A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia

Abstract

Background Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials. Methods We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient’s clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. Results A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200]. No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83 (95% confidence interval [CI], 0.52 to 1.35; P=0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of −0.46 percentage points (95% CI, −7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. Conclusions No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535 .)

A look-back at convalescent plasma to treat COVID-19

“…In aggregate, Joyner et al, having compiled (nearly) all submitted data—not necessarily peer-reviewed as many are loaded on the MedRXiv site—concluded in favor of a protective effect of convalescent plasma [ 30 ]. More recently, convalescent plasma was found to be not superior to placebo in a randomized trial involving hospitalized patients with COVID-19 pneumonia [ 29 ]. Apparent discrepancies in conclusions may well be the result of certain inconsistency in defining patient groups (severity, time-course of infection, and outcomes), as was observed in other main trials addressing controversies in blood transfusion; the same concerns were for e.g.…”

Epidemic trends of SARS-CoV-2 associated with immunity, race, and viral mutations

“…Heterologous serum from D614 infected hamster can neutralize G614 virus efficiently (6,7), but further analysis using monoclonal antibodies would be necessary. Furthermore, the definitive clinical effect of convalescent plasma has not been demonstrated (24) and it is desirable to investigate the effect of D614 antibodies in vivo in animals. It should be noted that dengue hemorrhagic fever, which reflects ADE, is not known to occur in non-human primates (25).…”

Epidemic trends of SARS-CoV-2 associated with immunity, race, and viral mutations

“…13,30 Heterologous serum from D614 infected hamster can neutralize G614 virus efficiently, 6,7 but further analysis using monoclonal antibodies would be necessary. Furthermore, the definitive clinical effect of convalescent plasma has not been demonstrated 31 and it is desirable to investigate the effect of D614 antibodies in vivo in animals. Even neutralizing antibodies may induce antibodydependent cellular phagocytosis (ADCP) 32 and release cytokines from cells with Fc receptors, leading to disease exacerbation.…”