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1.
Pol Merkur Lekarski ; 49(291): 227-230, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34218245

RESUMO

According to the data from November 29 2020, the SARS-CoV-2 coronavirus was responsible for 61 866 635 cases of infections and 1 448 990 deaths worldwide, and the number is still growing rapidly. The main problem is the rapid increase in the number of patients with pneumonia complicated by respiratory failure. In the treatment of COVID- 19 patients, a significant effect of convalescent plasma (CP) therapy from convalescent patients with SARS-CoV-2 IgG neutralizing antibodies is indicated. After this procedure, the total duration of the infection was shortened and the clinical condition improved faster than in patients who did not receive this form of therapy. The aim of the study was to explain the cause disqualifying women with anti-leucocyte anitibodies as CP plasma donors for COVID-19 patients. However, according to the literature, 2% of patients who received plasma from convalescents developed Transfusion Related Acute Lung Injury (TRALI). The most common causes of TRALI are anti-leukocyte antibodies directed against Human Leukocyte Antigens (HLA) class I and II and against Human Neutrophil Antigens (HNA). Therefore, patients with COVID-19 may only be transfused with plasma from convalescent women with a history of pregnancy after testing negative for anti-leucocyte antibodies in the pre-plasmapheresis blood sample.


Assuntos
COVID-19 , Infecções por Coronavirus , Complicações Infecciosas na Gravidez , Anticorpos Antivirais , COVID-19/terapia , Feminino , Humanos , Imunização Passiva , Gravidez , SARS-CoV-2
2.
Euro Surveill ; 26(27)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34240697

RESUMO

We compared the performance of SARS-CoV-2 neutralising antibody testing between 12 European laboratories involved in convalescent plasma trials. Raw titres differed almost 100-fold differences between laboratories when blind-testing 15 plasma samples. Calibration of titres in relation to the reference reagent and standard curve obtained by testing a dilution series reduced the inter-laboratory variability ca 10-fold. The harmonisation of neutralising antibody quantification is a vital step towards determining the protective and therapeutic levels of neutralising antibodies.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/terapia , Europa (Continente) , Humanos , Imunização Passiva
3.
BMC Infect Dis ; 21(1): 630, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210259

RESUMO

BACKGROUND: Convalescent plasma (CP) and hyperimmune plasma (HP) are passive immunotherapies consisting in the infusion of plasma from recovered people into infected patients. Following pre-existing evidence in many other viral diseases, such as SARS, MERS and Ebola, CP and HP have also been proposed for the treatment of COVID-19. Nevertheless, due to the lack of large, well-designed, clinical trials, no clear-cut guidelines exist about what subtype of patient CP and HP should be administered to. CASE PRESENTATION: We have reported the cases of 3 patients, all immunosuppressed and affected by non-severe, prolonged COVID-19. They were treated with HP, whose neutralizing titer was higher than 1/80. The first patient was a 55-year-old male, who had undergone lung transplant. He was under therapy with Tacrolimus and developed non-neutralizing antibodies against SARS-CoV2. The second patient was a 77-year-old female, affected by follicular lymphoma. She had tested positive for SARS-CoV2 after 6 months. The third was a 60-year-old patient, affected by chronic leukemia. He did not develop antibodies after 2-month disease. All 3 patients received HP and had tested negative for SARS-CoV2 within 2 weeks. CONCLUSION: Despite encouraging initial data, no strong evidence exist in support of CP and HP to treat COVID-19. In our experience, although limited due to the reduced number of patients, we found a good safety and efficacy of HP in 3 immuno-deficient subjects. Further data are needed in order to assess whether this subtype of patients may particularly benefit from passive immunization.


Assuntos
COVID-19/terapia , SARS-CoV-2 , Adulto , Idoso , Anticorpos Antivirais , Feminino , Humanos , Imunização Passiva , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Plasma , RNA Viral , Resultado do Tratamento
4.
Ann Ig ; 33(5): 521-523, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34223866

RESUMO

Abstract: The differences of the epidemiology (incidence, case-to-death rate, mortality, etc) of COVID-19 between USA and Italy are analyzed taking into account the social, economic and sanitary characteristics of the two countries, both severely hit be the pandemic; and the causes of the so many different behaviors of the disease in each of them are discussed and explained.


