Cold platelet transfusion: The effects of a fluid warmer on platelet function.

BACKGROUND: Recently the US Food and Drug Administration has granted variances to select blood centers to supply cold-stored platelet components (CSP). In hemorrhage resuscitation warming of blood components with approved fluid warming devices is common. STUDY DESIGN AND METHODS: Pathogen-reduced apheresis platelet units were collected and stored in one of two ways: (1) CSP-I, (2) CSP-D. CSP-I were collected and immediately stored at 1-6°C until used. CSP-D were collected and stored at 20-24°C for 5 days and transferred to storage at 1-6°C until use. Aggregometry using arachidonic acid (AA), adenosine diphosphate (ADP) and collagen as agonists was performed on the unit samples before and after the units were infused through a Ranger blood-warming device. RESULTS: CSP-I, 23 units, had very high aggregation responses to all agonists (all ≥47.6 ± 20.7). There was a statistically significant reduction in ADP-induced aggregometry results from 55.1 ± 23.2 before compared to 33.5 ± 14.6 following infusion of the PLT through the blood warmer (p < .001). There were no differences in AA and collagen aggregometry results before and after the infusion of the platelets through the blood warmer. CSP-D had 5 of the 15 units with visible clotting in the bag. The 10 CSP-Ds studied had lower aggregation than all agonists before and after infusion through the blood-warming device (all ≤49.9 ± 35.9). CONCLUSION: We detected a statistically significant reduction in ADP-induced aggregometry in CSP-I run through a Ranger blood-warming device with no change with AA or collagen agonist aggregometry.

Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis.

Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.

Demographics of first-time donors returning for donation during the pandemic: COVID-19 convalescent plasma versus standard blood product donors.

BACKGROUND: Previous studies have demonstrated low first-time donor return rates (DRR) following catastrophic events. Little is known, however, about the influence of demographic factors on the DRR of first-time donors during the COVID-19 pandemic, including the unique motivation of COVID-19 convalescent plasma (CCP) donors as compared to non-CCP donors. STUDY DESIGN AND METHODS: Thirteen blood collection organizations submitted deidentified data from first-time CCP and non-CCP donors returning for regular (non-CCP) donations during the pandemic. DRR was calculated as frequencies. Demographic factors associated with returning donors: race/ethnicity, gender, and generation (Gen Z: 19-24, Millennial: 25-40, Gen X: 41-56, and Boomer: ≥57 years old), within the CCP and non-CCP first-time cohorts were compared using chi-square test at p < .05 statistical significance. RESULTS: From March 2020 through December 2021, there were a total of 44,274 first-time CCP and 980,201 first-time non-CCP donors. DRR were 14.6% (range 11.9%-43.3%) and 46.6% (range 10.0%-76.9%) for CCP and non-CCP cohorts, respectively. Age over 40 years (Gen X and Boomers), female gender, and White race were each associated with higher return in both donor cohorts (p < .001). For the non-CCP return donor cohort, the Millennial and Boomers were comparable. CONCLUSION: The findings demonstrate differences in returning donor trends between the two donor cohorts. The motivation of a first-time CCP donor may be different than that of a non-CCP donor. Further study to improve first-time donor engagement would be worthwhile to expand the donor base with a focus on blood donor diversity emphasizing engagement of underrepresented minorities and younger donors.

Expanding the platelet inventory to mitigate the impact of severe shortages.

The platelet collection and distribution system, based on volunteer nonremunerated donors, apheresis platelet collections, and primarily 1-directional distribution of platelets for up to 5-day room temperature storage at hospitals, typically performs well and provides therapeutic support for hundreds of thousands of patients annually. However, direct and indirect effects of the coronavirus disease 2019 pandemic, particularly during the Omicron wave, produced dramatic systemic failures and severe shortages. We propose 4 initiatives to reinforce the existing platelet pipeline and buffer the platelet supply against future unexpected disruptions.

Detection of neutralizing antibodies against multiple SARS-CoV-2 strains in dried blood spots using cell-free PCR.

