Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
1.
Blood Adv ; 6(11): 3494-3506, 2022 06 14.
Article in English | MEDLINE | ID: covidwho-1765427

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe prothrombotic complication of adenoviral vaccines, including the ChAdOx1 nCoV-19 (Vaxzevria) vaccine. The putative mechanism involves formation of pathological anti-platelet factor 4 (PF4) antibodies that activate platelets via the low-affinity immunoglobulin G receptor FcγRIIa to drive thrombosis and thrombocytopenia. Functional assays are important for VITT diagnosis, as not all detectable anti-PF4 antibodies are pathogenic, and immunoassays have varying sensitivity. Combination of ligand binding of G protein-coupled receptors (protease-activated receptor-1) and immunoreceptor tyrosine-based activation motif-linked receptors (FcγRIIa) synergistically induce procoagulant platelet formation, which supports thrombin generation. Here, we describe a flow cytometry-based procoagulant platelet assay using cell death marker GSAO and P-selectin to diagnose VITT by exposing donor whole blood to patient plasma in the presence of a protease-activated receptor-1 agonist. Consecutive patients triaged for confirmatory functional VITT testing after screening using PF4/heparin ELISA were evaluated. In a development cohort of 47 patients with suspected VITT, plasma from ELISA-positive patients (n = 23), but not healthy donors (n = 32) or individuals exposed to the ChAdOx1 nCov-19 vaccine without VITT (n = 24), significantly increased the procoagulant platelet response. In a validation cohort of 99 VITT patients identified according to clinicopathologic adjudication, procoagulant flow cytometry identified 93% of VITT cases, including ELISA-negative and serotonin release assay-negative patients. The in vitro effect of intravenous immunoglobulin (IVIg) and fondaparinux trended with the clinical response seen in patients. Induction of FcγRIIa-dependent procoagulant response by patient plasma, suppressible by heparin and IVIg, is highly indicative of VITT, resulting in a sensitive and specific assay that has been adopted as part of a national diagnostic algorithm to identify vaccinated patients with platelet-activating antibodies.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , ChAdOx1 nCoV-19 , Flow Cytometry , Heparin/therapeutic use , Humans , Immunoglobulins, Intravenous/adverse effects , Platelet Factor 4 , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Receptors, Proteinase-Activated/therapeutic use , Thrombocytopenia/diagnosis , Thrombosis/drug therapy
2.
Lancet Respir Med ; 10(2): 158-166, 2022 02.
Article in English | MEDLINE | ID: covidwho-1751525

ABSTRACT

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury. METHODS: In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580. FINDINGS: Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 [IQR 0·0-8·0]) and the placebo group (0·0 [0·0-6·0]; difference estimate 0·0 [0·0-0·0]; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; p=0·089). INTERPRETATION: In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials. FUNDING: Programme Hospitalier de Recherche Clinique.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Double-Blind Method , Female , Humans , Immunoglobulins, Intravenous/adverse effects , Iron-Dextran Complex , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2 , Treatment Outcome
3.
Eur J Pediatr ; 181(5): 2135-2146, 2022 May.
Article in English | MEDLINE | ID: covidwho-1699807

ABSTRACT

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. CONCLUSIONS: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. WHAT IS KNOWN: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. WHAT IS NEW: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.


Subject(s)
COVID-19 , Adolescent , COVID-19/complications , COVID-19/drug therapy , Child , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/adverse effects , Respiration, Artificial , Systemic Inflammatory Response Syndrome
4.
Lancet Respir Med ; 10(2): 158-166, 2022 02.
Article in English | MEDLINE | ID: covidwho-1510505

ABSTRACT

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury. METHODS: In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580. FINDINGS: Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 [IQR 0·0-8·0]) and the placebo group (0·0 [0·0-6·0]; difference estimate 0·0 [0·0-0·0]; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; p=0·089). INTERPRETATION: In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials. FUNDING: Programme Hospitalier de Recherche Clinique.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Double-Blind Method , Female , Humans , Immunoglobulins, Intravenous/adverse effects , Iron-Dextran Complex , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2 , Treatment Outcome
6.
Int Immunopharmacol ; 98: 107891, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1267708

