Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies and public health implications

Serology-based tests have become a key public health element in the COVID-19 pandemic to assess the degree of herd immunity that has been achieved in the population. These tests differ between one another in several ways. Here, we conducted a systematic review and meta-analysis of the diagnostic accuracy of currently available SARS-CoV-2 serological tests, and assessed their real-world performance under scenarios of varying proportion of infected individuals. We included independent studies that specified the antigen used for antibody detection and used quantitative methods. We identified nine independent studies, of which six were based on commercial ELISA or CMIA/CLIA assays, and three on in-house tests. Test sensitivity ranged from 68% to 93% for IgM, from 65% to 100% for IgG, and from 83% to 98% for total antibodies. Random-effects models yielded a summary sensitivity of 82% (95%CI 75-88%) for IgM, and 85% for both IgG (95%CI 73-93%) and total antibodies (95%CI 74-94%). Specificity was very high for most tests, and its pooled estimate was 98% (95%CI 92-100%) for IgM and 99% (95%CI 98-100%) for both IgG and total antibodies. The heterogeneity of sensitivity and specificity across tests was generally high (I2≤50%). In populations with a low prevalence (≤5%) of seroconverted individuals, the positive predictive value would be ≤88% for most assays, except those reporting perfect specificity. Our data suggest that the use of serological tests for large-scale prevalence surveys (or to grant "immunity passports") are currently only justified in hard-hit regions, while they should be used with caution elsewhere.

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Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications

Eurosurveillance ◽

10.2807/1560-7917.es.2020.25.23.2000980 ◽

2020 ◽

Vol 25 (23) ◽

Cited By ~ 13

Author(s):

Saverio Caini ◽

Federica Bellerba ◽

Federica Corso ◽

Angélica Díaz-Basabe ◽

Gioacchino Natoli ◽

...

Keyword(s):

Public Health ◽

Positive Predictive Value ◽

Diagnostic Accuracy ◽

Random Effects ◽

Predictive Value ◽

Diagnostic Performance ◽

Meta Analysis ◽

Serological Tests ◽

Random Effects Models ◽

Health Implications

We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be ≤ 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.

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Pregnancy-related complications and incidence of atrial fibrillation: a systematic review and meta-analysis

EP Europace ◽

10.1093/europace/euab116.145 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

T Al Bahhawi ◽

A Aqeeli ◽

S L Harrison ◽

D A Lane ◽

I Buchan ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Cohort Studies ◽

Observational Studies ◽

Large Scale ◽

Data Extraction ◽

Meta Analysis ◽

Significant Heterogeneity ◽

Random Effects Models ◽

Increased Risk

Abstract Funding Acknowledgements Type of funding sources: None. Background Pregnancy-related complications have been previously associated with incident cardiovascular disease. However, data are scarce on the association between pregnancy-related complications and incident atrial fibrillation (AF). This systematic review examines associations between pregnancy-related complications and incident AF. Methods A systematic search of the literature utilising MEDLINE and EMBASE (Ovid) was conducted from 1990 to 6 April 2020. Observational studies examining the association between pregnancy-related complications including hypertensive disorders of pregnancy (HDP), gestational diabetes, placental abruption, preterm birth, low birth weight, small-for-gestational-age and stillbirth, and incidence of AF were included. Screening and data extraction were conducted independently by two reviewers. Inverse-variance random-effects models were used to pool hazard ratios. Results: Six observational studies met the inclusion criteria one case-control study and five retrospective cohort studies, with four studies eligible for meta-analysis. Sample sizes ranged from 1,839-1,303,365. Mean/median follow-up for the cohort studies ranged from 7-36 years. Most studies reported an increased risk of incident AF associated with pregnancy-related complications. The pooled summary statistic from four studies reflected a greater risk of incident AF for HDP (hazard ratio (HR) 1.47, 95% confidence intervals (CI) 1.18-1.84; I2 = 84%) and from three studies for pre-eclampsia (HR 1.71, 95% CI 1.41-2.06; I2 = 64%; Figure). Conclusions The results of this review suggest that pregnancy-related complications particularly pre-eclampsia appear to be associated with higher risk of incident AF. The small number of included studies and the significant heterogeneity in the pooled results suggest further large-scale prospective studies are required to confirm the association between pregnancy-related complications and AF. Abstract Figure.

