Canadian Blood Donors Research Articles

Epidemiology of Hepatitis C over 28 years of monitoring Canadian blood donors: Insight into a low-risk undiagnosed population

BackgroundHepatitis C is a blood-borne infection with the hepatitis C virus (HCV) that can progress to cirrhosis and liver cancer. About 70% (50–80%) of infections become chronic and exhibit anti-HCV and HCV nucleic acid (NAT) positivity. Direct acting oral pan genotypic antiviral treatment became available in 2014 and was free for most Canadians in 2018. Clinical screening for HCV infection is risk-based. About 1% of Canadians have been infected with HCV, with 0.5% chronically infected (about 25% unaware) disproportionately impacting marginalized groups. Blood donors are in good health, are deferred for risks such as injection drug use and can provide insight into the low-risk undiagnosed population. Here we describe HCV epidemiology in first-time blood donors over 28 years of monitoring.MethodsAll first-time blood donors in all Canadian provinces except Quebec (1993 to 2021) were analyzed. All blood donations were tested for HCV antibodies (anti-HCV) and since late 1999 also HCV NAT. A case-control study was also included. All HCV positive donors (cases) since 2005 and HCV negative donors (1:4 ratio controls) matched for age, sex and location were invited to complete a risk factor interview. Separate logistic regression models for anti-HCV positivity and chronic HCV assessed the association between age cohort, sex, region and neighbourhood material deprivation and ethnocultural concentration. Case: control data were analysed by logistic regression.ResultsThere were 2,334,238 donors from 1993 to 2021 included. Prevalence for anti-HCV was 0.33% (0.30,0.37) in 1993 and 0.07% (0.05,0.09) in 2021 (p < 0.0001). In 2021 0.03% (0.01,0.04) had chronic HCV. Predictors for both anti-HCV positivity and chronic HCV were similar, for chronic HCV were male sex (OR 1.8, 1.6,2.1), birth between 1945 and 1975 (OR 7.1, 5.9,8.5), living in the western provinces (OR 1.4, 1.2,1.7) and living in material deprived (OR 2.7, 2.1,3.5) and more ethnocultural concentrated neighbourhoods (OR 1.8, 1.3,2.5). There were 318 (35.4%) of chronic HCV positive and 1272 (39.6%) of controls who participated in case control interviews. The strongest risks for acquisition were injection drug use (OR 96.9, 22.3,420.3) and birth in a high prevalence country (OR 24.5, 11.2,53.6).ConclusionsBlood donors have 16 times lower HCV prevalence then the general population. Donors largely mirror population trends and highlight the ongoing prevalence of untreated infections in groups without obvious risks for acquisition missed by risk-based patient screening.

Higher rates of laboratory-confirmed cases of syphilis in Western Canadian blood donors compared with Eastern Canadian blood donors following a period of societal re-opening.

There is a growing infectious syphilis outbreak in Western Canada. Although blood donors are screened for syphilis risks, some blood donors will still be confirmed test-positive for syphilis. This study compares the characteristics of confirmed test-positive syphilis donations in both Western Canada and Eastern Canada, November 2022-August 2023. Donors were defined as Western or Eastern Canadian. Blood donations were tested for syphilis using the PK-TP assay (Beckman Coulter PK7300 Automated Microplate System). Confirmatory Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR) assays were performed by one of two reference laboratories. An RPR titre ≥1:8 was used as a proxy for possible infectious syphilis. Rates of laboratory-confirmed syphilis were higher in Western (n = 43, 13.4/100,000 donations) versus Eastern donors (n = 19, 4.7/100,000 donations; Fisher's exact test, two-sided, p ≤ 0.0001). Most syphilis confirmations were in first-time donors (Western Canada n = 31/43, 72.1%, Eastern Canada 12/19, 63.2%). Although rates of laboratory-confirmed syphilis were higher in Western versus Eastern donors, Western donors did not have higher rates of infectious syphilis. Further studies might assess whether donors with laboratory-confirmed syphilis understood pre-donation screening questions or were completely unaware of a past infection.

Prevalence of human T-cell lymphotropic virus-1/2 in Canada over 33years: A unique contribution of blood donors to public health surveillance.

