Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.498
Filtrar
1.
J Immunol Res ; 2020: 9465398, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134398

RESUMO

This new decade has started with a global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID-19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID-19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS-CoV-2 in chickens and extracted IgY (called IgY-S) from egg yolk. IgY-S exhibited high immunoreactivity against SARS-CoV-2 S, and by epitope mapping, we found five linear epitopes of IgY-S in SARS-CoV-2 S, two of which are cross-reactive with SARS-CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS-CoV-2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus-cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY-S or epitope SIIAYTMS-specific IgY as neutralizing antibody for preventing or treating SARS-CoV-2 infection is worth exploring.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/terapia , Mapeamento de Epitopos , Imunoglobulinas/isolamento & purificação , Pneumonia Viral/terapia , Administração Intranasal , Animais , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Galinhas , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas , Estudos de Viabilidade , Humanos , Imunização Passiva/métodos , Imunoglobulinas/administração & dosagem , Imunoglobulinas/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Glicoproteína da Espícula de Coronavírus/imunologia
2.
Trials ; 21(1): 905, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138867

RESUMO

OBJECTIVES: The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on severe and critically ill patients with COVID-19. TRIAL DESIGN: This is a phase I/II single centre, randomised controlled, single-blinded, superiority trial, through parallel-group design with sequential assignment. Participants will be randomised either to receive both C-IVIG and standard care or only standard care (4:1). PARTICIPANTS: The study is mono-centric with the participants including COVID19 infected individuals (positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs) admitted in institute affiliated with Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan. Consenting patients above 18 years that are classified by the treating physician as severely ill i.e. showing symptoms of COVID-19 pneumonia; dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93%, PaO2/FiO2 <300, and lung infiltrates >50% on CXR; or critically ill i.e. respiratory failure, septic shock, and multiple organ dysfunction or failure. Patients with reported IgA deficiency, autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents to maintain blood pressure and patients with acute or chronic kidney injury/failure, were also excluded from the study. INTERVENTION AND COMPARATOR: The study consists of four interventions and one comparator arm. All participants receive standard hospital care which includes airway support, anti-viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti-pyretics. Randomised test patients will receive single dose of C-IVIG in following four dosage groups: Group 1: 0.15g/Kg with standard hospital care Group 2: 0.2g/Kg with standard hospital care Group 3: 0.25g/Kg with standard hospital care Group 4: 0.3g/Kg with standard hospital care Group 5 (comparator) will receive standard hospital care only MAIN OUTCOMES: The primary outcomes are assessment and follow-up of participants to observe 28-day mortality and, • the level and duration of assisted ventilation during hospital stay, • number of days to step down (shifting from ICU to isolation ward), • number of days to hospital discharge, • adverse events (Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)) during hospital stay, • change in C-Reactive Protein (CRP) levels, • change in neutrophil lymphocyte ratio to monitor inflammation. RANDOMISATION: Consenting participants who fulfill the criteria are allocated to either intervention or comparator arm with a ratio of 4:1, using sequentially numbered opaque sealed envelope simple randomization method. The participant allocated for intervention will be sequentially assigned dosage group 1-4 in ascending order. Participants will not be recruited in the next dosage group before a set number of participants in one group (10) are achieved. BLINDING (MASKING): Single blinded study, with participants blinded to allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Total 50 patients are randomised. The intervention arms consist of 40 participants divided in four groups of 10 participants while the comparator group consists of 10 patients. TRIAL STATUS: Current version of the protocol is "Version 2" dated 29th September, 2020. Participants are being recruited. Recruitment started on June, 2020 and is estimated to primarily end on January, 2021. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov, NCT04521309 on 20 August 2020 and is retrospectively registered. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).


Assuntos
Infecções por Coronavirus/terapia , Imunização Passiva/métodos , Imunoglobulinas Intravenosas , Pneumonia Viral/terapia , Adulto , Betacoronavirus/isolamento & purificação , Estado Terminal/terapia , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/efeitos adversos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Masculino , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
3.
Medicine (Baltimore) ; 99(45): e23029, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157952

RESUMO

RATIONALE: Neuromyelitis optica spectrum disorder (NMOSD) patients, especially those with anti-aquaporin-4 antibody positivity, a water channel expressed on astrocytes, is often accompanied by autoimmune diseases (ADs) including Sjogren syndrome (SS). Here, we report a case of a young Chinese woman with recurrent optic neuritis who was diagnosed with asymptomatic SS and NMOSD. PATIENT CONCERNS: A 22-year-old Chinese woman suffered from optic neuritis for 3 years. The main manifestation was recurrent loss of vision. The anti-aquaporin-4 antibody was positive in the cerebrospinal fluid, and she was diagnosed with NMOSD. Other laboratory tests revealed positive anti-SSA and anti-SSB antibodies, and labial gland biopsy showed lymphocytic infiltration. She also fulfilled the international criteria for SS. DIAGNOSIS: On the basis of recurrent vision loss and laboratory examination, we defined the patient with SS accompanied by NMOSD. INTERVENTIONS: When the patient first experienced vision loss, the corticosteroid treatment in the external hospital was effective, and her visual acuity improved significantly. However, in several later attacks, such treatment was no longer obviously effective. Considering the patient's condition, she was treated with corticosteroids, cyclophosphamide, and immunoglobulin therapy on admission. OUTCOMES: The patient's visual acuity was increased to the right eye 20/800 and left eye finger counting when she was discharged from the hospital. LESSONS: SS accompanied with NMOSD is common in clinical practice, and always with the positive Anti-AQP4 antibody as a potential biomarker. Patients with SS and NMOSD showed significant neurological symptoms and had a worse prognosis than SS patients with negative anti-AQP4 antibody because of cross-immunity between anti-SSA antibody and anti-AQP4 antibody. Rheumatologists and ophthalmologists should pay attention to this and perform appropriate tests.


