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1.
Emerg Infect Dis ; 27(12)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499599

RESUMO

The Delta variant of concern of severe acute respiratory syndrome coronavirus 2 is dominant worldwide. We report a case cluster caused by Delta sublineage B.1.617.2 harboring the mutation E484K in Italy during July 11-July 29, 2021. This mutation appears to affect immune response and vaccine efficacy; monitoring its appearance is urgent.

2.
Viruses ; 13(8)2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34452459

RESUMO

COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In this review, we highlight the potential role of additional factors in CCP that can be either beneficial (e.g., AT-III, alpha-1 AT, ACE2+ extracellular vesicles) or detrimental (e.g., anti-ADAMTS13, anti-MDA5 or anti-interferon autoantibodies, pro-coagulant extracellular vesicles). Variations in these factors in CCP may contribute to varied outcomes in patients with COVID-19 and undergoing CCP therapy. We advise careful, retrospective investigation of such co-factors in randomized clinical trials that use fresh frozen plasma in control arms. Nevertheless, it might be difficult to establish a causal link between these components and outcome, given that CCP is generally safe and neutralizing antibody effects may predominate.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/terapia , SARS-CoV-2/imunologia , Anti-Inflamatórios/sangue , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Autoanticorpos/sangue , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Fatores de Coagulação Sanguínea/análise , Reações Cruzadas , Vesículas Extracelulares , Humanos , Imunização Passiva/efeitos adversos , Fatores Imunológicos/sangue , Imunossupressores/sangue
3.
Viruses ; 13(8)2021 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-34452380

RESUMO

SARS-CoV-2 spike is evolving to maximize transmissibility and evade the humoral response. The massive genomic sequencing of SARS-CoV-2 isolates has led to the identification of single-point mutations and deletions, often having the recurrence of hotspots, associated with advantageous phenotypes. We report the isolation and molecular characterization of a SARS-CoV-2 strain, belonging to a lineage (C.36) not previously associated with concerning traits, which shows decreased susceptibility to vaccine sera neutralization.


Assuntos
COVID-19/virologia , SARS-CoV-2/isolamento & purificação , Anticorpos Antivirais/imunologia , Humanos , Itália , Mutação , Testes de Neutralização , Filogenia , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
4.
Transfus Med ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34390068

RESUMO

BACKGROUND: Pathogen reduction technologies (PRT) based on nucleic-acid damaging chemicals and/or irradiation are increasingly being used to increase safety of blood components against emerging pathogens, such as convalescent plasma in the ongoing COVID-19 pandemic. Current methods for PRT validation are limited by the resources available to the blood component manufacturer, and quality control rely over pathogen spiking and hence invariably require sacrifice of the tested blood units: quantitative real-time PCR is the current pathogen detection method but, due to the high likelihood of detecting nonviable fragments, requires downstream pathogen culture. We propose here a new molecular validation of PRT based on the highly prevalent human symbiont torquetenovirus (TTV) and rolling circle amplification (RCA). MATERIALS AND METHODS: Serial apheresis plasma donations were tested for TTV before and after inactivation with Intercept® PRT using real-time quantitative PCR (conventional validation), RCA followed by real-time PCR (our validation), and reverse PCR (for cross-validation). RESULTS: While only 20% of inactivated units showed significant decrease in TTV viral load using real-time qPCR, all donations tested with RCA followed by real-time PCR showed TTV reductions. As further validation, 2 units were additionally tested with reverse PCR, which confirmed absence of entire circular genomes. DISCUSSION: We have described and validated a conservative and easy-to-setup protocol for molecular validation of PRT based on RCA and real-time PCR for TTV.

6.
Emerg Infect Dis ; 27(10): 2728-2731, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34314668

RESUMO

We report in vivo selection of a severe acute respiratory syndrome coronavirus 2 spike mutation (Q493R) conferring simultaneous resistance to bamlanivimab and etesivimab. This mutation was isolated from a patient who had coronavirus disease and was treated with these drugs.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Humanos , Mutação , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
7.
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
8.
Expert Opin Drug Discov ; : 1-12, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34304682

RESUMO

Introduction: In the COVID-19 pandemic emergency, research has been oriented toward the development of therapies that could cure critically ill patients and treatments that can reduce the number of hospitalized patients, in order to ease the pressure on health-care systems. Bamlanivimab, developed from human convalescent plasma, was the first monoclonal antibody to become available for emergency use in several countries. Expectations related to its use in COVID-19 patients as a single agent have been largely disregarded, especially against E484K-carrying SARS-CoV-2 variants.Areas covered: In this drug discovery case history, the development of the drug is described starting from the identification and selection of the antibody, from the pre-clinical and clinical trials up to the post-authorization phase.Expert opinion: Bamlanivimab has shown some efficacy in patients with mild to moderate COVID-19. Initially approved as a monotherapy, due to poor efficacy it is currently only usable in combination with etesevimab. Pharmacokinetic limitations and mainly the onset of SARS-CoV-2 variants are the main reasons for this limited clinical use. The use in preventing hospitalization also has ethical limits related to the sustainability of care, especially if, considering similar effectiveness, bamlanivimab is compared with convalescent plasma.

