiva , RNA/imunologia , SARS-CoV-2/imunologia
15.
Ann Clin Lab Sci ; 51(2): 267-270, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33941569

RESUMO

Managing a platelet blood product inventory in a hospital-based transfusion service (TS) is challenging. Thus, to optimize platelet inventory availability and to prevent excess outdating, most tertiary care center-based TSs do not require ABO-identical platelet (PLT) transfusions. To mitigate the risk of hemolysis associated with the transfusion of high titer ABO antibody-containing PLT, our institutional policy allows the transfusion of PLT containing ABO-incompatible plasma only if PLT is re-suspended in platelet additive solution (PAS). Despite the steps taken to reduce the risk of hemolytic transfusion reactions to PLT transfusions at our institution, our center has observed hemolytic reactions to PLT in PAS. The current case study highlights the importance of recognizing a hemolytic reaction (HTR) from ABO-incompatible PLT transfusions and discusses the current strategies and recommendations to mitigate this risk.


Assuntos
Hemólise/imunologia , Transfusão de Plaquetas/métodos , Reação Transfusional/imunologia , Sistema ABO de Grupos Sanguíneos/imunologia , Idoso , Tipagem e Reações Cruzadas Sanguíneas/métodos , Plaquetas/imunologia , Transfusão de Sangue/métodos , Feminino , Humanos , Plasma/imunologia
16.
Washington, D.C; Organización Panamericana de la Salud; Versión 3; Mayo, 10, 2021. 126 p. ilus.
Não convencional em Espanhol | BIGG - guias GRADE | ID: biblio-1253092

RESUMO

Esta guía de práctica clínica, en cuya elaboración se siguió el método GRADE, tiene por objeto proveer recomendaciones para el manejo de pacientes adultos críticos con COVID-19 atendidos en las unidades de cuidados intensivos. Ofrece recomendaciones basadas en evidencia para la identificación de marcadores y factores de riesgo de mortalidad de los pacientes críticos, el control de la infección, la recogida de muestras, el cuidado de los pacientes (ventilatorio y hemodinámico), el tratamiento farmacológico, la rehabilitación temprana, el uso de imágenes diagnósticas, la prevención de complicaciones y los criterios de egreso. En esta tercera versión se actualizan cinco preguntas incluidas en la primera versión y se añaden tres preguntas formuladas en formato PICO. Las recomendaciones están dirigidas a todo el personal de salud que atiende a pacientes en los servicios de urgencias y de emergencias y las unidades de cuidados intensivos. Asimismo, tienen por objetivo brindar apoyo a los responsables de la toma de decisiones y miembros de entidades gubernamentales relacionados con el manejo de pacientes con COVID-19 en las unidades de cuidados intensivos de la Región de las Américas. Esta guía se encuentra en proceso continuo de actualización de la evidencia con el fin de proporcionar las recomendaciones más actualizadas para el manejo de los pacientes críticos con COVID-19, en especial sobre las intervenciones de tratamiento farmacológico como el uso de antivirales, inmunomoduladores, plasma de convalecientes y antibióticos.


Assuntos
Humanos , Adulto , Administração dos Cuidados ao Paciente , Cuidados Críticos , SARS-CoV-2/efeitos dos fármacos , COVID-19/tratamento farmacológico , Plasma/imunologia , América/epidemiologia , Ventiladores Mecânicos , Fatores de Risco , Antirretrovirais/uso terapêutico , COVID-19/complicações , COVID-19/diagnóstico por imagem , Fatores Imunológicos/uso terapêutico , Antibacterianos/uso terapêutico
18.
Tuberk Toraks ; 69(1): 30-38, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33853303

