Comparison of allocation strategies of convalescent plasma to reduce excess infections and mortality from SARS-CoV-2 in a US-like population.

BACKGROUND: While the use of convalescent plasma (CP) in the ongoing COVID-19 pandemic has been inconsistent, CP has the potential to reduce excess morbidity and mortality in future pandemics. Given constraints on CP supply, decisions surrounding the allocation of CP must be made. STUDY DESIGN AND METHODS: Using a discrete-time stochastic compartmental model, we simulated implementation of four potential allocation strategies: administering CP to individuals in early hospitalization with COVID-19; administering CP to individuals in outpatient settings; administering CP to hospitalized individuals and administering any remaining CP to outpatient individuals and administering CP in both settings while prioritizing outpatient individuals. We examined the final size of SARS-CoV-2 infections, peak and cumulative hospitalizations, and cumulative deaths under each of the allocation scenarios over a 180-day period. We compared the cost per weighted health benefit under each strategy. RESULTS: Prioritizing administration to patients in early hospitalization, with remaining plasma administered in outpatient settings, resulted in the highest reduction in mortality, averting on average 15% more COVID-19 deaths than administering to hospitalized individuals alone (95% CI [11%-18%]). Prioritizing administration to outpatients, with remaining plasma administered to hospitalized individuals, had the highest percentage of hospitalizations averted (22% [21%-23%] higher than administering to hospitalized individuals alone). DISCUSSION: Convalescent plasma allocation strategy should be determined by the relative priority of averting deaths, infections, or hospitalizations. Under conditions considered, mixed allocation strategies (allocating CP to both outpatient and hospitalized individuals) resulted in a larger percentage of infections and deaths averted than administering CP in a single setting.

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.

Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma.

DESCRIPTION: Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP. METHODS: These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations. RECOMMENDATION 1 (OUTPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence). RECOMMENDATION 2 (INPATIENT): The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. RECOMMENDATION 3 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence). RECOMMENDATION 4 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence). RECOMMENDATION 5 (PROPHYLAXIS): The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence). GOOD CLINICAL PRACTICE STATEMENT: CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.

Acquired platelet storage container leaks and contamination with environmental bacteria: A preventable cause of bacterial sepsis.

BACKGROUND: Apheresis platelets (AP) may be contaminated by environmental bacteria via container defects acquired during processing, transport, storage, or transfusion, as highlighted by a recent series of septic reactions related to Acinetobacter spp. and other bacterial strains. STUDY DESIGN AND METHODS: The frequency and nature of acquired container defect reports to one manufacturer were evaluated from January 2019 to July 2020. The published incidence of contamination and sepsis due to environmental bacteria with culture screened AP in the United States was reviewed for the period of 2010-2019. RESULTS: Review of a manufacturers' records showed 23 US reports of leaks involving 24 containers attributed to postmanufacturing damage, at a rate of 44 per million distributed storage containers. Analysis of returned containers showed evidence of scratches, impressions, and/or piercings. Literature review of US hemovigilance data revealed that environmental bacteria comprised 7% of confirmed positive primary bacterial culture screens, were responsible for 14%-16% of reported septic, and 8 of 28 (29%) fatal reactions with bacterial-culture screened AP. Sepsis cases have been reported with culture screened, point-of-issue (POI) tested, or pathogen-reduced AP. DISCUSSION: Environmental contamination of AP is rare but can cause sepsis. Container damage provides a pathway for contamination after culture screening, POI bacteria testing, or pathogen reduction. Blood collectors and transfusion services should have procedures to ensure proper inspection, handling, storage, and transport of AP to avoid damage and should enhance efforts to detect defects prior to release and to eliminate bacteria from all contacting surfaces to minimize the risk of contamination.

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.

Progression and Predictors of SARS-CoV-2 Antibody Seroreactivity In US Blood Donors.