Assuntos
Aquaporina 4/líquido cefalorraquidiano , Neuromielite Óptica/complicações , Neurite Óptica/etiologia , Síndrome de Sjogren/complicações , Corticosteroides/uso terapêutico , Aquaporina 4/antagonistas & inibidores , Cegueira/diagnóstico , Cegueira/etiologia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Imunização Passiva/métodos , Imunossupressores/uso terapêutico , Neuromielite Óptica/imunologia , Neurite Óptica/tratamento farmacológico , Recidiva , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos , Adulto Jovem
4.
Cochrane Database Syst Rev ; 10: CD013600, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044747

RESUMO

BACKGROUND: Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are currently being investigated in trials as potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required.  OBJECTIVES: To continually assess, as more evidence becomes available, whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in treatment of people with COVID-19. SEARCH METHODS: We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trial registries to identify completed and ongoing studies on 19 August 2020. SELECTION CRITERIA: We followed standard Cochrane methodology. We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of study design, disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of bias' 2.0 tool for randomised controlled trials (RCTs), the Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tool for controlled non-randomised studies of interventions (NRSIs), and the assessment criteria for observational studies, provided by Cochrane Childhood Cancer for non-controlled NRSIs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality at hospital discharge, mortality (time to event), improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events (AEs), and serious adverse events (SAEs). MAIN RESULTS: This is the second living update of our review. We included 19 studies (2 RCTs, 8 controlled NRSIs, 9 non-controlled NRSIs) with 38,160 participants, of whom 36,081 received convalescent plasma. Two completed RCTs are awaiting assessment (published after 19 August 2020). We identified a further 138 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, of which 73 are randomised (3 reported in a study registry as already being completed, but without results). We did not identify any completed studies evaluating hyperimmune immunoglobulin. We did not include data from controlled NRSIs in data synthesis because of critical risk of bias. The overall certainty of evidence was low to very low, due to study limitations and results including both potential benefits and harms.  Effectiveness of convalescent plasma for people with COVID-19  We included results from two RCTs (both stopped early) with 189 participants, of whom 95 received convalescent plasma. Control groups received standard care at time of treatment without convalescent plasma. We are uncertain whether convalescent plasma decreases all-cause mortality at hospital discharge (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.22 to 1.34; 1 RCT, 86 participants; low-certainty evidence).  We are uncertain whether convalescent plasma decreases mortality (time to event) (hazard ratio (HR) 0.64, 95% CI 0.33 to 1.25; 2 RCTs, 189 participants; low-certainty evidence). Convalescent plasma may result in little to no difference in improvement of clinical symptoms (i.e. need for respiratory support) at seven days (RR 0.98, 95% CI 0.30 to 3.19; 1 RCT, 103 participants; low-certainty evidence). Convalescent plasma may increase improvement of clinical symptoms at up to 15 days (RR 1.34, 95% CI 0.85 to 2.11; 2 RCTs, 189 participants; low-certainty evidence), and at up to 30 days (RR 1.13, 95% CI 0.88 to 1.43; 2 studies, 188 participants; low-certainty evidence).  No studies reported on quality of life.  Safety of convalescent plasma for people with COVID-19 We included results from two RCTs, eight controlled NRSIs and nine non-controlled NRSIs assessing safety of convalescent plasma. Reporting of safety data and duration of follow-up was variable. The controlled studies reported on AEs and SAEs only in participants receiving convalescent plasma. Some, but not all, studies included death as a SAE.  The studies did not report the grade of AEs. Fourteen studies (566 participants) reported on AEs of possible grade 3 or 4 severity. The majority of these AEs were allergic or respiratory events. We are very uncertain whether convalescent plasma therapy affects the risk of moderate to severe AEs (very low-certainty evidence).  17 studies (35,944 participants) assessed SAEs for 20,622 of its participants. The majority of participants were from one non-controlled NRSI (20,000 participants), which reported on SAEs within the first four hours and within an additional seven days after transfusion. There were 63 deaths, 12 were possibly and one was probably related to transfusion. There were 146 SAEs within four hours and 1136 SAEs within seven days post-transfusion. These were predominantly allergic or respiratory, thrombotic or thromboembolic and cardiac events. We are uncertain whether convalescent plasma therapy results in a clinically relevant increased risk of SAEs (low-certainty evidence). AUTHORS' CONCLUSIONS: We are uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID-19. There was limited information regarding grade 3 and 4 AEs to determine the effect of convalescent plasma therapy on clinically relevant SAEs. In the absence of a control group, we are unable to assess the relative safety of convalescent plasma therapy.  While major efforts to conduct research on COVID-19 are being made, recruiting the anticipated number of participants into these studies is problematic. The early termination of the first two RCTs investigating convalescent plasma, and the lack of data from 20 studies that have completed or were due to complete at the time of this update illustrate these challenges. Well-designed studies should be prioritised. Moreover, studies should report outcomes in the same way, and should consider the importance of maintaining comparability in terms of co-interventions administered in all study arms.  There are 138 ongoing studies evaluating convalescent plasma and hyperimmune immunoglobulin, of which 73 are RCTs (three already completed). This is the second living update of the review, and we will continue to update this review periodically. Future updates may show different results to those reported here.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Viés , Causas de Morte , Infecções por Coronavirus/mortalidade , Humanos , Imunização Passiva/efeitos adversos , Imunização Passiva/métodos , Imunização Passiva/estatística & dados numéricos , Ensaios Clínicos Controlados não Aleatórios como Assunto/estatística & dados numéricos , Pandemias , Pneumonia Viral/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Resultado do Tratamento
6.
Trials ; 21(1): 883, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106167

