Current best evidence for clinical care (more info)
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.).
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Well done study evaluating an intervention that has received lots of attention. 2 things limit the importance of the findings: 1) there was no benefit, and this is an intervention that is not currently standard of care, at least not in Canada - perhaps more relevant in US where it is used more widely; 2) there are larger RCTs coming in the near future.
The most rigorously designed studies to date do not support using convalescent plasma as a standard treatment in COVID-19 pneumonia. This randomized study uses a single infusion of convalescent plasma in a defined group of patients with severe COVID-19 pneumonia. The negative results are consistent with other studies using convalescent plasma and might decrease enthusiasm for future studies using this modality, especially in light of emerging vaccines for prevention/mitigation of COVID-19 infection.
Well done analysis of convalescent serum in a randomized study suggesting that this therapy did not have a significant impact in a diverse group of patients admitted to hospital with COVID pneumonia.
Questions that remain include: what is the optimal timing of infusion, and what is the optimal plasma titer?