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Abstract Background Hepatitis 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. Methods All 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. Results There 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

Introduction: Blood 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. Methods: Canadian 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). Results: The 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

ABSTRACT The 50% plaque reduction neutralization assay (PRNT50) has been previously used to assess the neutralization capacity of donor plasma against wild-type and variant of concern (VOC) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging data suggest that plasma with an anti-SARS-CoV-2 level of ≥2 × 104 binding antibody units/mL (BAU/mL) protects against SARS-CoV-2 Omicron BA.1 infection. Specimens were collected using a cross-sectional random sampling approach. For PRNT50 studies, 63 previously analyzed specimens by PRNT50 versus SARS-CoV-2 wild-type, Alpha, Beta, Gamma, and Delta were analyzed by PRNT50 versus Omicron BA.1. The 63 specimens plus 4,390 specimens (randomly sampled regardless of serological evidence of infection) were also tested using the Abbott SARS-CoV-2 IgG II Quant assay (anti-spike [S]; Abbott, Chicago, IL, USA; Abbott Quant assay). In the vaccinated group, the percentages of specimens with any measurable PRNT50 versus wild-type or VOC were wild type (21/25 [84%]), Alpha (19/25 [76%]), Beta (18/25 [72%]), Gamma (13/25 [52%]), Delta (19/25 [76%]), and Omicron BA.1 (9/25 [36%]). In the unvaccinated group, the percentages of specimens with any measurable PRNT50 versus wild type or VOC were wild-type SARS-CoV-2 (16/39 [41%]), Alpha (16/39 [41%]), Beta (10/39 [26%]), Gamma (9/39 [23%]), Delta (16/39 [41%]), and Omicron BA.1 (0/39) (Fisher's exact tests, vaccinated versus unvaccinated for each variant, P

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.

ABSTRACT 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.

ABSTRACT There is evidence that COVID-19 convalescent plasma may improve outcomes of patients with impaired immune systems; however, more clinical trials are required. Although we have previously used a 50% plaque reduction/neutralization titer (PRNT50) assay to qualify convalescent plasma for clinical trials and virus-like particle (VLP) assays to validate PRNT50 methodologies, these approaches are time-consuming and expensive. Here, we characterized the ability of the Abbott severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG II Quant assay to identify high- and low-titer plasma for wild-type and variant (Alpha, Beta, Gamma, and Delta) SARS-CoV-2 characterized by both VLP assays and PRNT50. Plasma specimens previously tested in wild-type, Alpha, Beta, Gamma, and Delta VLP neutralization assays were selected based on availability. Selected specimens were evaluated by the Abbott SARS-CoV-2 IgG II Quant assay [Abbott anti-Spike (S); Abbott, Chicago, IL], and values in units per milliliter were converted to binding antibody units (BAU) per milliliter. Sixty-three specimens were available for analysis. Abbott SARS-CoV-2 IgG II Quant assay values in BAU per milliliter were significantly different between high- and low-titer specimens for wild-type (Mann-Whitney U = 42, P < 0.0001), Alpha (Mann-Whitney U = 38, P < 0.0001), Beta (Mann-Whitney U = 29, P < 0.0001), Gamma (Mann-Whitney U = 0, P < 0.0001), and Delta (Mann-Whitney U = 42, P < 0.0001). A conservative approach using the highest 95% confidence interval (CI) values from wild-type and variant of concern (VOC) SARS-CoV-2 experiments would identify a potential Abbott SARS-CoV-2 IgG II Quant assay cutoff of ≥7.1 × 103 BAU/mL. IMPORTANCE The United States Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the use of COVID-19 convalescent plasma (CCP) to treat hospitalized patients with COVID-19 in August 2020. However, by 4 February 2021, the FDA had revised the convalescent plasma EUA. This revision limited the authorization for high-titer COVID-19 convalescent plasma and restricted patient groups to hospitalized patients with COVID-19 early in their disease course or hospitalized patients with impaired humoral immunity. Traditionally our group utilized 50% plaque reduction/neutralization titer (PRNT50) assays to qualify CCP in Canada. Since that time, the Abbott SARS-CoV-2 IgG II Quant assay (Abbott, Chicago IL) was developed for the qualitative and quantitative determination of IgG against the SARS-CoV-2. Here, we characterized the ability of the Abbott SARS-CoV-2 IgG II Quant assay to identify high- and low-titer plasma for wild-type and variant (Alpha, Beta, Gamma, and Delta) SARS-CoV-2.

