Changes in transfusion-transmissible infection prevalence and demographics among US blood donors during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic impacted the US blood supply. We compared blood donor demography and infectious disease prevalence before and during the pandemic using a large multicenter database. METHODS: Data were categorized as "Before COVID-19" (March 2018-February 2020) or "During COVID-19" (March 2020-February 2022). Donor demographics, donation frequency, and infectious marker prevalence of HIV, HBV, and HCV were compared for the two time periods. The odds of a donor testing positive for these infections among the two time periods were calculated using multivariable logistic regression. RESULTS: Our study assessed a total of 26,672,213 donations including 13,430,380 before and 13,241,833 during COVID-19. There were significantly more donations from donors who were female, aged 40 and older, white, and repeat, during COVID-19. Donation frequency comparison quantified the increase in donations from donors who were white, female, older, and repeat during the pandemic. The prevalence of HIV and HCV decreased significantly during COVID-19 compared to before, but not for HBV. For HIV, the adjusted odds of infection during the pandemic did not differ but for HBV, the odds were significantly more likely during the pandemic and were significantly lower for HCV. DISCUSSION: Demographics and infectious disease marker prevalence changed during the COVID-19 pandemic in the United States. Prevalence of each infection in the donor population will continue to be monitored to determine if changes were specific to the pandemic period.

Syphilis seroprevalence and incidence in US blood donors from 2020 to 2022.

BACKGROUND: HIV, HBV, and HCV infections for ~60% of the US blood supply are monitored by TTIMS with syphilis added in 2020. STUDY DESIGN AND METHODS: Data were compiled from October 2020 to September 2022. Syphilis prevalence was estimated for allogeneic and directed donors who were consensus positive (CP) and the subset of those with confirmed-active infections (AI). Prevalence and incidence were stratified by demographics for two consecutive 1-year periods, starting October 1, 2020 and for both years combined. Incidence was estimated for repeat donors. Associations between syphilis positivity and other infections were evaluated. RESULTS: Among 14.75 million donations, syphilis prevalence was 28.4/100,000 donations and significantly higher during the second year compared to the first year. Overall, syphilis incidence for the two-year period was 10.8/100,000 person-years. The adjusted odds of a CP infection were 1.18 (95% CI: 1.11, 1.26) times higher in the second year compared to the first, and for AI, 1.22 (95% CI: 1.10, 1.35) times higher in year 2. Highest rates occurred among males, first-time, Black, and younger (ages 18-39) donors, and those in the South US Census region. Syphilis CP donors were 64 (95% CI: 46, 89) times more likely to be HIV CP, and AI donors 77 (95% CI: 52, 114) times more likely to be HIV CP than non-CP donors, when controlling for confounders. SUMMARY/CONCLUSIONS: Syphilis prevalence increased over the study period mirroring national trends reported by CDC and is significantly associated with HIV CP.

Involvement of Diverse Populations in Transfusion Medicine Research.

Communities of color and diverse communities (eg, race, socioeconomic status, language, sexual orientation etc.) have not been recruited and enrolled equitably to participate in research studies in transfusion medicine. The exclusion of diverse communities in transfusion research can lead to health disparities lack of access to approved therapeutics and unequal allocation of interventions, resulting in missed opportunities to optimize health for individuals and communities. Involvement of diverse populations in research goes beyond inclusion as research subjects. Strategies should include specific studies on health conditions of importance to diverse communities with stable funding sources and specific funding announcements to develop projects led by diverse researchers, mentorship of diverse researchers, and openness to various ways of communicating research plans. Qualitative approaches and interdisciplinary collaboration should be supported to enhance inclusivity.

HIV risk behavior profiles among men who have sex with men interested in donating blood: Findings from the Assessing Donor Variability and New Concepts in Eligibility study.

BACKGROUND: Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors. STUDY DESIGN AND METHODS: Cross-sectional survey and biomarker assessment were conducted in eight U.S. cities. Participants were sexually active MSM interested in blood donation aged 18-39 years, assigned male sex at birth. Participants completed surveys during two study visits to define eligibility, and self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, one of the drugs in oral HIV pre-exposure prophylaxis (PrEP). Associations were assessed between HIV infection status or HIV PrEP use and behaviors, including sex partners, new partners, and anal sex. RESULTS: A total of 1566 MSM completed the visit 1 questionnaire and blood draw and 1197 completed the visit 2 questionnaire. Among 1562 persons without HIV, 789 (50.4%) were not taking PrEP. Of those not taking PrEP, 66.2% reported one sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months. CONCLUSION: The study found that questions were able to identify sexually active, HIV-negative MSM who report lower risk sexual behaviors. About a quarter of enrolled study participants would be potentially eligible blood donors using individual risk assessment questions.