The second largest US blood center began testing for antibodies to SARS-CoV-2, the etiologic agent of Coronavirus Disease-2019 (COVID-19) to identify potential COVID-19 Convalescent Plasma (CCP) donors and encourage blood donation. We report the non-vaccine seroprevalence of total immunoglobulin directed against the S1 spike protein of SARS-CoV-2 in our donors. Unique non-CCP donor sera from June 01to December 31, 2020 were tested with the Ortho VITROS Anti-SARS-CoV-2 total immunoglobulin assay (reactive: signal-to-cutoff (S/C) ≥ 1). Multivariate regressions including age, sex, race-ethnicity, ABO, RhD, highest education level, donor experience, regional collection center and drive type factors were conducted to identify demographics associated with the presence of antibodies and with S/C values. Unique donors (n = 523,068) showed an overall seroprevalence of 6.12% over 7 months, with the highest prevalence in December 2020 around Lubbock, TX (24.3%). In a subset of donors with demographic information (n = 394,470), lower odds of antibody reactivity were associated with female sex, non-Hispanic White or Asian race/ethnicity, age ≥ 65, graduate education, blood Group O, and history of blood donation. In reactive donors (n = 24,028), antibody signal was associated with male sex, race/ethnicity other than non-Hispanic White, low educational attainment, age 16-17 years and geographic location. Seroprevalence continues to grow in US blood donors but varies significantly by region. Temporal trends in reactivity may be useful to estimate effectiveness of public health measures. Before generalizing these data from healthy donors to the general population, rates must be corrected for false-positive test results and adjusted to match the wider US demography.

An international comparison of HIV prevalence and incidence in blood donors and general population: a BEST Collaborative study.

BACKGROUND AND OBJECTIVES: Efficiency in mitigating HIV transmission risk by transfusion may vary internationally. We compared HIV prevalence and incidence in blood donors across different jurisdictions in relation to those rates in the general population and differences in deferral practices. MATERIALS AND METHODS: Data from 2007 to 2016 were collected in Australia, Brazil (São Paulo), Canada, England, France, Italy, Ireland, Japan, the Netherlands, New Zealand, Norway, Spain (Basque Country), USA (Vitalant) and Wales. For each country/region, the number of HIV antibody-positive donations and nucleic acid testing (NAT)-only-positive donations was broken down according to first-time or repeat donor status, along with the relevant denominators. RESULTS: There is a modest correlation between HIV prevalence among first-time donors and HIV prevalence in the general population. However, rates of HIV-positive donations in repeat donors, a proxy for incidence, do not correlate with incidence rates in the general population. Rates in donors from Italy and Basque Country, where deferral criteria for men having sex with men are less stringent, are higher compared with most other jurisdictions. Rates of NAT-only-positive donations are extremely low and do not differ significantly after adjustment for multiple comparisons. CONCLUSION: Donor HIV rates are only weakly associated with those observed in the general population. Countries with less stringent deferral criteria have higher HIV rates in their donor population, but the rates remain very low.

Pandemic blood donor demographics - Do changes impact blood safety?

BACKGROUND: COVID-19 safety measures and possibly SARS-CoV-2 antibody testing may alter blood donor demography, which has the potential to alter blood safety. We characterized pre-pandemic and pandemic rates of donor infectious disease marker (IDM) reactivity which reflect the residual risk of transfusion-transmitted infections (TTIs) undetectable by current testing. METHODS: This cross-sectional analysis of allogeneic blood donor presentations and successful donations in a large national US blood collector identifies changes in self-reported behavioral risk factors and IDM reactivity. Data on allogeneic blood donor presentations and successful donations from March 1 through August 31, 2020 and the same period in 2019 were retrieved from the blood center's computer system. Donor demographics and deferrals for reported behavioral risk factors and confirmed-positive IDMs were compared in pre-pandemic and pandemic periods. RESULTS: With increasing mobile blood drive cancellations, pandemic donors were more likely than 2019 donors to be female, over age 30, non-Hispanic Whites, and have a post-secondary degree. First-time donations (at highest risk for confirmed-positive IDMs) did not substantially increase. Pandemic donors reported fewer behavioral risks and IDMs declined among these donors. Mid-pandemic introduction of screening for SARS-CoV-2 antibodies did not affect IDM rates. CONCLUSIONS: Unlike disasters, which tend to bring out more first-time donors with increased IDM reactivity and TTI residual risk, COVID-19 donors had lower IDM rates which were not affected by SARS-CoV-2 antibody testing. Already-low TTI residual risk is likely to have declined as a result.

