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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests have had limited recommended clinical application during the coronavirus disease 2019 (COVID-19) pandemic. To inform clinical practice, an understanding is needed of current perspectives of United States–based infectious disease (ID) physicians on the use, interpretation, and need for SARS-CoV-2 antibody tests. Methods In March 2022, members of the Emerging Infections Network (EIN), a national network of practicing ID physicians, were surveyed on types of SARS-CoV-2 antibody assays ordered, interpretation of test results, and clinical scenarios for which antibody tests were considered. Results Of 1867 active EIN members, 747 (40%) responded. Among the 583 who managed or consulted on COVID-19 patients, a majority (434/583 [75%]) had ordered SARS-CoV-2 antibody tests and were comfortable interpreting positive (452/578 [78%]) and negative (405/562 [72%]) results. Antibody tests were used for diagnosing post–COVID-19 conditions (61%), identifying prior SARS-CoV-2 infection (60%), and differentiating prior infection and response to COVID-19 vaccination (37%). Less than a third of respondents had used antibody tests to assess need for additional vaccines or risk stratification. Lack of sufficient evidence for use and nonstandardized assays were among the most common barriers for ordering tests. Respondents indicated that statements from professional societies and government agencies would influence their decision to order SARS-CoV-2 antibody tests for clinical decision making. Conclusions Practicing ID physicians are using SARS-CoV-2 antibody tests, and there is an unmet need for clarifying the appropriate use of these tests in clinical practice. Professional societies and US government agencies can support clinicians in the community through the creation of appropriate guidance. [ABSTRACT FROM AUTHOR]

This paper provides a comprehensive summary of evidence to explore and position the role of serology testing in the context of coronavirus disease 19 (COVID-19) immunization and policy response in the Asia-Pacific (APAC) region. The document builds on a review of academic literature and existing policies followed by a process of discussion, validation, and feedback by a group of six experts. Six countries and territories—Australia, Hong Kong, India, Indonesia, Thailand, and Taiwan—were sampled to highlight the differing contexts and scenarios in the region. The review includes an overview of (1) the impact of the COVID-19 pandemic, including the emergence of Variants of Concern (VOCs), especially Omicron, (2) the introduction of immunization, (3) the available testing options and potential use of serology testing, (4) the landscape of guidelines and recommendations for their use, and (5) the barriers and challenges to implementing serology testing as a tool to support COVID-19 immunization. Based on the findings, the co-authors propose a set of recommendations to resolve knowledge gaps, to include the use of serology testing as part of the policy response, and to ensure adequate means of implementation. This paper’s target audience includes members of the academic community, medical societies, health providers and practitioners, and decision-makers.

The 1890s marked a significant milestone with the introduction of antibody-based agglutination and precipitation assays, revolutionizing the detection of bacterial pathogens in both animals and humans. This era also witnessed pivotal contributions to our understanding of humoral immunity, as researchers elucidated the structure and functions of antibody molecules, laying the groundwork for diagnostic applications. Among antibody isotypes, IgG is of paramount importance in diagnostic investigations given its definitive indication of infection or vaccination, coupled with its widespread presence and detectability across various specimen types, such as serum, colostrum, milk, oral fluids, urine, feces, and tissue exudate. Despite their resilience, immunoglobulins are susceptible to structural alterations induced by physicochemical and enzymatic processes, which can compromise the reliability of their detection. Here we review comprehensively the historical milestones, underlying mechanisms, and influencing factors (e.g., temperature, pH, storage) that shape the structural integrity and stability of IgG antibodies in aqueous solutions and various clinical specimens., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The emergence of the new coronavirus SARS-CoV-2 in late 2019 led to the global pandemic COVID-19, causing a profound socioeconomic crisis. Adequate diagnostic tools need to be developed to control the ongoing spread of infection. Virus-specific humoral immunity in COVID-19 patients and those vaccinated with specific vaccines has been characterized in numerous studies, mainly using Spike protein-based serology tests. However, Spike protein and specifically its receptor-binding domain (RBD) are mutation-prone, suggesting the reduced sensitivity of the validated serology tests in detecting antibodies raised to variants of concern (VOC). The viral nucleocapsid (N) protein is more conserved compared to Spike, but little is known about cross-reactivity of the N-specific antibodies between the ancestral B.1 virus and different VOCs. Here, we generated recombinant N phosphoproteins from different SARS-CoV-2 strains and analyzed the magnitude of N-specific antibodies in COVID-19 convalescent sera using an in-house N-based ELISA test system. We found a strong positive correlation in the magnitude of anti-N (B.1) antibodies and antibodies specific to various VOCs in COVID-19-recovered patients, suggesting that the N-binding antibodies are highly cross-reactive, and the most immunogenic epitopes within this protein are not under selective pressure. Overall, our study suggests that the RBD-based serology tests should be timely updated to reflect the constantly evolving nature of the SARS-CoV-2 Spike protein, whereas the validated N-based test systems can be used for the analysis of sera from COVID-19 patients regardless of the strain that caused the infection. [ABSTRACT FROM AUTHOR]