An easily implementable serological assay to accurately detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies is urgently needed to better track herd immunity, vaccine efficacy and vaccination rates. Herein, we report the Split-Oligonucleotide Neighboring Inhibition Assay (SONIA) which uses real-time qPCR to measure the ability of neutralizing antibodies to block binding between DNA-barcoded viral spike protein subunit 1 and the human angiotensin-converting enzyme 2 receptor protein. The SONIA neutralizing antibody assay using finger-prick dried blood spots displays 91-97% sensitivity and 100% specificity in comparison to the live-virus neutralization assays using matched serum specimens for multiple SARS-CoV-2 variants-of-concern. The multiplex version of this neutralizing antibody assay, using easily collectable finger-prick dried blood spots, can be a valuable tool to help reveal the impact of age, pre-existing health conditions, waning immunity, different vaccination schemes and the emergence of new variants-of-concern.

U.S. cities will not meet blood product resuscitation standards during major mass casualty incidents: Results of a THOR-AABB working party prospective analysis.

BACKGROUND: Mass casualty incidents (MCIs) create an immediate surge in blood product demand. We hypothesize local inventories in major U.S. cities would not meet this demand. STUDY DESIGN AND METHODS: A simulated blast in a large crowd estimated casualty numbers. Ideal resuscitation was defined as equal amounts of red blood cells (RBCs), plasma, platelets, and cryoprecipitate. Inventory was prospectively collected from six major U.S. cities at six time points between January and July 2019. City-wide blood inventories were classified as READY (>1 U/injured survivor), DEFICIENT (<10 U/severely injured survivor), or RISK (between READY and DEFICIENT), before and after resupply from local distribution centers (DC), and features of DEFICIENT cities were identified. RESULTS: The simulated blast resulted in 2218 injured survivors including 95 with severe injuries. Balanced resuscitation would require between 950 and 2218 units each RBC, plasma, platelets and cryoprecipitate. Inventories in 88 hospitals/health systems and 10 DCs were assessed. Of 36 city-wide surveys, RISK inventories included RBCs (n = 16; 44%), plasma (n = 24; 67%), platelets (n = 6; 17%), and cryoprecipitate (n = 22; 61%) while DEFICIENT inventories included platelets (n = 30; 83%) and cryoprecipitate (n = 12; 33%). Resupply shifted most RBC and plasma inventories to READY, but some platelet and cryoprecipitate inventories remained at RISK (n = 24; 67% and n = 12; 33%, respectively) or even DEFICIENT (n = 11; 31% and n = 6; 17%, respectively). Cities with DEFICIENT inventories were smaller (p <.001) with fewer blood products per trauma bed (p <.001). DISCUSSION: In this simulated blast event, blood product demand exceeded local supply in some major U.S. cities. Options for closing this gap should be explored to optimize resuscitation during MCIs.

The publication impact of the first 100 THOR Network publications by bibliometric and social network analyses.

BACKGROUND: A specialized international multidisciplinary group of investigators wanted to determine the performance and impact of publications presented at an annual conference over a 6 year period. Specifically, the group wanted to know if the influence of the conference publications extended beyond conference publication authors and attendees. Bibliometric methods and network analyses were used to evaluate the performance and impact of 100 peer-reviewed publications presented at the Trauma Hemostasis and Oxygenation Research (THOR) Network Remote Damage Control Resuscitation (RCDR) Symposia from 2012 to 2017 (published 2013-2018). Further analysis was performed on the affiliations of conference attendees who attended from the years of 2012 to 2017. STUDY DESIGN AND METHODS: This project used normative and relative bibliometric measures and social network analysis to evaluate the performance and impact of 100 peer-reviewed publications presented at the Trauma Hemostasis and Oxygenation Research (THOR) Network RDCR Symposia from 2012 to 2017. Publication and citation data were from Elsevier Scopus, a bibliographic citation database. Metrics from Elsevier SciVal were selected for the project to normalize for group size, year of publication, and document type. A six-year period of publications presented at the Symposia, published from 2013 to 2018, was selected for analysis. The publication and citation data were further analyzed using Elsevier SciVal and the iCite database from the National Institutes of Health Office of Portfolio Analysis. Sci2, VOSviewer, and Gephi were used for social network analyses and visualization. RESULTS: The 100 publications presented at the Trauma Hemostasis and Oxygenation Research (THOR) Network Remote Damage Control Resuscitation (RCDR) Symposia from 2012 to 2017 demonstrate reach and influence beyond the authors of the THOR publications or the THOR attendees. Citations to the THOR publications were published in 10 languages and 313 unique journals, with author affiliations from 62 countries. Citation metrics for the THOR publications exceed global averages with 65% of the THOR publications being in the 25% citation percentiles. When benchmarking the THOR publications using six homogenous comparator groups, the THOR publications demonstrate higher citation metrics than any of the comparator groups with more citations per publication, a higher average of cited publications, higher FWCI and outputs in the top citation percentiles among the six groups. The Office of Portfolio Analysis (OPA) iCite database was used to calculate potential to translate for the THOR publications with 57 of the THOR publications cited by clinical articles with an average approximate potential to translate score of 65.3%. CONCLUSIONS: The value of international groups with sharing of research and knowledge are instrumental in enhancing the uptake for best practices for in medicine and treatment of hemorrhagic shock resuscitation. The use of bibliometric methods and network analyses, along with benchmarking, demonstrated reach and impact beyond the THOR Network. Limitations include use of a single source for analysis of publication and citation; and that publication data alone does not provide a full overview of research performance. Despite these limitations, bibliometric methods, social network analyses, and benchmarking can help centers better understand their impact.