RESUMO

OBJECTIVES: General: To assess the safety, efficacy and dose response of convalescent plasma (CP) transfusion in severe COVID-19 patients Specific: a. To identify the appropriate effective dose of CP therapy in severe patients b. To identify the efficacy of the therapy with their end point based on clinical improvement within seven days of treatment or until discharge whichever is later and in-hospital mortality c. To assess the clinical improvement after CP transfusion in severe COVID-19 patients d. To assess the laboratory improvement after CP transfusion in severe COVID-19 patients TRIAL DESIGN: This is a multicentre, multi-arm phase II Randomised Controlled Trial. PARTICIPANTS: Age and sex matched COVID-19 positive (by RT-PCR) severe cases will be enrolled in this trial. Severe case is defined by the World Health Organization (W.H.O) clinical case definition. The inclusion criteria are 1. Respiratory rate > 30 breaths/min; PLUS 2. Severe respiratory distress; or SpO2 ≤ 88% on room air or PaO2/FiO2≤ 300 mm of Hg, PLUS 3. Radiological (X-ray or CT scan) evidence of bilateral lung infiltrate, AND OR 4. Systolic BP < 90 mm of Hg or diastolic BP <60 mm of Hg. AND/OR 5. Criteria 1 to 4 AND or patient in ventilator support Patients' below18 years, pregnant and lactating women, previous history of allergic reaction to plasma, patients who have already received plasma from a different source will be excluded. Patients will be enrolled at Bangabandhu Sheikh Mujib Medical University (BSMMU) hospital, Dhaka medical college hospital (DMCH) and Mugda medical college hospital (MuMCH). Apheretic plasma will be collected at the transfusion medicine department of SHNIBPS hospital, ELISA antibody titre will be done at BSMMU and CMBT and neutralizing antibody titre will be checked in collaboration with the University of Oxford. Patients who have recovered from COVID-19 will be recruited as donors of CP. The recovery criteria are normality of body temperature for more than 3 days, resolution of respiratory symptoms, two consecutively negative results of sputum SARS-CoV-2 by RT-PCR assay (at least 24 hours apart) 22 to 35 days of post onset period, and neutralizing antibody titre ≥ 1:160. INTERVENTION AND COMPARATOR: This RCT consists of three arms, a. standard care, b. standard care and 200 ml CP and c. standard care and 400 ml CP. Patients will receive plasma as a single transfusion. Intervention arms will be compared to the standard care arm. MAIN OUTCOMES: The primary outcome will be time to clinical improvement within seven days of treatment or until discharge whichever is later and in-hospital mortality. The secondary outcome would be improvement of laboratory parameters after therapy (neutrophil, lymphocyte ratio, CRP, serum ferritin, SGPT, SGOT, serum creatinine and radiology), length of hospital stay, length of ICU stay, reduction in proportion of deaths, requirement of ventilator and duration of oxygen and ventilator support. RANDOMISATION: Randomization will be done by someone not associated with the care or assessment of the patients by means of a computer generated random number table using an allocation ratio of 1:1:1. BLINDING (MASKING): This is an open level study; neither the physician nor the patients will be blinded. However, the primary and secondary outcome (oxygen saturations, PaO2/FiO2, BP, day specific laboratory tests) will be recorded using an objective automated method; the study staff will not be able to influence the recording of these data. NUMBER TO BE RANDOMISED (SAMPLE SIZE): No similar study has been performed previously. Therefore no data are available that could be used to generate a sample size calculation. This phase II study is required to provide some initial data on efficacy and safety that will allow design of a larger study. The trial will recruit 60 participants (20 in each arm). TRIAL STATUS: Protocol version 1.4 dated May 5, 2020 and amended version 1.5, dated June 16, 2020. First case was recruited on May 27, 2020. By August 10, 2020, the trial had recruited one-third (21 out of 60) of the participants. The recruitment is expected to finish by October 31, 2020. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT04403477 . Registered 26 May, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trial's website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


