Rapid and reliable detection of Leishmania antibodies in canine serum with double-antigen sandwich homogeneous chemical luminescence.

BACKGROUND: Leishmaniasis, caused by Leishmania spp. parasites, is an important zoonotic disease globally, posing severe threats to humans and animals. In the absence of effective vaccines, reliable serological diagnostic methods are critical for disease control. However, the enzyme-linked immunosorbent assay (ELISA) and immunochromatographic assay have limitations due to complexity, time required and/or sensitivity. Therefore, our objective was to develop an accurate, rapid and user-friendly detection method of canine leishmania antibody based on double-antigen sandwich homogeneous chemical luminescence. METHODS: Homogeneous chemiluminescent technology was employed, and expressed recombinant fusion proteins containing full-length K9, K39 and K26 repeat sequences were used as diagnostic antigens. To establish a dual-antigen sandwich serological assay capable of detecting various antibody types, a factorial design was used to optimize concentrations of diagnostic antigen-receptor microspheres and of biotinylated diagnostic antigens, as well as of reaction solution composition and reaction duration. To evaluate and validate this newly developed method, we collected 41 Leishmania-positive serum samples, 30 Leishmania-negative control serum samples and 78 clinical serum samples for which no diagnostic information was available. Comparative analyses were performed using parasitological testing and an indirect ELISA as reference methods, focusing on diagnostic sensitivity and specificity. RESULTS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the purification of the diagnostic antigens, which exhibited clear bands without impurities. Based on results from the 41 Leishmania-positive samples and 30 Leishmania-negative samples, there was sufficient sensitivity to detect samples diluted up to 256-fold, with analytical specificity of 100%. Overall diagnostic sensitivity was 100% and diagnostic specificity was 93.3%. Diagnostic performance was highly consistent between the newly developed method and the indirect ELISA (Kappa = 0.82, P < 0.01). Testing could be completed within 35 min with the new method CONCLUSIONS: We have developed a novel double-antigen sandwich homogeneous chemical luminescence method to detect canine Leishmania antibodies, with high sensitively and specificity, a short incubation interval and a simple protocol. This streamlined approach not only offers a sensitive and efficient method for clinical diagnosis but also has great potential for use in automated testing.

SARS-CoV-2 antibody levels and long COVID occurrence in blood donors.

BACKGROUND: Long COVID is a common condition lacking consensus definition; determinants remain incompletely understood. Characterizing immune profiles associated with long COVID could support the development of preventive and therapeutic strategies. METHODS: We used a survey to investigate blood donors' infection/vaccination history and acute/persistent symptoms following COVID-19. The prevalence of long COVID was evaluated using self-report and an adapted definition from the RECOVER study. We evaluated factors associated with long COVID, focusing on anti-spike and anti-nucleocapsid SARS-CoV-2 antibodies. Lastly, we investigated long COVID clinical subphenotypes using hierarchical clustering. RESULTS: Of 33,610 participants, 16,003 (48%) reported having had COVID-19; 1853 (12%) had self-reported long COVID, 685 (4%) met an adapted RECOVER definition, and 2050 (13%) met at least one definition. Higher anti-nucleocapsid levels measured 12-24 weeks post-infection were associated with higher risk of self-reported and RECOVER long COVID. Higher anti-spike IgG levels measured 12-24 weeks post-infection were associated with lower risk of self-reported long COVID. Higher total anti-spike measured 24-48 weeks post-infection was associated with lower risk of RECOVER long COVID. Cluster analysis identified four clinical subphenotypes; patterns included neurological and psychiatric for cluster 1; neurological and respiratory for cluster 2; multi-systemic for cluster 3; and neurological for cluster 4. DISCUSSION: Long COVID prevalence in blood donors varies depending on the adopted definition. Anti-SARS-CoV-2 antibodies were time-dependently associated with long COVID; higher anti-nucleocapsid levels were associated with higher risk; and higher anti-spike levels were associated with lower risk of long COVID. Different underlying pathophysiologic mechanisms may be associated with distinct clinical subphenotypes.

Differences in SARS-CoV-2 antibodies depending on age, blood group, and sex in a Swedish blood donor cohort.

This study aimed to describe differences in prevalence and the long-term presence of nucleocapsid antibodies (N-antibodies) elicited by SARS-CoV-2 infection in a Swedish blood donor population not subjected to lockdown. We tested 20,651 blood donor samples for nucleocapsid antibodies from the beginning of March 2020 and 27 months onwards using the Roche Elecsys Anti-SARS-CoV-2 assay. The proportion of positive SARS-CoV-2 antibody samples was determined each week. After the exclusions of one-time donors and subjects with incomplete data, 19,726 samples from 4003 donors remained. Differences in antibody prevalences stratified for age, sex, and blood groups (ABO and RhD) were determined, as well as antibody loss and recovery. Lower antibody prevalence was seen for older donors, blood group AB, and RhD-negative subjects. A significant decrease in antibody titer between the first and the second antibody-positive donation was seen for the whole study group, females, older subjects, blood group O, AB, and RhD-positive subjects. The titer waned below the detection limit in 60 (3.0%) of 1983 N-antibody-positive donors, and for 18 of these donors, a second episode with antibodies was detected. We showed that N-antibodies persist for months or years and that surprisingly few antibody-positive donors lost their antibodies. We also conclude that antibody prevalence in a Swedish population never subject to lockdown did not apparently differ from populations that were subject to stricter regulations.

Nine-Month Trend of IgG Antibody Persistence and Associated Symptoms Post-SARS-CoV-2 Infection.

Between 2 and 8.5% of patients who recover from COVID-19 do not develop antibodies, and the durability of IgG antibodies is under scrutiny. Therefore, the presence and persistence of IgM and IgG antibodies were evaluated in a group of patients diagnosed with SARS-CoV-2 from May to August 2020. Out of 2199 suspected COVID-19 cases, 1264 were confirmed for SARS-CoV-2 by rRT-PCR; 328 consented to participate in the study, with 220 participants followed for 9 months, including 124 men (56%) and 96 women (44%). The primary symptoms were headache, dry cough, and fever. IgG antibodies developed in 95% of patients within 4 weeks post-diagnosis, and a second evaluation at 9 months showed that 72.7% still had detectable IgG antibodies. The presence of IgM in one individual (0.45%) suggested the possibility of reinfection.

Long-term outcomes of the Italian Mycobacterium avium subspecies paratuberculosis control programme for dairy cattle.

BACKGROUND: The considerable epidemiological and economic implications of paratuberculosis, caused by Mycobacterium avium subspecies paratuberculosis (MAP), have placed importance on control efforts aimed at preventing MAP transmission. In this context, Italy issued national guidelines for the control and status certification of MAP in dairy cattle in 2013. METHODS: We assessed the long-term outcomes of the Italian MAP control programme for 14 dairy farms located in northern Italy by retrospectively reviewing the results of yearly serological tests, presence of clinical cases, MAP faecal shedding in serologically positive animals, farm management and health ranking as indicators of herd health between 2014 and 2021. RESULTS: A significantly higher number of serologically positive animals were observed between 2014 and 2016 than between 2017 and 2021, as well as an improving trend in the paratuberculosis health ranking for nine of the 14 farms. No clinical cases were reported. MAP shedding was detected in 9.4% of serologically positive animals. Discarding colostrum and prioritised culling of seropositive animals assisted by adoption of standardised serological testing were presumed to have a key role in MAP control, despite the reluctance of some farmers to address hygienic issues and improve the separation of calves from adult animals. LIMITATIONS: The small number of farms included in this study and the fact that these were not randomly selected may limit the generalisability of the findings. CONCLUSIONS: The Italian paratuberculosis control plan has provided measures to limit the uncontrolled spread of MAP infection within and between herds by promoting animal trading between farms certified as negative or low risk.

SARS-CoV-2 immunoassays in a predominantly vaccinated population: Performances and qualitative agreements obtained with two analytical approaches and four immunoassays.

BACKGROUND AND OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys are typically analysed by applying a fixed threshold for seropositivity ('conventional approach'). However, this approach underestimates the seroprevalence of anti-nucleocapsid (N) in vaccinated individuals-who often exhibit a difficult-to-detect anti-N response. This limitation is compounded by delays between the onset of infection and sample collection. To address this issue, we compared the performance of four immunoassays using a new analytical approach ('ratio-based approach'), which determines seropositivity based on an increase in anti-N levels. MATERIALS AND METHODS: Two groups of plasma donors and four immunoassays (Elecsys total anti-N, VITROS total anti-N, Architect anti-N Immunoglobulin G (IgG) and in-house total anti-N) were evaluated. First-group donors (N = 145) had one positive SARS-CoV-2 polymerase chain reaction (PCR) test result and had made two plasma donations, including one before and one after the PCR test (median = 27 days post-PCR). Second-group donors (N = 100) had made two plasma donations early in the Omicron wave. RESULTS: Among first-group donors (97.9% vaccinated), sensitivity estimates ranged from 60.0% to 89.0% with the conventional approach, compared with 94.5% to 98.6% with the ratio-based approach. Among second-group donors, Fleiss's κ ranged from 0.56 to 0.83 with the conventional approach, compared with 0.90 to 1.00 with the ratio-based approach. CONCLUSION: With the conventional approach, the sensitivity of four immunoassays-measured in a predominantly vaccinated population based on samples collected ~1 month after a positive test result-fell below regulatory agencies requirement of ≥95%. The ratio-based approach significantly improved the sensitivities and qualitative agreement among immunoassays, to the point where all would meet this requirement.

[Effectiveness and safety of COVID-19 vaccines in healthcare workers in Buenos Aires City, Argentina.] / Efectividad y seguridad de las vacunas contra la Covid-19 en trabajadores de la salud en la Ciudad de Buenos Aires, Argentina.

Introduction: COVID-19 vaccination aids pandemic limitation. In Argentina, three vaccines are approved, and healthcare workers are priorized (HCWs). The aim was to determine the effectiveness of COVID-19 vaccines, analyzing change in Immunoglobulin G levels and the incidence of new COVID-19 cases up to 12 months after the second dose. Methods: Prospective cohort of HCWs between March 2021- 2022. COVIDAR IgG test was used to measure antibodies. A mixed-effects model was employed to compare the levels of immunoglobulin G at different time points, Kaplan Meier was used to estimate incident COVID-19 cases. Results: 82 participants were included Adverse events were frequent but mild. All participant showed positive antibody at 12 months. Antibodies levels showed an increase one year after 2nd dose. Sinopharm took a long time to yield positive results. More than half of the people had mild COVID-19 disease. Conclusion: COVID-19 vaccines are safe and effective.

Introducción: La vacunación COVID-19 ayuda a limitar la pandemia. En Argentina, se aprobaron tres vacunas y se priorizó a los trabajadores de la salud (TDS). El objetivo fue determinar la efectividad de las vacunas COVID-19, analizando el cambio en los niveles de Inmunoglobulina G y la incidencia de nuevos casos de COVID-19 hasta 12 meses después de la segunda dosis. Métodos: Cohorte prospectiva de TDS entre marzo de 2021 y 2022. Se utilizó la prueba COVIDAR IgG para medir los anticuerpos. Se empleó un modelo de efectos mixtos para comparar los niveles de inmunoglobulina G en diferentes puntos temporales, se utilizó Kaplan Meier para estimar los casos de COVID-19 incidentes. Resultados: se incluyeron 82 participantes. Los eventos adversos fueron frecuentes pero leves. Todos los participantes mostraron anticuerpos positivos a los 12 meses. Los niveles de anticuerpos mostraron un aumento un año después de la segunda dosis. Sinopharm tardó mucho tiempo en arrojar resultados positivos. Más de la mitad de las personas tuvieron una enfermedad leve de COVID-19. Conclusión: Las vacunas COVID-19 son seguras y efectivas.

Behavioural Factors Influencing the Intention to Adopt Sheep Scab Control Measures in Northern Ireland.

Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, is an endemic disease in the Northern Ireland (NI) sheep flock and constitutes significant economic and welfare burdens for the NI farming industry. Despite its endemic nature, historically, little research has been undertaken to support the control of the disease in NI. This study offers the first attempt to analyse the psychological and behavioural factors influencing farmers' intentions to implement effective sheep scab control measures in NI. To achieve our objective, quantitative data from a sample of 126 sheep farmers were statistically analysed using an extended theory of planned behaviour approach in an ordered logistic regression modelling framework. Our analyses showed that sheep scab remains an issue of concern in Northern Ireland. The attitudes of the farmers, as well as perceived behavioural control, emotional effect, membership of Business Development Groups (BDGs), and higher education qualifications, were found to be statistically significant factors influencing farmers' intentions to adopt sheep scab control measures. This study provides a solid foundation for how to promote behavioural changes among sheep farmers to improve their ability to implement effective disease control measures, helping to tackle this challenging disease in a more sustainable way in the future.

Enhancing detection of SARS-CoV-2 re-infections using longitudinal sero-monitoring: demonstration of a methodology in a cohort of people experiencing homelessness in Toronto, Canada.

BACKGROUND: Accurate estimation of SARS-CoV-2 re-infection is crucial to understanding the connection between infection burden and adverse outcomes. However, relying solely on PCR testing results in underreporting. We present a novel approach that includes longitudinal serologic data, and compared it against testing alone among people experiencing homelessness. METHODS: We recruited 736 individuals experiencing homelessness in Toronto, Canada, between June and September 2021. Participants completed surveys and provided saliva and blood serology samples every three months over 12 months of follow-up. Re-infections were defined as: positive PCR or rapid antigen test (RAT) results > 90 days after initial infection; new serologic evidence of infection among individuals with previous infection who sero-reverted; or increases in anti-nucleocapsid in seropositive individuals whose levels had begun to decrease. RESULTS: Among 381 participants at risk, we detected 37 re-infections through PCR/RAT and 98 re-infections through longitudinal serology. The comprehensive method identified 37.4 re-infection events per 100 person-years, more than four-fold more than the rate detected through PCR/RAT alone (9.0 events/100 person-years). Almost all test-confirmed re-infections (85%) were also detectable by longitudinal serology. CONCLUSIONS: Longitudinal serology significantly enhances the detection of SARS-CoV-2 re-infections. Our findings underscore the importance and value of combining data sources for effective research and public health surveillance.

Association between severe acute respiratory syndrome coronavirus 2 antibody status and reinfection: A case-control study nested in a Colorado-based prospective cohort study.

The association between the presence of detectable antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV-2 reinfection is not well established. The objective of this study was to determine the association between antibody seronegativity and reinfection. METHODS: Participants in Colorado, USA, were recruited between June 15, 2020, and March 28, 2021, and encouraged to complete SARS-CoV-2 molecular ribonucleic acid (RNA) and serology testing for antibodies every 28 days for 10 months. Participants with reinfections (positive SARS-CoV-2 RNA test ≥ 90 days after the first positive RNA test) were matched to controls without reinfections by age, sex, date of the first positive RNA test, date of the last serology test, and serology test type. Using conditional logistic regression, case patients were compared to control patients on the last serologic test result, with adjustment for demographic and clinical confounders. RESULTS: The cohort (n = 4,235) included 2,033 participants with ≥ 1 positive RNA test, of whom 120 had reinfection. Among the 80 case patients who could be matched, the last serologic test was negative in 12 of the cases (15.0 %) whereas the last serologic test was negative in 77 of 1,034 (7.5 %) controls. Seronegativity (adjusted OR [aOR] 2.24; 95 % CI 1.07, 4.68), Hispanic ethnicity (aOR 1.87; 95 % 1.10, 3.18), and larger household size (aOR 1.15; 95 % 1.01, 1.30 for each additional household member) were associated with reinfection. CONCLUSIONS: Seronegative status, Hispanic ethnicity, and increasing household size were associated with reinfection. Serologic testing could be considered to reduce vaccine hesitancy in higher risk populations.

Eliminating mother-to-child transmission of hepatitis B virus: practice and progress in Baoan, a national pilot district of China.

BACKGROUND: While mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a significant challenge in China, research investigating the effectiveness of the September 2017 pilot program to eliminate MTCT of HIV, syphilis, and HBV is limited. Baoan district, which has a higher-than-average rate of hepatitis B infection among pregnant women and strong support from the government, was one of six national pilot districts selected for the program. Therefore, this study aims to assess the progress and implementation of the elimination of MTCT of HBV in Baoan district over a period of 5 years. METHODS: Data was collected from the national information system for the prevention of MTCT, registration forms, and follow-up forms of pregnant women and their live births from 2018 to 2022. Joinpoint models were used to analyze changing trends over time, calculating annual percentage change (APC) and the corresponding 95% confidence interval (95%CI). Multivariate logistic regression models were used to analyze risk factors for HBV MTCT. RESULTS: From 2018 to 2022, the coverage of HBV screening during pregnancy increased from 98.29 to 99.55% (APC = 0.30, P = 0.012). The coverage of HBV early screening within 13 gestational weeks increased from 40.76 to 86.42% (APC = 18.88, P = 0.033). The prevalence of maternal HBV infection declined by an APC of - 3.50 (95% CI -6.28 ~ - 0.63). The coverage of antiviral therapy among high-risk pregnant women increased from 63.59 to 90.04% (APC = 11.90, P = 0.031). Coverage for timely administration of hepatitis B immunoglobulin, hepatitis B birth dose vaccine, and three-dose hepatitis B vaccination remained consistently above 97.50%. The coverage of post-vaccination serological testing (PVST) in high-risk infants was 56.15% (1352/2408), and the MTCT rate of HBV was 0.18%. Mothers with high-school education or below (OR = 3.76, 95% CI 1.04 ~ 13.60, P = 0.04) and hepatitis B e antigen (HBeAg) positivity (OR = 18.89, 95% CI 1.98 ~ 18.50, P = 0.01) had increased MTCT risk. CONCLUSIONS: The implementation of comprehensive prevention strategies in Baoan district, including screening, treatment, and immunoprophylaxis, has proven effective in maintaining the MTCT of HBV at an extremely low level. However, it remains crucial to raise public awareness, specifically on the importance of improving the coverage of PVST for infants exposed to HBV.

Acceptability of self-administered antigen test for COVID-19 in the Philippines.

OBJECTIVES: In response to the Omicron surge in early 2022, the HTA Philippines evaluated the acceptability of Filipinos in using self-administered antigen tests (SAAgTs) as part of COVID-19 HTAs in the Philippines. METHODS: Scoping review from literature databases was initially conducted to identify preset codes in the use of SAAgT. Preset codes were used to establish the questions for focus group discussions (FGDs). Semi-structured questionnaires were created through Delphi technique. FGDs with four stakeholder groups (i.e., nine healthcare workers [HCWs], seven representatives of at-risk groups, six economic frontliners, and seven representatives of micro-small-medium-sized enterprises) were conducted. RESULTS: Discomfort in being a target of stigma and being prescribed an "illness identity" when suspected or confirmed COVID-19-positive, along with lack of confidence to perform self-test, caused hesitancy in self-testing among participants. The need for subsidies for test kits from the government or employers was emphasized to increase its accessibility. Having a designated access point and reporting system for SAAgT was highlighted to avoid nepotism (padrino system attributed to debt of gratitude), inequitable distribution, and lapses in reporting. A participatory approach to education was perceived as crucial to reduce any misconceptions associated with the use of SAAgT. CONCLUSIONS: All FGD groups expressed favorable reviews on the implementation of SAAgT because it can potentially reduce the burden of health facility-administered tests. These findings were considered by the HTA Council in the recommendation of SAAgT as part of the overarching national strategies for the diagnosis and screening of COVID-19.

Randomized controlled trial comparing the costs of gastric cancer screening systems between serological risk-based upper gastrointestinal endoscopy and the existing barium photofluorography: gastric cancer screening labeled by serum examination in place of aged gastric cancer organized screening systems (GALAPAGOS study).

BACKGROUND: Although the risk of gastric cancer can be stratified according to Helicobacter pylori (H. pylori) IgG antibody titer and pepsinogen levels (ABC classification), a population-based gastric cancer screening system combining serological tests and endoscopy has not been introduced. This study aimed to compare the total testing cost per participant between the ABC classification method and the existing protocol. METHODS: Using the minimization method with sex and age as allocation factors, 1206 participants were randomly assigned to the following two methods for a 5-year intervention: barium photofluorography as primary examination followed by detailed examination with upper gastrointestinal endoscopy (Ba-Endo) and risk-based upper gastrointestinal endoscopy by ABC classification (ABC-Endo). The primary endpoint was the total testing cost per participant over a 5-year period. The secondary endpoint was the expense required to detect one gastric cancer. RESULTS: The total testing cost per participant was 39,711 yen in Ba-Endo (604 participants) and 45,227 yen in ABC-Endo (602 participants), with the latter being significantly higher (p < 0.001). During the intervention period, gastric cancer was found in 11 and eight participants in Ba-Endo and ABC-Endo, respectively. The expenses required to detect one gastric cancer were 2,240,931 yen in Ba-Endo and 3,486,662 yen in ABC-Endo. CONCLUSIONS: The testing cost per participant turned out to be higher in the ABC-Endo group than in the Ba-Endo group. This superiority trial, based on the hypothesis that the cost of testing is lower for ABC-Endo than for Ba-Endo, was rejected.

Adherence to the three-component Hepatitis B virus vaccination protocol among healthcare workers in hepatitis B virus endemic settings in Ghana.

Background: The WHO and CDC recommend that HCWs who are at risk of HBV infection should vaccinate as adults early in their career by receiving 3 doses of HB vaccine at a schedule of months 0,1,6 and perform post-vaccination serological testing 1-2 months after vaccination. This study assessed adherence to all three components of the HBV vaccination program. Methods: The study was a hospital-based analytical cross-sectional study involving 340 HCWs who were randomly selected. A pretested questionnaire was used to collect data which was analyzed using SPSS version 21. The proportion of HCWs adhering to the three components of the HBV vaccination protocol was computed. The multivariable analysis procedure identified the factors associated with overall adherence. Odds ratios were estimated with corresponding confidence intervals with the level of significance set at 0.05. Results: HBV vaccination coverage was 60.9 % and adherence to 3-doses, 0,1,6 vaccination schedules and post-vaccination serological testing were 46.8 %, 38 % and 13 % respectively. Overall adherence was intermediate at the population level with only 6.2 % of the study participants adhering to all three components of the HBV vaccination protocol. HCWs who had low-risk perception for HBV had the lowest odds of completely adhering to all three indicators recommended for HBV vaccination (aOR = 0.15; 95 %CI = 0.04-0.58). Also, male HCWs have lower odds of adhering to all three components of HBV vaccination compared to their female counterparts (aOR = 0.65; 95 %CI = 1.17-2.50). Conclusion: Adherence to the three components of HBV vaccination recommended for HCWs is low in this study. Failure to receive the recommended three-dose series of HBV vaccine at the recommended 0,1,6 schedule has implications for achieving seroprotection or development of antibodies against HBV. Failure to perform post-vaccination testing 1-2 months after HBV vaccination has implications for timely PEP management following occupational exposures. All three components of an ideal HBV vaccination program are important and should be used collectively to guide facility led HCW vaccination programs. Occupational health and safety programs, Infection prevention and control, as well as health promotion campaigns in health facilities, should promote adherence to all three components of HBV vaccination programs.

A case of haemolytic disease of the fetus and newborn attributed to a novel antigen in the RHAG blood group system.

BACKGROUND AND OBJECTIVES: A newborn presented with jaundice in Thailand. The cord red cells tested positive by direct antiglobulin test (DAT) for an unknown maternal red cell antibody. Initial blood group sequencing suggested that the infant carried a novel variant RHAG c.140T>C, responsible for a low-prevalence antigen in the RHAG blood group system (ISBT 030). We report here on testing of samples from the infant's parents and older sibling to define a new antigen in the RHAG system. MATERIALS AND METHODS: Massive parallel sequencing (MPS) using a custom-designed panel was performed on all four family members. Extended serological testing was also performed to determine whether family members with the same variant as the infant showed reactivity with the antibody in the maternal plasma. RESULTS: We identified a novel single nucleotide variant (SNV) (RHAG c.140T>C, p.[Phe47Ser]) in samples from three of the four family members tested (the infant, the older sibling and the father). The variant was not detected in the mother's sample. Maternal plasma showed positive agglutination with all family members tested; however, when tested with routine panel cells, no reactivity was observed. CONCLUSION: This case study showed that the presence of the novel variant (RHAG c.140T>C), encoding a p.(Phe47Ser) change in the RhAG glycoprotein, was the apparent cause of incompatibility between maternal plasma and that of red cells from the proband, father and older sibling of the proband. We propose this variant to be a new low-prevalence antigen in the RHAG blood group system.

Diagnostic Efficacy of Serological Antibody Detection Tests for Hepatitis Delta Virus: A Systematic Review and Meta-Analysis.

Background and Aims Coinfection of hepatitis delta virus (HDV) with hepatitis B virus (HBV) causes the most severe form of viral hepatitis, and the global prevalence of HDV infection is underestimated. Although serological testing of anti-HDV antibodies is widely used in the diagnosis of HDV, its diagnostic efficacy remains unclear. This study aimed to evaluate the diagnostic efficacy of HDV serological tests, the results of which may assist in the diagnosis of HDV. Methods Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. The PubMed, Web of Science and Cochrane Library databases were searched from the beginning to 31 May 2023. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. STATA SE was used for the meta-analysis of the sensitivity, specificity, positive likelihood ratio and negative likelihood ratio. Results Among a total of 1376 initially identified studies, only 12 articles met the final inclusion criteria. The pooled sensitivity and specificity were 1.00 (95% CI: 0.00-1.00) and 0.71 (95% CI: 0.50-0.78) for HDV total antibodies, 0.96 (95% CI: 0.83-0.99) and 0.98 (95% CI: 0.82-1.00) for anti-HDV IgM and 0.95 (95% CI: 0.86-0.98) and 0.96 (95% CI: 0.67-1.00) for anti-HDV IgG. The pooled sensitivity and specificity for HDV serological tests were 0.99 (95% CI: 0.96-1.00) and 0.90 (95% CI: 0.79-0.96). Conclusions This meta-analysis suggests that serological tests have high diagnostic performance in detecting antibodies against HDV, especially in HDV IgM and IgG. However, this conclusion is based on studies of a limited number and quality, and the development of new diagnostic tools with higher precision and reliability is still necessary.

Vaccine-induced SARS-CoV-2 antibody response: the comparability of S1-specific binding assays depends on epitope and isotype discrimination.