ABSTRACT SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman correlation coefficients between wild-type viral neutralizing antibody titers and: anti-spike (total and IgG), anti-receptor-binding-domain (RBD), and anti-N-terminal-domain (NTD) antibodies; and ACE-2 binding by RBD. We performed three secondary analyses, dichotomizing samples by the first vaccination-to-blood collection interval, second vaccination-to-blood collection interval, and by the vaccine dosing interval (all groups divided by the median), and compared correlation coefficients (Fisher’s Z test). Of 120 participants, 63 (53%) were women, 91 (76%) and 29 (24%) received BNT162b2 and mRNA-1273 vaccines, respectively. Overall, live viral neutralization was correlated with anti-spike total antibody (correlation coefficient = 0.80), anti-spike IgG (0.63), anti-RBD IgG (0.62), anti-NTD IgG (0.64), and RBD ACE2 binding (0.65). Samples with long (>158 days) first vaccination-to-blood collection and long (>71 days) second vaccination-to-blood collection intervals demonstrated higher correlation coefficients, compared with short groups. When comparing cases divided by short (≤39 days) versus long vaccine dosing intervals, only correlation with RBD-ACE-2 binding inhibition was higher in the long group. Among COVID-negative mRNA vaccinees, anti-spike antibody and ACE-2 inhibition concentrations are correlated with live viral neutralizing antibody titers. Correlation was stronger among samples collected at later durations from vaccination. IMPORTANCE Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. Using samples from 120 two-dose mRNA vaccinees without previous COVID-19, we found that live viral neutralization was correlated with COVID-19 antibody and ACE2 binding levels. When grouping samples by the time interval between vaccination and sample blood collection, samples collected over 158 days after the first vaccine and over 71 days from the second vaccine demonstrated stronger correlation between live viral neutralization titers and both antibody and ACE2 levels, in comparison to those collected earlier.

ABSTRACT Our 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.

Serological tests are important diagnostic and disease surveillance tools for addressing the COVID-19 pandemic. Here, the authors present a tri-part Nanoluciferase based assay to detect antibodies against SARS-CoV-2.

ABSTRACT We 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.

ABSTRACT While mRNA vaccines are highly efficacious against short-term COVID-19, long-term immunogenicity is less clear. We compared humoral immunogenicity between BNT162b2 and mRNA-1273 vaccines 6 months after the first vaccine dose, examining the wild-type strain and multiple Delta-variant lineages. Using samples from a prospective observational cohort study of adult paramedics, we included COVID-19-negative participants who received two BNT162b2 or mRNA-1273 vaccines, and provided a blood sample 170 to 190 days post first vaccine dose. We compared wild-type spike IgG concentrations using the Mann-Whitney U test. We also compared secondary outcomes of: receptor binding domain (RBD) wild-type antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to spike proteins from the wild-type strain and five Delta-variant lineages. We included 571 adults: 475 BNT162b2 (83%) and 96 mRNA-1273 (17%) vaccinees, with a mean age of 39 (SD = 10) and 43 (SD = 10) years, respectively. Spike IgG antibody concentrations were significantly higher (P

ABSTRACT This 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.

ABSTRACT We 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.

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.

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.

Coronavirus disease 2019 (COVID-19), the current global pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various pharmaceuticals are being developed to counter the spread of the virus. The strategy of repurposing known drugs and bioactive molecules is a rational approach. A previously described molecule, Ile-Arg-Trp (IRW), is a bioactive tripeptide that exhibits an ability to boost angiotensin converting enzyme-2 (ACE2) expression in animals and cells. Given the importance of SARS-CoV-2 S receptor binding domain (RBD)-ACE2 interaction in SARS-CoV-2 pathophysiology, we synthesized various IRW analogs intending to mitigate the RBD-ACE-2 interaction. Herein, we describe two analogs of IRW, A9 (Acetyl-Ile-Arg-Trp-Amide) and A14 (Formyl-Ile-Arg-Trp-Amide) which lowered the SARS-CoV-2 S RBD-ACE2 (at 50 µM) in vitro. The free energy of binding suggested that A9 and A14 interacted with the SARS-CoV-2 S RBD more favorably than ACE2. The calculated MMGBSA ΔG of spike binding for A9 was −57.22 kcal/mol, while that of A14 was −52.44 kcal/mol. A14 also inhibited furin enzymatic activity at various tested concentrations (25, 50, and 100 µM). We confirmed the effect of the two potent analogs using SARS-CoV-2 spike protein overexpressing cells. Both peptides lowered the protein expression of SARS-CoV-2 spike protein at the tested concentration (50 µM). Similarly, both peptides, A9 and A14 (50 µM), also inhibited pseudotyped lentiviral particles with SARS-CoV-2 Spike in ACE2 overexpressing cells. Further, the molecular dynamics (MD) calculations showed the interaction of A9 and A14 with multiple residues in spike S1 RBD. In conclusion, novel peptide analogs of ACE2 boosting IRW were prepared and confirmed through in vitro, cellular, and computational evaluations to be potential seed candidates for SARS-CoV-2 host cell binding inhibition.

