A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia

Abstract

BackgroundAntibody-based strategies for COVID-19 have shown promise in prevention and treatment of early disease. COVID-19 convalescent plasma (CCP) has been widely used but results from randomized trials supporting its benefit in hospitalized patients with pneumonia are limited. Here, we assess the efficacy of CCP in severely ill, hospitalized adults with COVID-19 pneumonia.MethodsWe performed a randomized control trial (PennCCP2), with 80 adults hospitalized with COVID-19 pneumonia, comparing up to 2 units of locally sourced CCP plus standard care versus standard care alone. The primary efficacy endpoint was comparison of a clinical severity score. Key secondary outcomes include 14- and 28-day mortality, 14- and 28-day maximum 8-point WHO ordinal score (WHO8) score, duration of supplemental oxygenation or mechanical ventilation, respiratory SARS-CoV-2 RNA, and anti-SARS-CoV-2 antibodies.ResultsEighty hospitalized adults with confirmed COVID-19 pneumonia were enrolled at median day 6 of symptoms and day 1 of hospitalization; 60% were anti-SARS-CoV-2 antibody seronegative. Participants had a median of 3 comorbidities, including risk factors for severe COVID-19 and immunosuppression. CCP treatment was safe and conferred significant benefit by clinical severity score (median [MED] and interquartile range [IQR] 10 [5.5-30] vs. 7 [2.75-12.25], P = 0.037) and 28-day mortality (n = 10, 26% vs. n = 2, 5%; P = 0.013). All other prespecified outcome measures showed weak evidence toward benefit of CCP.ConclusionTwo units of locally sourced CCP administered early in hospitalization to majority seronegative participants conferred a significant benefit in clinical severity score and 28-day mortality. Results suggest CCP may benefit select populations, especially those with comorbidities who are treated early.Trial RegistrationClinicalTrials.gov NCT04397757.FundingUniversity of Pennsylvania.

Keywords: Adaptive immunity; COVID-19; Clinical Trials.

Conflict of interest statement

Conflict of interest: JLP reports consultancy fees from Pfizer; WRS reports consultancy fees from Viiv, Gilead, and Janssen; IF reports consultancy fees from Gilead and Merck; SEH reports consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck; PT reports consultancy fees from Merck, Gilead, Janssen, and Viiv.

Figures

Figure 1. Consort diagram.

Figure 2. Stacked cumulative incidence curves.

Incidence curves for the competing risks of remaining hospitalized, death, or discharge are shown over time, censored at 28 days for the control (A) and treatment arm (B) of the 79 participants of the ITT cohort. Deaths are shaded red and discharges blue. One participant who withdrew at day of discharge (day 9) is assumed to have survived 28 days.

Figure 3. Composite endpoint assessing respiratory sample viral load and clinical status, in which those who were discharged had the lowest score and those who died had the highest.

Control (red) and plasma (blue) arms are shown for baseline (prior to plasma administration) and study days 3 and 8. Imputed values are shown in filled symbols and measured virus levels are shown in open circles. Values were not significantly different at baseline and were significantly lower in treatment arm at day 3 (P = 0.0128 by Wilcoxon rank sum test).