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P463 Induction of endoscopic response: a network meta-analysis of induction studies comparing ontamalimab with other treatments for moderate-to-severe ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.592 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S410-S411

Author(s):

A Vickers ◽

A Nag ◽

B Devine ◽

B E Sands ◽

R Panaccione ◽

...

Keyword(s):

Ulcerative Colitis ◽

Large Scale ◽

Meta Analysis ◽

Placebo Response ◽

Study Data ◽

Induction Treatment ◽

Phase 2 ◽

Odds Ratios ◽

Phase 3 ◽

Random Effects Models

Abstract Background Clinicians, patients, payers and policymakers require relevant, high-quality evidence to support decision-making regarding the treatment of ulcerative colitis (UC). In the absence of head-to-head trials, network meta-analysis (NMA) can be used to compare treatments. We conducted an NMA to compare the efficacy of ontamalimab (anti-MAdCAM-1) using its phase 2 data, with all biologics and novel small molecules for which induction study data on endoscopic response were available. Methods A systematic literature review was conducted in November 2017 to identify published randomised controlled trials of induction treatment in patients with moderate-to-severe UC. An NMA of the identified studies was performed using random-effects models and methods based on NICE guidance. Odds ratios and 95% credible intervals were calculated to describe the relative differences between treatments and placebo in terms of efficacy in inducing endoscopic response. Results were examined by anti-TNF status (naïve vs. experienced). Results In total, 15 phase 2 and phase 3 induction studies of the following agents were available and included: adalimumab (160/80mg), etrolizumab (100mg and 300mg), golimumab (200/100mg), infliximab (5mg), ontamalimab (22.5mg and 75mg), ozanimod (0.5mg and 1mg), tofacitinib (10mg) and vedolizumab (300mg). The definition of endoscopic response (improvement) in all trials was a Mayo endoscopic subscore of ≤1. Homogeneity between studies was good, enabling pooling of results. Figure 1 shows odds ratios for induction of endoscopic response with treatments relative to placebo in anti-TNF-naïve and -experienced patients. All treatments performed significantly better than placebo in anti-TNF-naïve patients, with the exception of both doses of etrolizumab and ozanimod 0.5 mg. Significant differences between some treatments were observed; specifically, ontamalimab 22.5 mg (p = 0.0277), tofacitinib 10 mg (p = 0.0233) and infliximab 5 mg (p = 0.0047) were all superior to adalimumab 160/80 mg. Conclusion This study suggests that ontamalimab, infliximab and tofacitinib could be superior to adalimumab in inducing endoscopic healing, although it was conducted before any large-scale head-to-head trials of these drugs. Furthermore, large variances due to differing endpoint timings, the combination of phase 2 and phase 3 data, and lack of control for placebo response rates preclude firm conclusions being drawn.

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Diagnostic Accuracy of COVID-19 Antibody Tests Authorized by FDA Philippines: A Systematic Review and Meta-Analysis

SciMedicine Journal ◽

10.28991/scimedj-2021-0304-1 ◽

2021 ◽

Vol 3 (4) ◽

pp. 283-301

Author(s):

Carmel Reina R. Chua ◽

Esther Delle E. De los Santos ◽

Karla Veronica H. Escasa ◽

Richmond Louis G. Estolas ◽

Junnealyn Feliciano ◽

...

Keyword(s):

Systematic Review ◽

Diagnostic Accuracy ◽

Random Effects ◽

Meta Analysis ◽

Characteristic Curve ◽

Enzyme Linked Immunosorbent Assay ◽

Serological Tests ◽

Random Effects Models ◽

Specificity And Sensitivity ◽

Antibody Tests

Introduction: Coronavirus Disease (COVID-19) is a highly infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which has infected many people all over the world. One of the best ways to lessen its spread is through early detection and diagnosis. Various serological tests are now being used as a surveillance tool in the detection of antibodies as a response to SARS-CoV-2. The aim of this study is to evaluate the diagnostic accuracy and performance of the available COVID-19 antibody tests authorized by the Food and Drug Administration (FDA) Philippines that make use of Enzyme-Linked Immunosorbent Assay (ELISA), Chemiluminescence Immunoassay (CLIA) and Lateral Flow Immunoassay (LFIA). Method: Complete published journal articles relevant to the diagnostic accuracy of the three antibody tests were collected using trusted medical journal search engines. The quality of journals was assessed using QUADAS-2 to determine the risk of bias and assess the applicability judgments of diagnostic accuracy studies. Forest plots were used to summarize the performance of LFIA, ELISA and CLIA according to their specificity and sensitivity in detecting various antibodies. Pooled sensitivity and specificity were also done using bivariate random-effects models with its log-likelihood, a corresponding chi-square test statistic, and area under the summary Receiver-Operating Characteristic curve to see the potential heterogeneity in the data and to assess the diagnostic accuracy of the COVID-19 antibody tests. Results: Bivariate random-effects model and areas under the sROC curve were used to evaluate the diagnostic accuracy of COVID-19 antibody tests. The pooled sensitivity in detecting IgG based on CLIA, ELISA, and LFIA were 81.7%, 58.7%, and 74.3% respectively, with an overall of 72.0%. For IgM detection, LFIA has a higher pooled sensitivity of 69.6% than CLIA with 61.0%. Overall, the pooled sensitivity is 68.5%. In IgA detection, only ELISA based test was included with a pooled sensitivity of 84.8%. Lastly, pooled sensitivities for combined antibodies based on ELISA and LFIA were 89.0% and 81.6% respectively, with an overall of 82.5%. On the other hand, all tests excluding ELISA-IgA displayed high pooled specificities with a range of 94.0% to 100.0%. Diagnostic accuracies of the test in detecting IgG, IgM, and combined antibodies were found out to be almost perfect based on the computed area under the sROC with values of 0.973, 0.953, and 0.966, respectively. Conclusion: In this systematic review and meta-analysis, existing evidence on the diagnostic accuracy of antibody tests for COVID-19 were found to be characterized by high risks of bias, consistency in the heterogeneity of sensitivities, and consistency in the homogeneity of high specificities except in IgA detection using ELISA. The bivariate random-effects models showed that there are no significant differences in terms of sensitivity among CLIA, ELISA and LFIA in detecting IgG, IgM, and combined antibodies at a 95% confidence interval. Nonetheless, CLIA, ELISA and LFIA were found to have excellent diagnostic accuracies in the detection of IgG, IgM and combined antibodies as reflected by their AUC values. Doi: 10.28991/SciMedJ-2021-0304-1 Full Text: PDF

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Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), March 2020

Eurosurveillance ◽

10.2807/1560-7917.es.2020.25.16.2000421 ◽

2020 ◽

Vol 25 (16) ◽

Cited By ~ 82

Author(s):

Ranawaka APM Perera ◽

Chris KP Mok ◽

Owen TY Tsang ◽

Huibin Lv ◽

Ronald LW Ko ◽

...