Coagulation profile of human COVID-19 convalescent plasma.

Convalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII-XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized.

Management of externally manufactured cell therapy products: the Mayo Clinic approach.

BACKGROUND: The rise of investigative and commercially available cell therapy products adds a new dynamic to academic medical centers; that is, the management of patient-specific cell products. The scope of cell therapy has rapidly expanded beyond in-house collection and infusion of cell products such as bone marrow and peripheral blood transplant. The complexities and volumes of cell therapies are likely to continue to become more demanding. As patient-specific "living drugs," cell therapy products typically require material collection, product provenance, transportation and maintenance of critical quality attributes, including temperature and expiration dates. These requirements are complicated by variations in product-specific attributes, reporting requirements and interactions with industry not required of typical pharmaceuticals. METHODS: To manage these requirements, the authors set out to establish a framework within the Immune, Progenitor and Cell Therapeutics Lab, the Current Good Manufacturing Practice facility responsible for cell manufacturing at Mayo Clinic Rochester housed within the Division of Transfusion Medicine. The authors created a work unit (biopharmaceutical unit) dedicated to addressing the specialized procedures required to properly handle these living drugs from collection to delivery and housing the necessary processes to more easily integrate externally manufactured cell therapies into clinical practice. RESULTS: The result is a clear set of expectations defined for each step of the process, with logical documentation of critical steps that are concise and easy to follow. CONCLUSIONS: The authors believe this system is scalable for addressing the promised growth of cell therapy products well into the future. Here the authors describe this system and provide a framework that could be used by other centers to manage these important new therapies.

THOR-AABB Working Party Recommendations for a Prehospital Blood Product Transfusion Program.

The evidence for the lifesaving benefits of prehospital transfusions is increasing. As such, emergency medical services (EMS) might increasingly become interested in providing this important intervention. While a few EMS and air medical agencies have been providing exclusively red blood cell (RBC) transfusions to their patients for many years, transfusing plasma in addition to the RBCs, or simply using low titer group O whole blood (LTOWB) in place of two separate components, will be a novel experience for many services. The recommendations presented in this document were created by the Trauma, Hemostasis and Oxygenation Research (THOR)-AABB (formerly known as the American Association of Blood Banks) Working Party, and they are intended to provide a framework for implementing prehospital blood transfusion programs in line with the best available evidence. These recommendations cover all aspects of such a program including storing, transporting, and transfusing blood products in the prehospital phase of hemorrhagic resuscitation.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Implementation of a Comprehensive Patient Blood Management Program for Hospitalized Patients at a Large United States Medical Center.