Assuntos
COVID-19/mortalidade , Pandemias/estatística & dados numéricos , SARS-CoV-2 , COVID-19/prevenção & controle , COVID-19/terapia , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Comorbidade , Europa (Continente)/epidemiologia , Política de Saúde , Recursos em Saúde/provisão & distribuição , Humanos , Imunização Passiva , Itália/epidemiologia , Determinantes Sociais da Saúde , Estados Unidos/epidemiologia
5.
BMC Infect Dis ; 21(1): 630, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: covidwho-1295443

RESUMO

BACKGROUND: Convalescent plasma (CP) and hyperimmune plasma (HP) are passive immunotherapies consisting in the infusion of plasma from recovered people into infected patients. Following pre-existing evidence in many other viral diseases, such as SARS, MERS and Ebola, CP and HP have also been proposed for the treatment of COVID-19. Nevertheless, due to the lack of large, well-designed, clinical trials, no clear-cut guidelines exist about what subtype of patient CP and HP should be administered to. CASE PRESENTATION: We have reported the cases of 3 patients, all immunosuppressed and affected by non-severe, prolonged COVID-19. They were treated with HP, whose neutralizing titer was higher than 1/80. The first patient was a 55-year-old male, who had undergone lung transplant. He was under therapy with Tacrolimus and developed non-neutralizing antibodies against SARS-CoV2. The second patient was a 77-year-old female, affected by follicular lymphoma. She had tested positive for SARS-CoV2 after 6 months. The third was a 60-year-old patient, affected by chronic leukemia. He did not develop antibodies after 2-month disease. All 3 patients received HP and had tested negative for SARS-CoV2 within 2 weeks. CONCLUSION: Despite encouraging initial data, no strong evidence exist in support of CP and HP to treat COVID-19. In our experience, although limited due to the reduced number of patients, we found a good safety and efficacy of HP in 3 immuno-deficient subjects. Further data are needed in order to assess whether this subtype of patients may particularly benefit from passive immunization.


Assuntos
COVID-19/terapia , SARS-CoV-2 , Adulto , Idoso , Anticorpos Antivirais , Feminino , Humanos , Imunização Passiva , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Plasma , RNA Viral , Resultado do Tratamento
6.
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
7.
Viruses ; 13(7)2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206468

RESUMO

The treatment of COVID-19 is particularly critical in pregnant women, considering the potential teratogenic effects of antiviral agents and the immune-depression related with pregnancy. The aim of this review is to systematically examine the current evidence on the clinical use of convalescent plasma during pregnancy. The electronic databases Medline PubMed Advanced Search Builder, Scopus, Web Of Science and Google Scholar were searched (until 1 January 2021). Inclusion criteria were pregnant women with COVID-19 (or SARS-CoV-2 infection), in whom convalescent plasma (or hyperimmune plasma) was used as treatment. We searched clinical trial registries (censored 5 January 2021) for eligible studies under way. After elimination of duplications, the initial search yielded 79 potentially relevant records, of which 67 were subsequently excluded. The 12 remaining records were case reports involving 12 pregnancies. Six of the mothers were reported to be well, two were reported to have preeclampsia, and in one case each the maternal outcome was described as survival, clinical improvement, discharged with oxygen and rehabilitation. With regard to the neonates, two were declared to be well, four had transient morbidity, two were critically ill and one died; normal ongoing pregnancies, but no post-delivery information, were reported for the remaining three cases. Clinical trials under way or planned to investigate the use of convalescent plasma for COVID-19 during pregnancy are lacking. This is the first systematic review of the literature regarding the treatment of COVID-19 in pregnancy. The published literature data seem to indicate that convalescent plasma administered to pregnant women with severe COVID-19 provides benefits for both the mother and the fetus. The quality of the available studies is, however, very limited since they are all case reports and thus suffer from relevant reporting bias.


Assuntos
Antivirais/uso terapêutico , COVID-19/terapia , Complicações Infecciosas na Gravidez/terapia , Adulto , COVID-19/imunologia , Estado Terminal , Bases de Dados Factuais , Feminino , Humanos , Imunização Passiva/métodos , Imunização Passiva/normas , Recém-Nascido , Gravidez , Gestantes , Resultado do Tratamento
8.
Front Immunol ; 12: 678570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211469

RESUMO

Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , COVID-19/prevenção & controle , COVID-19/terapia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Técnicas de Visualização da Superfície Celular/métodos , Mineração de Dados/métodos , Epitopos/imunologia , Humanos , Imunização Passiva/métodos
9.
Front Immunol ; 12: 687869, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220844

