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1.
Acta Med Indones ; 53(1): 86-95, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33818411

RESUMEN

The global widespread mortality after the emergence of SARS-CoV-2 infection in China, has become a critical concern all around the world. Convalescent plasma (CP) therapy is one of the methods elevating the survival rate for COVID-19 infection cases. This technique, as a practicable therapy, was used in previous viral outbreaks including influenza, SARS and MERS. In CP therapy, the blood plasma is collected from persons rehabilitated from that specific infection in order to develop a passive immunity in other patients. Therefore, this review aimed to point out the role of CP therapy in aforementioned viral infections and illustrate different factors influencing the efficacy of CP therapy.


Asunto(s)
/terapia , Infecciones por Coronavirus/terapia , Síndrome Respiratorio Agudo Grave/terapia , Anticuerpos Antivirales/sangre , /inmunología , Humanos , Inmunización Pasiva/métodos , Resultado del Tratamiento
2.
Medicina (Kaunas) ; 57(3)2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33799535

RESUMEN

Background and Objectives: On 24 March 2020, the United States Food and Drug Administration (FDA) announced the approval of convalescent plasma therapy for critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergency investigational new drug. This pilot study from Romania aimed to determine if convalescent plasma transfusion can be beneficial in the treatment of selected critically ill patients diagnosed with a SARS-CoV-2 infection. Materials and Methods: Donor and receiver eligibility for critically ill coronavirus disease 2019 (COVID-19) patients was based on Romanian guidelines issued at the time of the study. Here, we describe the evolution of a total of five eligible patients diagnosed with COVID-19 who received convalescent plasma (CP) in Romania. Results: In spite of our efforts and convalescent plasma administration, three of the five patients did not survive, while the other two recovered completely. Over the course of our five-day laboratory record, the surviving patients had significantly lower values for C-reactive protein, interleukin-6, and white blood cells. Conclusions: This pilot study provides insufficient evidence to determine the efficacy of convalescent plasma use as a therapeutic option for critically ill COVID-19 patients.


Asunto(s)
/terapia , Adulto , Antibacterianos/uso terapéutico , Anticoagulantes/uso terapéutico , Antivirales/uso terapéutico , Proteína C-Reactiva/metabolismo , /fisiopatología , Enfermedad Crítica , Glucocorticoides/uso terapéutico , Humanos , Inmunización Pasiva/métodos , Interleucina-6/sangre , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Rumanía , Resultado del Tratamiento
3.
mBio ; 12(2)2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33653885

RESUMEN

Antibody therapies such as convalescent plasma and monoclonal antibodies have emerged as major potential therapeutics for coronavirus disease 2019 (COVID-19). Immunoglobulins differ from conventional antimicrobial agents in that they mediate direct and indirect antimicrobial effects that work in concert with other components of the immune system. The field of infectious diseases pioneered antibody therapies in the first half of the 20th century but largely abandoned them with the arrival of conventional antimicrobial therapy. Consequently, much of the knowledge gained from the historical development and use of immunoglobulins such as serum and convalescent antibody therapies was forgotten; principles and practice governing their use were not taught to new generations of medical practitioners, and further development of this modality stalled. This became apparent during the COVID-19 pandemic in the spring of 2020 when convalescent plasma was initially deployed as salvage therapy in patients with severe disease. In retrospect, this was a stage of disease when it was less likely to be effective. Lessons of the past tell us that antibody therapy is most likely to be effective when used early in respiratory diseases. This article puts forth three principles of antibody therapy, namely, specificity, temporal, and quantitative principles, connoting that antibody efficacy requires the administration of specific antibody, given early in course of disease in sufficient amount. These principles are traced to the history of serum therapy for infectious diseases. The application of the specificity, temporal, and quantitative principles to COVID-19 is discussed in the context of current use of antibody therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).


