Journal of Blood & Lymph

The COVID-19 pandemic so far caused millions of deaths, and the therapeutic options for high-risk patients are far from being satisfactory. Active immunization by vaccines against SARS-CoV-2 spike protein provides good protection from a severe course of COVID-19. It has been explored in numerous clinical trials, whether also passive immunization by transfusion of convalescent plasma could positively influence the course of COVID-19. Large randomized clinical trials failed to demonstrate a benefit for patients with advanced disease. However, the antibody dose and timing of transfusion might have contributed to this negative result. Randomized clinical trials are necessary to make evidence-based progress in the development of therapeutic options, and this holds true also for “natural” concepts. However, even highquality trials are just a tool to test predefined hypotheses. Arguments are presented that convalescent plasma should be further evaluated in clinical trials as proactive, quasi “prophylactic” treatment by giving a sufficient amount of CCP early enough (before massive virus replication). A solid scientific foundation for the principle of target specific and temporarily adapted passive immunization would be very important even beyond COVID-19 as fast and flexible instrument also in future outbreaks of novel pathogens.