Systematic review and meta-analysis of randomised controlled trials testing the safety and efficacy of convalescent plasma in the treatment of coronavirus disease 2019 (COVID-19): Evidence-base for practise and implications for research

Background Despite scientific advances, there is no effective medical therapy for coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis aimed to evaluate the safety and efficacy of convalescent plasma therapy in COVID-19. Methods This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Only prospective clinical trials randomly assigning COVID-19 patients to convalescent plasma plus standard of care therapy (test arm) versus placebo/standard of care (control arm) were included. Two reviewers independently read each preprint/publication and extracted relevant data from individual studies. Data were pooled using the random-effects model and expressed as risk ratio (RR) with 95% confidence interval (CI). Results A total of 13 206 patients from 12 randomised controlled trials were included. There was no significant difference in clinical improvement rate (RR = 1.00, 95% CI: 0.98-1.02, p = 0.96) or time to clinical improvement (median difference of 1.08 days with 95% CI ranging from -0.15 to +2.30 days) between convalescent plasma versus placebo/standard of care therapy. The use of convalescent plasma was not associated with significantly reduced risk of death (RR = 0.81, 95% CI: 0.65-1.02, p = 0.08). Reassuringly, overall incidence of infusion-related serious adverse events was low (3.25%) and not significantly different (RR = 1.14, 95% CI: 0.93-1.40, p = 0.22) for convalescent plasma transfusion compared to placebo/standard of care therapy. Conclusions There is low to moderate certainty evidence that the addition of convalescent plasma to current standard of care therapy is generally safe but, does not result in any significant clinical benefit or reduction of mortality in COVID-19.