Estimate HTLV-1/2 (human T-cell lymphotropic viruses)prevalence in Canadian blood donors and the association of demographic variables with infection and their corresponding risk factors. First-time blood donors in all Canadian provinces (except Quebec) from 1990 to 2022 were included. Blood samples were tested for HTLV-1/2 by enzyme-linked immunoassay, confirmed by Western blot. Multivariable logistic regression with year, age group, sex, region, neighbourhood material deprivation, and ethnocultural composition indices predicted HTLV-1/2. Since 2005, all HTLV-1/2-positive donors (cases) were invited to participate in a risk factor interview, and 4 non-positive donors (controls per case) were matched for age, sex, and region. Case-control predictors of HTLV-1/2 were analyzed using logistic regression. There were 3,085,554 first-time donors from 1990 to 2022. HTLV-1/2 prevalence remained low (12 per 100,000 in 2022, 95% CI 6.4-23.5). The odds ratios predicting HTLV-1/2 were higher in females (2.0, 95% CI 1.5-2.6), older age groups (50 + ; 6.3, 95% CI 4.3-9.2), British Columbia and Ontario, thosematerially deprived (1.9, 95% CI 1.2-2.9), and those inethnocultural neighbourhoods (7.5, 95% CI 3.2-17.3). Most HTLV-1/2 in Ontario was HTLV-1, whereas in British Columbia half were HTLV-2. Forty-three of 149 (28.8%) cases and 172 of 413 (41.6%) controlscompleted an interview. The strongest predictor of HTLV-1/2 in case-control analysis was birth in a high-prevalence country (OR 39.8, 95% CI 7.8-204.3) but about 50% of HTLV-1 and 90% of HTLV-2 were Canadian-born. HTLV-1/2 prevalence is low in blood donors. High-prevalence country of birth accounts for about half of HTLV-1; HTLV-2 positives are usually Canadian-born. HTLV-1/2 transmission likely occurs overseas and within Canada.

SARS-CoV-2 vaccination in Canadian blood donors: Insight into donor representativeness of the general population

IntroductionBlood donors world-wide were indispensable for monitoring anti-SARS-CoV-2 antibodies generated by infection and vaccination during the pandemic. Prior to the pandemic, donor vaccination behaviours were under-studied. We aimed to compare the percentage of Canadian blood donors with SARS-CoV-2 vaccination antibodies with the percentage of the general population who received at least one dose of vaccine each month during initial vaccine deployment. We also report donor attitudes towards SARS-CoV-2 vaccination. MethodsCanadian blood donors were randomly selected for SARS-CoV-2 antibody testing over 2021 (N = 165,240). The percentage of donor samples with vaccination antibodies were compared with the percentage of general population who received at least one dose of vaccine in each month of 2021 except February. A random sample of Canadian blood donors were surveyed about vaccination intent and attitudes (N = 4,558 participated, 30.4 % response rate). ResultsThe percentages of the general population vaccinated and donors with vaccination antibodies increased from 1 % to over 90 %. General population vaccination was greater early in vaccine deployment than donors (p < 0.05), greater in donors than the general population by mid-2021 (p < 0.05) but they were similar by the end of 2021. While 52.6 % of surveyed donors had received vaccine in May 2021, a further 41.1 % intended to when eligible. Most donors thought COVID-19 infection could be serious (83.5 %) and that it was important to be vaccinated even if previously infected (77.8 %). ConclusionEarly pandemic vaccine prioritization to at-risk individuals and healthcare workers gave rise to higher general population vaccination percentages, while donors had higher vaccine antibody percentages as vaccine was deployed to progressively younger age groups. Since blood donors may be more willing to receive vaccination, under pandemic conditions they may be valuable for monitoring vaccination-induced seroprevalence.

Temporal trends in disparities in COVID-19 seropositivity among Canadian blood donors.