Asunto(s)
/terapia , Anticuerpos Antivirales/inmunología , /prevención & control , Humanos , Inmunización Pasiva/métodos , Pandemias
4.
Sci Rep ; 11(1): 5558, 2021 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-33692386

RESUMEN

The recent COVID-19 pandemic poses a serious threat to global public health, thus there is an urgent need to define the molecular mechanisms involved in SARS-CoV-2 spike (S) protein-mediated virus entry that is essential for preventing and/or treating this emerging infectious disease. In this study, we examined the blocking activity of human COVID-19 convalescent plasma by cell-cell fusion assays using SARS-CoV-2-S-transfected 293 T as effector cells and ACE2-expressing 293 T as target cells. We demonstrate that the SARS-CoV-2 S protein exhibits a very high capacity for membrane fusion and is efficient in mediating virus fusion and entry into target cells. Importantly, we find that COVID-19 convalescent plasma with high titers of IgG neutralizing antibodies can block cell-cell fusion and virus entry by interfering with the SARS-CoV-2-S/ACE2 or SARS-CoV-S/ACE2 interactions. These findings suggest that COVID-19 convalescent plasma may not only inhibit SARS-CoV-2-S but also cross-neutralize SARS-CoV-S-mediated membrane fusion and virus entry, supporting its potential as a preventive and/or therapeutic agent against SARS-CoV-2 as well as other SARS-CoV infections.


Asunto(s)
/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Fusión Celular/métodos , Femenino , Humanos , Inmunización Pasiva/métodos , Masculino , Fusión de Membrana/efectos de los fármacos , Persona de Mediana Edad , Pandemias/prevención & control , Plasma/química , Receptores Virales/metabolismo , /patogenicidad , Glicoproteína de la Espiga del Coronavirus/metabolismo , Internalización del Virus/efectos de los fármacos
5.
Sci Rep ; 11(1): 5563, 2021 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-33692457

RESUMEN

While there are various attempts to administer COVID-19-convalescent plasmas to SARS-CoV-2-infected patients, neither appropriate approach nor clinical utility has been established. We examined the presence and temporal changes of the neutralizing activity of IgG fractions from 43 COVID-19-convalescent plasmas using cell-based assays with multiple endpoints. IgG fractions from 27 cases (62.8%) had significant neutralizing activity and moderately to potently inhibited SARS-CoV-2 infection in cell-based assays; however, no detectable neutralizing activity was found in 16 cases (37.2%). Approximately half of the patients (~ 41%), who had significant neutralizing activity, lost the neutralization activity within ~ 1 month. Despite the rapid decline of neutralizing activity in plasmas, good amounts of SARS-CoV-2-S1-binding antibodies were persistently seen. The longer exposure of COVID-19 patients to greater amounts of SARS-CoV-2 elicits potent immune response to SARS-CoV-2, producing greater neutralization activity and SARS-CoV-2-S1-binding antibody amounts. The dilution of highly-neutralizing plasmas with poorly-neutralizing plasmas relatively readily reduced neutralizing activity. The presence of good amounts of SARS-CoV-2-S1-binding antibodies does not serve as a surrogate ensuring the presence of good neutralizing activity. In selecting good COVID-19-convalescent plasmas, quantification of neutralizing activity in each plasma sample before collection and use is required.


Asunto(s)
/inmunología , Inmunoglobulina G/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Femenino , Humanos , Inmunización Pasiva/métodos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Plasma/química , Receptores Virales/metabolismo , /patogenicidad
6.
BMJ Case Rep ; 14(3)2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33762283

RESUMEN

COVID-19 has now emerged from a respiratory illness to a systemic viral illness with multisystem involvement. There is still a lot to learn about this illness as new disease associations with COVID-19 emerge consistently. We present a unique case of a neurological manifestation of a patient with structural brain disease who was COVID-19 positive and developed mental status changes, new-onset seizures and findings suggestive of viral meningitis on lumbar puncture. We also review the literature and discuss our case in the context of the other cases reported. We highlight the value of considering seizures and encephalopathy as one of the presenting features of COVID-19 disease.