RESUMO

To determine whether the neutralization activity of monoclonal antibodies, convalescent sera and vaccine-elicited sera was affected by the top five epidemic SARS-CoV-2 variants in the UK, including D614G+L18F+A222V, D614G+A222V, D614G+S477N, VOC-202012/01(B.1.1.7) and D614G+69-70del+N439K, a pseudovirus-neutralization assay was performed to evaluate the relative neutralization titers against the five SARS-CoV-2 variants and 12 single deconvolution mutants based on the variants. In this study, 18 monoclonal antibodies, 10 sera from convalescent COVID-19 patients, 10 inactivated-virus vaccine-elicited sera, 14 mRNA vaccine-elicited sera, nine RBD-immunized mouse sera, four RBD-immunized horse sera, and four spike-encoding DNA-immunized guinea pig sera were tested and analyzed. The N501Y, N439K, and S477N mutations caused immune escape from nine of 18 mAbs. However, the convalescent sera, inactivated virus vaccine-elicited sera, mRNA vaccine-elicited sera, spike DNA-elicited sera, and recombinant RBD protein-elicited sera could still neutralize these variants (within three-fold changes compared to the reference D614G variant). The neutralizing antibody responses to different types of vaccines were different, whereby the response to inactivated-virus vaccine was similar to the convalescent sera.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/terapia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Linhagem Celular , Células HEK293 , Humanos , Imunização Passiva , Camundongos , Testes de Neutralização/métodos , Reino Unido , Vacinação
10.
Vaccine ; 39(32): 4423-4428, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34210573

RESUMO

A correlate of protection (CoP) is urgently needed to expedite development of additional COVID-19 vaccines to meet unprecedented global demand. To assess whether antibody titers may reasonably predict efficacy and serve as the basis of a CoP, we evaluated the relationship between efficacy and in vitro neutralizing and binding antibodies of 7 vaccines for which sufficient data have been generated. Once calibrated to titers of human convalescent sera reported in each study, a robust correlation was seen between neutralizing titer and efficacy (ρ = 0.79) and binding antibody titer and efficacy (ρ = 0.93), despite geographically diverse study populations subject to different forces of infection and circulating variants, and use of different endpoints, assays, convalescent sera panels and manufacturing platforms. Together with evidence from natural history studies and animal models, these results support the use of post-immunization antibody titers as the basis for establishing a correlate of protection for COVID-19 vaccines.


Assuntos
Anticorpos Neutralizantes , COVID-19 , Animais , Anticorpos Antivirais , COVID-19/terapia , Vacinas contra COVID-19 , Humanos , Imunização Passiva , SARS-CoV-2
11.
Dtsch Med Wochenschr ; 146(13-14): 899-903, 2021 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-34256404

RESUMO

Infection with SARS-CoV-2 has a profound influence on the hematopoetic system that mediates clinical symptoms and mortality. Several studies have shown that treatment of the cytokine storm (CRS) with anti-inflammatory drugs like dexamethasone and tocilizumab can significantly improve survival. Systematic reviews confirm the safety of convalescent plasma administration and offer initial indications of its effectiveness in certain groups. COVID-associated coagulopathy (CAC) and vaccine-induced immune thrombotic thrombocytopenia (VITT) represent severe infection- or vaccination associated complications that require a specific diagnostic and therapeutic workup.


Assuntos
COVID-19/sangue , COVID-19/complicações , Hematologia , Hematopoese , Hemostasia , SARS-CoV-2/fisiologia , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/prevenção & controle , Transtornos da Coagulação Sanguínea/terapia , COVID-19/mortalidade , COVID-19/terapia , Humanos , Imunização Passiva
12.
BMJ Case Rep ; 14(6)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34083194

RESUMO

A 76-year-old man with hypogammaglobulinemia on monthly intravenous immunoglobulin infusions presented to the hospital with fever, cough, and shortness of breath and was diagnosed with COVID-19 pneumonia requiring intensive care unit admission but not intubation. He was treated with convalescent plasma, remdesivir and corticosteroids. Sixteen days into his hospitalisation he began to report weakness without sensory symptoms and was found on biopsy to have a necrotising myopathy.


