Background Previous SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) vaccination, independently and combined (“hybrid immunity”), result in partial protection from subsequent infection and strong protection from severe disease. Proportions of the U.S. population that have been infected, vaccinated, or with hybrid immunity remain unclear, posing a challenge for assessing effective pandemic mitigation strategies. Methods In this serial cross-sectional study, nationwide blood donor specimens collected during January–December 2021 were tested for spike and nucleocapsid antibodies, and donor COVID-19 vaccination history of ≥1 dose was collected. Monthly seroprevalence induced from SARS-CoV-2 infection, COVID-19 vaccination, or both, were estimated. Estimates were weighted to account for demographic differences from the general population, and were compared temporally and by demographic factors. Results Overall, 1,123,855 blood samples were assayed. From January to December 2021, the weighted percentage of donations with seropositivity due to: vaccination without previous infection increased from 3.5% (95% CI, 3.4%-3.7%) to 64.0%, (95% CI, 63.5%-64.5%); previous infection without vaccination decreased from 15.6% (95% CI, 15.2%-16.0%) to 11.7% (95% CI, 11.4%-12.0%); hybrid immunity increased from 0.7% (95% CI, 0.6%-0.7%) to 18.9% (95% CI, 18.5%-19.3%); and from infection, vaccination, or both increased from 19.8% (95% CI (19.3-20.2) to 94.5% (95% CI, 93.5%-94.0% 0.1%). Infection- and vaccination-induced antibody responses varied significantly by age, race-ethnicity, and region, but not by gender. Conclusions Our results indicate substantial increases in population humoral immunity from SARS-CoV-2 infection, COVID-19 vaccination, and hybrid immunity during 2021. These findings are important to consider in future COVID-19 studies and long-term pandemic mitigation efforts.

BACKGROUND: Characteristics of US blood donors with recent (RBI) or occult (OBI) hepatitis B virus (HBV) infection are not well defined. METHODS: Donors with RBI and OBI were identified by nucleic acid and serologic testing among 34.4 million donations during 2009-2015. Consenting donors were interviewed and their HBV S-gene sequenced. RESULTS:The overall rate of HBV-infected donors was 7.95 per 100,000; of these, 0.35 per 100,000 and 1.70 per 100,000 were RBI and OBI, respectively. RBI (n = 120) and OBI (n = 583) donors constituted 26% of all HBV-infected (n = 2735) donors. Detection of HBV DNA in 92% of OBI donors required individual donation nucleic acid testing. Donors with OBI compared to RBI were older (mean age, 48 vs 39 years; p < 0.0001) with lower median viral loads (9 vs. 529 IU/mL; p < 0.0001). A higher proportion of OBI than RBI donors were born or resided in an endemic country (39% vs. 5%; p = 0.0078). Seventy-seven percent of all RBI and OBI donors had multiple sex partners, an HBV-risk factor. Of 40 RBI and 10 OBI donors whose S gene was sequenced, 33 (83%) and 6 (60%), respectively, carried HBV subgenotype A2; 18 (55%) and 2 (33%), respectively, shared an identical sequence. Infection with 1 or more putative HBVimmune-escape mutants was identified in 5 (50%) of OBI but no RBI donors. CONCLUSION: RBI and OBI continue to be identified at low rates, confirming the importance of comprehensive HBV DNA screening of US blood donations. HBV-infected donors require referral for care and evaluation and contact tracing; their HBV strains may provide important information on emergent genotypes. ABBREVIATIONS: ARC = American Red Cross; CI = confidence interval; HBcAb = hepatitis B core antibody; HBsAb = antibody to hepatitis B surface antigen; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; ID = individual; MPs = minipools; NAT = nucleic acid testing; OBI = occult HBV infection; OR = odds ratio; PCR = polymerase chain reaction; RBI = recent HBV-infected; TMA = transcription-mediated amplification From the

BACKGROUND US blood donors are tested for Trypanosoma cruzi antibodies only at their first presentation, based on studies, reviewed here, demonstrating the absence of incident infections. Reports of autochthonous human transmissions of the parasite in Texas have raised concern about the safety of one‐time testing. METHODS Positive donation frequencies were evaluated among first‐time blood donations from 2007 to 2015. Rates and their temporal changes were evaluated in an area of high T. cruzi infection and compared with rates elsewhere. Donors with positive results were surveyed for risk factors and relevant demographic characteristics. RESULTS Data from 9.1 million first‐time donations were analyzed; 585 (1:15,544) were confirmed positive by radioimmunoprecipitation assay (RIPA) or concordantly positive with a second screening test/licensed assay. Seroprevalence in first‐time donors in Southern California (an area of high endemicity) was 1:2,747, or 5.7‐fold higher than the overall rate. Rates did not change over time nationally but showed a nonsignificant consistent downward trend in Southern California. The majority (92%) of donors who responded to a questionnaire had one or more T. cruzi endemic‐area risk factors. Five donors with likely autochthonous infection were identified (2007–2013); nine additional donors had RIPA false positivity. CONCLUSION T. cruzi seroprevalence among donors nationally and in an area of high enzootic infection were stable or declining. Almost all interviewed seropositive donors had known risk factors indicating likely infection years earlier while residing in T. cruzi–endemic areas. In the United States, there was no evidence of increased T. cruzi prevalence among first‐time donors.

Background SARS‐CoV‐2 RNA prevalence in blood donors from large geographic areas of high community transmission is limited. We tested residual donor plasma minipools (MPs) to determine SARS‐CoV‐2 RNAemia prevalence in six United States areas. Study Design/Methods Blood donations collected from 7 March 2020 to 25 September 2020 were tested for SARS‐CoV‐2 RNA (vRNA) in MP of 6 or 16 donations using the Grifols Procleix SARS‐CoV‐2 research‐use only (RUO) transcription‐mediated amplification (TMA) assay. Reactive results were confirmed using an alternate target region TMA assay. Reactive MPs were tested by TMA after serial dilution to estimate viral load. Testing for anti‐SARS‐CoV‐2 antibodies and infectivity was performed. Results A total of 17,995 MPs corresponding to approximately 258,000 donations were tested for vRNA. Three confirmed reactive MP16 were identified. The estimated prevalence of vRNA reactive donations was 1.16/100,000 (95% CI 0.40, 3.42). The vRNA‐reactive samples were non‐reactive for antibody, and the estimated viral loads of the (presumed single) positive donations within each MP ranged from <1000 to <4000 copies/ml. When tested, no infectivity was observed in inoculated permissive cell cultures. Discussion Blood donation MP‐nucleic acid testing (NAT) indicated that SARS‐CoV‐2 RNAemia is infrequent and, when detected, the vRNA was at low concentrations. Only one RNA‐reactive MP could be tested for infectivity for operational reasons and was not infectious in cell culture. These findings support current recommendations from international and national regulatory agencies to not screen donors by NAT.

BACKGROUND Despite West Nile virus (WNV) blood donation screening using nucleic acid testing (NAT), donors with low viral loads not detected by mini‐pool‐NAT have led to transfusion transmitted (TT)‐WNV infection. We describe a probable case of fatal TT‐WNV infection from an individual donor (ID)‐NAT non‐reactive apheresis platelet donation. STUDY DESIGN AND METHODS An apheresis platelet donation was WNV ID‐NAT reactive and prior donations from the same donor were investigated. A WNV ID‐NAT non‐reactive apheresis platelet unit collected 26 days earlier was transfused during heart transplantation to a patient who subsequently developed WNV neuroinvasive disease and expired. The source of the recipient's WNV infection was investigated. RESULTS Twenty‐six days after collection of the suspect platelet unit, a donation from the same donor was WNV ID‐NAT reactive and WNV IgM and IgG positive. In addition to the suspect platelet unit, the heart transplant recipient who developed WNV infection received 17 blood components from 24 donors. Serologic testing performed on 11 of the remaining 24 donors (46%) was WNV IgM negative. Pre‐transplant recipient and heart donor samples tested WNV RNA and IgM negative. CONCLUSION A probable case of fatal neuroinvasive TT‐WNV was linked to an infectious apheresis platelet unit undetected by WNV ID‐NAT. It is hypothesized that the suspect unit was collected early in the viremic period when viral RNA was below the limit‐of‐detection of the ID‐NAT assay. Implementation of ID‐NAT screening of blood donors has not entirely eliminated the risk of TT‐WNV infections, which may best be addressed by pathogen inactivation technologies.