In Canada's largest COVID-19 serological study, SARS-CoV-2 antibodies in blood donors have been monitored since 2020. No study has analysed changes in the association between anti-N seropositivity (a marker of recent infection) and geographic and sociodemographic characteristics over the pandemic. Using Bayesian multi-level models with spatial effects at the census division level, we analysed changes in correlates of SARS-CoV-2 anti-N seropositivity across three periods in which different variants predominated (pre-Delta, Delta and Omicron). We analysed disparities by geographic area, individual traits (age, sex, race) and neighbourhood factors (urbanicity, material deprivation and social deprivation). Data were from 420319 blood donations across four regions (Ontario, British Columbia [BC], the Prairies and the Atlantic region) from December 2020 to November 2022. Seropositivity was higher for racialized minorities, males and individuals in more materially deprived neighbourhoods in the pre-Delta and Delta waves. These subgroup differences dissipated in the Omicron wave as large swaths of the population became infected. Across all waves, seropositivity was higher in younger individuals and those with lower neighbourhood social deprivation. Rural residents had high seropositivity in the Prairies, but not other regions. Compared to generalized linear models, multi-level models with spatial effects had better fit and lower error when predicting SARS-CoV-2 anti-N seropositivity by geographic region. Correlates of recent COVID-19 infection have evolved over the pandemic. Many disparities lessened during the Omicron wave, but public health intervention may be warranted to address persistently higher burden among young people and those with less social deprivation.

Prevalence of Hepatitis B in Canadian First-Time Blood Donors: Association with Social Determinants of Health.

Hepatitis B is transmitted sexually, by blood contact, and vertically from mother to child. Chronic hepatitis B is often seen in immigrants from higher-prevalence countries and their Canadian-born children. We assessed the relationship between hepatitis B and social determinants of health. Included were 1,539,869 first-time Canadian blood donors from April 2005 to December 2022. All donations were tested for hepatitis B markers. Logistic regression was fit with chronic hepatitis B as the dependent variable and age, sex, year, and ethnocultural composition and material deprivation quintiles as independent variables. Chronic hepatitis B prevalence was 47.5/100,000 (95% CI 41.5-53.5, years 2017-2022). Chronic hepatitis B prevalence was elevated in males, older age groups, and those living in more materially deprived and higher ethnocultural neighbourhoods. Of 212,518 donors from 2020 to 2022 with race/ethnicity data, chronic hepatitis B prevalence was highest in East Asians. The findings are consistent with infections in immigrants, acquired in their country of origin, in their Canadian-born children and in those with other risks. As blood donors are a low-risk population unaware of their infection and unlikely to seek testing, our results highlight the ongoing public health challenges of diagnosing chronic hepatitis B and treating it when appropriate.

Hepatitis B virus genotype surveillance in Canadian blood donors and a referred patient population, 2016-2021.

Hepatitis B virus (HBV) genotypes (A-H) have a distinct geographic distribution and are highly associated with the country of birth. Canada has experienced increased immigration over the past decade, primarily from regions where HBV is endemic. This study investigated the proportions and trends of HBV genotypes within blood donor and clinical populations of Canada over the period 2016-2021. Study samples involved two cohorts: (1) Canadian blood donors (n = 246) deferred from donation due to HBV test positivity and (2) chronic HBV patients from across Canada (clinically referred population, n = 3539). Plasma or serum was extracted, and the surface antigen and/or polymerase-coding region was amplified and sequenced to determine genotype by phylogenetic analysis. Six (A-E, G) and eight (A-H) HBV genotypes were detected among deferred blood donors and the clinically referred population, respectively. Differences in HBV genotype proportions between the two cohorts were observed across Canada. Males comprised most of the referred population among genotypes A-E (p < 0.0001), except for genotypes B and C. The median age was younger among blood donors (36 years [range 17-72]) compared with the referred population (41 years [range 0-99]). Distinct trends of increasing (E, referred; B, blood donor) and decreasing genotype prevalence were observed over the study period. HBV genotypes in Canada are highly diverse, suggesting a large immigrant population. Observed trends in genotype prevalence and proportional differences among cohorts imply shifts among the HBV-infected population of Canada, which warrants continued surveillance.

Risk of variant Creutzfeldt-Jakob disease in a simulated cohort of Canadian blood donors.