This paper provides a comprehensive summary of evidence to explore and position the role of serology testing in the context of coronavirus disease 19 (COVID-19) immunization and policy response in the Asia-Pacific (APAC) region. The document builds on a review of academic literature and existing policies followed by a process of discussion, validation, and feedback by a group of six experts. Six countries and territories—Australia, Hong Kong, India, Indonesia, Thailand, and Taiwan—were sampled to highlight the differing contexts and scenarios in the region. The review includes an overview of (1) the impact of the COVID-19 pandemic, including the emergence of Variants of Concern (VOCs), especially Omicron, (2) the introduction of immunization, (3) the available testing options and potential use of serology testing, (4) the landscape of guidelines and recommendations for their use, and (5) the barriers and challenges to implementing serology testing as a tool to support COVID-19 immunization. Based on the findings, the co-authors propose a set of recommendations to resolve knowledge gaps, to include the use of serology testing as part of the policy response, and to ensure adequate means of implementation. This paper's target audience includes members of the academic community, medical societies, health providers and practitioners, and decision-makers. [ABSTRACT FROM AUTHOR]

Objective Numerous manufacturers market lateral flow assays for the detection of SARS-CoV-2 antibodies, but there are many questions about the reliability and efficacy of these tests. Materials and Methods Serum specimens from 60 individuals were analyzed using 2 lateral flow antibody assays, an in-house enzyme-linked immunosorbent assay (ELISA), and the Abbott SARS-CoV-2 IgG chemiluminescent immunoassay. Results The BioMedomics and Premier Biotech lateral flow assays were positive for IgM in 73.3% and 70% and for IgG in 80% and 73.3% of specimens, respectively. The ELISA assay was positive for IgM and IgG in 73.3% and 86.7% of specimens from infected individuals, whereas the Abbott assay was positive in 80%. The specificities of the 4 assays ranged from 96.7% to 100% for IgM and from 93.3% to 100% for IgG. Conclusion Results of the 2 lateral flow assays were comparable to those of the ELISA and Abbott assays. Assay efficacy depended on length of time after SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. Methods: A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG−); (2) IgG-positive but IgM-negative (IgG+IgM−); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/−); (5) IgG-positive without IgM information (IgG+IgM+/−); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). Results: Sixty-eight studies were included. Pooled sensitivities for IgM+IgG−, IgG+IgM−, IgM+IgG+, IgM+IgG+/−, IgG+IgM+/−, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. Discussion: These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.

