Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

On the Semantics of Revision and Model-Fitting in Weighted Case

Revision and update operators add new information to same old information represented by a logical theory. Katzuno and Mendelzon show that both revision and update operators can be characterized as accomplishing a minimal change in the old information to accommodate the new one. In this paper we generalize the result of the revision by considering weighted knowledgebases, where weights indicate the relative importance of the information. Furthermore we give a modified version of weighted model-fitting based on the model-fitting introduced by Revesz. Categories and subject descriptors: F. 4.1 [Mathematical Logic]: Model Theor

CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease

Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. Multicenter prospective cohort study. Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years’ initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0mL/min/1.73m2 in estimated glomerular filtration rate per year. Current follow-up can only detect large differences in ESKD and death outcomes. Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes

Association of COVID-19 Versus COVID-19 Vaccination With Kidney Function and Disease Activity in Primary Glomerular Disease: A Report of the Cure Glomerulonephropathy Study

Patients with glomerular disease (GN) may be at increased risk of severe COVID-19, yet concerns over vaccines causing disease relapse may lead to vaccine hesitancy. We examined the associations of COVID-19 with longitudinal kidney function and proteinuria and compared these to similar associations with COVID-19 vaccination. Observational cohort study from July 1, 2021 to Jan. 1, 2023. & Participants: A prospective observational study network of 71 centers from North America and Europe (CureGN) with children and adults with primary minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy. COVID-19 and COVID-19 vaccination. Repeated measure of estimated glomerular filtration rate (eGFR); recurrent time-to-event outcome of GN disease worsening as defined by doubling of UPCR to at least 1.5g/g or increase in dipstick urine protein by two ordinal levels to 3+ (300mg/dL) or above. Interrupted time series analysis for eGFR. Prognostic matched sequential stratification recurrent event analysis for GN disease worsening. Among 2,055 participants, 722 (35%) reported COVID-19; of these, 92 (13%) were hospitalized and 3 died (<1%). eGFR slope pre-COVID-19 was -1.40ml/min/1.73m2 (SD 0.29), and -4.26ml/min/1.73m2 (SD 3.02) within 6 months post-COVID-19, which were not significantly different (p=0.34). COVID-19 was associated with increased risk of worsening GN disease activity (HR 1.35, 95% CI 1.01-1.80). Vaccination was not associated with change in eGFR (-1.34ml/min/1.73m2, SD 0.15 vs -2.16ml/min/1.73m2, SD 1.74; p=0.6) or subsequent GN disease worsening (HR 1.02, 95% CI 0.79–1.33) in this cohort. Infrequent or short follow-up. Among patients with primary GN, COVID-19 was severe for 1 in 8 cases and was associated with subsequent worsening of GN disease activity, as defined by proteinuria. In contrast, vaccination against COVID-19 was not associated with change in disease activity or kidney function decline. These results support COVID-19 vaccination for patients with GN. In this cohort study of 2,055 patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy, COVID-19 resulted in hospitalization or death for 1 in 8 cases and was associated with a 35% increase in risk for worsening proteinuria. In contrast, vaccination did not appear to adversely affect kidney function or proteinuria. Our data support vaccination for COVID-19 in patients with glomerular disease

Additional file 2 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Additional file 2. Email invitation

Additional file 7 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Additional file 7. Sensitivity analyses: various meta-analytic approaches