Management of COVID patients with convalescent plasma: Do we have the final word?

•Several randomized clinical trials (RCT) have been conducted on convalescent plasma (CP).•In patients with moderate to severe COVID-19 and the majority of these suggested that CP does not reduce the progression to severe respiratory failure or death within 30 days.•Factors that may have influenced the results of RCT are the titer of neutralizing antibodies in CP, the presence of anti-spike antibodies in the CP recipients, and the timing of CP infusion (early or late use from onset of symptoms).•A potential benefit of early (within the first 72 h from symptoms onset), high titer CP in patients with mild COVID-19 (pO2/FiO2 > 300) cannot be definitively excluded.•New therapies, such as monoclonal antibodies (mAbs) developed from CP, showed efficacy in reducing the risk of disease progression and death and were approved either in outpatients with early COVID-19 infection or in hospitalized patients with negative anti-spike antibodies.