BackgroundMore than 200 countries are experiencing the coronavirus disease (COVID-19) pandemic. COVID-19 vaccination strategies have been implemented worldwide, and repeat COVID-19 outbreaks have been seen. The purpose of this study was to investigate the impact of COVID-19 vaccination on the reduction of perceived anxiety and the association between public anxiety and antibody testing intention during the COVID-19 pandemic.MethodsChinese adults aged 18 and over were surveyed using an anonymous online questionnaire in April and May 2021. The questionnaire collected sociodemographic characteristics, vaccination characteristics, perceived anxiety due to COVID-19, and attitudes toward future antibody testing after COVID-19 vaccination. Perceived anxiety was assessed on a visual analog scale (VAS). Multivariate logistic regression analysis was used to determine the factors influencing future antibody detection.ResultsA total of 3,233 people were investigated, 3,209 valid questionnaires were collected, and the response rate was 99.3%. Of the 3,209 respondents, 2,047 were vaccinated, and 1,162 were unvaccinated. There was a significant difference in anxiety levels between vaccinated and unvaccinated respondents (24.9±25.4 vs. 50.0±33.1, respectively). With the local spread of COVID-19 in mainland China, the public anxiety VAS scores increased by 15.4±25.6 (SMD=120%) and 33.8±31.7 (SMD=49%) among vaccinated and unvaccinated respondents, respectively. Of the 2,047 respondents who were vaccinated, 1,626 (79.4%) thought they would accept antibody testing. Those who displayed more anxiety about acquiring COVID-19 disease were more likely to accept COVID-19 antibody testing. If the antibody test results showed protective antibodies, 1,190 (58.1%) were more likely to arrange travel plans in China, while 526 (25.7%) thought they would feel safer traveling abroad.ConclusionCOVID-19 vaccination strategies help reduce public anxiety. However, public anxiety may be elevated as the local transmission of COVID-19 occurs in mainland China, which is usually caused now by imported cases. Those who display more anxiety choose to have antibody testing. Improving the accessibility of COVID-19 antibody tests can help ease public anxiety and enhance the confidence of some people to participate in social activities.

Novel coronavirus (nCoV) first emerged in Hubei province of China in December 2019. The virus initially known as 2019-nCoV was renamed to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. The associated disease is known as coronavirus disease 2019 (COVID-19). As the COVID-19 pandemic has unfolded, interest has grown in antibody testing as a way to measure how far the infection has spread and to identify individuals who may be immune. Molecular diagnostic tests like polymerase chain reaction are developed rapidly, however they are not able to fulfill all the requirements of an epidemic reaction. Hence, to complement molecular diagnostic tests, serology tests emerged as a vital aspect of the overall response by confirming the presence of antibodies during the early stage of the infection. Antibody tests help in assessing herd immunity, data about the ongoing phase of infection, identifying potential donors for convalescent plasma therapy, etc. This review currently focuses on giving an overview about the antibody tests in SARS-CoV-2 infections.

