Why does convalescent plasma therapy for severe COVID-19 show mixed success? Treatment modalities against the coronavirus disease 2019 (COVID-19) pandemic are limited in efficacy. This has led many centers to use convalescent plasma from recovered COVID-19 patients in the management of this condition. A surprising new preprint, released on the medRxiv* server, suggests that the beneficial effects of convalescent plasma (CP) in this disease stem not only from the presence of neutralizing antibodies, but also the immunomodulatory effects of this plasma that shapes the host immune response. Discrepancy in results from convalescent plasma trials Randomized controlled trials have failed to yield evidence of significant benefit from CP when administered late in the course of illness. However, within three days of symptom onset, CP with high titers of antibodies led to a 73% reduction in the risk of progressive COVID-19.