Dataset Information

Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

ABSTRACT:

Background

Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy.

Research question

Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19?

Study design and methods

This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for < 14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n = 487) or placebo (n = 473). The primary outcome was clinical status (disease severity) 14 days following study infusion measured with a seven-category ordinal scale ranging from discharged from the hospital with resumption of normal activities (lowest score) to death (highest score). The primary outcome was analyzed with a multivariable ordinal regression model, with an adjusted odds ratio (aOR) < 1.0 indicating more favorable outcomes with convalescent plasma than with placebo. In secondary analyses, trial participants were stratified according to the presence of endogenous anti-SARS-CoV-2 antibodies ("serostatus") at randomization. The trial included 13 secondary efficacy outcomes, including 28-day mortality.

Results

Among 974 randomized patients, 960 were included in the primary analysis. Clinical status on the ordinal outcome scale at 14 days did not differ between the convalescent plasma and placebo groups in the overall population (aOR, 1.04; one-seventh support interval [1/7 SI], 0.82-1.33), in patients without endogenous antibodies (aOR, 1.15; 1/7 SI, 0.74-1.80), or in patients with endogenous antibodies (aOR, 0.96; 1/7 SI, 0.72-1.30). None of the 13 secondary efficacy outcomes were different between groups. At 28 days, 89 of 482 (18.5%) patients in the convalescent plasma group and 80 of 465 (17.2%) patients in the placebo group had died (aOR, 1.04; 1/7 SI, 0.69-1.58).

Interpretation

Among adults hospitalized with COVID-19, including those seronegative for anti-SARS-CoV-2 antibodies, treatment with convalescent plasma did not improve clinical outcomes.

Clinical trial registration

ClinicalTrials.gov; No.: NCT04362176; URL: www.

Clinicaltrials

gov.

SUBMITTER: Self WH

PROVIDER: S-EPMC9247217 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

Self Wesley H WH Wheeler Allison P AP Stewart Thomas G TG Schrager Harry H Mallada Jason J Thomas Christopher B CB Cataldo Vince D VD O'Neal Hollis R HR Shapiro Nathan I NI Higgins Conor C Ginde Adit A AA Chauhan Lakshmi L Johnson Nicholas J NJ Henning Daniel J DJ Jaiswal Stuti J SJ Mammen Manoj J MJ Harris Estelle S ES Pannu Sonal R SR Laguio-Vila Maryrose M El Atrouni Wissam W de Wit Marjolein M Hoda Daanish D Cohn Claudia S CS McWilliams Carla C Shanholtz Carl C Jones Alan E AE Raval Jay S JS Mucha Simon S Ipe Tina S TS Qiao Xian X Schrantz Stephen J SJ Shenoy Aarthi A Fremont Richard D RD Brady Eric J EJ Carnahan Robert H RH Chappell James D JD Crowe James E JE Denison Mark R MR Gilchuk Pavlo P Stevens Laura J LJ Sutton Rachel E RE Thomsen Isaac I Yoder Sandra M SM Bistran-Hall Amanda J AJ Casey Jonathan D JD Lindsell Christopher J CJ Wang Li L Pulley Jill M JM Rhoads Jillian P JP Bernard Gordon R GR Rice Todd W TW

Chest 20220701 5

<h4>Background</h4>Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy.<h4>Research question</h4>Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19?<h4>Study design and methods</h4>This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-Co ...[more]

PMID: 35780813

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Project description:The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. 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 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. 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). 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). The antibody content significantly modulated the therapeutic effect of convalescent plasma. 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). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

Project description:BackgroundConvalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease.MethodsA randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients.ResultsAn early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results.ConclusionCP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

Dataset Information

Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

Background

Research question

Study design and methods

Results

Interpretation

Clinical trial registration

Clinicaltrials

Publications

Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

Similar Datasets

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