Background: Biomarker guided therapy could improve management of COVID-19 inpatients. Although some results indicate that antibody tests are prognostic, little is known about patient management using point-of-care (POC) antibody tests., Methods: COVID-19 inpatients were recruited to evaluate 2 POC tests: LumiraDX and RightSign. Ease of use data was collected. Blood was also collected for centralized testing using established antibody assays (GenScript cPass). A nested case-control study assessed if POC tests conducted on stored specimens were predictive of time to sustained recovery, mortality, and a composite safety outcome., Results: While both POC tests exhibited moderate agreement with the GenScript assay (both agreeing with 89% of antibody determinations), they were significantly different from the GenScript assay. Treating the GenScript assay as the gold standard, the LumiraDX assay had 99.5% sensitivity and 58.1% specificity while the RightSign assay had 89.5% sensitivity and 84.0% specificity. The LumiraDX assay frequently gave indeterminant results. Both tests were significantly associated with clinical outcomes., Conclusions: Although both POC tests deviated moderately from the GenScript assay, they predicted outcomes of interest. The RightSign test was easier to use and was more likely to detect those lacking antibody compared to the LumiraDX test treating GenScript as the gold standard., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A novel clinical assay for the detection and quantitation of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was adapted from an in-house, research-based enzyme-linked immunosorbent assay (ELISA). Development and validation were performed under regulatory guidelines, and the test obtained emergency use authorization (EUA) from the New York State Department of Health (NYSDOH) and the Food and Drug Administration (FDA). The Mount Sinai coronavirus disease 2019 (COVID-19) antibody assay is an orthogonal, quantitative direct ELISA test which detects antibodies reactive to the receptor binding domain (RBD) and the spike protein of the novel SARS-CoV-2. The assay is performed on 96-well plates coated with either SARS-CoV-2 recombinant RBD or spike proteins. The test is divided into two stages, a qualitative screening assay against RBD and a quantitative assay against the full-length spike protein. The test uses pooled high titer serum as a reference standard. Negative pre-COVID-19 and positive post-COVID-19, PCR-confirmed specimens were incorporated in each ELISA test run, and the assays were performed independently at two different locations.The Mount Sinai COVID-19 serology performed with high sensitivity and specificity, 92.5% (95% CI: 0.785–0.980) and 100% (CI: 0.939–1.000) respectively. Between-run precision was assessed with a single run repeated over 22 days; and within-run precision was assessed with 10 replicates per day over 22 days. Both were within reported acceptance criteria (CV ≤ 20%).This population-based study reveals the applicability and reliability of this novel orthogonal COVID-19 serology test for the detection and quantitation of antibodies against SARS-CoV-2, allowing a broad set of clinical applications, including the broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different population subsets.

Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests exists commercially; however, their performance using clinical samples is limited. Although insufficient to detect SARS-CoV-2 in the early phase of infection, antibody assays can be of great use for surveillance studies or for some coronavirus disease 2019 (COVID-19) patients presenting late to the hospital. This study evaluated the sensitivity and specificity of four commercial SARS-CoV-2 lateral flow antibody tests using 213 serum specimens from 90 PCR-positive confirmed COVID-19 patients. Of 59 negative control sera, 50 were obtained from patients with other respiratory infectious diseases before COVID-19 pandemic began while nine were from patients infected with other respiratory viruses, including two seasonal coronaviruses. The varied sensitivities for the four commercial kits were 70.9%, 65.3%, 45.1%, and 65.7% for BioMedomics, Autobio Diagnostics, Genbody, and KURABO, respectively, between sick days 1 and 155 in COVID-19 patients. The sensitivities of the four tests gradually increased over time after infection before sick day 5 (15.0%, 12.5%, 15.0%, and 20.0%); from sick day 11–15 (95.7%, 87.2%, 53.2%, and 89.4%); and after sick day 20 (100%, 100%, 68.6%, and 96.1%), respectively. For severe illness, the sensitivities were quite high in the late phase after sick day 15. The specificities were over 96% for all four tests. No cross-reaction due to other pathogens, including seasonal coronaviruses, was observed. Our results demonstrated the large differences in the antibody test performances. This ought to be considered when performing surveillance analysis. [ABSTRACT FROM AUTHOR]

Novel coronavirus (nCoV) first emerged in Hubei province of China in December 2019. The virus initially known as 2019-nCoV was renamed to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. The associated disease is known as coronavirus disease 2019 (COVID-19). As the COVID-19 pandemic has unfolded, interest has grown in antibody testing as a way to measure how far the infection has spread and to identify individuals who may be immune. Molecular diagnostic tests like polymerase chain reaction are developed rapidly, however they are not able to fulfill all the requirements of an epidemic reaction. Hence, to complement molecular diagnostic tests, serology tests emerged as a vital aspect of the overall response by confirming the presence of antibodies during the early stage of the infection. Antibody tests help in assessing herd immunity, data about the ongoing phase of infection, identifying potential donors for convalescent plasma therapy, etc. This review currently focuses on giving an overview about the antibody tests in SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