No transfusion-associated cases of variant Creutzfeldt-Jakob disease (vCJD) have occurred in more than 20 years. Yet, many countries have maintained blood donor deferral criteria for vCJD. We developed a risk simulation model to reassess the need for vCJD-related deferral criteria in Canada. The model provides results separately for Héma-Québec (HQ) and Canadian Blood Services (CBS). The model used a Monte Carlo simulation approach to estimate the risk of having a vCJD-contaminated blood donation ('risk of vCJD') in a simulated cohort of 10 million donors followed for up to 85 years. The model assumed current deferral criteria for vCJD were lifted, which would allow new 'at-risk' donors to give blood. The model accounted for disease prevalence, donors' travel/immigration history, PRNP genotype at codon 129, demographics and the type of labile blood product. In the base case, the risk of vCJD was estimated at zero at both blood services. In the most pessimistic scenario, the risk of vCJD was 6.4 × 10-9 (i.e., 1 in 157 million donations) at HQ, or ≤1 in 77 million based on the upper bound of the 95% confidence interval (CI). At CBS, this risk was 4.8 × 10-8 (i.e., 1 in 21 million donations), or ≤1 in 16 million based on the upper bound of the 95% CI. vCJD poses minimal risks to the Canadian blood supply. Current vCJD deferral criteria may, therefore, be lifted with virtually no impact on safety, while significantly expanding the donor base.

SARS-CoV-2 cross-sectional seroprevalence study among public school staff in Metro Vancouver after the first Omicron wave in British Columbia, Canada

ObjectiveTo determine the SARS-CoV-2 seroprevalence among school workers within the Greater Vancouver area, British Columbia, Canada, after the first Omicron wave.DesignCross-sectional study by online questionnaire, with blood serology testing.SettingThree main...

Hepatitis B Blood Donor Screening Data: An Under-Recognized Resource for Canadian Public Health Surveillance.

Hepatitis B surveillance is essential to achieving Canada's goal of eliminating hepatitis B by 2030. Hepatitis B rates, association of infection with vaccine age-eligibility, and risk factors were analyzed among 1,401,603 first-time Canadian blood donors from 2005 to 2020. Donors were classified as having likely chronic or likely resolved/occult infections based on hepatitis B surface antigen, anti-hepatitis B core antigen, and hepatitis B nucleic acid test results. Likely chronically infected and control donors (ratio 1:4) participated in risk-factor interviews. The 2019 rate of likely chronic infection was 61.9 per 100,000 (95% CI 46.5-80.86) and 1449.5 per 100,000 for likely resolved/occult infections (95% CI 1370.7-1531.7). Likely chronic infections were higher in males (OR 3.2; 95% CI 2.7-3.7) and the vaccine-ineligible birth cohort (OR 1.9; 95% CI 1.6-2.2). The main risk factors were living with someone who had hepatitis (OR 12.5; 95% CI 5.2-30.0) and ethnic origin from a high-prevalence country (OR 8.4; 95% CI 5.9-11.9). Undiagnosed chronic hepatitis B may be more prevalent in Canada than currently determined by traditional passive hepatitis B reporting. Blood donor data can be useful in informing hepatitis B rates and evaluating vaccination programs in Canada.

Cross-Canada Variability in Blood Donor SARS-CoV-2 Seroprevalence by Social Determinants of Health.

We compared the seroprevalence of SARS-CoV-2 anti-nucleocapsid antibodies in blood donors across Canadian regions in 2021. The seroprevalence was the highest in Alberta and the Prairies, and it was so low in Atlantic Canada that few correlates were observed. Being male and of young age were predictive of seropositivity. Racialization was associated with higher seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. Living in a materially deprived neighborhood predicted higher seroprevalence, but it was more linear across quintiles in Alberta and the Prairies, whereas in British Columbia and Ontario, the most affluent 60% were similarly low and the most deprived 40% similarly elevated. Living in a more socially deprived neighborhood (more single individuals and one parent families) was associated with lower seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. These data show striking variability in SARS-CoV-2 seroprevalence across regions by social determinants of health. IMPORTANCE Canadian blood donors are a healthy adult population that shows clear disparities associated with racialization and material deprivation. This underscores the pervasiveness of the socioeconomic gradient on SARS-CoV-2 infections in Canada. We identify regional differences in the relationship between SARS-CoV-2 seroprevalence and social determinants of health. Cross-Canada studies, such as ours, are rare because health information is under provincial jurisdiction and is not available in sufficient detail in national data sets, whereas other national seroprevalence studies have insufficient sample sizes for regional comparisons. Ours is the largest seroprevalence study in Canada. An important strength of our study is the interpretation input from a public health team that represented multiple Canadian provinces. Our blood donor seroprevalence study has informed Canadian public health policy at national and provincial levels since the start of the SARS-CoV-2 pandemic.

Medication use in Canadian blood donors.

Policies regarding medication use vary between blood centres. We evaluated medication use in eligible Canadian Blood Services whole blood donors to inform possible process improvements and allow comparisons between donors and the general population. All donors are asked about medication use in the last 3 days, and medications and their reason for use are documented in our donor computer system. Donor computer records were reviewed from January 1, 2020, to March 31, 2022 to extract information on medications by donor age and sex; medications were grouped into therapeutic classes. Stability of medication use over time was determined in a random sample of 100 donors who made at least two donations in the study period. One-third of successful (eligible) donors were taking medications; of these, 80% were on one or two medications. Five classes of medication accounted for 72% of medication use, and 13 classes account for 93% of use. Use remains relatively stable over time. Medication use is common, with a few classes accounting for most use. Drop-down lists and storage of information from one donation to the next may enhance efficiency.

SARS-CoV-2 Seroprevalence among Canadian Blood Donors: The Advance of Omicron.

With the emergence of the SARS-CoV-2 Omicron variant in late 2021, Canadian public health case/contact testing was scaled back due to high infection rates with milder symptoms in a highly vaccinated population. We monitored the seroprevalence of SARS-CoV-2 nucleocapsid (anti-N) and spike protein (anti-S) antibodies in blood donors across Canada from September 2021 to June 2022 in 202,123 randomly selected samples. Multivariable logistic regression of anti-N positivity with month, age, sex, racialization, region, material and social deprivation (based on postal code) identified as independent predictors. Piece-wise logistic regression analysed the association between anti-S concentration and month, and anti-N/anti-S positivity. Infection-related seroprevalence (anti-N positive) was 4.38% (95% CI: 3.96, 4.81) in September reaching 50.70% (50.15, 52.16) in June; nearly 100% were anti-S positive throughout. Anti-N positivity was associated with younger age, male sex, the Alberta and Prairies regions, greater material deprivation and less social deprivation (p < 0.001). Anti-S concentration was high initially (3306 U/mL, IQR 4280 U/mL), increased to (13,659 U/mL, IQR 28,224 U/mL) by June (p < 0.001), following the pattern of deployment of the third and fourth vaccine doses and was higher in those that were anti-N positive (p < 0.001). Despite already high vaccination-related seroprevalence, infection-related seroprevalence increased dramatically with the emergence of the Omicron SARS-CoV-2 variant.

A Qualitative Comparison of the Abbott SARS-CoV-2 IgG II Quant Assay against Commonly Used Canadian SARS-CoV-2 Enzyme Immunoassays in Blood Donor Retention Specimens, April 2020 to March 2021.

ABSTRACTOur group has previously used laboratory and commercially developed assays to understand the IgG responses to SARS-CoV-2 antigens, including nucleocapsid (N), spike (S), and receptor binding domain (RBD), in Canadian blood donors. In this current study, we analyzed 17,428 available and previously characterized retention samples collected from April 2020 to March 2021. The analysis compared the characteristics of the Abbott SARS-CoV-2 IgG II Quant assay (Abbott anti-spike [S], Abbott, Chicago, IL) against four other IgG assays. The Abbott anti-S assay has a qualitative threshold of 50 AU/mL. The four comparator assays were the Abbott anti-nucleocapsid (N) assay and three commonly used Canadian in-house IgG enzyme-linked immunosorbent assays (ELISAs) recognizing distinct recombinant viral antigens, full-length spike glycoprotein, glycoprotein RBD, and nucleocapsid. The strongest qualitative relationship was between Sinai RBD and the Abbott anti-S assay (kappa, 0.707; standard error [SE] of kappa, 0.018; 95% confidence interval, 0.671 to 0.743). We then scored each previously characterized specimen as positive when two anti-SARS-COV-2 assays identified anti-SARS-CoV-2 IgG in the specimen. Using this composite reference standard approach, the sensitivity of the Abbott anti-S assay was 95.96% (95% confidence interval [CI], 93.27 to 97.63%). The specificity of the Abbott anti-S assay was 99.35% (95% CI, 99.21 to 99.46%). Our study provides context on the use of commonly used SARS-CoV-2 serologies in Canada and identifies how these assays qualitatively compare to newer commercial assays. Our next steps are to assess how well the Abbott anti-S assays quantitatively detect wild-type and SARS-CoV-2 variants of concern.IMPORTANCE We describe the qualitative test characteristics of the Abbott SARS-CoV-2 IgG II Quant assay against four other anti-SARS-CoV-2 IgG assays commonly used in Canada. Although there is no gold standard for identifying anti-SARS-CoV-2 seropositivity, aggregate standards can be used to assess seropositivity. In this study, we used a specimen bank of previously well-characterized specimens collected between April 2020 and March 2021. The Abbott anti-S assay showed the strongest qualitative relationship with a widely used laboratory-developed IgG assay for the SARS-CoV-2 receptor binding domain. Using the composite reference standard approach, we also showed that the Abbott anti-S assay was highly sensitive and specific. As new anti-SARS-CoV-2 assays are developed, it is important to compare their test characteristics against other assays that have been extensively used in prior research.

Changing Patterns of SARS-CoV-2 Seroprevalence among Canadian Blood Donors during the Vaccine Era.

ABSTRACTWe monitored the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (anti-N; proxy of natural infection) and spike protein (anti-S; proxy for humoral immunity) antibodies in blood donors across Canada from January to November 2021. The first and second doses of vaccine were deployed over this time. Anti-N seroprevalence remained low overall (about 5% or lower) from January to November but was higher in racialized groups, younger age groups, and those living in materially deprived neighborhoods. Anti-S seroprevalence corresponded with the roll out of vaccines across the country, increasing in April in older donors and then progressively to younger age groups consistent with vaccination policies targeting oldest to youngest. By November, close to 100% of blood donors were positive for anti-S. Anti-S concentrations peaked by July and began waning by September to November particularly in older donors. These data have informed national and provincial public health policy in Canada throughout vaccination rollout.IMPORTANCE Throughout the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, our blood donor seroprevalence study has informed Canadian public health policy at national and provincial levels. We describe the only continuously running national seroprevalence study in Canada, which spans the full length of the pandemic and per capita is one of the largest programs in the world. The benefit of seroprevalence studies is that they identify a broad range of asymptomatic and symptomatic infection histories that may not be identified with active SARS-CoV-2 nucleic acid testing programs or when case definitions change. As vaccination was deployed in Canada, we estimated the proportion of donors with vaccine-related antibodies and developed population-level estimates of SARS-CoV-2 spike antibody concentrations. Monthly predictive mathematical models and our results engaged public health organizations in new ways. In the future, we intend to continue to expand on these interactions with provincial and national public health teams.

Estimating SARS-CoV-2 Seroprevalence in Canadian Blood Donors, April 2020 to March 2021: Improving Accuracy with Multiple Assays.

ABSTRACTWe have previously used composite reference standards and latent class analysis (LCA) to evaluate the performance of laboratory assays in the presence of tarnished gold standards. Here, we apply these techniques to repeated, cross-sectional study of Canadian blood donors, whose sera underwent parallel testing with four separate SARS-CoV-2 antibody assays. We designed a repeated cross-sectional design with random cross-sectional sampling of all available retention samples (n = 1500/month) for a 12 -month period from April 2020 until March 2021. Each sample was evaluated for SARS-CoV-2 IgG antibodies using four assays an Abbott Architect assay targeting the nucleocapsid antigen (Abbott-NP, Abbott, Chicago IL) and three in-house IgG ELISAs recognizing distinct recombinant viral antigens: full-length spike glycoprotein (Spike), spike glycoprotein receptor binding domain (RBD) and nucleocapsid (NP). We used two analytic approaches to estimate SAR-CoV-2 seroprevalence: a composite reference standard and LCA. Using LCA to estimate true seropositivity status based on the results of the four antibody tests, we estimated that seroprevalence increased from 0.8% (95% CI: 0.5–1.4%) in April 2020 to 6.3% (95% CI: 5.1–7.6%) in March 2021. Our study provides further support for the use of LCA in upcoming public health crises, epidemics, and pandemics when a gold standard assay may not be available or identifiable.IMPORTANCE Here, we describe an approach to estimating seroprevalence in a low prevalence setting when multiple assays are available and yet no known gold standard exists. Because serological studies identify cases through both diagnostic testing and surveillance, and otherwise silent, unrecognized infections, serological data can be used to estimate the true infection fatality ratio of a disease. However, seroprevalence studies rely on assays with imperfect sensitivity and specificity. Seroreversion (loss of antibody response) also occurs over time, and with the advent of vaccination, distinction of antibody response resulting from vaccination as opposed to antibody response due to infection has posed an additional challenge. Our approach indicates that seroprevalence on Canadian blood donors by the end of March 2021was less than 10%. Our study supports the use of latent class analysis in upcoming public health crises, epidemics, and pandemics when a gold standard assay may not be available or identifiable.

SARS-CoV-2 Virus-Like Particle Neutralizing Capacity in Blood Donors Depends on Serological Profile and Donor-Declared SARS-CoV-2 Vaccination History.

ABSTRACTThis study attempted to understand the levels of neutralizing titers and the breadth of antibody protection against wild-type and variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Canadian blood donors during the first 3 months of 2021. During this period, it is unlikely that many of the blood donors had received a second dose, since vaccine rollout had not yet ramped up, and less than 2% of the Canadian population had received a second dose of vaccine. A repeated cross-sectional design was used. A random cross-sectional sampling of all available Canadian Blood Services retention samples (n = 1,500/month) was drawn monthly for January, February, and March 2021. A tiered testing approach analyzed 4,500 Canadian blood donor specimens for potential evidence of a signal for anti-spike (anti-S), anti-receptor-binding domain (anti-RBD), and anti-nucleocapsid protein (anti-N). Specimens were stratified based on donor-declared vaccination history and then stratified on the presence or absence of anti-N as follows: (i) “vaccinated plus anti-N” (n = 5), (ii) “vaccinated and no anti-N” (n = 20), (iii) “unvaccinated plus anti-N” (n = 20), and (iv) “unvaccinated and no anti-N” (n = 20). Randomized specimens were then characterized for neutralizing capacity against wild-type as well as SARS-CoV-2 variants of concern (VOCs) (Alpha [B.1.1.7], Beta [B.1.351], Gamma [P.1], and Delta [B.1.617.2]) using S-pseudotyped virus-like particle (VLP) neutralization assays. There was no neutralizing capacity against wild-type and VOC VLPs within the “no vaccine and no anti-N” group. Neutralization of Beta VLPs was less than wild-type VLPs within “vaccinated plus anti-N,” “vaccinated and no anti-N”, and “unvaccinated plus anti-N” groups.IMPORTANCE In the first 3 months of 2021 as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination was in the initial stages of a mass rollout, Canadian blood donors had various levels of humoral protection against wild-type and variant of concern (VOC) SARS-CoV-2. Very few Canadians would have received a second dose of a SARS-CoV-2 vaccine. In this study, we identified elevated levels of neutralizing capacity, albeit with reduced neutralization capacity against one or more SARS-CoV-2 strains (wild type and VOCs) in vaccinated blood donors. This broad neutralizing response we present regardless of evidence of natural SARS-CoV-2 infection. Neutralizing capacity against wild type and VOCs varied significantly within the unvaccinated group, with one subset of unvaccinated plasma specimens (unvaccinated and no anti-N) having no measurable wild type- nor variant-neutralizing capacity. The study is important because it indicates that vaccination can be associated with a broad neutralizing antibody capacity of donor plasma against SARS-CoV-2 VOCs.

Resistance of SARS-CoV-2 beta and gamma variants to plasma collected from Canadian blood donors during the spring of 2020.

BackgroundThis pilot study assesses the ability of plasma collected from Canadian blood donors in the first wave of the SARS‐CoV‐2 pandemic to neutralize later SARS‐CoV‐2 variants of concern (VOCs).Study design and methodsA repeated cross‐sectional design was used, and a random cross‐sectional sample of all available Canadian Blood Services retention samples (n = 1500/month) was drawn monthly for April and May of 2020. Qualitative IgG analysis was performed on aliquots of specimens using anti‐spike, anti‐receptor binding domain, and anti‐nucleocapsid protein enzyme‐linked immunosorbent assays as well as the Abbott Architect SARS CoV‐2 IgG assay (Abbott Laboratories) against the anti‐nucleocapsid protein. Selected plasma specimens were then assessed for neutralization against VOCs using pseudotyped lentivirus inhibition assays as well as plaque reduction neutralization test 50% (PRNT50).ResultsSix specimens with a high neutralizing titer against wild‐type SARS‐CoV‐2 and three specimens with a low neutralizing titer against wild‐type SARS‐CoV‐2 were chosen for further analysis against VOCs. Four of six high neutralizing titer specimens had a reduced neutralizing capacity against beta VOCs by both neutralization methods. Three of six high neutralizing titer specimens had reduced neutralization capacity against gamma VOCs.ConclusionsThis preliminary data can be used as a justification for limiting the use of first wave plasma products in upcoming clinical trials but cannot be used to speculate on general trends in the immunity of Canadian blood donors to SARS‐CoV‐2.

Hepatitis E in Canadian blood donors.

Hepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine as studies on blood donors and other populations demonstrate that the prevalence of endemic cases is higher than previously recognized and the risk to vulnerable transfusion recipients is not insignificant. We carried out an HEV prevalence study on 13,993 Canadian blood donors with polymerase chain reaction (PCR) testing on all donors and antibody testing on a subset of 4102 donors. HEV antibody-positive and age- and sex-matched antibody-negative donors were invited to participate in a scripted telephone interview about risk factors. There were no PCR-positive samples found (95% confidence interval [CI], 0%-0.026%). The seroprevalence of HEV in our tested population was 5.9% (95% CI, 5.16%-6.59%). HEV antibody positivity was associated with male sex and increasing age. In case-control analysis history of living outside Canada (odds ratio [OR], 2.9; 95% CI, 1.56-5.32) and contact with farm animals (OR, 1.5; 95% CI, 1.01-2.28) were associated with HEV seropositivity. This is the largest data set to date on HEV infection in Canada. Results suggest low lifetime exposure to HEV and that infectious donations are rare.

A large national study of ferritin testing in Canadian blood donors.

We assessed risk groups for iron deficiency and the feasibility and efficacy of ferritin testing in a large blood center. Donors were informed of possible testing in the predonation pamphlet. Plasma ferritin was measured on retention samples (n = 12,595) from representative clinics. Low-ferritin donors (<25 µg/L) were sent a letter and information sheet and not called for 6 months. Ferritin testing was repeated on 25% of donors; donor return rate and frequency were monitored. Low-ferritin donors represented 2.9% of first-time and reactivated (no donation in past 12 months) male donors, 32.2% of first-time and reactivated female donors, 41.6% of repeat male donors, and 65.1% of repeat female donors. A mean of 11.7 months after index donation, the return rate was 76% for normal and 58% for low-ferritin donors; returning low-ferritin donors had made approximately one fewer donation. Ferritin increased by 16.3 and 12.1 µg/L in male and female low-ferritin donors and decreased by 17 µg/L in male and female normal-ferritin donors. The minimum hemoglobin level will be increased to 130 g/L for male donors and the minimum interdonation interval changed to 84 days (four donations yearly) for female donors based on iron deficiency risk groups. Large-scale ferritin testing was feasible. Donors informed of low-ferritin results had a lower return rate, donated less often, and had an increase in ferritin on return, approximately 1 year after initial testing, compared to donors with normal ferritin results.