Keyword(s):

Public Health ◽

Severe Acute Respiratory Syndrome ◽

Large Scale ◽

Herd Immunity ◽

Cross Reactivity ◽

Spike Protein ◽

Infectious Dose ◽

Virus Challenge ◽

Illness Onset ◽

Public Health Decision

Background The ongoing coronavirus disease (COVID-19) pandemic has major impacts on health systems, the economy and society. Assessing infection attack rates in the population is critical for estimating disease severity and herd immunity which is needed to calibrate public health interventions. We have previously shown that it is possible to achieve this in real time to impact public health decision making. Aim Our objective was to develop and evaluate serological assays applicable in large-scale sero-epidemiological studies. Methods We developed an ELISA to detect IgG and IgM antibodies to the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated its sensitivity and specificity in combination with confirmatory microneutralisation (MN) and 90% plaque reduction neutralisation tests (PRNT90) in 51 sera from 24 patients with virologically confirmed COVID-19 and in age-stratified sera from 200 healthy controls. Results IgG and IgM RBD ELISA, MN and PRNT90 were reliably positive after 29 days from illness onset with no detectable cross-reactivity in age-stratified controls. We found that PRNT90 tests were more sensitive in detecting antibody than MN tests carried out with the conventional 100 tissue culture infectious dose challenge. Heparinised plasma appeared to reduce the infectivity of the virus challenge dose and may confound interpretation of neutralisation test. Conclusion Using IgG ELISA based on the RBD of the spike protein to screen sera for SARS-CoV-2 antibody, followed by confirmation using PRNT90, is a valid approach for large-scale sero-epidemiology studies.

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Seroprevalence of Anti-SARS-CoV-2 Antibodies in a Cohort of New York City Metro Blood Donors using Multiple SARS-CoV-2 Serological Assays: Implications for Controlling the Epidemic and “Reopening”

10.1101/2020.11.06.20220087 ◽

2020 ◽

Author(s):

Daniel K. Jin ◽

Daniel. J. Nesbitt ◽

Jenny Yang ◽

Haidee Chen ◽

Julie Horowitz ◽

...

Keyword(s):

Public Health ◽

New York ◽

New York City ◽

High Throughput ◽

Blood Donor ◽

York City ◽

Blood Donors ◽

Herd Immunity ◽

Serological Tests ◽

Public Health Decision

AbstractProjections of the stage of the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic and local, regional and national public health policies designed to limit the spread of the epidemic as well as “reopen” cities and states, are best informed by serum neutralizing antibody titers measured by reproducible, high throughput, and statically credible antibody (Ab) assays. To date, a myriad of Ab tests, both available and authorized for emergency use by the FDA, has led to confusion rather than insight per se. The present study reports the results of a rapid, point-in-time 1,000-person cohort study using serial blood donors in the New York City metropolitan area (NYC) using multiple serological tests, including enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). These were then tested and associated with assays for neutralizing Ab (NAb). Of the 1,000 NYC blood donor samples in late June and early July 2020, 12.1% and 10.9% were seropositive using the Ortho Total Ig and the Abbott IgG HTSA assays, respectively. These serological assays correlated with neutralization activity specific to SARS-CoV-2. The data reported herein suggest that seroconversion in this population occurred in approximately 1 in 8 blood donors from the beginning of the pandemic in NYC (considered March 1, 2020). These findings deviate with an earlier seroprevalence study in NYC showing 13.7% positivity. Collectively however, these data demonstrate that a low number of individuals have serologic evidence of infection during this “first wave” and suggest that the notion of “herd immunity” at rates of ∼60% or higher are not near. Furthermore, the data presented herein show that the nature of the Ab-based immunity is not invariably associated with the development of NAb. While the blood donor population may not mimic precisely the NYC population as a whole, rapid assessment of seroprevalence in this cohort and serial reassessment could aid public health decision making.

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Seroprevalence of anti-SARS-CoV-2 antibodies in a cohort of New York City metro blood donors using multiple SARS-CoV-2 serological assays: Implications for controlling the epidemic and “Reopening”

PLoS ONE ◽

10.1371/journal.pone.0250319 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0250319

Author(s):

Daniel K. Jin ◽

Daniel J. Nesbitt ◽

Jenny Yang ◽

Haidee Chen ◽

Julie Horowitz ◽

...