Assuntos
COVID-19 , Doenças Musculares , Tireoidite , Idoso , COVID-19/terapia , Humanos , Imunização Passiva , Masculino , SARS-CoV-2
13.
Comput Math Methods Med ; 2021: 6676987, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122618

RESUMO

Progressive acute respiratory distress syndrome (ARDS) is the most lethal cause in patients with severe COVID-19 pneumonia due to uncontrolled inflammatory reaction, for which we found that early intervention of combined treatment with methylprednisolone and human immunoglobulin is a highly effective therapy to improve the prognosis of COVID-19-induced pneumonia patients. Objective. Herein, we have demonstrated the clinical manifestations, laboratory, and radiological characteristics of patients with severe Coronavirus Disease-2019 (COVID-19) pneumonia, as well as measures to ensure early diagnosis and intervention for improving clinical outcomes of COVID-19 patients. Summary Background Data. The COVID-19 is a new infection caused by a severe acute respiratory syndrome- (SARS-) like coronavirus that emerged in China in December 2019 and has claimed millions of lives. Methods. We included 37 severe COVID-19 pneumonia patients who were hospitalized at Taizhou Public Health Medical Center in Zhejiang province from January 17, 2020, to February 18, 2020. Demographic, clinical, and laboratory features; imaging characteristics; treatment history; and clinical outcomes of all patients were collected from electronic medical records. Results. The patients' mean age was 54 years (interquartile range, 43-64), with a slightly higher male preponderance (57%). The most common clinical features of COVID-19 pneumonia were fever (29 (78%)), dry cough (28 (76%)), dyspnea (9 (24%)), and fatigue (9 (24%)). Serum interleukin (IL)-6 and IL-10 were elevated in 35 (95%) and 19 (51%) patients, respectively. Chest computerized tomography scan revealed bilateral pneumonia in 35 (95%) patients. Early intervention with a combination of methylprednisolone and human immunoglobulin was highly effective in improving the prognosis of these patients. Conclusions. Progressive acute respiratory distress syndrome is the most common cause of death in patients with severe COVID-19 pneumonia owing to an uncontrolled inflammatory response. Early intervention with methylprednisolone and human immunoglobulin was highly effective in improving their prognosis.


Assuntos
COVID-19/diagnóstico , COVID-19/terapia , Pandemias , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , China/epidemiologia , Biologia Computacional , Diagnóstico Precoce , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença
14.
Rheumatol Int ; 41(8): 1509-1514, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34091704

RESUMO

A 77-year-old man with past medical history of granulomatosis with polyangiitis (GPA) on rituximab and prednisone, presented to the hospital with worsening cough and shortness of breath. He had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by nasal swab polymerase chain reaction (PCR) while asymptomatic, 6 weeks earlier. He started with cough and shortness of breath 2 weeks after his initial positive test. After developing symptoms, he tested negative twice by nasal swab PCR, but the PCR of his bronchioloalveolar lavage was positive for SARS-CoV-2. He did not develop antibodies against coronavirus. Prednisone 15 mg daily was continued, and he received remdesivir, and convalescent plasma with quick recovery. We reviewed the literature to search for similar cases. Our case suggests that SARS-CoV-2 infection in patients on rituximab may have an atypical presentation and the diagnosis may be delayed due to negative PCR testing in the nasal swab. Patients may benefit from treatment with convalescent plasma.


Assuntos
COVID-19/virologia , Granulomatose com Poliangiite/tratamento farmacológico , Imunossupressores/efeitos adversos , Rituximab/efeitos adversos , SARS-CoV-2/patogenicidade , Idoso , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/terapia , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/imunologia , Interações Hospedeiro-Patógeno , Humanos , Imunização Passiva , Hospedeiro Imunocomprometido , Masculino , SARS-CoV-2/imunologia , Resultado do Tratamento
15.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071276

RESUMO

Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic inflammatory disease that occurs in arteries, is considered to be the main cause of cardiovascular diseases such as ischemic heart disease or stroke. In addition, the inflammatory response caused by atherosclerosis confers a significant effect on chronic inflammatory diseases such as psoriasis and rheumatic arthritis. Here, we review the mechanism of action of the main causes of atherosclerosis such as plasma LDL level and inflammation; furthermore, we review the recent findings on the preclinical and clinical effects of antibodies that reduce the LDL level and those that neutralize the cytokines involved in inflammation. The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies, but failed to significantly reduce carotid inflammation plaques in clinical trials. The monoclonal antibodies against PCSK9 (alirocumab, evolocumab), which are used as a treatment for hyperlipidemia, lowered cholesterol levels and the incidence of cardiovascular diseases. Antibodies that neutralize inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17, and IL-12/23) have shown promising but contradictory results and thus warrant further research.


Assuntos
Anticorpos/farmacologia , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Imunização Passiva/métodos , Animais , Anticorpos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/uso terapêutico , Apolipoproteínas B , Autoanticorpos , LDL-Colesterol/sangue , Citocinas/imunologia , Humanos , Inflamação/tratamento farmacológico , Fragmentos de Peptídeos , Pró-Proteína Convertase 9/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico
16.
Viruses ; 13(5)2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065987

RESUMO

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expanded, it was clear that effective testing for the presence of neutralizing antibodies in the blood of convalescent patients would be critical for development of plasma-based therapeutic approaches. To address the need for a high-quality neutralization assay against SARS-CoV-2, a previously established fluorescence reduction neutralization assay (FRNA) against Middle East respiratory syndrome coronavirus (MERS-CoV) was modified and optimized. The SARS-CoV-2 FRNA provides a quantitative assessment of a large number of infected cells through use of a high-content imaging system. Because of this approach, and the fact that it does not involve subjective interpretation, this assay is more efficient and more accurate than other neutralization assays. In addition, the ability to set robust acceptance criteria for individual plates and specific test wells provided further rigor to this assay. Such agile adaptability avails use with multiple virus variants. By February 2021, the SARS-CoV-2 FRNA had been used to screen over 5000 samples, including acute and convalescent plasma or serum samples and therapeutic antibody treatments, for SARS-CoV-2 neutralizing titers.


Assuntos
Anticorpos Neutralizantes/análise , COVID-19/imunologia , Testes de Neutralização/métodos , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , COVID-19/metabolismo , COVID-19/terapia , Chlorocebus aethiops , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imunização Passiva , Imunoglobulina G/sangue , Pandemias , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero
17.
Viruses ; 13(5)2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066932

RESUMO

More than one year into the novel coronavirus disease 2019 (COVID-19) pandemic, healthcare systems across the world continue to be overwhelmed with soaring daily cases. The treatment spectrum primarily includes ventilation support augmented with repurposed drugs and/or convalescent plasma transfusion (CPT) from recovered COVID-19 patients. Despite vaccine variants being recently developed and administered in several countries, challenges in global supply chain logistics limit their timely availability to the wider world population, particularly in developing countries. Given the measured success of conventional CPT in treating several infections over the past decade, recent studies have reported its effectiveness in decreasing the duration and severity of COVID-19 symptoms. In this review, we conduct a literature search of published studies investigating the use of CPT to treat COVID-19 patients from January 2020 to January 2021. The literature search identified 181 records of which 39 were included in this review. A random-effects model was used to aggregate data across studies, and mortality rates of 17 vs. 32% were estimated for the CPT and control patient groups, respectively, with an odds ratio (OR) of 0.49. The findings indicate that CPT shows potential in reducing the severity and duration of COVID-19 symptoms. However, early intervention (preferably within 3 days), recruitment of donors, and plasma potency introduce major challenges for its scaled-up implementation. Given the low number of existing randomized clinical trials (RCTs, four with a total of 319 patients), unanticipated risks to CPT recipients are highlighted and discussed. Nevertheless, CPT remains a promising COVID-19 therapeutic option that merits internationally coordinated RCTs to achieve a scientific risk-benefit consensus.


Assuntos
COVID-19/terapia , Transfusão de Componentes Sanguíneos , COVID-19/imunologia , Humanos , Imunização Passiva/métodos , Imunização Passiva/tendências , Pandemias , Plasma , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Resultado do Tratamento
18.
Viruses ; 13(6)2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072720

RESUMO

Identification of therapeutics against emerging and re-emerging viruses remains a continued priority that is only reinforced by the recent SARS-CoV-2 pandemic. Advances in monoclonal antibody (mAb) isolation, characterization, and production make it a viable option for rapid treatment development. While mAbs are traditionally screened and selected based on potency of neutralization in vitro, it is clear that additional factors contribute to the in vivo efficacy of a mAb beyond viral neutralization. These factors include interactions with Fc receptors (FcRs) and complement that can enhance neutralization, clearance of infected cells, opsonization of virions, and modulation of the innate and adaptive immune response. In this review, we discuss recent studies, primarily using mouse models, that identified a role for Fc-FcγR interactions for optimal antibody-based protection against emerging and re-emerging virus infections.