Assuntos
Betacoronavirus/genética , Transfusão de Sangue/métodos , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Bangladesh/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Relação Dose-Resposta Imunológica , Feminino , Mortalidade Hospitalar/tendências , Humanos , Imunização Passiva/efeitos adversos , Imunização Passiva/métodos , Masculino , Pandemias , Alta do Paciente/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Segurança , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Ventiladores Mecânicos/estatística & dados numéricos
7.
Trials ; 21(1): 875, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092632

RESUMO

OBJECTIVES: The primary objective is to demonstrate that COVID-19 convalescent plasma (CCP) prevents progression to severe pneumonia in elderly COVID-19 pneumonia patients with chronic comorbidities. Secondary objectives are to demonstrate that CCP decreases the viral load in nasopharyngeal swabs and increases the anti-SARS-CoV-2 antibody titre in recipients. TRIAL DESIGN: This is a randomized, open-label, parallel group, phase II/III study with a superiority framework. The trial starts with a screening phase II designed with two-tailed alpha=0.2. In case of positive results, the trial will proceed in a formally comparative phase III (alpha=0.05). PARTICIPANTS: Adult patients with confirmed or suspected COVID-19 who are at risk according to CDC definition are eligible. Inclusion criteria are all the following: age ≥ 65; pneumonia at CT scan; PaO2/FiO2 ≥300 mmHg; presence of one or more comorbidities; signed informed consent. Exclusion criteria are one of the following: age < 65; PaO2/FiO2 < 300 mmHg; pending cardiopulmonary arrest; refusal to blood product transfusions; severe IgA deficiency; any life-threatening comorbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion. The trial is being conducted at three reference COVID-19 centres in the middle of Italy. INTERVENTION AND COMPARATOR: Intervention: COVID-19 Convalescent Plasma (CCP) in addition to standard therapy. Patients receive three doses (200 ml/day on 3 consecutive days) of ABO matched CCP. Comparator: Standard therapy MAIN OUTCOMES: A. Primary outcome for Phase II: Proportion of patients without progression in severity of pulmonary disease, defined as worsening of 2 points in the ordinal scale of WHO by day 14. B. Primary outcome for Phase III: Proportion of patients without progression in severity of pulmonary disease, defined as worsening of 2 points in the ordinal scale of WHO by day 14. Secondary outcomes for Phase III: Decreased viral load on nasopharyngeal swab at days 6, 9 and 14; Decreased viremia at days 6 and 9; Increased antibody titer against SARS-CoV2 at days 30 and 60; Proportion of patients with negative of SARS-CoV2 nasopharyngeal swab at day 30; Length of hospital stay; Mortality rate at day 28; Total plasma related adverse event (day 60); Total non-plasma related adverse events (day 60); Severe adverse events (SAE) (day 60). RANDOMISATION: Treatment allocation is randomized with a ratio 1:1 in both phase II and phase III. Randomization sequences will be generated at Fondazione Policlinico Gemelli IRCCS through the RedCap web application. Randomized stratification is performed according to age (under/over 80 years), and sex. BLINDING (MASKING): None, this is an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Phase II: 114 patients (57 per arm). Phase III: 182 patients (91 per arm) TRIAL STATUS: The trial recruitment started on May 27, 2020. The anticipated date of recruitment completion is April 30, 2021. The protocol version is 2 (May 10, 2020). TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov (May 5, 2020). The Identifier number is NCT04374526 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Betacoronavirus/genética , Transfusão de Sangue/métodos , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Progressão da Doença , Feminino , Humanos , Imunização Passiva/efeitos adversos , Imunização Passiva/métodos , Consentimento Livre e Esclarecido/ética , Itália/epidemiologia , Masculino , Mortalidade/tendências , Pandemias , Pneumonia/diagnóstico por imagem , Pneumonia/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Tomografia Computadorizada por Raios X/métodos , Carga Viral/imunologia , Carga Viral/estatística & dados numéricos
8.
Int J Occup Environ Med ; 11(4): 157-178, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33098401