Asunto(s)
Encefalopatías/etiología , Convulsiones/etiología , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adulto , Alanina/análogos & derivados , Alanina/uso terapéutico , Anticonvulsivantes/uso terapéutico , Antivirales/uso terapéutico , Encefalopatías/diagnóstico , Encefalopatías/terapia , /terapia , Confusión/complicaciones , Humanos , Inmunización Pasiva/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Reacción en Cadena de la Polimerasa , Radiografía/métodos , Convulsiones/terapia , Resultado del Tratamiento
7.
Eur J Cancer ; 147: 154-160, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33676266

RESUMEN

The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated infectious coronavirus disease (COVID-19) has posed a unique challenge to medical staff, patients and their families. Patients with cancer, particularly those with haematologic malignancies, have been identified to be at high risk to develop severe COVID-19. Since publication of our previous guideline on evidence-based management of COVID-19 in patients with cancer, research efforts have continued and new relevant data has come to light, maybe most importantly in the field of vaccination studies. Therefore, an update of our guideline on several clinically important topics is warranted. Here, we provide a concise update of evidence-based recommendations for rapid diagnostics, viral shedding, vaccination and therapy of COVID-19 in patients with cancer. This guideline update was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology by critically reviewing the currently available data on these topics applying evidence-based medicine criteria.


Asunto(s)
/normas , Neoplasias , Esparcimiento de Virus/fisiología , Antivirales/uso terapéutico , /epidemiología , /virología , Medicina Basada en la Evidencia/normas , Medicina Basada en la Evidencia/estadística & datos numéricos , Alemania/epidemiología , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/virología , Hematología/organización & administración , Hematología/normas , Humanos , Inmunización Pasiva/métodos , Inmunización Pasiva/normas , Infectología/organización & administración , Infectología/normas , Oncología Médica/organización & administración , Oncología Médica/normas , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/terapia , Neoplasias/virología , Sociedades Médicas/normas , Vacunación/métodos , Vacunación/normas
8.
Virology ; 557: 70-85, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33676349

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged into the human population in late 2019 and caused the global COVID-19 pandemic. SARS-CoV-2 has spread to more than 215 countries and infected many millions of people. Despite the introduction of numerous governmental and public health measures to control disease spread, infections continue at an unabated pace, suggesting that effective vaccines and antiviral drugs will be required to curtail disease, end the pandemic, and restore societal norms. Here, we review the current developments in antibody and vaccine countermeasures to limit or prevent disease.


Asunto(s)
Anticuerpos Antivirales/biosíntesis , /prevención & control , Pandemias , /inmunología , Animales , /inmunología , /virología , /biosíntesis , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Vectores Genéticos/química , Vectores Genéticos/inmunología , Humanos , Inmunidad Innata/efectos de los fármacos , Inmunización Pasiva/métodos , Inmunogenicidad Vacunal , Seguridad del Paciente , /patogenicidad , Vacunas Atenuadas , Vacunas de ADN , Vacunas de Subunidad , Vacunas de Partículas Similares a Virus/administración & dosificación , Vacunas de Partículas Similares a Virus/biosíntesis , Vacunas de Partículas Similares a Virus/inmunología
9.
Cell Rep ; 34(10): 108837, 2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33662255

RESUMEN

Passive transfer of convalescent plasma or serum is a time-honored strategy for treating infectious diseases. Human convalescent plasma containing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently being used to treat patients with coronavirus disease 2019 where clinical efficacy trials are ongoing. Here, we assess therapeutic passive transfer in groups of SARS-CoV-2-infected African green monkeys with convalescent sera containing either high or low anti-SARS-CoV-2 neutralizing antibody titers. Differences in viral load and pathology are minimal between monkeys that receive the lower titer convalescent sera and untreated controls. However, lower levels of SARS-CoV-2 in respiratory compartments, reduced severity of virus-associated lung pathology, and reductions in coagulopathy and inflammatory processes are observed in monkeys that receive high titer sera versus untreated controls. Our data indicate that convalescent plasma therapy in humans may be an effective strategy provided that donor sera contain high anti-SARS-CoV-2 neutralizing titers given in early stages of the disease.