Background: Quantification of the SARS-CoV-2-specific immune response by serological immunoassays is critical for the management of the COVID-19 pandemic. In particular, neutralizing antibody titers to the viral spike (S) protein have been proposed as a correlate of protection (CoP). The WHO established the First International Standard (WHO IS) for anti-SARS-CoV-2 immunoglobulin (Ig) (NIBSC 20/136) to harmonize binding assays with the same antigen specificity by assigning the same unitage in binding antibody units (BAU)/ml. Method: In this study, we analyzed the S1-specific antibody response in a cohort of healthcare workers in Germany (n = 76) during a three-dose vaccination course over 8.5 months. Subjects received either heterologous or homologous prime-boost vaccination with ChAdOx1 nCoV-19 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) or three doses of BNT162b2. Antibodies were quantified using three anti-S1 binding assays (ELISA, ECLIA, and PETIA) harmonized to the WHO IS. Serum levels of neutralizing antibodies were determined using a surrogate virus neutralization test (sVNT). Binding assays were compared using Spearman's rank correlation and Passing-Bablok regression. Findings: All assays showed good correlation and similar antibody kinetics correlating with neutralizing potential. However, the assays show large proportional differences in BAU/ml. ECLIA and PETIA, which detect total antibodies against the receptor- binding domain (RBD) within the S1 subunit, interact similarly with the convalescent plasma-derived WHO IS but differently with vaccine serum, indicating a high sensitivity to the IgG/IgM/IgA ratio. Conclusion: All three binding assays allow monitoring of the antibody response in COVID-19-vaccinated individuals. However, the assay-specific differences hinder the definition of a common protective threshold in BAU/ml. Our results highlight the need for the thoughtful use of conversion factors and consideration of method-specific differences. To improve the management of future pandemics and harmonize total antibody assays, we should strive for reference material with a well-characterized Ig isotype composition.

Two-phase Bayesian latent class analysis to assess diagnostic test performance in the absence of a gold standard: COVID-19 serological assays as a proof of concept.

BACKGROUND AND OBJECTIVES: In this proof-of-concept study, which included blood donor samples, we aimed to demonstrate how Bayesian latent class models (BLCMs) could be used to estimate SARS-CoV-2 seroprevalence in the absence of a gold standard assay under a two-phase sampling design. MATERIALS AND METHODS: To this end, 6810 plasma samples from blood donors who resided in Québec (Canada) were collected from May to July 2020 and tested for anti-SARS-CoV-2 antibodies using seven serological assays (five commercial and two non-commercial). RESULTS: SARS-CoV-2 seroprevalence was estimated at 0.71% (95% credible interval [CrI] = 0.53%-0.92%). The cPass assay had the lowest sensitivity estimate (88.7%; 95% CrI = 80.6%-94.7%), while the Héma-Québec assay had the highest (98.7%; 95% CrI = 97.0%-99.6%). CONCLUSION: The estimated low seroprevalence (which indicates a relatively limited spread of SARS-CoV-2 in Quebec) might change rapidly-and this tool, developed using blood donors, could enable a rapid update of the prevalence estimate in the absence of a gold standard. Further, the present analysis illustrates how a two-stage BLCM sampling design, along with blood donor samples, can be used to estimate the performance of new diagnostic tests and inform public health decisions regarding a new or emerging disease for which a perfect reference standard does not exist.

Analysis of COVID-19 Incidence and Protective Potential of Persisting IgG Class Antibodies against SARS-CoV-2 Infection in Hospital Staff in Poland.

The immune responses to both SARS-CoV-2 infection and vaccines are of key importance in prevention efforts. In April and May 2020, 703 study participants tested for COVID-19 by PCR tests were registered. In June and July 2020, they were examined for the presence of SARS-CoV-2 S1/S2 IgG. From October 2020 to January 2021, those among the study population with COVID-19 confirmed by PCR tests were registered, and the same group of participants was invited to be examined again for the presence of SARS-CoV-2 antibodies. In June 2020, antibodies were detected in only 88% of those who had PCR-confirmed COVID-19 in April-May 2020, which suggests that a significant proportion of persons in the Polish population do not produce antibodies after contact with SARS-CoV-2 antigens or rapidly lose them and reach levels below the lab detection limit. The levels of IgG class anti-SARS-CoV-2 antibodies were significantly lower among people who previously had COVID-19 than for those who had received COVID-19 vaccination, which confirms the high immunogenicity of the vaccines against COVID-19 in the Polish population. The study confirms that a detectable level of IgG class anti-SARS-CoV-2 antibodies cannot be considered a reliable marker of the presence and strength of COVID-19 immunity preventing individuals from acquiring SARS-CoV-2 infection.

Correction to "Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis: An experimental study in Brazil".

[This corrects the article on p. 100 in vol. 12, PMID: 36196438.].