RESUMO

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and has created a worldwide pandemic. Many patients with this infection have an asymptomatic or mild illness, but a small percentage of patients require hospitalization and intensive care. Patients with respiratory tract involvement have a spectrum of presentations that range from scattered ground-glass infiltrates to diffuse infiltrates with consolidation. Patients with the latter radiographic presentation have severe hypoxemia and usually require mechanical ventilation. In addition, some patients develop multiorgan failure, deep venous thrombi with pulmonary emboli, and cytokine storm syndrome. The respiratory management of these patients should focus on using low tidal volume ventilation with low intrathoracic pressures. Some patients have significant recruitable lung and may benefit from higher positive end-expiratory pressure (PEEP) levels and/or prone positioning. There is no well-established anti-viral treatment for this infection; the United States Food and Drug Administration (FDA) has provided emergency use authorization for convalescent plasma and remdesivir for the treatment of patients with COVID-19. In addition, randomized trials have demonstrated that dexamethasone improves outcomes in patients on mechanical ventilators or on oxygen. There are ongoing trials of other drugs which have the potential to moderate the acute inflammatory state seen in some of these patients. These patients often need prolonged high-level intensive care. Hospitals are confronted with significant challenges in patient management, supply management, health care worker safety, and health care worker burnout.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Síndrome do Desconforto Respiratório do Adulto/virologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Humanos , Imunização Passiva/métodos , Pulmão/virologia , Pandemias , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório do Adulto/terapia , Estados Unidos
9.
Am J Case Rep ; 21: e927812, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009361

RESUMO

BACKGROUND This is a case report of an immunocompromised patient with a history of non-Hodgkin lymphoma and persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who was seronegative and successfully treated with convalescent plasma. CASE REPORT A 63-year-old woman with a past medical history of non-Hodgkin lymphoma in remission while on maintenance therapy with the anti-CD20 monoclonal antibody, obinutuzumab, tested positive for SARS-CoV-2 via nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) testing over 12 weeks and persistently tested seronegative for immunoglobulin G (IgG) antibodies using SARS-CoV-2 IgG chemiluminescent microparticle immunoassay technology. During this time, the patient experienced waxing and waning of symptoms, which included fever, myalgia, and non-productive cough, but never acquired severe respiratory distress. She was admitted to our hospital on illness day 88, and her symptoms resolved after the administration of convalescent plasma. CONCLUSIONS As the understanding of the pathogenesis of SARS-CoV-2 continues to evolve, we can currently only speculate about the occurrence of chronic infection vs. reinfection. The protective role of antibodies and their longevity against SARS-CoV-2 remain unclear. Since humoral immunity has an integral role in SARS-CoV-2 infection, various phase 3 vaccine trials are underway. In the context of this pandemic, the present case demonstrates the challenges in our understanding of testing and treating immunocompromised patients.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Hospedeiro Imunocomprometido , Linfoma não Hodgkin/imunologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Antineoplásicos Imunológicos/administração & dosagem , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/terapia , Feminino , Seguimentos , Humanos , Imunização Passiva/métodos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Pessoa de Meia-Idade , Pandemias , Reação em Cadeia da Polimerase em Tempo Real/métodos , Testes Sorológicos/métodos , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Medicina (B Aires) ; 80(5): 417-424, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-33048783

RESUMO

This is a preliminary, multicenter, retrospective cohort study, including 272 consecutive patients with COVID-19 admitted to hospitals in Buenos Aires Province, between May 15th and July 1st, 2020, included in an expanded access program to convalescent plasma. Our objectives were to analyze mortality and its independent risk factors, and to assess the occurrence of a favorable evolution, defined as hospital discharge, or stay at the ward, or transfer from ICU to ward. Patients were stratified int o 4 subgroups: admission to the ward with pneumonia and/or oxygen requirement (WARD; n = 100); ICU admission (ICU; n = 87); ICU admission with requirement of mechanical ventilation (ICU-MV; n = 56), and ICU-MV plus septic shock (ICU-MV-SS; N = 29). Mortality at 28 days was 26.1% for the entire group, 14.0% for WARD group, 18.4% for ICU, 44.6% for ICU-MV, and 55.2% for ICU-MV-SS. Mean survival time (days) was 25.6 ± 0.6 (WARD); 25.3 ± 0.7 (ICU); 20.8 ± 1.2 (ICU-MV) and 18.2 ± 1.8 (ICU-MV-SS). Independent predictors of mortality were MV, septic shock and weight. A favorable evolution occurred in 81.4% of WARD patients; in 70.9% of ICU; in 39.6% of ICU-MV and in 27.6% of ICU-MV-SS patients. Severity of illness on admission, age, weight and heart rate were independently associated with evolution. No major adverse effects were recorded. The lack of a control group precluded the estimation of efficacy. However, our 26% mortality rate was higher than that of the treatment arm of clinical trials comparing plasma with usual treatment, which might be ascribed to higher proportion of patients with MV and septic shock in our cohort.