Introduction: Diagnostic tests play a critical role in the management of Sars-CoV-2, the virus responsible for COVID-19. There are two groups of tests, which are in widespread use to identify patients who have contracted the virus. The commonly used reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test becomes negative once viral shedding ceases by approximately 2-3weeks. Antibody tests directed to viral antigens become positive after the second week of infection. IgG antibody responses to the virus are muted in children, pregnant females, and those with mild symptoms. IgA and IgM antibodies rapidly wane, although IgG antibodies directed to the receptor-binding domain (RBD) of the spike (S) glycoprotein are more durable. Current data show variability in the sensitivity of commercial and in-house antibody tests to SARS-CoV-2. Areas covered: The role of T cells in acute illness is uncertain, but long-term protection against the virus may rely on memory T cell responses. Measuring memory T cell responses is important for retrospective confirmation of cases, who may have been infected early in the pandemic before reliable RT-qPCR tests were available and whose SARS-CoV-2 antibodies may have become undetectable. Relevant peer-reviewed published references from PubMed are included up to 15 March 2021. Expert opinion: After surveying the literature, the authors present the case for urgent development of diagnostic T cell assays for SARS-CoV-2 by accredited laboratories. [ABSTRACT FROM AUTHOR]

Antibody tests for detecting past infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have many uses for public health decision making, but demand has largely come from individual consumers. This review focuses on the individual relevance of antibody tests: their accuracy in detecting prior infection, what past SARS-CoV-2 infection can currently infer about future immunity or possible medical sequelae, and the potential future importance of antibody tests for vaccine selection and medical screening. Given uncertainty about the antibody tests (quality, accuracy level, positive predictive value) and what those tests might indicate immunologically (durability of antibodies and necessity for protection from reinfection), seropositive test results should not be used to inform individual decision making, and antibody testing should remain a tool of public health at this time. There is high consumer demand for antibody tests to detect past infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but there is a great deal of uncertainty about what a positive test means immunologically. Uneven test accuracy and statistical challenges, especially in areas of low disease prevalence, further complicate use of antibody tests for individual decision making. Antibody tests are important for convalescent plasma donation and may have future utility to identify coronavirus disease 2019 medical sequelae and for vaccine selection and prioritization. At the population level, tests are needed to support serosurveillance studies, to determine the case fatality rate, and to track increases or decreases in incidence and prevalence, but currently they are of limited utility for individuals. [ABSTRACT FROM AUTHOR]

Accurate diagnostic tests that provide results in a timely manner are essential for the clinical and public health management of COVID-19 disease. The choice as to which test to use will depend on the clinical presentation and the stage of the illness. Nucleic acid tests, using real-time reverse transcriptase-polymerase chain reaction, are the most appropriate for diagnosing acute infection. Combined deep nasal (or nasopharyngeal) and throat swabs are the preferred sample. Serology can be used to diagnose previous infection, more than 14 days after the onset of symptoms. Antigen tests are in development and their role is not yet defined. Interpretation of results must take into account the pre-test probability of the patient having the disease. This is based on their clinical presentation and epidemiological risk. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) serological assays are urgently needed for rapid diagnosis, contact tracing, and for epidemiological studies. So far, there is limited data on how commercially available tests perform with real patient samples, and if positive tested samples show neutralizing abilities. Focusing on IgG antibodies, we demonstrate the performance of two enzyme‐linked immunosorbent assay (ELISA) assays (Euroimmun SARS‐CoV‐2 IgG and Vircell COVID‐19 ELISA IgG) in comparison to one lateral flow assay (FaStep COVID‐19 IgG/IgM Rapid Test Device) and two in‐house developed assays (immunofluorescence assay [IFA] and plaque reduction neutralization test [PRNT]). We tested follow up serum/plasma samples of individuals polymerase chain reaction‐diagnosed with COVID‐19. Most of the SARS‐CoV‐2 samples were from individuals with moderate to the severe clinical course, who required an in‐patient hospital stay. For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5‐9) and from 93.8% to 100% for the later period (days 10‐18). Highlights: With the exception of one sample, all positive tested COVID‐19 follow up‐samples, using the commercially available assays examined (including the in‐house developed IFA), demonstrated neutralizing properties in the PRNT.Regarding specificity, some samples of endemic coronavirus (HCoV‐OC43, HCoV‐229E) and Epstein Barr virus‐infected individuals cross‐reacted in the ELISA assays and IFA, in one case generating a false‐positive result. [ABSTRACT FROM AUTHOR]

This review aims to explore the role and value of serology testing in the context of COVID-19 immunization policies in Latin American countries and the barriers and challenges to the adequate use and uptake of this tool. It builds on a review of the academic literature, evidence, and existing policies, and includes a multistage process of discussion and feedback by a group of five experts. Regional and country-level evidence and resources from five focus countries—Argentina, Brazil, Chile, Colombia, and Mexico—were collected and analyzed. This review contains an overview of (1) the impact of the SARS-CoV-2 pandemic, the variants of concern and current testing strategies, (2) the introduction of COVID-19 vaccination, (3) the potential use of serology testing to support immunization initiatives, (4) the current frameworks for the use of serology testing in the region, and (5) the barriers and challenges to implementing serology testing in the context of COVID-19 immunization policies, including a discussion on the potential actions required to address these barriers and facilitate the uptake of this strategy in the region. Stakeholders can use elements of this document to guide timely decision-making, raise awareness, and inspire further studies.

SARS-CoV-2 infection has generated the biggest pandemic since the influenza outbreak of 1918–1919. One clear difference between these pandemics has been the ability to test for the presence of the virus or for evidence of infection. This review examined the performance characteristics of sample types via PCR detection of the virus, of antibody testing, of rapid viral antigen detection kits and computerised tomography (CT) scanning. It was found that combined detection approaches, such as the incorporation of CT scans, may reduce the levels of false negatives obtained by PCR detection in both symptomatic and asymptomatic patients, while sputum and oral throat washing sample types should take precedence over swabbing when available. Rt-PCR assays for detection of the virus remain the gold-standard method for SARS-CoV-2 diagnosis and can be used effectively on pooled samples for widespread screening. The novel Oxford antibody assay was found to have the highest sensitivity and specificity of four currently available commercial antibody kits but should only be used during a specific timeframe post-symptom onset. Further research into transmission modes between symptomatic and asymptomatic patients is needed. Analysis of the performance characteristics of different sampling and detection methods for SARS-CoV-2 showed that timing of sampling and testing methods used can greatly influence the rate of false-positive and false-negative test results, thereby influencing viral spread.

The COVID-19 pandemic has thrust not only a novel virus onto the world, but new challenges resulting in novel approaches. Governments have reduced regulation in order to facilitate timely advances to combat the disease. Antibody testing has rapidly been deployed but it is creating challenges for staff and patients. Mask use has come to the forefront and human factor (HF) strategies must be examined to reduce risk associated with lack of engagement from both healthcare staff and patients. In this we explore these issues and suggest some solutions. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests of varying specificity and sensitivity are now available. For informing individuals whether they have had coronavirus disease 2019 (COVID-19), they need to be very accurate. For measuring population prevalence of past infection, the numbers of false positives and negatives need to be roughly equal. With a series of worked examples for a notional population of 100,000 people, we show that even test systems with a high specificity can yield a large number of false positive results, especially where the population prevalence is low. For example, at a true population prevalence of 5%, using a test with 99% sensitivity and specificity, 16% of positive results will be false and thus 950 people will be incorrectly informed they have had the infection. Further confirmatory testing may be needed. Giving false reassurance on which personal or societal decisions might be based could be harmful for individuals, undermine public confidence and foster further outbreaks. • COVID-19 antibody tests need to be very reliable to inform individual decisions. • Even with high specificity, antibody tests can produce many false positives. • Giving false reassurance could undermine public confidence and foster new outbreaks. [ABSTRACT FROM AUTHOR]

Histoplasmosis and blastomycosis are the two most common midwestern endemic mycoses. A history of exposure to the geographic areas in which these organisms occur is central to raising suspicion for an endemic fungal infection. For infection with these organisms, the diagnosis is definitively established by recovery of the organism in tissue or body fluids, which may take weeks. A rapid diagnosis can be made by finding the distinctive yeasts in tissues or body fluids. Antigen testing allows a presumptive diagnosis of these endemic fungal infections while awaiting culture results, but cross-reactivity between assays for Histoplasma and Blastomyces is routinely seen. Antibody tests provide supportive evidence for infection with either of these endemic mycoses but are less useful in immunosuppressed patients. [ABSTRACT FROM AUTHOR]

In situations of diagnostic tests studies where the gold standard (GS) test is not absolutely perfect, validity measures of index tests vary in subgroups with varying disease prevalence. This is called reference standard misclassification. Although this is widely known, little is explained about the variations in the performance of index tests when the validity of the GS test itself varies with the time duration of illness. This article attempts to expand the concept of reference standard misclassification specifically on the effect of time dependence of diagnostic tests. A brief literature review is also presented which documents the existent knowledge among researchers about the concept and the methods they usually employ to adjust. A list of solutions which can address the issue has also been discussed to enable researchers to design and analyse diagnostic test studies in better ways.

In situations of diagnostic tests studies where the gold standard (GS) test is not absolutely perfect, validity measures of index tests vary in subgroups with varying disease prevalence. This is called reference standard misclassification. Although this is widely known, little is explained about the variations in the performance of index tests when the validity of the GS test itself varies with the time duration of illness. This article attempts to expand the concept of reference standard misclassification specifically on the effect of time dependence of diagnostic tests. A brief literature review is also presented which documents the existent knowledge among researchers about the concept and the methods they usually employ to adjust. A list of solutions which can address the issue has also been discussed to enable researchers to design and analyse diagnostic test studies in better ways. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases. The presence of antibodies to cyclic citrullinated peptide (CCP) is better at discriminating RA patients and is also associated with significantly more disease activity compared to serum rheumatoid factor. In this study, we assessed two new automated second generation tests to detect the presence of anti-CCP antibodies in 226 serum samples submitted to the Clinical Immunology Laboratory for anti-CCP antibody testing. We compared CCP antibody results on these samples obtained using the ImmunoCAP 250 (Phadia) and the Architect i2000SR (Abbott Laboratories) instruments to our currently used CCP IgG third generation manual ELISA (Inova Diagnostics). One hundred and fifty-four samples were negative while 52 were positive by all three tests. Eighteen samples were negative by the automated tests but weakly/moderately positive by manual ELISA yielding an overall concordance of 79%. When we compared the discordant test results to patient diagnosis, we observed a better correlation with clinical RA diagnosis for the new automated tests compared to the manual ELISA. These two new anti-CCP antibody tests have the benefit of automation and may have better positive predictive value for the diagnosis of RA than our current manual ELISA. [ABSTRACT FROM AUTHOR]

This review aims to explore the role and value of serology testing in the context of COVID-19 immunization policies in Latin American countries and the barriers and challenges to the adequate use and uptake of this tool. It builds on a review of the academic literature, evidence, and existing policies, and includes a multistage process of discussion and feedback by a group of five experts. Regional and country-level evidence and resources from five focus countries—Argentina, Brazil, Chile, Colombia, and Mexico—were collected and analyzed. This review contains an overview of (1) the impact of the SARS-CoV-2 pandemic, the variants of concern and current testing strategies, (2) the introduction of COVID-19 vaccination, (3) the potential use of serology testing to support immunization initiatives, (4) the current frameworks for the use of serology testing in the region, and (5) the barriers and challenges to implementing serology testing in the context of COVID-19 immunization policies, including a discussion on the potential actions required to address these barriers and facilitate the uptake of this strategy in the region. Stakeholders can use elements of this document to guide timely decision-making, raise awareness, and inspire further studies. [ABSTRACT FROM AUTHOR]