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.

Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021.

Importance: People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain. Objective: To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population. Design, Setting, and Participants: In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021. Exposure: Calendar time. Main Outcomes and Measures: Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates. Results: Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred. Conclusions and Relevance: Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population.

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.

Rapid development of a de novo convalescent plasma program in response to a global pandemic: A large southeastern U.S. blood center's experience.

BACKGROUND: During the pandemic in the spring of 2020 with no vaccine or treatment for SARS-CoV-2 and its associated disease, COVID-19, convalescent plasma from recovered COVID-19 (CCP) patients offered a potential therapy. In March 2020, the United States (U.S.) Food and Drug Administration (FDA) authorized CCP under emergency Investigational New Drug (eIND) exemption and an IRB-approved Expanded Access Program (EAP) to treat severe COVID-19. Hospital demand grew rapidly in the Southeastern U.S., resulting in backlogs of CCP orders. We describe a large U.S. blood center's (BC) rapid implementation of a CCP program in response to community needs. STUDY DESIGN AND METHODS: From April 2 to May 17, 2020, CCP was collected by whole blood or apheresis. Initial manual approaches to donor intake, collection, and distribution were rapidly replaced with automated processes. All CCP donors and products underwent FDA-required screening and testing. RESULTS: A total of 619 CCP donors (299 females, 320 males) presented for CCP donation (161 [25.7%] whole blood, 466 [74.3%] plasmapheresis) resulting in 1219 CCP units. Production of CCP increased as processes were automated and streamlined, from a mean of 11 donors collected/day for the first month to a mean of 25 donors collected/day in the subsequent 2 weeks. Backlogged orders were cleared, and inventory began to accumulate 4 weeks after project initiation. CONCLUSION: The BC was able to implement an effective de novo CCP collection program within 6 weeks in response to a community need in a global pandemic. Documentation of the experience may inform preparedness for future pandemics.

Selecting COVID-19 convalescent plasma for neutralizing antibody potency using a high-capacity SARS-CoV-2 antibody assay.

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 NT50 titers using receiver operating characteristics. RESULTS: Seven hundred and fifty-three CCPs were tested with median CoV2T S/Co and NT50 of 71.2 of 527.5. Proportions of donors with NT50 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 NT50 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.

HIV, HCV, and HBV incidence and residual risk in US blood donors before and after implementation of the 12-month deferral policy for men who have sex with men.

BACKGROUND: In December 2015, the men who have sex with men (MSM) deferral was reduced to 12 months in the United States. We compared human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) incidence and residual risk before and after this policy change using data from >50% of the US blood supply. STUDY DESIGN AND METHODS: Three estimation intervals from the Transfusion-Transmissible Infections Monitoring System were compared: 15-months pre- and two consecutive, nonoverlapping 15-month post-MSM deferral implementation. Repeat, first-time, and weighted all-donor incidences were estimated. Residual risk was calculated for all incidence estimates using the incidence/window-period method. RESULTS: HIV repeat donor incidence was 1.57 per 100 000 person-years (phtpy) in the second 15-month post change and not significantly different from pre-MSM incidence of 2.19 phtpy. Similar values were seen for HCV (1.49 phtpy vs 1.46 phtpy) and HBV (1.14 phtpy vs 0.97 phtpy). In some cases, higher estimated incidence, but without significant change from pre-MSM to the second post change period occurred for males and first-time donors (eg, first-time donors, second post change period: 6.12 phtpy HIV, 6.41 phtpy HCV and 5.34 phtpy HBV). Estimated per donation residual risk was 1:1.6 million for HIV, 1:2.0 million for HCV and 1:1.0 million for HBV based on weighted incidence for all donors. CONCLUSIONS: Repeat, first-time, and overall donor incidence did not vary significantly comparing pre-MSM to either of the post-MSM estimation intervals. Residual risk estimates vary by study, but all yield residual risks in the United States of ≤1 per million, and thus far have not shown increasing risk with the 12-month MSM policy change.