Assuntos
Infecções por Coronavirus/terapia , Pandemias , Pneumonia Viral/terapia , Adulto , Idoso , Argentina/epidemiologia , Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Imunização Passiva/métodos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
11.
Biomed Res Int ; 2020: 2606058, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029499

RESUMO

On March 11th, 2020, the World Health Organization declared COVID-19 infection as a pandemic. Since it is a novel virus, there are basically no proven drugs or therapies; although many laboratories in different countries are working to develop a vaccine, it will take time to make it available. Passive immunization is the therapy born from the intuition of Behring and Kisato in the late 19th century. It was widely used for the treatment of bacterial infections until the discovery of antibiotics, as well as during the viral pandemics of the 20th century and of the beginning of the 21st; it still has clinical applications (e.g., tetanus prevention). This paper summarizes the basic principles of passive immunization, with particular reference to convalescent plasma. The literature concerning its use during past epidemics and the results of the first clinical studies concerning its use during the current pandemic are discussed too. A large section is dedicated to the analysis of the possible, although rare, side effects. Recently, in 2017, the WHO Blood Regulators Network (BRN) published a position paper, recommending convalescent plasma as the first-choice treatment to be tested in the absence of authorized drugs; however, this strategy has not been followed. In the current epidemic, the principle of passive immunization through convalescent plasma has been applied in several circumstances and particularly in patients with serious complications. The first reported results are encouraging and confirm the effectiveness of plasma therapy and its safety. Also, the FDA has proposed plasma treatment in order to face the increasingly complex situation and manage patients with serious or immediately life-threatening COVID-19 disease. Several studies and clinical programs are still ongoing.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Humanos , Imunização Passiva/efeitos adversos , Imunização Passiva/métodos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Segurança , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration , Organização Mundial da Saúde
12.
Signal Transduct Target Ther ; 5(1): 219, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024082

RESUMO

Convalescent plasma (CP) transfusion has been indicated as a promising therapy in the treatment for other emerging viral infections. However, the quality control of CP and individual variation in patients in different studies make it rather difficult to evaluate the efficacy and risk of CP therapy for coronavirus disease 2019 (COVID-19). We aimed to explore the potential efficacy of CP therapy, and to assess the possible factors associated with its efficacy. We enrolled eight critical or severe COVID-19 patients from four centers. Each patient was transfused with 200-400 mL of CP from seven recovered donors. The primary indicators for clinical efficacy assessment were the changes of clinical symptoms, laboratory parameters, and radiological image after CP transfusion. CP donors had a wide range of antibody levels measured by serology tests which were to some degree correlated with the neutralizing antibody (NAb) level. No adverse events were observed during and after CP transfusion. Following CP transfusion, six out of eight patients showed improved oxygen support status; chest CT indicated varying degrees of absorption of pulmonary lesions in six patients within 8 days; the viral load was decreased to a negative level in five patients who had the previous viremia; other laboratory parameters also tended to improve, including increased lymphocyte counts, decreased C-reactive protein, procalcitonin, and indicators for liver function. The clinical efficacy might be associated with CP transfusion time, transfused dose, and the NAb levels of CP. This study indicated that CP might be a potential therapy for severe patients with COVID-19.


Assuntos
Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Betacoronavirus/patogenicidade , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Adulto , Idoso , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Progressão da Doença , Feminino , Humanos , Imunização Passiva/métodos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pró-Calcitonina/sangue , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Carga Viral
13.
Trials ; 21(1): 828, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023671

