Population (Antibody) Testing for COVID-19—Technical Challenges, Application and Relevance, an English Perspective

In the UK, population virus or antibody testing using virus swabs, serum samples, blood spots or oral fluids has been performed to a limited extent for several diseases including measles, mumps, rubella and hepatitis and HIV. The collection of population-based infection and immunity data is key to the monitoring of disease prevalence and assessing the effectiveness of interventions such as behavioural modifications and vaccination. In particular, the biological properties of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its interaction with the human host have presented several challenges towards the development of population-based immunity testing. Measuring SARS-CoV-2 immunity requires the development of antibody assays of acceptable sensitivity and specificity which are capable of accurately detecting seroprevalence and differentiating protection from non-protective responses. Now that anti-COVID-19 vaccines are becoming available there is a pressing need to measure vaccine efficacy and the development of herd immunity. The unprecedented impact of the SARS-CoV-2 pandemic in the UK in terms of morbidity, mortality, and economic and social disruption has mobilized a national scientific effort to learn more about this virus. In this article, the challenges of testing for SARS-CoV-2 infection, particularly in relation to population-based immunity testing, will be considered and examples given of relevant national level studies.

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Neuronal antibody prevalence in children with seizures under 3 years

Neurology ◽

10.1212/wnl.0000000000010318 ◽

2020 ◽

Vol 95 (11) ◽

pp. e1590-e1598

Author(s):

Joseph D. Symonds ◽

Teresa C. Moloney ◽

Bethan Lang ◽

Ailsa McLellan ◽

Mary E. O'Regan ◽

...

Keyword(s):

Early Childhood ◽

Gaba Receptor ◽

Glycine Receptor ◽

Autoimmune Encephalitis ◽

Febrile Seizures ◽

Population Based ◽

Clinical Test ◽

Antibody Testing ◽

Serum Samples ◽

Antibody Positivity

ObjectiveTo report the prevalence of anti-neuronal antibodies in a prospective whole-nation cohort of children presenting with seizures before their third birthday.MethodsThis was a prospective population-based national cohort study involving all children presenting with new-onset epilepsy or complex febrile seizures before their third birthday over a 3-year period. Patients with previously identified structural, metabolic, or infectious cause for seizures were excluded. Serum samples were obtained at first presentation and tested for 7 neuronal antibodies using live cell-based assays. Clinical data were collected with structured proformas at recruitment and 24 months after presentation. In addition, patients with seizures and clinically suspected autoimmune encephalitis were independently identified by a review of the case records of all children <3 years of age in Scotland who had undergone EEG.ResultsTwo hundred ninety-eight patients were identified and recruited and underwent autoantibody testing. Antibody positivity was identified in 18 of 298 (6.0%). The antibodies identified were GABA receptor B (n = 8, 2.7%), contactin-associated protein 2 (n = 4, 1.3%), glycine receptor (n = 3, 1.0%), leucine-rich glioma inactivated 1 (n = 2, 0.7%), NMDA receptor (n = 1, 0.3%), and GABA receptor A (n = 1, 0.3%). None of these patients had a clinical picture of autoimmune encephalitis. Seizure classification and clinical phenotype did not correlate with antibody positivity.ConclusionsAutoimmune encephalitis is very rare in early childhood. However serum neuronal antibodies are identified in 6.4% of children presenting with seizures at <3 years of age. Antibody testing should not be a routine clinical test in early childhood-onset epilepsy because, in the absence of other features of autoimmune encephalitis, antibody positivity is of doubtful clinical significance. Antibody testing should be reserved for patients with additional features of encephalitis.

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Assessing the deprivation gap in stillbirths and neonatal deaths by cause of death: a national population-based study

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2018-316124 ◽

2019 ◽

Vol 104 (6) ◽

pp. F624-F630 ◽

Cited By ~ 2

Author(s):

Kate E Best ◽

Sarah E Seaton ◽

Elizabeth S Draper ◽

David J Field ◽

Jennifer J Kurinczuk ◽

...