Prevalence of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus in United States blood donations, 2015 to 2019: The Transfusion-Transmissible Infections Monitoring System (TTIMS).

BACKGROUND: The Transfusion-Transmissible Infections Monitoring System (TTIMS) combines data from four US blood collection organizations including approximately 60% of all donations to monitor demographic and temporal trends in infectious disease markers and policy impacts. STUDY DESIGN AND METHODS: Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) consensus-positive definitions combined serology and nucleic acid testing results. These along with donor and donation characteristics were assembled into a single data set. Overall donation prevalence and demographic subsets were compared pre- and post-implementation of the 2015 change in men who have sex with men (MSM) deferral policy, among other prevalence comparisons. RESULTS: From October 2015 to September 2019, there were 712 HIV-, 1735 HBV-, and 5217 HCV-positive samples identified from approximately 27.5 million donations (>9.4 million donors). Prevalences per 100 000 donations were 2.6 (HIV), 6.3 (HBV), and 19.0 (HCV), and the highest for all three agents were in donations from first-time male donors. Two slight but significant increases in HIV prevalence were observed, both for comparisons of Year 1 (pre-MSM policy change) versus Year 4 (post-MSM policy change) for first-time males and first-time females; in contrast, similar comparisons demonstrated decreases in HCV prevalence (all donors and general trends for males and females). Except for HIV, prevalence increased with age; for all agents, prevalence was markedly higher in the south. CONCLUSIONS: No major trends were observed over 4 years covering the MSM policy change from indefinite to a 12-month deferral, but ongoing monitoring is warranted. Demographic trends are consistent with those observed in other donor studies and community trends.

Recently acquired infection among HIV-seropositive donors in the US from 2010-2018.

BACKGROUND: Monitoring of transfusion-transmissible infections in the blood supply is essential for blood safety, as the donor population is not static, and changes in policy, donor behavior, or other factors could increase the risk of recipient infection. We assessed patterns of recently acquired HIV infection in US blood donors, including before and after the implementation of the 12-month deferral for men who have sex with men (MSM). STUDY DESIGN AND METHODS: A large convenience sample of donations from donors testing HIV-1 nucleic acid testing (NAT) and serology-reactive were further tested with the Sedia HIV-1 Limiting Antigen enzyme immunoassay. Samples were analyzed across available demographic and donation data to provide an assessment of recently acquired HIV infection in US blood donors from 2010 to 2018. RESULTS: Overall, 317 of 1154 (27.5%; 95% confidence interval, 24.9%-30.1%) donations from HIV NAT and serology-reactive donors had recently acquired HIV infection. There was no evidence of change in the percentages of recent HIV infection by year over the study period, either in all donors or in male donors, including after the MSM policy change. In multivariable logistic regression analysis, donors aged 24 years or younger were over 2.7 times more likely and repeat donors 2.2 times more likely to have recently acquired HIV infection compared to donors aged 55 years or older and first-time donors, respectively. CONCLUSION: Patterns of recently acquired HIV infection varied by demographics but not over time. These findings suggest no impact of the MSM policy change on recently acquired HIV infection in US blood donors.

HIV antiretroviral therapy and prevention use in US blood donors: a new blood safety concern.

Antiretroviral therapy (ART) to treat and pre-exposure prophylaxis (PrEP) to prevent HIV infection are effective tools to help end the HIV epidemic. However, their use could affect HIV transfusion-transmission risk. Three different ART/PrEP prevalence analyses in blood donors were conducted. First, blood samples from HIV-positive and a comparison group of infection-nonreactive donors were tested under blind using liquid chromatography-tandem mass spectrometry for ART. Second, blood donor samples from infection-nonreactive, 18- to 45-year-old, male, first-time blood donors in 6 US locations were tested for emtricitabine and tenofovir. Third, in men who have sex with men (MSM) participating in the 2017 Centers for Disease Control and Prevention National HIV Behavioral Surveillance (NHBS) from 5 US cities, self-reported PrEP use proximate to donation was assessed. In blind testing, no ART was detected in 300 infection-nonreactive donor samples, but in 299 HIV confirmed-infected donor samples, 46 (15.4%; 95% confidence interval [CI], 11.5% to 20.0%) had evidence of ART. Of the 1494 samples tested from first-time male donors, 9 (0.6%; 95% CI, 0.03% to 1.1%) had tenofovir and emtricitabine. In the NHBS MSM survey, 27 of 591 respondents (4.8%; 95% CI, 3.2% to 6.9%) reported donating blood in 2016 or 2017 and PrEP use within the same time frame as blood donation. Persons who are HIV positive and taking ART and persons taking PrEP to prevent HIV infection are donating blood. Both situations could lead to increased risk of HIV transfusion transmission if blood screening assays are unable to detect HIV in donations from infected donors.