RESUMO

OBJECTIVES: Primary objectives • To assess the time from randomisation until an improvement within 84 days defined as two points on a seven point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of SARS-CoV-2 infection or standard of care. Secondary objectives • To assess overall survival, and the overall survival rate at 28 56 and 84 days. • To assess SARS-CoV-2 viral clearance and load as well as antibody titres. • To assess the percentage of patients that required mechanical ventilation. • To assess time from randomisation until discharge. TRIAL DESIGN: Randomised, open-label, multicenter phase II trial, designed to assess the clinical outcome of SARS-CoV-2 disease in high-risk patients (group 1 to group 4) following treatment with anti-SARS-CoV-2 convalescent plasma or standard of care. PARTICIPANTS: High-risk patients >18 years of age hospitalized with SARS-CoV-2 infection in 10-15 university medical centres will be included. High-risk is defined as SARS-CoV-2 positive infection with Oxygen saturation at ≤ 94% at ambient air with additional risk features as categorised in 4 groups: • Group 1, pre-existing or concurrent hematological malignancy and/or active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or less. • Group 2, chronic immunosuppression not meeting the criteria of group 1. • Group 3, age ≥ 50 - 75 years meeting neither the criteria of group 1 nor group 2 and at least one of these criteria: Lymphopenia < 0.8 x G/l and/or D-dimer > 1µg/mL. • Group 4, age ≥ 75 years meeting neither the criteria of group 1 nor group 2. Observation time for all patients is expected to be at least 3 months after entry into the study. Patients receive convalescent plasma for two days (day 1 and day 2) or standard of care. For patients in the standard arm, cross over is allowed from day 10 in case of not improving or worsening clinical condition. Nose/throat swabs for determination of viral load are collected at day 0 and day 1 (before first CP administration) and subsequently at day 2, 3, 5, 7, 10, 14, 28 or until discharge. Serum for SARS-Cov-2 diagnostic is collected at baseline and subsequently at day 3, 7, 14 and once during the follow-up period (between day 35 and day 84). There is a regular follow-up of 3 months. All discharged patients are followed by regular phone calls. All visits, time points and study assessments are summarized in the Trial Schedule (see full protocol Table 1). All participating trial sites will be supplied with study specific visit worksheets that list all assessments and procedures to be completed at each visit. All findings including clinical and laboratory data are documented by the investigator or an authorized member of the study team in the patient's medical record and in the electronic case report forms (eCRFs). INTERVENTION AND COMPARATOR: This trial will analyze the effects of convalescent plasma from recovered subjects with SARS-CoV-2 antibodies in high-risk patients with SARS-CoV-2 infection. Patients at high risk for a poor outcome due to underlying disease, age or condition as listed above are eligible for enrollment. In addition, eligible patients have a confirmed SARS-CoV-2 infection and O2 saturation ≤ 94% while breathing ambient air. Patients are randomised to receive (experimental arm) or not receive (standard arm) convalescent plasma in two bags (238 - 337 ml plasma each) from different donors (day 1, day 2). A cross over from the standard arm into the experimental arm is possible after day 10 in case of not improving or worsening clinical condition. MAIN OUTCOMES: Primary endpoints: The main purpose of the study is to assess the time from randomisation until an improvement within 84 days defined as two points on a seven-point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of a SARS-CoV-2 infection or standard of care. Secondary endpoints: • Overall survival, defined as the time from randomisation until death from any cause 28-day, 56-day and 84-day overall survival rates. • SARS-CoV-2 viral clearance and load as well as antibody titres. • Requirement mechanical ventilation at any time during hospital stay (yes/no). • Time until discharge from randomisation. • Viral load, changes in antibody titers and cytokine profiles are analysed in an exploratory manner using paired non-parametric tests (before - after treatment). RANDOMISATION: Upon confirmation of eligibility (patients must meet all inclusion criteria and must not meet exclusion criteria described in section 5.3 and 5.4 of the full protocol), the clinical site must contact a centralized internet randomization system ( https://randomizer.at/ ). Patients are randomized using block randomisation to one of the two arms, experimental arm or standard arm, in a 1:1 ratio considering a stratification according to the 4 risk groups (see Participants). BLINDING (MASKING): The study is open-label, no blinding will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total number of 174 patients is required for the entire trial, n=87 per group. TRIAL STATUS: Protocol version 1.2 dated 09/07/2020. A recruitment period of approximately 9 months and an overall study duration of approximately 12 months is anticipated. Recruitment of patients starts in the third quarter of 2020. The study duration of an individual patient is planned to be 3 months. After finishing all study-relevant procedures, therapy, and follow-up period, the patient is followed in terms of routine care and treated if necessary. Total trial duration: 18 months Duration of the clinical phase: 12 months First patient first visit (FPFV): 3rd Quarter 2020 Last patient first visit (LPFV): 2nd Quarter 2021 Last patient last visit (LPLV): 3rd Quarter 2021 Trial Report completed: 4th Quarter 2021 TRIAL REGISTRATION: EudraCT Number: 2020-001632-10, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE , registered on 04/04/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). The eCRF is attached (Additional file 3).


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus , Infecções por Coronavirus , Pandemias , Plasma/imunologia , Pneumonia Viral , Idoso , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Ensaios Clínicos Fase II como Assunto , Convalescença , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Imunização Passiva/métodos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Estudos Multicêntricos como Assunto , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco Ajustado , Índice de Gravidade de Doença
14.
Discov Med ; 29(158): 145-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007190

RESUMO

Coronavirus disease 2019 (COVID-19), a newly identified acute respiratory disease caused by a strain of novel coronavirus (SARS-CoV-2), has become a worldwide pandemic. From December 2019 to present, millions of cases have been reported, bringing unprecedented pressure on both health and epidemic prevention services in every country. As frontline healthcare workers, ophthalmologists face an increased threat of viral infection, not only because of close contact with patients during examinations or operations, but also due to evidence showing that ocular fluids such as tears or conjunctival secretions may carry the virus. The risk that healthcare workers face is emphasized by the loss of our colleagues who have sacrificed themselves in combating the virus. As a result, it is necessary to have a comprehensive understanding of the threats that we face. In the first part of this review, we start by explaining the structure of SARS-CoV-2 and examining its transmission and means of infection. Next, we summarize the latest scientific advancements of epidemiology, clinical presentations, and current treatments of COVID-19. In the second half of the review, we emphasize the ocular transmission, symptomatic manifestations, and the essential knowledge in an ophthalmology clinic setting. As the pandemic of COVID-19 continues to pose a threat to global health, we hope that this review makes a contribution to combating COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Oftalmopatias/virologia , Pneumonia Viral/complicações , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Reposicionamento de Medicamentos , Oftalmopatias/diagnóstico , Oftalmopatias/imunologia , Oftalmopatias/terapia , Humanos , Imunização Passiva/métodos , Fatores Imunológicos/uso terapêutico , Medicina Tradicional Chinesa/métodos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão
15.
Mil Med Res ; 7(1): 45, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32962760