Keyword(s):

Public Health ◽

New York ◽

New York City ◽

High Throughput ◽

Blood Donor ◽

York City ◽

Blood Donors ◽

Herd Immunity ◽

Serological Tests ◽

Public Health Decision

Projections of the stage of the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic and local, regional and national public health policies to limit coronavirus spread as well as “reopen” cities and states, are best informed by serum neutralizing antibody titers measured by reproducible, high throughput, and statically credible antibody (Ab) assays. To date, a myriad of Ab tests, both available and FDA authorized for emergency, has led to confusion rather than insight per se. The present study reports the results of a rapid, point-in-time 1,000-person cohort study using serial blood donors in the New York City metropolitan area (NYC) using multiple serological tests, including enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). These were then tested and associated with assays for neutralizing Ab (NAb). Of the 1,000 NYC blood donor samples in late June and early July 2020, 12.1% and 10.9% were seropositive using the Ortho Total Ig and the Abbott IgG HTSA assays, respectively. These serological assays correlated with neutralization activity specific to SARS-CoV-2. The data reported herein suggest that seroconversion in this population occurred in approximately 1 in 8 blood donors from the beginning of the pandemic in NYC (considered March 1, 2020). These findings deviate with an earlier seroprevalence study in NYC showing 13.7% positivity. Collectively however, these data demonstrate that a low number of individuals have serologic evidence of infection during this “first wave” and suggest that the notion of “herd immunity” at rates of ~60% or higher are not near. Furthermore, the data presented herein show that the nature of the Ab-based immunity is not invariably associated with the development of NAb. While the blood donor population may not mimic precisely the NYC population as a whole, rapid assessment of seroprevalence in this cohort and serial reassessment could aid public health decision making.

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Mass Vaccination Programme: Public Health Success and Ethical Issues – Bangladesh Perspective

Bangladesh Journal of Bioethics ◽

10.3329/bioethics.v9i3.48912 ◽

2020 ◽

Vol 9 (3) ◽

pp. 11-15

Author(s):

Abu Sadat Mohammad Nurunnabi ◽

Miliva Mozaffor ◽

Mohammad Akram Hossain ◽

Sadia Akther Sony

Keyword(s):

Public Health ◽

Vaccination Programme ◽

Large Scale ◽

Ethical Issues ◽

Herd Immunity ◽

Mass Vaccination ◽

Global Public Health ◽

National Programme ◽

Serious Infections ◽

Individual Protection

Vaccines are responsible for many global public health successes, such as the eradication of smallpox and significant reductions in other serious infections like diphtheria, pertussis, tetanus, polio and measles. However, mass vaccination has also been the subject of various ethical controversies for decades. Several factors need to be considered before any vaccine is deployed at national programme like the potential burden of disease in the country or region, the duration of the protection conferred, herd immunity in addition to individual protection, vaccine-related risks, financing and the logistical feasibility of the large-scale vaccination. Moreover, several ethical dilemmas revolve around authority and mandates for vaccination, informed consent, benefits vs. risks, and disparities in access to vaccination. This review paper aims to elaborate the ethical issues involved in mass vaccination programme and present some additional challenges in the context of a resource-poor settings of public health in Bangladesh.

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Prevalence of human T-lymphotropic virus 1/2 in Nigeria’s capital territory and meta-analysis of Nigerian studies

SAGE Open Medicine ◽

10.1177/2050312119843706 ◽

2019 ◽

Vol 7 ◽

pp. 205031211984370

Author(s):

Nneoma Confidence JeanStephanie Anyanwu ◽

Elijah Ekah Ella ◽

Maryam Aminu ◽

Maleeha Azam ◽

Muhammad Ajmal ◽

...