HIV incidence in US first-time blood donors and transfusion risk with a 12-month deferral for men who have sex with men.

In 2015, the US Food and Drug Administration published revised guidance that recommended a change in blood donor deferral of men who have sex with men (MSM) from an indefinite to a 12-month deferral since the donor last had sex with a man. We assessed whether HIV incidence in first-time blood donors or associated transfusion risk increased. Donations in 4 major blood collection organizations were monitored for 15 months before and 2 years after implementation of the 12-month MSM deferral policy. HIV-positive donations were classified as recently acquired or long-term using a recent infection testing algorithm and incidence in both periods estimated. Residual transfusion transmission risk was estimated by multiplying incidence by the length of the infectious window period. The latter was estimated using a model based on infectious dose and the sensitivity of nucleic acid testing. Factors associated with incident infection in each period were assessed using Poisson regression. Overall HIV incidence in first-time donors before implementation of the 12-month MSM deferral was estimated at 2.62 cases per 100 000 person-years (105 PY) (95% credible interval [CI], 1.53-3.93 cases/105 PY), and after implementation at 2.85 cases/105 PY (95% CI, 1.96-3.93 cases/105 PY), with no statistically significant change. In male first-time donors, the incidence difference was 0.93 cases/105 PY (95% CI, -1.74-3.58 cases/105 PY). The residual risk of HIV transfusion transmission through components sourced from first-time donors was estimated at 0.32 transmissions per million (106) packed red blood cell transfusions (95% CI, 0.29-0.65 transmissions/106 transfusions) before and 0.35 transmissions/106 transfusions (95% CI, 0.31-0.65 transmissions/106 transfusions) after implementation. The difference was not statistically significant. Factors associated with incident infection were the same in each period. We observed no increase in HIV incidence or HIV transfusion transmission risk after implementation of a 12-month MSM deferral policy.

Transcription-mediated amplification blood donation screening for Babesia.

BACKGROUND: Transfusion-transmitted Babesia microti is well recognized in the Northeast and upper Midwestern United States. Blood donation screening in Babesia-endemic states has occurred under investigational protocols prior to US Food and Drug Administration-licensed test availability. Here, we provide a prospective screening summary of nucleic acid testing (NAT) as part of a multicenter Babesia pivotal trial followed by extended investigational use. METHODS: From June 2017 to February 2018, 176,928 donation samples were tested with Procleix Babesia Assay (Grifols Diagnostic Solutions), a blood screening NAT for Babesia species ribosomal RNA detection using whole blood samples. During the pivotal trial, donations were collected in 11 endemic states plus Washington, DC, and Florida (nonendemic). Whole blood lysate samples were either tested in pools of 16 or individually. Reactive samples were confirmed by Babesia microti antibody and polymerase chain reaction (PCR) testing. If unconfirmed, further testing used a second PCR assay capable of detecting multiple Babesia species. Follow-up samples were also tested. Extended investigational testing followed pivotal trial completion. RESULTS: The pivotal trial identified 61 confirmed positives (176,608 donations): 35 (57%) PCR positive, 59 (97%) antibody positive, and two (3%) NAT positive/antibody negative, for a total yield of one positive per 2895 donations, including one Florida resident; others were from seven endemic states. During extended investigational testing of 496,270 donations in endemic states through January 2019, 211 (1:2351) repeat reactive donations were identified. CONCLUSIONS: Babesia was detected in donors from multiple US states, including one previously not associated with positive blood donors. This study supports the use of the Procleix Babesia Assay using individual testing or pools of up to 16.