Recovery of Iron Stores After Adolescents Donate Blood.

BACKGROUND: Teenagers aged 16 to 18 are at increased risk for iron deficiency, exacerbated by losses with whole blood (WB) or double red blood cell (2RBC) donations. Required 56-day (WB) or 112-day (2RBC) interdonation intervals (IDIs) are too short for many to replace lost iron without supplements. METHODS: Teenagers donating WB or 2RBCs at Vitalant, a national blood provider, had serum ferritin measured at their first and immediately subsequent successful donation from December 2016 to 2018. We modeled postindex log-ferritin as a function of IDI to estimate the shortest intervals that corresponded with 50% to 95% prevalence of adequate donor iron stores (ferritin ≥20 ng/mL female donors, ≥30 ng/mL male donors) at the subsequent donation. RESULTS: Among 30 806 teenagers, 11.4% of female and 9.7% of male donors had inadequate iron stores at index donation. Overall, 92.6% had follow-up ferritin values within 13 months. Approximately 12 months after WB index donations, >60% of female and >80% of male donors had adequate iron stores (>50% and >70% after 2RBC donations). Follow-up-donation iron stores were highly dependent on index ferritin. Less than half of WB donors with low ferritin at index achieved adequate stores within 12 months. Achieving a ≥90% prevalence of adequate ferritin at 12 months required index values >50 ng/mL. CONCLUSIONS: These findings suggest that postdonation low-dose iron supplements should be strongly encouraged in teenagers with borderline or low iron stores to permit donation without increased risk for symptoms of mild iron depletion. Increasing the minimum recommended IDI to allow time for replacing donation-related iron losses may be desirable for teenagers.

Donor iron depletion: beneficial or burdensome?

Most purported benefits of blood donation have not been proven. While studies suggest individuals with type II diabetes have transiently improved postdonation glycemic control, the mechanism is unknown. Blood donors with nonanemic or mildly anemic iron deficiency can develop pica and undergo unnecessary diagnostic procedures. Lower infant birth weight has been documented in female blood donors. In other healthy populations, reversible fatigue and exercise capacity impairment occur with mild iron deficiency. The effects of donor iron depletion on cognition and neurocognitive outcomes after pregnancy continue to be studied. Blood collectors are beginning to implement enhanced educational and interventional measures to prevent iron depletion in at-risk donors.

Safety of blood donation by individuals over age 70 and their contribution to the blood supply in five developed countries: a BEST Collaborative group study.

BACKGROUND: Some countries impose an upper age limit on whole blood and double RBC donation while others do not. We evaluated the safety of blood donation in older individuals (≥71 years), and their contribution to the blood supply of five countries. STUDY DESIGN AND METHODS: Twelve blood center members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative from four countries with no upper age limit for whole blood and double RBC donation (Canada, New Zealand, England, and the United States) or an upper age limit of 80 (Australia) provided 2016 data on donors and donations, deferral rates, and vasovagal reactions by donor age and sex. Donors under age 24 were included in the number of total donors and donations, but not in deferral and reaction rate comparisons. RESULTS: Older donors accounted for 1.0% (New Zealand) to 4.3% (United States) of donors, and 1.5% (New Zealand) to 5.6% (United States) of donations; most were between ages 71 and 76. The deferral rate was higher in older compared to 24- to 70-year-old males, but very similar between older and younger females. In contrast, vasovagal reaction rates were either lower (male donors) or similar (female donor for reactions with loss of consciousness) in older compared to 24- to 70-year-old donors. CONCLUSIONS: Exclusion solely based on older age appears to be unwarranted based on safety concerns such as donor reactions. Healthy older individuals can continue to safely donate and make a significant contribution to the blood supply past arbitrary age limits.

Impact of changes to donor hemoglobin criteria on the rate of donor deferral.