Humans interact with virus-infected animal hosts, travel globally, and maintain social networks that allow for novel viruses to emerge and develop pandemic potential. There are key lessons-learned from the coronavirus diseases 2019 (COVID-19) pandemic that blood operators can apply to the next pandemic. Warning signals to the COVID-19 pandemic included outbreaks of Severe acute respiratory syndrome-related coronavirus-1 (SARS-CoV-1) and Middle East respiratory syndrome-related coronavirus (MERS-CoV) in the prior two decades. It will be critical to quickly determine whether there is a risk of blood-borne transmission of a new pandemic virus. Prior to the next pandemic blood operators should be prepared for changes in activities, policies, and procedures at all levels of the organization. Blood operators can utilize “Plan-Do-Study-Act” cycles spanning from: vigilance for emerging viruses, surveillance activities and studies, operational continuity, donor engagement and trust, and laboratory testing if required. Occupational health and donor safety issues will be key areas of focus even if the next pandemic virus is not transfusion transmitted. Blood operators may also be requested to engage in new activities such as the development of therapeutics or supporting public health surveillance activities. Activities such as scenario development, tabletop exercises, and drills will allow blood operators to prepare for the unknowns of the next pandemic.

Abstract Background The purpose of this paper is to systematically review the literature on the relationship between socioeconomic status (SES) and influenza immunization and to examine how certain measures of SES may influence interpretations of this relationship. Methods We conducted a systematic review of existing peer-reviewed literature to evaluate the above relationship in the general population. Electronic databases (MEDLINE and EMBASE) were searched from January 2012 to May 2017 to identify English-language studies relevant to this review. Studies were included where influenza vaccination was explicitly reported as the dependent variable and SES as the independent variable. We limited our review to measures of SES that focus on education, income, social class, occupation, and deprivation. Studies that measured SES using other variables (e.g., race, ethnicity, geographic location, rural or urban status, or insurance status) were excluded. Studies were also excluded if they did not report on the human population or did not analyze original data. The population of interest included all age groups, levels of health status, and sociodemographic backgrounds. The review was also limited to World Bank high-income countries. Two authors independently screened full-text articles after obtaining a Kappa score of K = 0.867. The methodological quality of manuscripts was assessed using the appraisal tools developed by the Joanna Briggs Institute. Results were qualitatively reported and synthesized. Results Of the 42 articles included in this review, 52.4% (n = 22) found that higher levels of SES resulted in higher levels of influenza vaccination; 4.5% (n = 2) reported a negative association; and 14.3% (n = 6) found no association. Just over a quarter (26.2%, n = 12) of articles reported mixed results. Conclusions There was consistently a relationship between SES and influenza immunization, which varied according to how SES was measured. It is recommended that authors be explicit in defining the SES concept they are trying to capture and that they utilize multiple measures of SES (e.g., education, income, class).

Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin-converting enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an ELISA for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of 2 viral-based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus and a spike pseudotyped viral vector–based assay.

Abstract Background Rates of Bordetella pertussis have been increasing in Alberta, Canada despite vaccination programs. Waning immunity from existing acellular component vaccines may be contributing to this. Vaccine effectiveness can be estimated using a variety of data sources including diagnostic codes from physician billing claims, public health records, reportable disease and laboratory databases. We sought to determine if diagnostic codes from billing claims (administrative data) are adequately sensitive and specific to identify pertussis cases among patients who had undergone disease-specific laboratory testing. Methods Data were extracted for 2004–2014 from a public health communicable disease database that contained data on patients under investigation for B. pertussis (both those who had laboratory tests and those who were epidemiologically linked to laboratory-confirmed cases) in Alberta, Canada. These were deterministically linked using a unique lifetime person identifier to the provincial billing claims database, which contains International Classification of Disease version 9 (ICD-9) diagnostic codes for physician visits. We examined visits within 90 days of laboratory testing. ICD-9 codes 033 (whooping cough), 033.0 (Bordetella pertussis), 033.1 (B. parapertussis), 033.8 (whooping cough, other specified organism), and 033.9 (whooping cough, other unspecified organism) in any of the three diagnostic fields for a claim were classified as being pertussis-specific codes. We calculated sensitivity, specificity, positive (PPV) and negative (NPV) predictive values. Results We identified 22,883 unique patients under investigation for B. pertussis. Of these, 22,095 underwent laboratory testing. Among those who had a laboratory test, 2360 tested positive for pertussis. The sensitivity of a pertussis-specific ICD-9 code for identifying a laboratory-confirmed case was 38.6%, specificity was 76.9%, PPV was 16.0%, and NPV was 91.6%. Conclusion ICD-9 codes from physician billing claims data have low sensitivity and moderate specificity to identify laboratory-confirmed pertussis among persons tested for pertussis.