Asunto(s)
/terapia , Enfermedades de los Primates/terapia , Enfermedades de los Primates/virología , /inmunología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , /virología , Chlorocebus aethiops/inmunología , Femenino , Inmunización Pasiva/métodos , Inmunización Pasiva/veterinaria , Masculino , Enfermedades de los Primates/inmunología , Primates/inmunología , Carga Viral
10.
J Immunol Res ; 2021: 6680337, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33644235

RESUMEN

COVID-19 is a pandemic caused by SARS-CoV-2. In Chile, half a million people have been infected and more than 16,000 have died from COVID-19. As part of the clinical trial NCT04384588, we quantified IgG against S1-RBD of SARS-CoV-2 (anti-RBD) in recovered people in Santiago and evaluated their suitability as COVID-19 convalescent plasma donors. ELISA and a luminescent SARS-CoV-2 pseudotype were used for IgG and neutralizing antibody quantification. 72.9% of the convalescent population (468 of 639) showed seroconversion (5-55 µg/mL anti-RBD IgG) and were suitable candidates for plasma donation. Analysis by gender, age, and days after symptom offset did not show significant differences. Neutralizing activity correlated with an increased concentration of anti-RBD IgG (p < 0.0001) and showed a high variability between donors. We confirmed that the majority of the Chilean patients have developed anti-SARS-CoV-2 antibodies. The quantification of anti-RBD IgG in convalescent plasma donors is necessary to increase the detection of neutralizing antibodies.


Asunto(s)
/inmunología , /fisiología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adolescente , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/uso terapéutico , Chile , Femenino , Humanos , Inmunización Pasiva/métodos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Pandemias , Seroconversión , Adulto Joven
11.
PLoS Med ; 18(3): e1003415, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33657114

RESUMEN

BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.


Asunto(s)
/terapia , Intervención Médica Temprana/métodos , Tiempo de Tratamiento , Adulto , Anciano , Anciano de 80 o más Años , /mortalidad , Chile , Progresión de la Enfermedad , Intervención Médica Temprana/estadística & datos numéricos , Femenino , Mortalidad Hospitalaria , Humanos , Inmunización Pasiva/métodos , Inmunización Pasiva/mortalidad , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Mortalidad , Respiración Artificial/mortalidad , Respiración Artificial/estadística & datos numéricos , Tiempo de Tratamiento/normas , Resultado del Tratamiento
12.
Cell Rep ; 34(9): 108790, 2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33596407

RESUMEN

Characterization of the humoral response to SARS-CoV-2, the etiological agent of COVID-19, is essential to help control the infection. The neutralization activity of plasma from patients with COVID-19 decreases rapidly during the first weeks after recovery. However, the specific role of each immunoglobulin isotype in the overall neutralizing capacity is still not well understood. In this study, we select plasma from a cohort of convalescent patients with COVID-19 and selectively deplete immunoglobulin A, M, or G before testing the remaining neutralizing capacity of the depleted plasma. We find that depletion of immunoglobulin M is associated with the most substantial loss of virus neutralization, followed by immunoglobulin G. This observation may help design efficient antibody-based COVID-19 therapies and may also explain the increased susceptibility to SARS-CoV-2 of autoimmune patients receiving therapies that impair the production of immunoglobulin M (IgM).


Asunto(s)
/terapia , Inmunoglobulina M/inmunología , Inmunoglobulina M/uso terapéutico , /inmunología , Adulto , Anciano , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , /inmunología , Canadá/epidemiología , Estudios de Cohortes , Femenino , Humanos , Inmunidad Humoral/inmunología , Inmunización Pasiva/métodos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven
13.
Int Immunopharmacol ; 93: 107239, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33582019

RESUMEN

Since SARS-CoV-2 infection is rapidly spreading all around the world, affecting many people and exhausting health care resources, therapeutic options must be quickly investigated in order to develop a safe and effective treatment. The present study was designed to evaluate the safety and efficacy of convalescent plasma (CP) for treating severe cases of COVID-19 who developed acute respiratory distress syndrome (ARDS). Among 64 confirmed cases of severe COVID-19 with ARDS in this study, 32 patients received CP besides first line treatment. Their clinical response and outcome in regard to disease severity and mortality rate were evaluated and compared with the other 32 patients in the control group who were historically matched while randomly chosen from previous patients with the same conditions except for receiving CP therapy. Analysis of the data was performed using SPSS software. Patients with plasma therapy showed improvements in their clinical outcomes including a reduction in disease severity in terms of SOFA and APACHE II scores, the length of ICU stay, need for noninvasive ventilation and intubation and also showed an increase in oxygenation. They also showed reduction in mortality which was statistically significant in less severe cases with mild or moderate ARDS. Early administration of the convalescent plasma could successfully contribute to the treatment of severe COVID-19 patients with mild or moderate ARDS at risk of progressing to critical state.


