Convalescent plasma has been proposed as a treatment for COVID-19 but its effectiveness has not been subjected to a systematic review.
The use of plasma derived from patients who have recovered from infection with COVID-19, represents rich source of antibodies to the virus and is termed “convalescent plasma” (CP). In the absence of a vaccine, CP has been perceived as an effective form of therapy, particularly among those with a weakened immune system or for patients without a functioning immune system. In the US, the FDA approved the use of CP therapy as a treatment in August 2020; however, there have been few published trials reporting on the efficacy of this treatment modality. Furthermore, in January 2021, the UK RECOVERY trial, which is exploring a range of different COVID-19 treatments, halted recruitment to the CP arm of the trial. But what is the efficacy of CP therapy in the trials that have been published? This was the question addressed by a team from the Department of Clinical Research, University Hospital Basel, Switzerland. The team searched for published randomised, controlled trials that were specifically designed to examine the value of CP therapy in suspected or confirmed cases of COVID-19 and in which participants were allocated to either CP or placebo plus standard care. The researchers considered a number of potential outcomes including all-cause mortality at any time-point, length of hospital stay, the proportion of patients with a clinical improvement or deterioration and the number of individuals experiencing adverse effects.
A total of four, peer-reviewed published randomised controlled trials and six randomised trials, five pre-prints and one press release were located. The four published trials included 1060 patients (595 randomised to CP therapy) and there were 10,722 patients in the other six trials. In a primary analysis of the 4 published trials, the mortality rate was 11.6% (CP therapy) vs 12.7% (standard care). This gave a summary risk ratio, RR for all-cause mortality of 0.93 (95% CI 0.63–1.38, p = 0.60). Across the 10 trials, the summary RR was 1.02 (95% CI 0.92–1.12, p = 0.68) and there was no significant heterogeneity across the trials. Furthermore, across the four published trials, there was no significant effect of CP therapy on reductions in the length of hospital stay or for other outcomes assessed. Commenting on these findings the authors noted that while there was no apparent benefit from CP therapy, the certainty of the evidence on all-cause mortality was low when only including the published trials but moderate with inclusion of the pre-print data. Moreover, it was not possible to combine data on clinical outcomes other than mortality due to inconsistent definitions.
They concluded that the evidence of benefit for CP therapy was low-moderate for mortality but low for all other outcomes assessed.
Janiaud P et al. Association of Convalescent Plasma Treatment with Clinical Outcomes in Patients With COVID-19. A Systematic Review and Meta-analysis. JAMA 2021