Abstract Background We describe the epidemiology of pertussis in Alberta, Canada by person, place, and time between 2004 and 2015, identify outbreak years, and examine vaccination coverage and vaccination timeliness. Methods We used health data from Alberta’s Communicable Disease Registry System for the period of January 1, 2004 through August 31, 2015 to identify unique cases of pertussis. Unique cases were deterministically linked to data in Alberta’s immunization repository and health care insurance plan registry. Population estimates and vaccination coverage were extracted from Alberta’s online Interactive Health Data Application. We estimated pertussis incidence rates per 100,000 persons by year, age group, gender, and health zone. Outbreak years were identified using a one-sided cumulative sum (CUSUM) analysis by comparing annual incidence rates to baseline rates. Results Over the period, 3510 cases of pertussis were confirmed by laboratory testing or epidemiological linkage. Incidence rates per 100,000 persons were highest in 2004 (20.5), 2005 (13.6), and 2015 (10.4) for all age groups. Incidence rates were highest among the youngest age groups and decreased as age groups increased. Based on CUSUM analysis, 2008 and 2012 met the criteria for outbreak years. Vaccination coverage was over 90% among the general population, however only 61% of cases received at least one dose. About 60% of cases were diagnosed 5+ years after receiving the vaccine. Approximately 87–91% of vaccinated cases did not receive the first three vaccine doses in a timely manner. Conclusion Pertussis incidence rates fluctuated over the period across all age groups. The majority of cases had no record of vaccination or were delayed in receiving vaccines. CUSUM analysis was an effective method for identifying outbreaks.

Full-genome analysis was conducted on the first isolate of a highly pathogenic avian influenza A(H5N1) virus from a human in North America. The virus has a hemagglutinin gene of clade 2.3.2.1c and is a reassortant with an H9N2 subtype lineage polymerase basic 2 gene. No mutations conferring resistance to adamantanes or neuraminidase inhibitors were found.

Objectives: The purpose of this study was to undertake an epidemiological analysis of an increase in Bordetella pertussis activity during the period January 1 to August 31, 2012 in Alberta, Canada. B. pertussis testing was done using an IS481 real-time PCR assay with PCR-positive and indeterminate specimens cultured and stored for further analysis. Methods: Laboratory data were linked to Alberta Health (AH) cases that were reported in the Communicable Disease Reporting System (CDRS) to identify case isolates; exclusion criteria were used to avoid biases. Case isolates were analyzed at the National Microbiology Laboratory (NML) by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Pertussis immunization data were extracted from the Alberta Provincial Immunization Repository (Imm/ARI) and linked to the pertussis cases. Results: Using PFGE and MLST, 52 case isolates could be divided into two main sequence type groups: 41 cases belonged to the ST-1 group (ST-1 and the novel ST-19) and 11 cases belonged to the ST-2 group (ST-2 and the novel ST-20). Of the total cases genotyped (N = 52), 18 (34.6%) had a history of immunization, 28 (53.8%) were not immunized, and six (11.6%) had an unknown immunization history. Of the total non-immunized cases, 25/28 (89.2%) belonged to the ST-1 group. Furthermore, of the 41 ST-1 group cases, 25 were not immunized compared to only three of the ST-2 group cases (p = 0.0004, Fisher's exact test). Conclusions: This study shows the dominance of two genotypes of B. pertussis in our jurisdiction and indicates less pertussis immunization in individuals infected with the ST-1 group.

We investigated the proportions of mono vs. mixed infections for human metapneumovirus (hMPV) as compared to adenovirus (ADV), four types of coronavirus (CRV), parainfluenza virus (PIV), RSV, and enterovirus/rhinovirus (ERV) in Alberta, Canada. Using the Data Integration for Alberta Laboratories (DIAL) platform, 26,226 respiratory specimens at ProvLab between 1 July 2009 and 30 June 2012 were selected and included in the study. Using the Respiratory Virus Panel these specimens tested positive for one or more respiratory virus and negative for influenza A and B. From our subset hMPV was the fourth most common virus (n=2,561) with 373 (15%) identified as mixed infection using DIAL. Mixed infection with hMPV was most commonly found in infants less than 6 months old and ERV was most commonly found in mixed infection with hMPV (230/373, 56%) across all age groups. The proportion of mixed-infection vs. mono-infection was highest for ADV (46%), followed by CRV 229E (32%), CRV HKU1 (31%), CRV NL63 (28%), CRV OC43 (23%), PIV (20%), RSV (17%), hMPV (15%) and ERV (13%). hMPV was significantly more likely to be identified in mono infection as compared with ADV, CRV, PIV, and RSV with the exception of ERV [p < 0.05].