RESUMO

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by airflow restriction and systemic inflammation. Netrin-1 is a protein mainly produced in the central nervous system and has proven anti-inflammatory activity. The aim of this study was to determine netrin-1 level and its relationship with comorbidities in patients with acute exacerbation of COPD. MATERIALS AND METHODS: The study included 232 patients aged over 40 years who were divided into 3 groups: Group 1: ex-smokers (≥ 20 pack-years) with COPD hospitalized for COPD exacerbation (n= 142), Group 2: current-smokers (≥ 20 pack-years) without COPD (n= 30), Group 3: a control group comprising healthy non-smokers (n= 60). Plasma netrin-1 levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kit. RESULT: There were significant differences in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, C-reactive protein (CRP), and plasma netrin-1 levels between patients with acute exacerbation of COPD and current smokers without COPD, healthy controls (p= 0.001 for all). Netrin-1 levels at discharge were lower in COPD patients with diabetes mellitus (DM) compared to nondiabetic COPD patients (p= 0.01). Weak correlation was observed between netrin-1 level at admission and FEV1, FVC, partial pressure of oxygen, and CRP levels (r= 0.394, p= 0.01; r= -0.366, p= 0.01; r= -0.19, p= 0.05; r= 0.306, p= 0.01). Netrin-1 level at admission was also moderately correlated with smoking history (pack-years) (r= 0.579, p= 0.01). CONCLUSIONS: Netrin-1 was elevated in acute exacerbation of COPD and may be an important element in inflammatory balance. Patients with both COPD and DM were found to have lower netrin-1 levels at discharge after resolution of the acute exacerbation.


Assuntos
Inflamação/imunologia , Inflamação/fisiopatologia , Netrina-1/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Idoso , Proteína C-Reativa/análise , Estudos de Casos e Controles , Comorbidade , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Plasma/imunologia , Testes de Função Respiratória , Fumar/imunologia , Capacidade Vital
19.
Front Cell Infect Microbiol ; 11: 650487, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796489

RESUMO

Background: Convalescent plasma (CP) transfusion is considered to be the priority therapeutic option for COVID-19 inpatients when no specific drugs are available for emerging infections. An alternative, simple, and sensitive method is urgently needed for clinical use to detect neutralization activity of the CP to avoid the use of inconvenient micro-neutralization assay. Method: This study aims to explore optimal index in predicting the COVID-19 CP neutralization activity (neutralizing antibody titers, NAb titers) in an indirect ELISA format. Fifty-seven COVID-19-recovered patients plasma samples were subjected to anti-SARS-CoV-2 RBD, S1, and N protein IgG antibody by indirect ELISA. Results: ELISA-RBD exhibited high specificity (96.2%) and ELISA-N had high sensitivity (100%); while ELISA-S1 had low sensitivity (86.0%) and specificity (73.1%). Furthermore, ELISA-RBD IgG titers and pseudovirus-based NAb titers correlated significantly, with R2 of 0.2564 (P < 0.0001). Conclusion: ELISA-RBD could be a substitute for the neutralization assay in resource-limited situations to screen potential plasma donors for further plasma infusion therapy.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/sangue , COVID-19/terapia , Imunização Passiva/métodos , Plasma/imunologia , Animais , Anticorpos Antivirais/uso terapêutico , Antivirais/uso terapêutico , Doadores de Sangue , China , Chlorocebus aethiops , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Células HEK293 , Humanos , Imunoglobulina G/sangue , SARS-CoV-2 , Sensibilidade e Especificidade , Células Vero
20.
Viruses ; 13(3)2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800528

RESUMO

The use of convalescent plasma in the treatment of COVID-19 may lead to a milder course of infection and has been associated with improved outcomes. Determining optimal treatments in high risk populations is crucial, as is the case in those with hematological malignancies. We analyzed a cohort of 23 patients with hematological malignancies and COVID-19 who had received plasma 48-72 h after the diagnosis of infection and compared it with a historical group of 22 patients who received other therapy. Overall survival in those who received convalescent plasma was significantly higher than in the historical group (p = 0.03460). The plasma-treated group also showed a significantly milder course of infection (p = 0.03807), characterized by less severe symptoms and faster recovery (p = 0.00001). In conclusion, we have demonstrated that convalescent plasma is an effective treatment and its early administration leads to clinical improvement, increased viral clearance and longer overall survival in patients with hematological malignancies and COVID-19. To our knowledge, this is the first report to analyze the efficacy of convalescent plasma in a cohort of patients with hematological malignancies.


Assuntos
COVID-19/terapia , Neoplasias Hematológicas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , Estudos de Coortes , Feminino , Neoplasias Hematológicas/terapia , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Plasma/imunologia , Sobrevida , Resultado do Tratamento , Adulto Jovem
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