RESUMO

BACKGROUND: Gastrointestinal symptoms are not rare among coronavirus disease 2019 (COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients. CASE PRESENTATION: We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration. CONCLUSION: When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Diarreia/terapia , Hemorragia Gastrointestinal/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Idoso , Infecções por Coronavirus/diagnóstico , Diarreia/etiologia , Feminino , Seguimentos , Hemorragia Gastrointestinal/etiologia , Humanos , Imunização Passiva/métodos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Recidiva , Amostragem , Índice de Gravidade de Doença , Taiwan , Resultado do Tratamento
16.
JCI Insight ; 5(19)2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-32870820

RESUMO

Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin-converting enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an ELISA for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of 2 viral-based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus and a spike pseudotyped viral vector-based assay.


Assuntos
Anticorpos Neutralizantes/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Antivirais/sangue , Área Sob a Curva , Ensaio de Imunoadsorção Enzimática , Humanos , Imunização Passiva/métodos , Testes de Neutralização , Pandemias , Análise de Regressão , Amostragem , Resultado do Tratamento , Proteínas do Envelope Viral/imunologia
17.
Curr Top Med Chem ; 20(26): 2362-2378, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32962613

RESUMO

The article highlights an up-to-date progress in studies on structural and the remedial aspects of novel coronavirus 2019-nCoV, renamed as SARS-CoV-2, leading to the disease COVID-19, a pandemic. In general, all CoVs including SARS-CoV-2 are spherical positive single-stranded RNA viruses containing spike (S) protein, envelope (E) protein, nucleocapsid (N) protein, and membrane (M) protein, where S protein has a Receptor-binding Domain (RBD) that mediates the binding to host cell receptor, Angiotensin Converting Enzyme 2 (ACE2). The article details the repurposing of some drugs to be tried for COVID-19 and presents the status of vaccine development so far. Besides drugs and vaccines, the role of Convalescent Plasma (CP) therapy to treat COVID-19 is also discussed.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Pandemias , Peptidil Dipeptidase A/química , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Glicoproteína da Espícula de Coronavírus/genética , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Betacoronavirus/ultraestrutura , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Expressão Gênica , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva/métodos , Ivermectina/uso terapêutico , Modelos Moleculares , Niclosamida/uso terapêutico , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Domínios e Motivos de Interação entre Proteínas/efeitos dos fármacos , Estrutura Secundária de Proteína , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Vírus da SARS/ultraestrutura , Síndrome Respiratória Aguda Grave , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/biossíntese
19.
S Afr Med J ; 110(8): 759-760, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32880303

RESUMO

Convalescent plasma is being considered as a potential therapy for COVID-19. We highlight and contextualise the findings of a recent Cochrane rapid review that evaluated the effectiveness and safety of convalescent plasma or hyperimmune immunoglobulin transfusion in the treatment of people with COVID-19. The review found low-certainty evidence of the therapeutic effectiveness and safety of convalescent plasma. As the novel coronavirus continues to spread in South Africa (SA), convalescent plasma may offer a therapeutic ray of hope for mitigating the morbidity and mortality burdens of the disease. Further investigation of the clinical benefits of the therapy in well-designed studies is needed to provide more evidence that will guide COVID-19 treatment decision-making in the SA context.


Assuntos
Infecções por Coronavirus , Imunoglobulinas Intravenosas/uso terapêutico , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Humanos , Imunização Passiva/métodos , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , África do Sul , Revisões Sistemáticas como Assunto , Resultado do Tratamento
20.
Infez Med ; 28(3): 357-366, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920571

RESUMO

The current COVID-19 pandemic needs unconventional therapies to tackle the resulted high morbidity and mortality. Convalescent plasma is one of the therapeutic approaches that might be of benefit. Forty nine early-stage critically-ill COVID-19 patients residing in Respiratory Care Units (RCU) of three hospitals in Baghdad, Iraq, were included: 21 received convalescent plasma while 28, namely control group, did not receive it. Recovery or death, length of stay in hospital, and improvement in the clinical course of the disease were monitored clinically along with laboratory monitoring through SARS-CoV-2 RNA detection via PCR, and SARS-CoV-2 IgG and IgM serological monitoring. Patients who received convalescent plasma showed reduced duration of infection in about 4 days and showed less death rate [1/21 versus 8/28 in control group]. In addition, all the patients who were given convalescent plasma showed high levels of SARS-CoV-2 IgG and IgM three days after plasma transfusion. Plasma from donors with high levels of SARS-CoV-2 IgG and donors with positive SRAS-CoV-2 IgM showed better therapeutic results than other donors. Convalescent plasma therapy is an effective therapy if donors with high level of SARS-Cov2 antibodies are selected and if recipients are at their early stage of critical illness, being no more than three days in RCUs.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/terapia , Plasma/imunologia , Pneumonia Viral/terapia , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Estado Terminal/terapia , Feminino , Humanos , Imunização Passiva/métodos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Iraque/epidemiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA