Background With coronavirus disease 2019 (COVID‐19) convalescent plasma (CCP) offering an early treatment option for COVID‐19, blood collectors needed to quickly overcome obstacles to recruiting and qualifying eligible donors. We provide attributes of CCP donors and products and compare to standard donors and products. Study Design and Methods Information on CCP donors was gathered from the American Red Cross qualification website through product collection. Data from 2019 for standard plasma/platelet apheresis (SA) and whole blood (WB) donor demographics and SA donations including product disposition and reactions were used for comparison. Results Of almost 59 000 donors registering on the website, 75% reported an existing COVID‐19 diagnostic polymerase chain reaction or an antibody test. The majority (56.2%) of 10 231 CCP donors were first‐time donors in contrast to SA or WB donor populations, which were only 3.0% and 30.6%, respectively, first‐time donors. The number of female donors was 12% higher than SA donors. Older (≥ 65 years) and younger (16‐19 years) were comparatively underrepresented in CCP donors. Deferral (10.2%) and Quantity Not Sufficient rates (6.4%) for presenting CCP donations were higher than SA (8.2% and 1.1%, respectively). Human leukocyte antigen antibody reactivity was the highest cause of product loss for CCP donations vs SA donations (9.6% vs 1.3%). Acute adverse events also occurred at a higher rate among both first‐time and repeat CCP donations compared to SA. Conclusions CCP donors were more likely to be first‐time and female donors than WB or SA donors. CCP donations had a higher rate of donor adverse reactions, deferrals, and product loss than SA donations.

Background Efficacy of COVID‐19 convalescent plasma (CCP) is hypothesized to be associated with the concentration of neutralizing antibodies (nAb) to SARS‐CoV‐2. High capacity serologic assays detecting binding antibodies (bAb) have been developed; nAb assays are not adaptable to high‐throughput testing. We sought to determine the effectiveness of using surrogate bAb signal‐to‐cutoff ratios (S/Co) in predicting nAb titers using a pseudovirus reporter viral particle neutralization (RVPN) assay. Methods CCP donor serum collected by three US blood collectors was tested with a bAb assay (Ortho Clinical Diagnostics VITROS Anti‐SARS‐CoV‐2 Total, CoV2T) and a nAb RVPN assay. Prediction effectiveness of various CoV2T S/Co criteria was evaluated for RVPN nAb NT 50 titers using receiver operating characteristics. Results Seven hundred and fifty‐three CCPs were tested with median CoV2T S/Co and NT 50 of 71.2 of 527.5. Proportions of donors with NT 50 over target nAb titers were 86% ≥1:80, 76% ≥1:160, and 62% ≥1:320. Increasing CoV2T S/Co criterion reduced the sensitivity to predict NT 50 titers, while specificity to identify those below increased. As target NT50 titers increase, the CoV2T assay becomes less accurate as a predictor with a decline in positive predictive value and rise in negative predictive value. Conclusion Selection of a clinically effective nAb titer will impact availability of CCP. Product release with CoV2T assay S/Co criterion must balance the risk of releasing products below target nAb titers with the cost of false negatives. A two‐step testing scheme may be optimal, with nAb testing on CoV2T samples with S/Cos below criterion.

Background There are limited standards guiding the selection and processing of blood components specific for neonatal and pediatric transfusions. Therefore, blood banks (BBs) and transfusion services must create their own policies and procedures. Study Design and Methods The American Association of Blood Banks (AABB) Pediatric Transfusion Medicine Subsection Committee developed a 74‐question survey to capture neonatal and pediatric BB practices in the United States. Results Thirty‐five centers completed the survey: a response rate 15.8%. Responses indicated that most carry a mixed inventory of red blood cells (RBCs); 94.2% allow more than one type of RBC product for small‐volume (SV) and large‐volume (LV) transfusions to neonatal and pediatric patients. Many had storage age thresholds for RBCs transfused to neonates (SV = 60%, LV = 67.7%) but not older pediatric patients. The use of Group O for nonurgent RBC transfusion in neonates was common (74.2%). Responses related to special processing of RBCs and platelets indicated that 100% RBC and platelets are leukocyte‐reduced (LR) for neonates and 97% for non‐neonates. Irradiation of RBCs and platelets was commonly performed for neonatal transfusion (88.6%). Providing cytomegalovirus (CMV) seronegative products, volume reduction, and washing were variable. All centers transfused single‐donor apheresis platelets; 20% allowed pathogen reduction (PR). The majority of centers have strategies limiting the amount of incompatible plasma transfused; however, few titrate ABO isoagglutinins in plasma‐containing products (20% for platelets and 9.1% for plasma). Conclusions Variability exists in BB practice for neonatal and pediatric transfusion. Future studies are needed to understand and define best BB practices in these patient populations.