10.
Lancet Haematol ; 8(8): e593-e604, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34329579

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a serious and usually fatal CNS infection caused by the John Cunningham virus. CD4+ and CD8+ T-cell lymphopenia, resulting from HIV infection, chemotherapy, or immunosuppressive therapy, are primary risk factors for PML. Following its introduction in 1997, the immunomodulatory anti-CD20 monoclonal antibody, rituximab, has received regulatory approval worldwide for treatment of non-Hodgkin lymphoma, rheumatoid arthritis, chronic lymphocytic leukaemia, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulagris. Rituximab leads to prolonged B-lymphocyte depletion, potentially allowing John Cunningham viral infection to occur. Six unexpected cases of PML infection developing in rituximab-treated patients were first reported in 2002. We review 20 years of information on clinical findings, pathology, epidemiology, proposed pathogenesis, and risk-management issues associated with PML infection developing after rituximab treatment. Since the first case series report of 52 cases of rituximab-associated PML among patients with non-Hodgkin lymphoma or chronic lymphocytic leukaemia in 2009, updated and diligent pharmacovigilance efforts have provided reassurance that this fatal toxicity is a rare clinical event with concurring causal factors. International harmonisation of safety warnings around rituximab-associated PML should be considered, with these notifications listing rituximab-associated PML under a section titled warnings and precautions as is the case in most countries, rather than a boxed warning as is the case in the USA.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Leucoencefalopatia Multifocal Progressiva/patologia , Neoplasias/tratamento farmacológico , Rituximab/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Prognóstico
11.
Emerg Microbes Infect ; 10(1): 1254-1256, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34110974

RESUMO

We report 11 cases of SARS-CoV-2 infection in healthcare workers (HCW) naïve for COVID-19 and seropositive after the second dose of the BNT162b2 mRNA vaccine. Based on voluntary-based surveillance, they tested positive for different strains of SARS-CoV-2, as Spike gene sequencing showed. Five of them reported mild symptoms. Given the risk for SARS-CoV-2 introduction from asymptomatic vaccinees, this case series suggests the need to continue nasopharyngeal screening programmes.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Adulto , COVID-19/virologia , Feminino , Pessoal de Saúde , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , SARS-CoV-2/genética
12.
Hum Vaccin Immunother ; 17(9): 2959-2961, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-33950788

RESUMO

SARS-CoV-2 has infected more than 122 million persons worldwide. Most currently licensed COVID-19 vaccines require a two-dose course and many health systems are on a shortage of doses. The requirement for boosting the response after priming with the first dose is uncertain in convalescents already primed by the natural infection. Mounting evidences suggest that, after a single vaccine dose, convalescents develop antibody (total and neutralizing) levels similar to the ones measured in naïve vaccinees after the full two-dose course. While concerns remain on the equivalent duration of such response, optimizing vaccine delivery to convalescents seems effective and could accelerate achievement of herd immunity.


Assuntos
COVID-19 , SARS-CoV-2 , Vacinas contra COVID-19 , Humanos
13.
Expert Rev Vaccines ; : 1-8, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34015243

RESUMO

INTRODUCTION: : The ongoing SARS-CoV-2 pandemic is a serious threat for the health of immunocompromised patients. Among neutralizing antibody-based therapeutics, convalescent plasma containing polyclonal anti-SARS-CoV-2 immunoglobulins has promising results in both congenital and iatrogenic immunodeficiencies in oncohematological and transplant patients. AREAS COVERED: : This article discusses case reports, case series and controlled studies detailing the efficacy of convalescent plasma in immunocompromised patients. EXPERT OPINION: : Convalescent plasma, when administered at high neutralizing antibody titers, is a safe and effective treatment for frail immunocompromised patients. Genetic monitoring of refractory patients is recommended to intercept intra-host emergence of SARS-CoV-2 variants.

15.
16.
Vox Sang ; 116(9): 935-942, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33794556
18.
Clin Microbiol Infect ; 27(7): 987-992, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33878505

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is being extensively investigated as a treatment, with mixed results to date. Overall, there has been a generalized lack of appropriateness in prescriptions, which, in the field of transfusion medicine, is termed patient-blood management. OBJECTIVES: We aimed to separate study design variables that could affect clinical outcome after CCP therapy. We focus here on variables such as pretransfusion antibody testing in recipients, dose adjustments and antibody affinity measurements. SOURCES: We searched PubMed and preprint servers for relevant preclinical and clinical studies discussing each of these variables in the field of CCP therapy. CONTENT: We show evidence that neglecting those variables has affected the outcomes of the vast majority of CCP clinical trials to date. IMPLICATIONS: A better understanding of such variables will improve the design of the next generation of CCP clinical trials. This will likely lead to better clinical outcomes and will minimize risks of immune evasion from subneutralizing doses of neutralizing antibodies.


Assuntos
Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , COVID-19/terapia , Anticorpos Antivirais/imunologia , Doadores de Sangue , Relação Dose-Resposta Imunológica , Farmacoeconomia , Humanos , Imunização Passiva/métodos , Imunoglobulina G/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento
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