OBJECTIVE: To assess changes in inpatient transfusion utilization and patient outcomes with implementation of a comprehensive patient blood management (PBM) program at a large US medical center. PATIENTS AND METHODS: This is an observational study of graduated PBM implementation for hospitalized adults (age ≥18 years) from January 1, 2010, through December 31, 2017, at two integrated hospital campuses at a major academic US medical center. Allogeneic transfusion utilization and clinical outcomes were assessed over time through segmented regression with multivariable adjustment comparing observed outcomes against projected outcomes in the absence of PBM activities. RESULTS: In total, 400,998 admissions were included. Total allogeneic transfusions per 1000 admissions decreased from 607 to 405 over the study time frame, corresponding to an absolute risk reduction for transfusion of 6.0% (95% confidence interval [CI]: 3.6%, 8.3%; P<.001) and a 22% (95% CI: 6%, 37%; P=.006) decrease in the rate of transfusions over projected. The risk of transfusion decreased for all blood components except cryoprecipitate. Transfusion reductions were experienced for all major surgery types except liver transplantation, which remained stable over time. Hospital length of stay (multiplicative increase in geometric mean 0.85 [95% CI: 0.81, 0.89]; P<.001) and incident in-hospital adverse events (absolute risk reduction: 1.5% [95% CI: 0.1%, 3.0%]; P=.04) were lower than projected at the end of the study time frame. CONCLUSION: Patient blood management implementation for hospitalized patients in a large academic center was associated with substantial reductions in transfusion utilization and improved clinical outcomes. Broad-scale implementation of PBM in US hospitals is feasible without signal for patient harm.

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.

Civilian walking blood bank emergency preparedness plan.

BACKGROUND: The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine-tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place. METHODS AND MATERIALS: During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high-level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage. RESULTS AND CONCLUSIONS: Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high-level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well-thought-out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.

The safety of COVID-19 convalescent plasma donation: A multi-institutional donor hemovigilance study.

BACKGROUND: Although the safety and therapeutic efficacy of COVID-19 convalescent plasma (CCP) has been extensively evaluated, the safety of CCP donation has not been explored in a multi-institutional context. STUDY DESIGN AND METHODS: Nine blood collection organizations (BCOs) participated in a multi-institutional donor hemovigilance effort to assess the safety of CCP donation. Donor adverse events (DAEs) were defined according to the Standard for Surveillance of Complications Related to Blood Donation, and severity was assessed using the severity grading tool. Multivariate analysis was performed to determine attributes associated with DAE severity. RESULTS: The overall DAE rate was 37.7 per 1000 donations. Repeat apheresis and apheresis-naïve donors experienced adverse event rates of 19.9 and 49.8 per 1000 donations, respectively. Female donors contributed 51.9% of CCP donations with a DAE rate of 49.4 per 1000 donations. The DAE rate for male donors was 27.4 per 1000 donations. Vasovagal reactions accounted for over half of all reported DAEs (51.1%). After adjustment, volume of CCP donated was associated with vasovagal reaction severity (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.5-17.1). Donor age and donation history were also associated with DAE severity. Considerable differences in DAE types and rates were observed across the participating BCOs despite the use of standardized hemovigilance definitions. CONCLUSION: The safety of CCP donation appears comparable to that of conventional apheresis plasma donation with similar associated risk factors for DAE types and severity.

Program and patient characteristics for the United States Expanded Access Program to COVID-19 convalescent plasma.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to COVID-19 convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19). While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents particularly for vulnerable racial and ethnic minority populations who were disproportionately affected by the pandemic. The objective of this study is to report on the demographic, geographic, and chronological access to COVID-19 convalescent plasma in the US via the EAP. METHODS AND FINDINGS: Mayo Clinic served as the central IRB for all participating facilities and any US physician could participate as local physician-principal investigator. Registration occurred through the EAP central website. Blood banks rapidly developed logistics to provide convalescent plasma to hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal trends in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate on a state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions as well as assessing enrollment in metropolitan and less populated areas which did not have access to COVID-19 clinical trials.From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. A majority of patients were older than 60 years of age (57.8%), male (58.4%), and overweight or obese (83.8%). There was substantial inclusion of minorities and underserved populations, including 46.4% of patients with a race other than White, and 37.2% of patients were of Hispanic ethnicity. Severe or life-threatening COVID-19 was present in 61.8% of patients and 18.9% of patients were mechanically ventilated at time of convalescent plasma infusion. Chronologically and geographically, increases in enrollment in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled patients in the EAP, including both in metropolitan and less populated areas. CONCLUSIONS: The EAP successfully provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The efficient study design of the EAP may serve as an example framework for future efforts when broad access to a treatment is needed in response to a dynamic disease affecting demographic groups and areas historically underrepresented in clinical studies.

Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.

BACKGROUND: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. METHODS: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. RESULTS: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). CONCLUSIONS: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).