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Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trial
Alemany A, Millat-Martinez P, Corbacho-Monné M, Suñer C, Galvan-Casas C, Carrera C, Ouchi D, Prat N, Ara J, Nadal N, et al
EClinicalMedicine. 2023;57:101898
Abstract
BACKGROUND Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. METHODS We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. FINDINGS 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. INTERPRETATION Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. FUNDING Grifols.
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Characteristics, treatment, and outcomes of Myasthenia Gravis in COVID-19 patients: A systematic review
Abbas AS, Hardy N, Ghozy S, Dibas M, Paranjape G, Evanson KW, Reierson NL, Cowie K, Kamrowski S, Schmidt S, et al
Clinical Neurology and Neurosurgery. 2022;213:107140
Abstract
OBJECTIVE Recent studies suggest that the clinical course and outcomes of patients with coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG) are highly variable. We performed a systematic review of the relevant literature with a key aim to assess the outcomes of invasive ventilation, mortality, and hospital length of stay (HLoS) for patients presenting with MG and COVID-19. METHODS We searched the PubMed, Scopus, Web of Science, and MedRxiv databases for original articles that reported patients with MG and COVID-19. We included all clinical studies that reported MG in patients with confirmed COVID-19 cases via RT-PCR tests. We collected data on patient background characteristics, symptoms, time between MG and COVID-19 diagnosis, MG and COVID-19 treatments, HLoS, and mortality at last available follow-up. We reported summary statistics as counts and percentages or mean±SD. When necessary, inverse variance weighting was used to aggregate patient-level data and summary statistics. RESULTS Nineteen studies with 152 patients (mean age 54.4 ± 12.7 years; 79/152 [52.0%] female) were included. Hypertension (62/141, 44.0%) and diabetes (30/141, 21.3%) were the most common comorbidities. The mean time between the diagnosis of MG and COVID-19 was7.0 ± 6.3 years. Diagnosis of COVID-19 was confirmed in all patients via RT-PCR tests. Fever (40/59, 67.8%) and ptosis (9/55, 16.4%) were the most frequent COVID-19 and MG symptoms, respectively. Azithromycin and ceftriaxone were the most common COVID-19 treatments, while prednisone and intravenous immunoglobulin were the most common MG treatments. Invasive ventilation treatment was required for 25/59 (42.4%) of patients. The mean HLoS was 18.2 ± 9.9 days. The mortality rate was 18/152 (11.8%). CONCLUSION This report provides an overview of the characteristics, treatment, and outcomes of MG in COVID-19 patients. Although COVID-19 may exaggerate the neurological symptoms and worsens the outcome in MG patients, we did not find enough evidence to support this notion. Further studies with larger numbers of patients with MG and COVID-19 are needed to better assess the clinical outcomes in these patients.
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Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review
Wang Z, Zhao S, Tang Y, Wang Z, Shi Q, Dang X, Gan L, Peng S, Li W, Zhou Q, et al
European journal of pediatrics. 2022;:1-12
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.
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Efficacy and safety of prothrombin complex concentrate for vitamin K antagonist-associated intracranial hemorrhage: a systematic review and meta-analysis
Pan R, Cheng J, Lai K, Huang Q, Wu H, Tang Y
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2019
Abstract
BACKGROUND Prothrombin complex concentrate (PCC) is the treatment of choice in vitamin K antagonist-associated intracranial hemorrhage (VKA-ICH). However, the efficiency and safety associated with their use remain unclear. AIMS This study aimed to assess the current evidence of the clinical outcomes in patients with VKA-ICH treated with or without PCC. A meta-analysis was conducted. Two randomized controlled trials and 19 observational studies were included. PCC use demonstrated a significant increased likelihood of international normalized ratio (INR) normalization (OR = 3.76; 95% CI 1.74-8.12), shortened time to INR correction (MD = - 1.30; 95% CI - 2.08 to - 0.53) and reduction of hematoma expansion (HE) rate (OR = 0.37; 95% CI 0.23-0.60). Although PCC use revealed a statistical reduction at 30-day mortality (OR = 0.62; 95% CI 0.50-0.78), the result was inconsistent with mortality at discharge (OR = 1.03; 95% CI 0.68-1.57) and 90-day follow-up (OR = 0.50; 95% CI 0.24-1.07), both of which yielded no significant difference. When subgroup analyses were performed focus on PCC only treatment with FFP, no statistically significant difference was observed in 30-day mortality (OR = 0.43; 95% CI 0.11-1.71) as well. Besides, significant difference was not found in neurologic improvement at discharge (OR = 1.85; 95% CI 0.32-10.75), 30-day follow-up (OR = 3.00; 95% CI 0.93-9.70), or 90-day follow-up (OR = 1.55; 95% CI 0.84-2.86). No statistically significant difference was noted in the risk of thromboembolism following PCC administration (OR = 0.61; 95% CI 0.23-1.63). CONCLUSIONS PCC use for VKA-ICH reversal was associated with a significant reduction in INR and HE rate, without an increased risk of thromboembolic events. However, this reduction was not associated with improvement in neurologic deficits or overall survival. Well-designed randomized trials with special considerations to the aspect are necessary.
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Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases
Li X, Chen Y, Tang Y, Ding Y, Xu Q, Sun L, Qian W, Qian G, Qin L, Lv H
European Journal of Pediatrics. 2018;177((8):):1279-1292
Abstract
The purpose of this study was to identify the clinical features and laboratory factors that are predictive of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease. Multiple databases were searched for relevant studies on IVIG-resistant Kawasaki disease published from January 2002 to April 2017. Eligible studies were retrieved by manual review of the references. Stata 12 was used for the meta-analysis. Weighted mean differences and odds ratios with 95% confidence intervals were calculated for several indices. Twenty-eight studies involving 26,260 patients comprising 4442 IVIG-resistant Kawasaki disease patients and 21,818 IVIG-sensitive Kawasaki disease patients were included. The meta-analysis showed that the erythrocyte sedimentation rate (ESR) in the IVIG-resistant group was significantly higher than that in the IVIG-sensitive group, and that platelet count and hemoglobin levels were significantly lower in the IVIG-resistant group. The patients with oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, polymorphous rash, and initial administration of IVIG ≤ 4.0 days after the onset of symptoms were more likely to be IVIG resistant. CONCLUSION The initial administration of IVIG ≤ 4.0 days after the onset of symptoms increased ESR and decreased hemoglobin and platelet counts, oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, and polymorphous rash and are the risk factors for IVIG-resistant Kawasaki disease. What is Known: * Recent reports on this topic are about aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl transferase, total bilirubin, white blood cells, platelets, erythrocyte sedimentation rate (ESR), polymorphonuclear leukocytes (PMN), C-reactive protein (CRP), pro-brain natriuretic peptide (BNP), albumin, and sodium as the risk factors in the IVIG-resistant Kawasaki disease; however, no studies have been published on clinical features as predictors of IVIG resistance. What is New: * This meta-analysis identified the clinical features, the initial administration of IVIG ≤ 4.0 days after the onset of symptoms, and much more comprehensive laboratory indicators, such as hemoglobin, as predictors of IVIG-resistant Kawasaki disease.