Convalescent plasma in COVID-19: renewed focus on the timing and effectiveness of an old therapy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has strained health care systems worldwide and resulted in high mortality. The current COVID-19 treatment is based on supportive and symptomatic care. Therefore, convalescent plasma (CP), which provides passive immunization against many infectious diseases, has been studied for COVID-19 management. To date, a large number of randomized and non-randomized clinical trials as well as many systematic reviews have revealed conflicting results. This article summarizes the basic principles of passive immunization, particularly addressing CP in COVID-19. It also evaluates the effectiveness of CP as a therapy in patients with COVID-19, clinical trial reports and systematic reviews, regulatory considerations and different protocols that are authorized in different countries to use it safely and effectively. An advanced search was carried out in major databases (PubMed, Cochrane Library, and MEDLINE) and Google Scholar using the following key words: SARS-CoV-2, COVID-19, convalescent plasma, and the applied query was "convalescent plasma" AND "COVID-19 OR SARS-CoV-2". The results were filtered and duplicate data were removed. Collective evidence indicates that two cardinal players determine the effectiveness of CP use, time of infusion, and quality of CP. Early administration of CP with high neutralizing anti-spike IgG titer is hypothesized to be effective in improving clinical outcome, prevent progression, decrease the length of hospital stay, and reduce mortality. However, more reliable, high quality, well-controlled, double-blinded, randomized, international and multicenter collaborative trials are still needed.