ABSTRACT

BACKGROUND: Intravenous immunoglobulins (IVIg) have been used in management of severe Covid-19. Here in this study, we report our single-center experience regarding IVIg treatment in management of severe Covid-19. MATERIALS AND METHOD: Among hospitalized adult Covid-19 patients between April 1 and December 31, 2020, patients with confirmed diagnosis of Covid-19 who had Brescia-COVID respiratory severity scale score ≥ 3, hyperinflammation and received IVIg treatment in addition to standard of care were retrospectively investigated. We grouped IVIg recipients into three according to reasons for IVIg administration: Group 1 patients requiring anti-inflammatory treatment but complicated with secondary infection and/or sepsis , group 2 patients with Covid-19 related complications including progressive disease refractory to other anti-inflammatory agents, myocarditis, adult multisystem inflammatory syndrome, hemophagocytic lymphohystiocytosis like syndrome and group 3 patients with other complications non-specific to Covid-19. Mortality and clinical data was compared among groups. RESULTS: A total of 46 IVIg recipients were enrolled. Group 1 comprised 17 (36.9%), group 2 comprised 18 (39.1%) and group 3 comprised 11 (23.9%) patients. No significant differences in means of age, gender and comorbidities were observed among groups. Mortality was significantly lower in group 3 when compared to group 1 (64.7% vs 18.2%, p = 0.016) and close to significance when compared to group 2 (50% vs 18.2% p = 0.087). CONCLUSIONS: IVIg seemed to be used mostly in severe, refractory and complicated cases in our population. As a rescue agent in severe cases refractory to other anti-inflammatory strategies, 33.7% survival rate was observed with IVIg.


Subject(s)
COVID-19/drug therapy , Immunoglobulins, Intravenous/administration & dosage , Administration, Intravenous , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Cross-Sectional Studies , Female , Humans , Immunoglobulins, Intravenous/adverse effects , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Time Factors , Treatment Outcome , Turkey
7.
Am J Health Syst Pharm ; 78(12): 1112-1117, 2021 06 07.
Article in English | MEDLINE | ID: covidwho-1093474

ABSTRACT

PURPOSE: Intravenous immune globulin (IVIG) therapy is used in patients with hypogammaglobulinemia to lower the risk of infections. IVIG and subcutaneous IVIG (SCIG) therapy have been to shown to be safe and effective when administered as clinic-based infusions. Concern from both patients and providers for increased transmission of the coronavirus disease 2019 (COVID-19) virus to immunosuppressed patients with scheduled medical visits and procedures made it necessary for us to reassess our process of how we manage patient care in general and chronic clinic infusions in particular. Here we describe our experience of transitioning patients from clinic-based to home based IVIG and/or SCIG infusions to decrease the risk of COVID-19 exposure. METHODS: Criteria were developed to identify high-risk immunosuppressed patients who would be appropriate candidates for potential conversion to home based IVIG infusions. Data were collected via chart review, and cost analysis was performed using Medicare Part B reimbursement data. A patient outcome questionnaire was developed for administration through follow-up phone calls. RESULTS: From March to May 2020, 45 patients met criteria for home-based infusion, with 27 patients (60%) agreeing to home-based infusion. Posttransition patient outcomes assessment, conducted in 26 patients (96%), demonstrated good patient understanding of the home-based infusion process. No infusion-related complications were reported, and 24 patients (92%) had no concerns about receiving future IVIG and/or SCIG doses at home. No patient tested positive for COVID-19 during the study period. Clinic infusion visits decreased by 26.6 visits per month, resulting in a total of 106 hours of additional available infusion chair time per month and associated cost savings of $12,877. CONCLUSION: Transition of clinic based to home based IVIG/SCIG infusion can be successfully done to decrease potential exposure during a pandemic in a high-risk immunosuppressed population, with no impact on patient satisfaction, adherence, or efficacy. The home-based infusion initiative was associated with a reduction in costs to patients and an increase in available chair time in the infusion clinic.


Subject(s)
COVID-19/prevention & control , Home Care Services/organization & administration , Immunocompromised Host , Immunoglobulins, Intravenous/administration & dosage , Adult , Aged , Aged, 80 and over , Ambulatory Care Facilities/organization & administration , Female , Humans , Immunoglobulins, Intravenous/adverse effects , Immunoglobulins, Intravenous/economics , Male , Middle Aged , Patient Care Team , Patient Satisfaction , SARS-CoV-2 , United States
8.
J Med Virol ; 93(5): 2675-2682, 2021 05.
Article in English | MEDLINE | ID: covidwho-972847