Keyword(s):

Congenital Anomalies ◽

Neonatal Death ◽

National Level ◽

Mortality Rates ◽

Population Based ◽

Intervention Strategies ◽

Population Based Study ◽

Neonatal Deaths ◽

The Uk ◽

Deprived Areas

ObjectiveTo investigate socioeconomic inequalities in cause-specific stillbirth and neonatal mortality to identify key areas of focus for future intervention strategies to achieve government ambitions to reduce mortality rates.DesignRetrospective cohort study.SettingEngland, Wales, Scotland and the UK Crown Dependencies.ParticipantsAll singleton births between 1 January 2014 and 31 December 2015 at ≥24 weeks’ gestation.Main outcome measureCause-specific stillbirth or neonatal death (0–27 days after birth) per 10 000 births by deprivation quintile.ResultsData on 5694 stillbirths (38.1 per 10 000 total births) and 2368 neonatal deaths (15.9 per 10 000 live births) were obtained from Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK). Women from the most deprived areas were 1.68 (95% CI 1.56 to 1.81) times more likely to experience a stillbirth and 1.67 (95% CI 1.48 to 1.87) times more likely to experience a neonatal death than those from the least deprived areas, equating to an excess of 690 stillbirths and 231 neonatal deaths per year associated with deprivation. Small for gestational age (SGA) unexplained antepartum stillbirth was the greatest contributor to excess stillbirths accounting for 33% of the deprivation gap in stillbirths. Congenital anomalies accounted for the majority (59%) of the deprivation gap in neonatal deaths, followed by preterm birth not SGA (24–27 weeks, 27%).ConclusionsCause-specific mortality rates at a national level allow identification of key areas of focus for future intervention strategies to reduce mortality. Despite a reduction in the deprivation gap for stillbirths and neonatal deaths, public health interventions should primarily focus on socioeconomic determinants of SGA stillbirth and congenital anomalies.

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SARS-CoV-2 IgG detection in human oral fluids

10.1101/2021.07.07.21260121 ◽

2021 ◽

Author(s):

Katja Hoschler ◽

Samreen Ijaz ◽

Nick Andrews ◽

Sammy Ho ◽

Steve Dicks ◽

...

Keyword(s):

Target Population ◽

Population Based ◽

Lower Sensitivity ◽

Non Invasive ◽

Capture Assay ◽

Oral Fluids ◽

Paired Serum ◽

The Uk ◽

Antibody Kinetics ◽

Higher Sensitivity

Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Non-invasive sampling methods are advantageous to reduce the need for venepuncture, which may be a barrier to investigations particularly in paediatric populations. Oral Fluids are obtained by gingiva-crevicular sampling from children and adults and are very well accepted. ELISA based on these samples have acceptable sensitivity and specificity compared to conventional serum-based antibody ELISAs and are suitable for population-based surveillance. We describe the development and evaluation of SARS-COV-2 IgG ELISAs using SARS-CoV-2 viral nucleoprotein (NP) and spike (S) proteins in IgG isotype capture format and an indirect receptor-binding-domain (RBD) IgG ELISA, intended for use in children. All three assays were assessed using a panel of 1999 paired serum and oral fluids from children and adults participating in national primary school SARS-CoV-2 surveillance studies during and after the first and second pandemic wave in the UK. The anti NP IgG capture assay was the best candidate, with an overall sensitivity of 75% (95% CI: 71–79%) specificity of 99% (95% CI: 78–99%) when compared with paired serum antibodies measured using a commercial assay SARS-CoV-2 nucleoprotein IgG assay (Abbott, Chicago, IL, USA). Higher sensitivity was observed in children (80%, 95% CI: 71–88%) compared to adults (67%, CI: 60%-74%). Oral fluid assays using spike protein and RBD antigens were also 99% specific and achieved reasonable but lower sensitivity in the target population (78%, 95% CI (68%-86%) and 53%, 95% CI (43%-64%), respectively).

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Seroprevalence of SARS-CoV-2 in Palestine: a cross-sectional seroepidemiological study

10.1101/2020.08.28.20180083 ◽

2020 ◽

Cited By ~ 1

Author(s):

Nouar Qutob ◽

Faisal Awartani ◽

Zaidoun Salah ◽

Mohammad Asia ◽

Imad Abu Khader ◽

...