Keyword(s):

Risk Factors ◽

Polymerase Chain Reaction ◽

Immunosorbent Assay ◽

Large Scale ◽

Meta Analysis ◽

Antibody Detection ◽

Enzyme Linked Immunosorbent Assay ◽

Chain Reaction ◽

T Lymphotropic Virus ◽

Polymerase Chain

Objectives: This study was aimed at determining human T-lymphotropic virus 1/2 prevalence among apparently healthy, immunocompromised and haematologic malignant individuals in Nigeria’s capital, as well as meta-analysis of all Nigerian studies until date. Methods: A total of 200 participants were recruited into a cross-sectional study. In total, 1 mL each of sera and plasma were obtained from 5 mL blood of each participant and analysed for antibodies to human T-lymphotropic virus 1/2 using enzyme-linked immunosorbent assay; positive samples confirmed with qualitative real-time polymerase chain reaction, followed by statistical and meta-analysis. Sociodemographic characteristics and possible risk factors were assessed via questionnaires. Results: Enzyme-linked immunosorbent assay yielded 1% prevalence which was confirmed to be zero via polymerase chain reaction. A total of 119 (59.5%) of the participants were male, while the mean age was 35.28 ± 13.61 years. Apart from sex and blood reception/donation, there was generally a low rate of exposure to human T-lymphotropic virus–associated risk factors. Meta-analysis revealed pooled prevalence of human T-lymphotropic virus 1 and 2 to be 3% and 0%, respectively, from Nigerian studies. Conclusion: This study discovered zero prevalence of human T-lymphotropic virus 1/2 from five major hospitals in Nigeria’s capital, exposing the importance of confirmatory assays after positive antibody detection assay results. Meta-analysis highlighted the existence of very few reliable Nigerian studies compared to the demography of the nation. Large-scale epidemiological studies and routine screening of risk populations are therefore needed since Nigeria lies in the region of endemicity.

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Rates and causes of readmissions following index admissions for Takotsubo syndrome-a meta-analysis of 118,941 index hospitalizations

European Heart Journal ◽

10.1093/ehjci/ehaa946.1246 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

R Desai ◽

S Sachdeva ◽

S Singh ◽

S.K Rajan ◽

A.S Shaik ◽

...

Keyword(s):

Readmission Rate ◽

Large Scale ◽

Meta Analysis ◽

Young Patients ◽

Takotsubo Syndrome ◽

Short Term ◽

Random Effects Models ◽

Study Heterogeneity ◽

The Usa

Abstract Background Rising trends in takotsubo syndrome (TTS)-related complications warrant data to identify the rate, causes and predictors of readmission on a large scale. We conducted the first-ever meta-analysis to evaluate the pooled rate of short-term and long-term readmissions after index TTS admissions. Methods PubMed/Medline, EMBASE and SCOPUS databases were systematically reviewed to find studies through October 2019 reporting rates and causes of readmission following index TTS admissions. Random effects models were used to estimate pooled rates and causes of readmissions and I2 statistics were used to report inter-study heterogeneity. Results A total of 16 cohorts with 118,941 TTS index admissions (mean age 65–75 yrs; female >85%, median follow-up 272.5 days) revealed a 16.6% [95% CI-13.2%-20.3%, I2=99%] pooled rate of readmission. Short-term and long-term pooled readmission rates are displayed in Fig.1. The readmission rate was higher in cohorts with young patients (<70 vs. >70 yrs), smaller sample size (n<100 vs. n>100) and single-centres vs. multicentres. Studies published from the USA (16.4% vs. 14.9%) had a higher readmission rate as compared to Italy. The most frequent causes were cardiac (40.6%), respiratory (15.7%) and renal (7.0%). Among readmissions with cardiac diagnoses, heart failure was most common (40.1%). Conclusions This global meta-analysis revealed that the pooled rate of readmission following index TTS admissions was ∼17% and causes were mainly cardiac or respiratory. Funding Acknowledgement Type of funding source: None

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