Transfusion | 2021
COVID‐19 convalescent plasma; time for “goal directed therapy”?
Abstract
In the field of transfusion medicine, laboratory results are commonly used to identify patients most likely to benefit from transfusion. While the primary purpose of transfusions is to reduce mortality/morbidity, laboratory values are commonly used as surrogates to help guide transfusion therapy. Common examples include measuring hemoglobin or hematocrit to determine who will benefit from red blood cells and platelet count to determine who will benefit from platelet transfusion. Similarly, fibrinogen level or INR are commonly used to determine whether a patient might benefit from cryoprecipitate or plasma. The short-term “goal” of these transfusions is to correct or partially correct the abnormal laboratory values that had been identified prior to transfusion. Providers commonly use this paradigm when ordering many if not most transfusions. Since March of 2020, the US and many other countries sought to establish procedures for the collection and transfusion of COVID-19 Convalescent plasma (CCP) to treat patients with COVID-19. The efficacy of CCP remains to be clearly proven with several studies and even meta-analysis suggesting this may be a promising therapy.1–3 Other trials have failed to show benefit of CCP in hospitalized patients including the REMAP-CAP trial (NCT02735707) and the RECOVERY trial (NCT04381936) which were halted due to futility. Recently, a randomized control trial of CCP given early (within 72 h of symptom onset) reduced the progression to severe disease by nearly half. Despite these mixed results, CCP continues to be widely used in the US and other countries. As with all transfusions, the objective of this therapy is to reduce morbidity and mortality in these patients. Since CCP was first utilized, a great deal of effort has been put into identifying donors/units that are believed to provide the maximum benefit to patients.5–7 While there are many potential mechanisms by which CCP may benefit patients, neutralizing antibodies found in CCP are likely important mediators of protection. Recent studies have demonstrated that CCP with high levels of antibody may be more effective than CCP with low level of antibody. Therefore, many efforts are made to identify donors with high levels of antibodies able to inhibit or neutralize viral growth. Neutralization assays are not readily amenable to routine laboratory use so antibody binding assays (ELISAs) are commonly used as a surrogate test for neutralizing antibodies and have been shown to correlate to some degree with Neutralizing antibodies.10–12 In the US, current FDA recommendations involve testing donors using a variety of binding assays to qualify products as CCP and to label them as either highor low-titer CCP. In contrast to efforts to improve the quality of CCP, little has been done to identify recipients most likely to benefit from CCP. In the US, many patients were initially enrolled as part of a nationwide expanded access program (EAP) (NCT04338360) and are currently being treated under the emergency use authorization (EUA) that the FDA granted for CCP on August 23, 2020. The EUA is very broad regarding patient eligibility for CCP and simply requires patients have confirmed COVID-19 and be hospitalized. Some have suggested patients be treated early within 10 days of symptom onset or be treated within 3 days of hospitalization. One recent study found that CCP treatment within 72 h of symptom onset significantly reduced the onset of severe respiratory disease. Both studies seem to support the concept that CCP likely works best in seronegative donors by increasing SARS-COV2 antibody levels and patients later in disease are more likely to be antibody positive and thus less likely to benefit from CCP. Multiple studies demonstrate that CCP is being used in antibody-positive patients. A randomized controlled study in the Netherlands was halted due to antibody positivity rates near 80% in subjects in this Received: 10 December 2020 Revised: 1 February 2021 Accepted: 6 February 2021