BACKGROUND: Efficacy of COVID-19 convalescent plasma (CCP) to treat COVID-19 is hypothesized to be associated with the concentration of neutralizing antibodies (nAb) to SARS-CoV-2. High capacity serologic assays detecting binding antibodies (bAb) have been developed, nAb assays are not adaptable to high-throughput testing. We sought to determine the effectiveness of using surrogate bAb signal-to-cutoff ratios (S/CO) in predicting nAb titers using a pseudovirus reporter viral particle neutralization (RVPN) assay. METHODS: CCP donor serum collected by 3 US blood collectors was tested with a bAb assay (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 Total, CoV2T) and a nAb RVPN assay. CoV2T prediction effectiveness at S/CO thresholds was evaluated for RVPN nAb NT50 titers using receiver operating characteristic analysis. RESULTS: 753 CCPs were tested with median CoV2T S/CO of 71.2 and median NT50 of 527.5. Proportions of CCP donors with NT50 over various target nAb titers were 86% ≥1:80, 76% ≥1:160, and 62%≥1:320. Increasing CoV2Ts reduced the sensitivity to predict NT50 titers, while specificity to identify those below thresholds increased. As the targeted NT50 increased, the positive predictive value fell with reciprocal increase in negative predictive value. S/CO thresholds were thus less able to predict target NT50 titers. CONCLUSION: Selection of a clinically effective nAb titer will impact availability of CCP. Product release with CoV2T assay S/CO thresholds must balance the risk of releasing products below target nAb titers with the cost of false negatives. A two-step testing scheme may be optimal, with nAb testing on CoV2T samples with S/COs below thresholds.

The novel coronavirus, SARS-CoV-2 that causes COVID-19 has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination, and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization with a theoretical risk of antibody-dependent enhancement (ADE) of viral infection. Though vaccines elicit a strong and protective immune response and transfusion of CCP with high titers of neutralization activity are correlated with better clinical outcomes, the question of whether antibodies in CCP can enhance infection of SARS-CoV-2 has not been directly addressed. In this study, we analyzed for and observed passive transfer of neutralization activity with CCP transfusion. Furthermore, to specifically understand if antibodies against the spike protein (S) enhance infection, we measured the anti-S IgG, IgA, and IgM responses and adapted retroviral-pseudotypes to measure virus neutralization with target cells expressing the ACE2 virus receptor and the Fc alpha receptor (FcαR) or Fc gamma receptor IIA (FcγRIIA). Whereas neutralizing activity of CCP correlated best with higher titers of anti-S IgG antibodies, the neutralizing titer was not affected when Fc receptors were present on target cells. These observations support the absence of antibody-dependent enhancement of infection (ADE) by IgG and IgA isotypes found in CCP. The results presented, therefore, not only supports the therapeutic use of currently available antibody-based treatment, including the continuation of CCP transfusion strategies, but also the use of various vaccine platforms in a prophylactic approach.

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BackgroundThe novel coronavirus, SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.31 million people within the last year and yet no cure exists. Whereas passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable option, selection of optimal units for therapy and lack of clear therapeutic benefit from transfusion remain as barriers to the use of CCP.Study design and methodsTo identify plasma that is expected to benefit recipients, we measured anti-SARS-CoV2 antibody levels using clinically available serological assays and correlated with the neutralizing activity of CCP from donors. Neutralizing titer of plasma samples was measured by assaying infectivity of SARS-CoV-2 spike protein pseudotyped retrovirus particles in the presence of dilutions of plasma samples. We also used this assay to identify evidence of passive transfusion of neutralizing activity in CCP recipients.ResultsViral neutralization and anti-spike protein antibodies in 109 samples from 87 plasma donors were highly varied but modestly correlated with each other. Recipients who died of COVID-19 were found to have been transfused with units with lower anti-spike antibody levels and neutralizing activity. Passive transfer of neutralization activity was documented in 62% of antibody naive plasma recipients.ConclusionsSince viral neutralization is the goal of CCP transfusion, our observations not only support the use of anti-spike SARS-CoV2 serology tests to identify beneficial CCP units, but also support the therapeutic value of convalescent plasma with high titers of anti-spike antibodies.

The novel coronavirus SARS-CoV2, which causes COVID-19, has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization, with the theoretical risk of antibody-dependent enhancement (ADE) of viral infection remaining undetermined. Though vaccines elicit a strong and protective immune response, and transfusion of CCP with high titers of neutralization activity are correlated with better clinical outcomes, the question of whether antibodies in CCP can enhance infection of SARS-CoV2 has not been directly addressed. In this study, we analyzed for and observed passive transfer of neutralization activity with CCP transfusion. Furthermore, to specifically understand if antibodies against the spike protein (S) enhance infection, we measured the anti-S IgG, IgA, and IgM responses and adapted retroviral-pseudotypes to measure virus neutralization with target cells expressing the ACE2 virus receptor and the Fc alpha receptor (FcaR) or Fc gamma receptor IIA (FcgRIIA). Whereas neutralizing activity of CCP correlated best with higher titers of anti-S IgG antibodies, the neutralizing titer was not affected when Fc receptors were present on target cells. These observations support the absence of antibody-dependent enhancement of infection (ADE) by IgG and IgA isotypes found in CCP. The results presented, therefore, support the clinical use of currently available antibody-based treatment including the continued study of CCP transfusion strategies.