Molecular biological methods that use antibodies and nucleic acids to detect specific foodborne bacterial pathogens were scarcely known a decade and a half ago. Few scientists could have predicted that these tools of basic research would come to dominate the field of food diagnostics. Today, a large number of cleverly designed assay formats using these technologies are available commercially for the detection in foods of practically all major established pathogens and toxins, as well as of many emerging pathogens. These tests range from very simple antibody-bound latex agglutination assays to very sophisticated DNA amplification methods. Although molecular biological assays are more specific, sensitive, and faster than conventional (often cultural) microbiological methods, the complexities of food matrices continue to offer unique challenges that may preclude the direct application of these molecular biological methods. Consequently, a short cultural enrichment period is still required for food samples prior to analysis with these assays. The greater detection sensitivity of molecular biological methods may also affect existing microbiological specifications for foods; this undoubtedly will have repercussions on the regulatory agencies, food manufacturers, and also consumers. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection has generated the biggest pandemic since the influenza outbreak of 1918–1919. One clear difference between these pandemics has been the ability to test for the presence of the virus or for evidence of infection. This review examined the performance characteristics of sample types via PCR detection of the virus, of antibody testing, of rapid viral antigen detection kits and computerised tomography (CT) scanning. It was found that combined detection approaches, such as the incorporation of CT scans, may reduce the levels of false negatives obtained by PCR detection in both symptomatic and asymptomatic patients, while sputum and oral throat washing sample types should take precedence over swabbing when available. Rt-PCR assays for detection of the virus remain the gold-standard method for SARS-CoV-2 diagnosis and can be used effectively on pooled samples for widespread screening. The novel Oxford antibody assay was found to have the highest sensitivity and specificity of four currently available commercial antibody kits but should only be used during a specific timeframe post-symptom onset. Further research into transmission modes between symptomatic and asymptomatic patients is needed. Analysis of the performance characteristics of different sampling and detection methods for SARS-CoV-2 showed that timing of sampling and testing methods used can greatly influence the rate of false-positive and false-negative test results, thereby influencing viral spread. [ABSTRACT FROM AUTHOR]

Background: Serological surveillance of COVID-19 through conducting repetitive population-based surveys can be useful in estimating and monitoring changes in the prevalence of infection across the country. This paper presents the protocol of nationwide population-based surveys of the Iranian COVID-19 Serological Surveillance (ICS) program. Methods: The target population of the surveys is all individuals ≥6 years in Iran. Stratified random sampling will be used to select participants from those registered in the primary health care electronic record systems in Iran. The strata are the 31 provinces of the country, in which sampling will be done through simple random sampling. The sample size is estimated 858 individuals for each province (except for Tehran province, which is 2574) at the first survey. It will be recalculated for the next surveys based on the findings of the first survey. The participants will be invited by the community health workers to the safe blood sampling centers at the district level. After obtaining written informed consent, 10 mL of venous blood will be taken from the participants. The blood samples will be transferred to selected reference laboratories in order to test IgG and IgM antibodies against COVID-19 using an Iranian SARS-CoV-2 ELISA Kit (Pishtaz Teb). A serologically positive test is defined as a positive IgG, IgM, or both. After adjusting for the measurement error of the laboratory test, nonresponse bias, and sampling design, the prevalence of COVID-19 will be estimated at the provincial and national levels. Also, the approximate incidence rate of infection will be calculated based on the data of both consecutive surveys. Conclusion: The implementation of these surveys will provide a comprehensive and clear picture of the magnitude of COVID-19 infection and its trend over time for health policymakers at the national and subnational levels., Competing Interests: Conflicts of Interest: SN and AR are the Minister of Health and Medical Education and Deputy Minister of Public Health of MOHME in Iran, respectively. SMS, SMH, SA, MMR, KT, HNT, JST, and AO have also a position in MOHME. The rest of the authors declare no conflict of interest, real or perceived., (© 2021 Iran University of Medical Sciences.)