Towards characterized convalescent plasma for COVID-19: The dose matters

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, remains a global health crisis with limited treatment options. While randomized controlled trials have demonstrated some efficacy of the antiviral agent remdesivir and the corticosteroid dexamethasone in COVID-19 treatment, any beneficial role of convalescent plasma (CP) has been less clear [1,2]. Since the early 20th century convalescent blood products and their antibody derivatives have been used for the treatment and prevention of infectious diseases. The discovery of potent antibiotics has largely supplanted any role for CP in treating bacterial infections, yet CP remains an important tool in the early stages of outbreaks of emerging or reemerging viral pathogens for which therapeutic options are limited. A historical meta-analysis by Luke et al. [3] on the 1918 H5N1 influenza pandemic found a significant reduction in mortality associated with CP use. This finding is consistent with reductions in both viral load and mortality with CP use among severely ill patients in the more recent 2009 H1N1 swine flu pandemic [4]. Evidence from other coronavirus outbreaks, including MERS and SARS-CoV-1, as well as the 2014 Ebola virus outbreak, is less conclusive [5 7], relying on limited patient cohorts and case series. These conflicting results are to be expected given the heterogeneous nature of CP, the common practice of transfusing CP prior to its characterization, and the clinical severity and diversity of recipients qualifying for its empirical use. The total antibody amount, class, subclass, specificity, neutralizing activity, and potential to induce antibody-dependent cell-mediated cytotoxicity are just some of the complex factors that may influence CP-associated outcomes. A broad consensus among physicians and scientists has emerged in the current pandemic that characterization of the antibodies within CP units is essential for determining correlates of efficacy. In recent weeks, a multi-center study including 35,322 patients from