Too Early to Abandon Convalescent Plasma for Supportive Treatment of COVID-19

The authors of a systematic review and meta-analysis conclude that the benefit of convalescent plasma (CP) in the treatment of COVID-19 is limited. Among other systematic reviews, only one found an indication of benefit of CP. However, a meta-analysis needs a focused and meaningful clinical question and should include studies which are designed to test a reasonable hypothesis. Clinical trials to support the licensing of medicines should aim to define as exactly as possible the investigational drug and target disease. In the case of COVID-19, trial details (e.g., duration, stage and severity of disease, and antibody content and dose of CP) are quite heterogeneous. The so far available evidence suggests that the hypothesis should be sharpened as to treat COVID -19 patients at risk for developing severe disease as early enough with a sufficiently high dose of specific antibodies. It has been demonstrated that such an approach is feasible, and the lack of an independent reproduction by further trials with a really comparable design can probably not be compensated by compiling all available, heterogenous trials, even with the best methodology of a systematic review and meta-analysis. Though the COVID-19 pandemic appears to be fading, we should not neglect the search for effective prevention and treatments, given the still high death toll of COVID-19. Monoclonal antibodies were found effective in the early phase of the pandemic; however, due to new variants of SARS-COV2 undermining their efficacy they are no longer recommended by the current NIH guidelines. CP can provide a spectrum of polyclonal antibodies in close timely and regional connection to the particular prevalent virus variant. It would be extremely valuable to obtain a solid scientific foundation for the principle of target specific and temporarily adapted passive immunization, which could be a fast and flexible instrument also in future outbreaks of novel pathogens.