ABSTRACT

Since December 31, 2019, unknown causes of pneumonia have been reported in Wuhan, China. This special pneumonia associated with a novel coronavirus was named 2019-nCoV by the World Health Organization (WHO) in January 2020. From the beginning of this infectious disease, clinicians and researchers have been endeavoring to discover an effective and suitable treatment for affected patients. To date, there is no definitive and specific treatments for coronavirus disease-19 (COVID-19) infection while drugs introduced are still in the clinical trial phase. Intravenous immune globulin (IVIG) is a biological product prepared from the serum and an optional treatment for patients with antibody deficiencies. In many countries, much attention has been paid to the use of IVIG in the treatment of patients with COVID-19. Due to the therapeutic importance of IVIG in virus infections, in the current study, we reviewed the possible effect of IVIG in viral infections and potential evidence of IVIG therapy in patients with COVID-19 virus.


Subject(s)
COVID-19/drug therapy , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/therapeutic use , Humans , Immunization, Passive , Immunoglobulins, Intravenous/adverse effects , SARS-CoV-2 , Virus Diseases/drug therapy
9.
Trials ; 21(1): 905, 2020 Nov 02.
Article in English | MEDLINE | ID: covidwho-901916

ABSTRACT

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).


Subject(s)
Coronavirus Infections/therapy , Immunization, Passive/methods , Immunoglobulins, Intravenous , Pneumonia, Viral/therapy , Adult , Betacoronavirus/isolation & purification , COVID-19 , Critical Illness/therapy , Female , Humans , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/adverse effects , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Male , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
10.
Dermatol Ther ; 33(6): e14265, 2020 11.
Article in English | MEDLINE | ID: covidwho-742079

ABSTRACT

COVID-19 is a serious multisystem disease caused by severe acute respiratory syndrome coronavirus 2. Due to the COVID-19 crisis, that still keeps its impacts worldwide, numerous scheduled medical activities have been postponed and this interruption has a potential to modify the management of many cutaneous conditions including pemphigus. This narrative review aims to discuss the management of pemphigus in the era of COVID-19, considering the necessity to balance suitable pemphigus treatment with minimal risk of COVID-19-related mortality and morbidity. The data on the effect of treatments used for pemphigus on COVID-19 are limited. However, the evidence to manage patients properly is evolving and our knowledge is updated. Current expert recommendations include that patients with pemphigus should be informed clearly to avoid mismanagement and they should be monitored regularly for symptoms of COVID-19. Patients with mild disease can be managed with topical or intralesional corticosteroids, dapsone, or doxycycline. Systemic corticosteroids should be tapered to the lowest effective dose during the pandemic. Prednis(ol)one ≤10 mg/d can be continued in patients with COVID-19 while prednis(ol)one >10 mg/d may be reduced considering the activity of the disease. Conventional immunosuppressive therapies should only be discontinued in confirmed cases of COVID-19. Postponing rituximab treatment should be considered on a case by case basis. Intravenous immunoglobulin is not likely to increase the risk of infection and may be considered a safe option in patients with COVID-19. Given the psychological burden brought by COVID 19, online or face-to-face psychological support programs should be considered.


Subject(s)
COVID-19 , Dermatologic Agents/administration & dosage , Pemphigus/drug therapy , Dapsone/administration & dosage , Dermatologic Agents/adverse effects , Doxycycline/administration & dosage , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/adverse effects , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects
11.
Clin Immunol ; 216: 108459, 2020 07.
Article in English | MEDLINE | ID: covidwho-642982

ABSTRACT

The COVID-19 pandemic is one of the greatest infectious challenges in recent history. Presently, few treatment options exist and the availability of effective vaccines is at least one year away. There is an urgent need to find currently available, effective therapies in the treatment of patients with COVID-19 infection. In this review, we compare and contrast the use of intravenous immunoglobulin and hyperimmune globulin in the treatment of COVID-19 infection.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/pathology , Immunoglobulins, Intravenous/administration & dosage , Immunologic Factors/administration & dosage , Pandemics , Pneumonia, Viral/drug therapy , Adaptive Immunity/drug effects , Angiotensin-Converting Enzyme 2 , Antibody-Dependent Enhancement/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Coronavirus Infections/virology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/prevention & control , Gene Expression , Humans , Immunity, Innate/drug effects , Immunization, Passive/adverse effects , Immunization, Passive/methods , Immunoglobulins, Intravenous/adverse effects , Immunologic Factors/adverse effects , Molecular Targeted Therapy , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/virology
SELECTION OF CITATIONS
SEARCH DETAIL