8/11/2023 0 Comments Danielle ward patterson schwartzA randomized trial of convalescent plasma in Covid-19 severe pneumonia. Rapid establishment of a COVID-19 convalescent plasma program in a regional health care delivery network. How should we use convalescent plasma therapies for the management of COVID-19? Blood. Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis. Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. These combinations were therefore excluded from this figure. For the combination of anti-S IgG with ADCC or anti-S IgG with anti-RBD, the general additive logistic regression models led to a complex equation that was not statistically significant nor clinical interpretable. The contour lines with positive slope suggest combinations of high (or low) values for both markers yield similar effects of CCP the contour lines with negative slopes suggest high values of both markers yield strong CCP effects. Contours were obtained from fitting generalized additive logistic regression models for the primary outcome adjusting for blood supply center, treatment and the log transformed and standardized biomarkers - smoothing splines were used to relax linearity assumptions. Data points for individual patients are overlaid with colours denoting the blood supply centre. The contours convey pairwise combinations of antibody markers yielding similar odds ratios for the CCP effect with the black line corresponding to an odds ratio of 1 (that is no effect of CCP). Mfi, mean fluorescence intensity OD, optical density S, SARS-CoV-2 spike protein SOC, standard of care. Overlaid data points indicate the value of the two markers for each CCP transfusion. c, d, Contour plots of the OR for the primary outcome as a function of marker combinations. The histograms present the frequency distribution by marker. The P values (two-sided test for trend without adjustment for multiple comparisons) refer to the effect modification observed with each marker (Supplementary Table 10). The horizontal dotted line represents CCP with no effect (OR = 1). Marker values are expressed as standard deviations of log values centered around the mean (standardized log). The top row presents the trends in CCP effect compared to SOC as a function of the marker value, along with 95% CIs. b, Effect-modifying role of CCP content for the primary outcome for each marker. Center line: median box limits: 25th and 75th percentiles whiskers: 1.5× IQR points: outliers. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.Ī, Absolute antibody amounts transfused per patient ( n = 597) in the CCP arm for each marker, expressed as the product of volume and concentration. Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). The antibody content significantly modulated the therapeutic effect of convalescent plasma. Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4% RR = 1.27, 95% CI 1.02-1.57, P = 0.034). Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The composite primary outcome was intubation or death by 30 d. Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear.
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