BACKGROUND: The Food and Drug Administration's requirements for "Blood and Blood Components Intended for Transfusion or Further Manufacturing Use" (Final Rule) effective May 2016 changed eligibility criteria for blood donors. A multivariate analysis was performed to measure its impact on donor deferral rates. STUDY DESIGN AND METHODS: Four blood centers submitted data for similar 6-month periods before and after implementation of the Final Rule. Data included presenting donors, units collected, deferrals, intended products from deferred donors, deferral reasons, presenting donor demographics, donor hemoglobin (Hgb), hematocrit (HCT), pulse, blood pressure (BP), temperature, and other reasons for deferral. Data were aggregated and periods compared. RESULTS: After Final Rule implementation, successful donations decreased by 1.3% (83.1%-81.9%), despite a 0.2% increase in presenting donors. The rate of Hgb/HCT, pulse, and deferrals increased, while deferrals for other reasons decreased. Male Hgb/HCT deferral rates increased 1.2% (4213 total). Black male donors' Hgb/HCT deferral rate increased (2.7%-5.2%) but was counterbalanced by an overall 3.7% decrease in black female Hgb/HCT deferrals. While Hgb/HCT deferrals of black donors remained stable overall (17.0% vs. 16.2%), this trend was not observed by all centers. Deferrals for pulse increased (0.2%), as did BP deferrals (0.2%). CONCLUSION: Although there was a small increase in presenting donors after implementation of the Final Rule, there was a decrease in successful donations. While it appeared that deferral in black donors was unchanged, this trend was not observed across all centers. Pulse and BP deferrals rose dissimilarly among centers, according to individual procedures.

Ferritin testing to characterize and address iron deficiency in young donors.

BACKGROUND: Iron deficiency is observed in blood donors who meet hemoglobin requirements for donation. Frequent donation results in negative iron balance, and teenage donors may thus be at risk for adverse health consequences. STUDY DESIGN AND METHODS: Blood Systems implemented ferritin testing on all successful 16- to 18-year-old (teen) donations. Low ferritin (LF) was defined as less than 20 ng/mL in females and less than 30 ng/mL in males. Donors with LF were deferred from red blood cell (RBC) donations (12 months for females, and 6 for males) and counseled to take low-dose iron for 60 days. A ferritin value less than 26 ng/mL indicated iron-deficient erythropoiesis and less than 12 ng/mL absent iron stores. RESULTS: Over 16 months, 110,417 teen donations were tested and represented 10.5% of all successful donations. The rate of absent iron stores was 9.0% (1.9% male; 15.9% female) and of iron-deficient erythropoiesis, 31.9% (12.4% male; 50.6% female). The rate of LF deferrals was 26.9% (16.7% male; 36.6% female). The proportion of LF donors decreased with increasing predonation hemoglobin and rose with increasing RBC donations in the prior 24 months. Seasonality in LF deferrals and the RBC contribution from teen donors was observed. CONCLUSIONS: Ferritin testing of teen donors identified individuals with LF who might benefit from risk mitigation. LF is more common in teenage female than male donors and those with RBC donations in the prior 24 months. An appreciable number of new/lapsed donors presented with LF, however. These data may be useful in guiding future risk mitigation efforts.

How do we manage iron deficiency after blood donation?

Blood donors and the RBCs and other components they willingly provide are essential in the delivery of healthcare in all parts of the world. Nearly 70% of donated blood comes from repeat or committed donors. The amount of iron removed in the 10 min or so it takes to withdraw a unit of blood (500 ml, plus 25 ml for testing) requires over 24 weeks to replace on a "standard" diet, i.e., without added iron in the form of supplements The cumulative effect of repeat blood donations without adequate iron replacement or a longer wait between donations results in iron deficiency (ID) in many donors, low haemoglobin deferral (~8% of donation attempts), and frank anaemia in some. Moreover, ID can be associated with side effects that can impact a blood donor's health, such as fatigue, cognitive changes and other neuromuscular symptoms. In an effort to better identify and prevent ID, blood collection agencies are recommending various strategies, including changes in the donation interval, donation frequency, testing of iron status and iron supplementation. In this review, we present the evidence basis for these strategies and suggest our own approaches to improving iron balance in blood donors.