Keyword(s):

West Bank ◽

Herd Immunity ◽

Population Based ◽

Seroprevalence Rate ◽

Serum Samples ◽

The West ◽

Serological Tests ◽

Cross Sectional ◽

Blood Samples ◽

Palestinian Population

Seroprevalence rates are important indicators to the epidemiology of COVID-19 and the extent of the pandemic given the existence of asymptomatic cases. The purpose of this study is to assess the seroprevalence rate in the Palestinian population residing in the West Bank. Blood samples were collected between 15th June 2020 and 30th June 2020 from 1355 individuals from randomly selected households in the West Bank in addition to 1136 individuals visiting Palestinian medical laboratories between the 1st May 2020 and 9th July 2020 for a routine checkup. Out of the 2491 blood samples collected, serological tests for 2455 adequate serum samples were done using an Immunoassay for qualitative detection of antibodies against SARS-CoV-2 .The random sample of Palestinians living in the West Bank yielded 0% seroprevalence with 95% CI [0,0.0036], while the lab referrals sample yielded an estimated seroprevalence of 0.354% with 95% CI [0.0011,0096]. Our results indicate that as of July 2020, seroprevalence in Palestine persist low and is inadequate to provide herd immunity, emphasizing the need to maintain health measures to keep the outbreak under control. Population-based seroprevalence studies are to be conducted periodically to monitor the SARS-CoV-2 seroprevalence in Palestine and inform policy makers about the efficacy of their surveillance system.

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Population immunity to measles, rubella, mumps, and varicella among adults in Khanh Hoa province, Socialist Republic of Vietnam; residual sample analysis from multistage cluster sampling survey

10.21203/rs.3.rs-60952/v1 ◽

2020 ◽

Author(s):

Thai Hung Do ◽

Kim Mai Huynh ◽

Quang Mai Vien ◽

Tien Thanh Hoang ◽

Bao Trieu Nguyen ◽

...

Keyword(s):

Herd Immunity ◽

Population Based ◽

Cluster Sampling ◽

Serum Samples ◽

Socialist Republic ◽

Population Immunity ◽

Congenital Rubella ◽

Child Bearing ◽

Specific Immunoglobulin ◽

Ig G

Abstract Objective: Measles, rubella, mumps, and varicella are currently endemic in Vietnam, but population immunity to the four diseases among the general population has not been well investigated. This study measured specific immunoglobulin (Ig)G in 362 randomly selected adults between 20 and 70 years old, using residual serum samples to evaluate age-specific immunity to the four diseases in Khanh Hoa province.Results: Age-specific anti-measles IgG prevalence was lowest, at 89.3% (95% confidence interval 71.8–97.7%) at 20–24 years old, below the herd immunity threshold of 95% to prevent epidemics. About 71.4–90.3% of women of child-bearing age (20–49 years old) were seropositive for rubella, indicating that a certain proportion of babies are at risk of congenital rubella syndrome. A large proportion of young adults (20–29 years) are susceptible to mumps and varicella, with population immunity of 71.4–78.1% to mumps and 48.8–53.6% to varicella. Population-based seroprevalence surveys of both children and adults are needed to evaluate population immunity and improve current immunization programs by expanding the target ages for immunization and introducing new vaccines.

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Are commercial antibody assays substantially underestimating SARS-CoV-2 ever infection? An analysis on a population-based sample in a high exposure setting

10.1101/2020.12.14.20248163 ◽

2020 ◽

Cited By ~ 1

Author(s):

Gheyath K. Nasrallah ◽

Soha R. Dargham ◽

Farah Shurrab ◽

Duaa W. Al-Sadeq ◽

Hadeel Al-Jighefee ◽

...

Keyword(s):