Asunto(s)
/terapia , /terapia , Adulto , Anciano , Antivirales/uso terapéutico , /virología , Femenino , Humanos , Inmunización Pasiva/efectos adversos , Inmunización Pasiva/métodos , Masculino , Persona de Mediana Edad , /virología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
14.
Mo Med ; 118(1): 74-80, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33551490

RESUMEN

Convalescent plasma is an old treatment for a new disease. The coronavirus disease 2019 (COVID-19) pandemic caused the analysis of convalescent plasma to reemerge as a possible treatment. First, a systematic review summarizes the available research examining the use of convalescent plasma for the treatment of patients with COVID-19. Second, we describe our experience in establishing a single-center convalescent plasma donation program.


Asunto(s)
Donantes de Sangre/provisión & distribución , Inmunización Pasiva/métodos , Adulto , Anciano , Anciano de 80 o más Años , Donantes de Sangre/estadística & datos numéricos , /epidemiología , Selección de Donante/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , /aislamiento & purificación , Resultado del Tratamiento
15.
Curr Opin Pulm Med ; 27(3): 169-175, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33606409

RESUMEN

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is an acute multisystem disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Investigations are ongoing in the search for effective therapeutics, with clinical approaches evolving based upon such evidence. RECENT FINDINGS: The antiviral agent, remdesivir, and the immunomodulator, dexamethasone, are the first therapeutics for which there is evidence of efficacy from randomized trials. Subgroup analyses suggest remdesivir is beneficial in hospitalized patients whose severity of illness falls at the lower end of the spectrum, while dexamethasone is more beneficial in hospitalized patients whose severity of illness falls at the higher end of the spectrum. We recommend that inpatients who require supplemental oxygen but are not mechanically ventilated receive both remdesivir and dexamethasone, and inpatients who require mechanical ventilation receive dexamethasone monotherapy. Additional evidence regarding anti-SARS-CoV-2 antibodies, convalescent plasma, and a variety of antiinterleukin therapies is forthcoming. SUMMARY: The body of evidence related to COVID-19 therapeutics continues to evolve and, as a result, management is likely to change with time. As new evidence is generated and published, the optimal approach to managing patients with COVID-19 should be reconsidered.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Dexametasona/farmacología , Respiración Artificial/métodos , Adenosina Monofosfato/farmacología , Alanina/farmacología , Antivirales/farmacología , Humanos , Inmunización Pasiva/métodos , Factores Inmunológicos/farmacología , Selección de Paciente , /efectos de los fármacos
16.
Trials ; 22(1): 112, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33522939

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infection with possible serious consequences. The plasma of recovered patients might serve as treatment, which we aim to assess in the form of a prospective meta-analysis focusing on mortality, multi-organ failure, duration of intensive care unit stay, and adverse events. METHODS: A systematic search was conducted to find relevant registered randomized controlled trials in five trial registries. A comprehensive search will be done continuously on a monthly basis in MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to find the results of previously registered randomized controlled trials. The selection will be done by two independent authors. Data extraction will be carried out by two other independent reviewers. Disagreements will be resolved by a third investigator. An update of the search of the registries and the first search of the databases will be done on the 21st of July. Data synthesis will be performed following the recommendations of the Cochrane Collaboration. In the case of dichotomous outcomes (mortality and organ failure), we will calculate pooled risk ratios with a 95% confidence interval (CI) from two-by-two tables (treatment Y/N, outcome Y/N). Data from models with multivariate adjustment (hazard ratios, odds ratio, risk ratio) will be preferred for the analysis. P less than 0.05 will be considered statistically significant. In the case of ICU stay, weighted mean difference with a 95% confidence interval will be calculated. Heterogeneity will be tested with I2, and χ2 tests. Meta-analysis will be performed if at least 3 studies report on the same outcome and population. DISCUSSION: Convalescent plasma therapy is a considerable alternative in COVID-19, which we aim to investigate in a prospective meta-analysis.