Assuntos
Doenças Transmissíveis Emergentes/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Receptores de IgG/imunologia , Viroses/imunologia , Vírus/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Citotoxicidade Celular Dependente de Anticorpos , Doenças Transmissíveis Emergentes/terapia , Doenças Transmissíveis Emergentes/virologia , Humanos , Imunização Passiva , Fagocitose , Viroses/terapia , Viroses/virologia , Vírus/classificação
19.
Ther Adv Respir Dis ; 15: 17534666211028077, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34190621

RESUMO

AIMS: Given the variability of previously reported results, this systematic review aims to determine the clinical effectiveness of convalescent plasma employed in the treatment of hospitalized patients diagnosed with COVID-19. METHODS: We conducted a systematic review of controlled clinical trials assessing treatment with convalescent plasma for hospitalized patients diagnosed with SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, and ventilation requirement. RESULTS: A total of 51 studies were retrieved from the databases. Five articles were finally included in the data extraction and qualitative and quantitative synthesis of results. The overall risk of bias in the reviewed articles was established at low-risk only in two trials. The meta-analysis suggests that there is no benefit of convalescent plasma compared with standard care or placebo in reducing the overall mortality and the ventilation requirement. However, there could be a benefit for the clinical improvement in patients treated with plasma. CONCLUSION: Current results led to assume that the convalescent plasma transfusion cannot reduce the mortality or ventilation requirement in hospitalized patients diagnosed with SARS-CoV-2 infection. More controlled clinical trials conducted with methodologies that ensure a low risk of bias are still needed.The reviews of this paper are available via the supplemental material section.


Assuntos
COVID-19/terapia , Hospitalização , COVID-19/diagnóstico , COVID-19/mortalidade , Mortalidade Hospitalar , Humanos , Imunização Passiva/efeitos adversos , Imunização Passiva/mortalidade , Recuperação de Função Fisiológica , Respiração Artificial , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Front Immunol ; 12: 683902, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1282386

RESUMO

Respiratory syncytial virus (RSV) is a public health concern that causes acute lower respiratory tract infection. So far, no vaccine candidate under development has reached the market and the only licensed product to prevent RSV infection in at-risk infants and young children is a monoclonal antibody (Synagis®). Polyclonal human anti-RSV hyper-immune immunoglobulins (Igs) have also been used but were superseded by Synagis® owing to their low titer and large infused volume. Here we report a new drug class of immunoglobulins, derived from human non hyper-immune plasma that was generated by an innovative bioprocess, called Ig cracking, combining expertises in plasma-derived products and affinity chromatography. By using the RSV fusion protein (F protein) as ligand, the Ig cracking process provided a purified and concentrated product, designated hyper-enriched anti-RSV IgG, composed of at least 15-20% target-specific-antibodies from normal plasma. These anti-RSV Ig displayed a strong in vitro neutralization effect on RSV replication. Moreover, we described a novel prophylactic strategy based on local nasal administration of this unique hyper-enriched anti-RSV IgG solution using a mouse model of infection with bioluminescent RSV. Our results demonstrated that very low doses of hyper-enriched anti-RSV IgG can be administered locally to ensure rapid and efficient inhibition of virus infection. Thus, the general hyper-enriched Ig concept appeared a promising approach and might provide solutions to prevent and treat other infectious diseases. Importance: Respiratory Syncytial Virus (RSV) is the major cause of acute lower respiratory infections in children, and is also recognized as a cause of morbidity in the elderly. There are still no vaccines and no efficient antiviral therapy against this virus. Here, we described an approach of passive immunization with a new class of hyper-enriched anti-RSV immunoglobulins (Ig) manufactured from human normal plasma. This new class of immunoglobulin plasma derived product is generated by an innovative bioprocess, called Ig cracking, which requires a combination of expertise in both plasma derived products and affinity chromatography. The strong efficacy in a small volume of these hyper-enriched anti-RSV IgG to inhibit the viral infection was demonstrated using a mouse model. This new class of immunoglobulin plasma-derived products could be applied to other pathogens to address specific therapeutic needs in the field of infectious diseases or even pandemics, such as COVID-19.


Assuntos
Anticorpos Antivirais/administração & dosagem , Imunização Passiva , Imunoglobulina G/administração & dosagem , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano/imunologia , Administração Intranasal , Animais , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Modelos Animais de Doenças , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Pulmão/efeitos dos fármacos , Pulmão/virologia , Testes de Neutralização , Infecções por Vírus Respiratório Sincicial/virologia , Conchas Nasais/efeitos dos fármacos , Conchas Nasais/virologia , Proteínas Virais de Fusão/imunologia , Replicação Viral/efeitos dos fármacos
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