Kappa Statistic ◽

Population Based ◽

Serological Testing ◽

Infection Rates ◽

Antibody Testing ◽

High Exposure ◽

Antibody Assays ◽

Comparable Performance ◽

Current Infection ◽

Exposure Setting

AbstractBackgroundPerformance of three automated commercial serological IgG-based assays was investigated for assessing SARS-CoV-2 ever (past or current) infection in a population-based sample in a high exposure setting.MethodsPCR and serological testing was performed on 394 individuals.ResultsSARS-CoV-2-IgG seroprevalence was 42.9% (95% CI 38.1%-47.8%), 40.6% (95% CI 35.9%-45.5%), and 42.4% (95% CI 37.6%-47.3%) using the CL-900i, VidasIII, and Elecsys assays, respectively. Between the three assays, overall, positive, and negative percent agreements ranged between 93.2%-95.7%, 89.3%-92.8%, and 93.8%-97.8%, respectively; Cohen kappa statistic ranged from 0.86-0.91; and 35 specimens (8.9%) showed discordant results. Among all individuals, 12.5% (95% CI 9.6%-16.1%) had current infection, as assessed by PCR. Of these, only 34.7% (95% CI 22.9%-48.7%) were seropositive by at least one assay. A total of 216 individuals (54.8%; 95% CI 49.9%-59.7%) had evidence of ever infection using antibody testing and/or PCR during or prior to this study. Of these, only 78.2%, 74.1%, and 77.3% were seropositive in the CL-900i, VidasIII, and Elecsys assays, respectively.ConclusionsAll three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.

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Evaluation of dried blood spots as alternative sampling material for serological detection of anti-SARS-CoV-2 antibodies using established ELISAs

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-1436 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Heike Weisser ◽

Katja Steinhagen ◽

Ralf Höcker ◽

Viola Borchardt-Lohölter ◽

Özlem Anvari ◽

...

Keyword(s):

Large Scale ◽

Correlation Coefficients ◽

Dried Blood Spots ◽

Population Based ◽

Sample Collection ◽

Antibody Testing ◽

Serum Samples ◽

Perfect Agreement ◽

Blood Spots ◽

Paired Samples

Abstract Objectives During the current pandemic, antibody testing based on venous serum helps to determine whether the tested person has been previously infected with SARS-CoV-2. Alternatively, capillary blood can be taken via a finger prick (dried blood spots, DBS). In this study, paired DBS and venipuncture samples were tested using two serological assays to evaluate the usability of DBS for the detection of anti-SARS-CoV-2 antibodies. Methods Paired samples of DBS and venous serum were collected from 389 volunteers, of whom 75 had a recent PCR-confirmed SARS-CoV-2 infection, and tested for anti-SARS-CoV-2 IgG antibodies against both viral S1 and nucleocapsid protein (NCP) antigens using two ELISAs. Degree of agreement and correlation coefficients between ELISA results based on the two sampling methods were calculated. Results Results of DBS showed almost perfect agreement and high correlations with results from corresponding serum samples in both the S1-based ELISA and the NCP-based ELISA. Conclusions ELISA results derived from DBS showed very high agreement to those obtained with serum, supposing adequate usability and robustness of DBS as sample material for detection of anti-SARS-CoV-2 antibodies. In the near future, large-scale epidemiological screening for antibodies against SARS-CoV-2 will be carried out. Since DBS reduce the strain on healthcare institutions regarding sample collection, they have a potential to facilitate efficient community- and population-based screening in the current SARS-CoV-2 pandemic.

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SARS-CoV-2 Antibody Testing in Healthcare Workers: a comparison of the clinical performance of three commercially available antibody assays

10.1101/2021.05.25.21257772 ◽

2021 ◽

Author(s):

Niamh Allen ◽

Melissa Brady ◽

Antonio Isidro Carrion Martin ◽

Lisa Domegan ◽

Cathal Walsh ◽

...

Keyword(s):

Clinical Performance ◽

Natural Infection ◽

Sample Selection ◽

High Sensitivity ◽

Population Based ◽

Serological Response ◽

Antibody Testing ◽

Serum Samples ◽

Entire Study ◽

Asian Ethnicity

SARS-CoV-2 antibodies are an excellent indicator of past COVID-19 infection. As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies. We compared 5788 healthcare worker (HCW) serum samples on two serological assays (Abbott SARS-CoV-2 anti-nucleocapsid IgG and Roche Anti-SARS-CoV-2 anti-nucleocapsid Total Antibody) and a subset of samples (all Abbott assay positive or grayzone, n=485) on Wantai SARS-CoV-2 anti-spike Antibody ELISA. For 367 samples from HCW with previous PCR-confirmed SARS-CoV-2 infection we correlated the timing of infection with assay results. Overall seroprevalence was 4.2% on Abbott, 9.5% on Roche. Of those with previously confirmed infection, 41% (150/367) and 95% (348/367) tested positive on Abbott and Roche respectively. At 21 weeks (150 days) after confirmed infection, positivity on Abbott started to decline. Roche positivity was retained for the entire study period (33 weeks). Factors associated (P≤ 0.050) with Abbott seronegativity in those with previous PCR-confirmed infection included sex (male OR0.30;95%CI0.15-0.60), symptom severity (OR0.19 severe symptoms;95%CI0.05-0.61), ethnicity (OR0.28 Asian ethnicity;95%CI0.12-0.60) and time since PCR diagnosis (OR2.06 for infection 6 months previously;95%CI1.01-4.30. Wantai detected all previously confirmed infections. In our population, Roche detected antibodies up to at least seven months after natural infection with SARS-CoV-2. This may indicate that Roche is better suited than Abbott to population-based studies. Wantai demonstrated high sensitivity but sample selection was biased. The relationship between serological response and functional immunity to SARS-CoV-2 infection needs to be delineated.