Asunto(s)
/terapia , /mortalidad , Humanos , Inmunización Pasiva/métodos , Inmunización Pasiva/mortalidad , Unidades de Cuidados Intensivos , Tiempo de Internación , Metaanálisis como Asunto , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
17.
JCI Insight ; 6(4)2021 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-33476300

RESUMEN

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as a treatment for coronavirus disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200 mL of CCP with a spike protein IgG titer ≥ 1:2430 (median 1:47,385) within 72 hours of admission with propensity score-matched controls cared for at a medical center in the Bronx, between April 13 and May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroid use, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared with matched controls, CCP recipients less than 65 years had 4-fold lower risk of mortality and 4-fold lower risk of deterioration in oxygenation or mortality at day 28. For CCP recipients, pretransfusion spike protein IgG, IgM, and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients less than 65 years, but data from controlled trials are needed to validate this finding and establish the effect of aging on CCP efficacy.


Asunto(s)
Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Antivirales/administración & dosificación , /inmunología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , /mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Inmunización Pasiva/métodos , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Puntaje de Propensión , Estudios Retrospectivos , Glicoproteína de la Espiga del Coronavirus/inmunología , Resultado del Tratamiento
18.
Int J Antimicrob Agents ; 57(3): 106275, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33400975

RESUMEN

The COVID-19 pandemic, caused by SARS-CoV-2, has led to a rapid search for therapeutic and preventive measures because of the potentially severe course of infection. The antiviral drug, remdesivir, and the anti-inflammatory agent, dexamethasone, have shown beneficial effects. As the current COVID-19 vaccines are not yet fully available to everyone, or they may not be readily and universally accepted, various treatment options are being evaluated and will still be needed under these conditions. One of these treatment options, passive immunization, has shown promise in some studies. Further research is needed to determine the utility of immunotherapy with convalescent plasma or artificially produced monoclonal antibodies for the treatment of symptomatic patients, and potentially for use as post-exposure prophylaxis, at least until more effective drugs are available or safe and effective vaccines are distributed and administered to everyone.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Inmunización Pasiva/métodos , Antivirales/uso terapéutico , Humanos , /inmunología
19.
Sci Rep ; 11(1): 2062, 2021 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-33479465

RESUMEN

In order to support vaccine development, and to aid convalescent plasma therapy, it would be important to understand the kinetics, timing and persistence of SARS-CoV-2 neutralizing antibodies (NAbs), and their association with clinical disease severity. Therefore, we used a surrogate viral neutralization test to evaluate their levels in patients with varying severity of illness, in those with prolonged shedding and those with mild/asymptomatic illness at various time points. Patients with severe or moderate COVID-19 illness had earlier appearance of NAbs at higher levels compared to those with mild or asymptomatic illness. Furthermore, those who had prolonged shedding of the virus, had NAbs appearing faster and at higher levels than those who cleared the virus earlier. During the first week of illness the NAb levels of those with mild illness was significantly less (p = 0.01), compared to those with moderate and severe illness. At the end of 4 weeks (28 days), although 89% had NAbs, 38/76 (50%) in those with > 90 days had a negative result for the presence of NAbs. The Ab levels significantly declined during convalescence (> 90 days since onset of illness), compared to 4 to 8 weeks since onset of illness. Our data show that high levels of NAbs during early illness associated with clinical disease severity and that these antibodies declined in 50% of individuals after 3 months since onset of illness.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , /inmunología , Inmunidad Adaptativa/inmunología , Adulto , Anticuerpos Neutralizantes/análisis , Anticuerpos Antivirales/inmunología , /terapia , Convalecencia , Femenino , Humanos , Inmunización Pasiva/métodos , Masculino , Persona de Mediana Edad , Pruebas de Neutralización/métodos , Índice de Severidad de la Enfermedad , Sri Lanka/epidemiología
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