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Analytic comparison between three high-throughput commercial SARS-CoV-2 antibody assays reveals minor discrepancies in a high-incidence population

Scientific Reports ◽

10.1038/s41598-021-91235-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Gheyath K. Nasrallah ◽

Soha R. Dargham ◽

Farah Shurrab ◽

Duaa W. Al-Sadeq ◽

Hadeel Al-Jighefee ◽

...

Keyword(s):

Kappa Statistic ◽

Population Based ◽

Infection Rates ◽

Antibody Testing ◽

High Exposure ◽

High Incidence ◽

Antibody Assays ◽

Comparable Performance ◽

Current Infection ◽

Exposure Setting

AbstractPerformance of three automated commercial serological IgG-based assays was investigated for assessing SARS-CoV-2 “ever” (past or current) infection in a population-based sample in a high exposure setting. PCR and serological testing was performed on 394 individuals. SARS-CoV-2-IgG seroprevalence was 42.9% (95% CI 38.1–47.8%), 40.6% (95% CI 35.9–45.5%), and 42.4% (95% CI 37.6–47.3%) using the CL-900i, VidasIII, and Elecsys assays, respectively. Between the three assays, overall, positive, and negative percent agreements ranged between 93.2–95.7%, 89.3–92.8%, and 93.8–97.8%, respectively; Cohen’s kappa statistic ranged from 0.86 to 0.91; and 35 specimens (8.9%) showed discordant results. Among all individuals, 12.5% (95% CI 9.6–16.1%) had current infection, as assessed by PCR. Of these, only 34.7% (95% CI 22.9–48.7%) were seropositive by at least one assay. A total of 216 individuals (54.8%; 95% CI 49.9–59.7%) had evidence of ever infection using antibody testing and/or PCR during or prior to this study. Of these, only 78.2%, 74.1%, and 77.3% were seropositive in the CL-900i, VidasIII, and Elecsys assays, respectively. All three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.

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Ethnic Differences in Self-Poisoning Across South London

Crisis ◽

10.1027/0227-5910/a000258 ◽

2014 ◽

Vol 35 (4) ◽

pp. 268-272

Author(s):

Sean Cross ◽

Dinesh Bhugra ◽

Paul I. Dargan ◽

David M. Wood ◽

Shaun L. Greene ◽

...

Keyword(s):

Black Women ◽

Data Collection ◽

White Women ◽

Population Based ◽

Care Services ◽

Self Harm ◽

Managing Risk ◽

The Uk ◽

Incident Cases ◽

Minority Ethnic

Background: Self-poisoning (overdose) is the commonest form of self-harm cases presenting to acute secondary care services in the UK, where there has been limited investigation of self-harm in black and minority ethnic communities. London has the UK’s most ethnically diverse areas but presents challenges in resident-based data collection due to the large number of hospitals. Aims: To investigate the rates and characteristics of self-poisoning presentations in two central London boroughs. Method: All incident cases of self-poisoning presentations of residents of Lambeth and Southwark were identified over a 12-month period through comprehensive acute and mental health trust data collection systems at multiple hospitals. Analysis was done using STATA 12.1. Results: A rate of 121.4/100,000 was recorded across a population of more than half a million residents. Women exceeded men in all measured ethnic groups. Black women presented 1.5 times more than white women. Gender ratios within ethnicities were marked. Among those aged younger than 24 years, black women were almost 7 times more likely to present than black men were. Conclusion: Self-poisoning is the commonest form of self-harm presentation to UK hospitals but population-based rates are rare. These results have implications for formulating and managing risk in clinical services for both minority ethnic women and men.

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