Towards the next phase: evaluation of serological assays for diagnostics and exposure assessment

GeurtsvanKessel, Corine H.; Okba, Nisreen M.A.; Iglói, Zsófia; Embregts, Carmen W.E.; Laksono, Brigitta M.; Leijten, Lonneke; Rahamat‐Langendoen, Janette; Akker, Johannes P. C. van den; Kampen, Jeroen J. A. van; Eijk, Annemiek A. van der; Binnendijk, Rob van; Haagmans, Bart L.; Koopmans, Marion

doi:10.1101/2020.04.23.20077156

Cited by 59 publications

(77 citation statements)

References 4 publications

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“…Manufacturers' sensitivity estimates ranged from 96·8% to 100% on samples taken at least 14 days post symptom onset or RT-PCR, and specificity estimates ranged from 98·5% to 99·8% on pre-pandemic samples ( appendix p 14 ). 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18…”

Section: Methodsmentioning

confidence: 99%

Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison

Ainsworth¹,

Andersson²,

Auckland³

et al. 2020

The Lancet Infectious Diseases

356

291

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic in 2020. Testing is crucial for mitigating public health and economic effects. Serology is considered key to population-level surveillance and potentially individual-level risk assessment. However, immunoassay performance has not been compared on large, identical sample sets. We aimed to investigate the performance of four high-throughput commercial SARS-CoV-2 antibody immunoassays and a novel 384-well ELISA. Methods We did a head-to-head assessment of SARS-CoV-2 IgG assay (Abbott, Chicago, IL, USA), LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy), Elecsys Anti-SARS-CoV-2 assay (Roche, Basel, Switzerland), SARS-CoV-2 Total assay (Siemens, Munich, Germany), and a novel 384-well ELISA (the Oxford immunoassay). We derived sensitivity and specificity from 976 pre-pandemic blood samples (collected between Sept 4, 2014, and Oct 4, 2016) and 536 blood samples from patients with laboratory-confirmed SARS-CoV-2 infection, collected at least 20 days post symptom onset (collected between Feb 1, 2020, and May 31, 2020). Receiver operating characteristic (ROC) curves were used to assess assay thresholds. Findings At the manufacturers' thresholds, for the Abbott assay sensitivity was 92·7% (95% CI 90·2–94·8) and specificity was 99·9% (99·4–100%); for the DiaSorin assay sensitivity was 95·0% (92·8–96·7) and specificity was 98·7% (97·7–99·3); for the Oxford immunoassay sensitivity was 99·1% (97·8–99·7) and specificity was 99·0% (98·1–99·5); for the Roche assay sensitivity was 97·2% (95·4–98·4) and specificity was 99·8% (99·3–100); and for the Siemens assay sensitivity was 98·1% (96·6–99·1) and specificity was 99·9% (99·4–100%). All assays achieved a sensitivity of at least 98% with thresholds optimised to achieve a specificity of at least 98% on samples taken 30 days or more post symptom onset. Interpretation Four commercial, widely available assays and a scalable 384-well ELISA can be used for SARS-CoV-2 serological testing to achieve sensitivity and specificity of at least 98%. The Siemens assay and Oxford immunoassay achieved these metrics without further optimisation. This benchmark study in immunoassay assessment should enable refinements of testing strategies and the best use of serological testing resource to benefit individuals and population health. Funding Public Health England and UK National Institute for Health Research.

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Section: Methodsmentioning

confidence: 99%

Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison

Ainsworth¹,

Andersson²,

Auckland³

et al. 2020

The Lancet Infectious Diseases

356

291

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“…Table 5 shows data on positive and negative likelihood ratios, allowing an easy estimation of positive (PPV) and negative (NPV) predictive values given disease prevalence. Considering two different scenarios of disease prevalence settings: (a) 4%, as found in a Veneto Region (Italy) survey [13] ; (b) 10%, as described in a survey conducted in Geneva [14] , PPV and NPV were then estimated, using VITROS Anti-SARS-CoV-2 Total and Architect SARS-CoV-2 IgG immunoassays for comparative purposes. Regarding performances calculated 12 days after the onset of symptoms, VITROS Anti-SARS-CoV-2 Total PPV (95%CI) and NPV (95%CI) were 66.3% (22.0–93.2%) and 99.5% (99.2–99.7%) with a prevalence of 4%, 84% (43.0%–97.3%) and 98.6% (97.8%–99.1%) with a prevalence of 10%.…”

Section: Resultsmentioning

confidence: 99%

Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity

et al. 2020

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Background Reliable high-throughput serological assays for SARS-CoV-2 antibodies are urgently needed for the effective containment of the COVID-19 pandemic, as it is of crucial importance to understand the strength and duration of immunity after infection, and to make informed decisions concerning the activation or discontinuation of physical distancing restrictions. Methods In 184 serum samples from 130 COVID-19 patients and 54 SARS-CoV-2 negative subjects, the analytical and clinical performances of four commercially available chemiluminescent assays (Abbott SARS-Cov-2 IgG, Roche Elecsys anti-SARS-CoV-2, Ortho SARS-CoV-2 total and IgG) and one enzyme-linked immunosorbent assay (Diesse ENZY-WELL SARS-CoV-2 IgG) were evaluated and compared with the neutralization activity achieved using the plaque reduction neutralization test (PRNT). Findings Precision results ranged from 0.9% to 11.8% for all assays. Elecsys anti-SARS-CoV-2 demonstrated linearity of results at concentrations within the cut-off value. Overall, sensitivity ranged from 78.5 to 87.7%, and specificity, from 97.6 to 100%. On limiting the analysis to samples collected 12 days after onset of symptoms, the sensitivity of all assays increased, the highest value (95.2%) being obtained with VITRO Anti-SARS-CoV-2 Total and Architect SARS-CoV-2 IgG. The strongest PRNT 50 correlation with antibody levels was obtained with ENZY-Well SARS-CoV-2 IgG (R 2 adj = 0.569). Interpretation The results confirmed that all immunoassays had an excellent specificity, whereas sensitivity varied across immunoassays, depending strongly on the time interval between symptoms onset and sample collection. Further studies should be conducted to achieve a stronger correlation between antibody measurement and PRNT 50 in order to obtain useful information for providing a better management of COVID-19 patients, effective passive antibody therapy, and developing a vaccine against the SARS-CoV-2 virus. Funding None.

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“…Such tests have already been deployed in a few cases. 75,76 In contrast to the PCR testing procedures mainly discussed in this paper, the main intention of serological testing is to obtain accurate estimations of the number of unidentified previous infections as a measure for the progress towards herd immunity. Group testing can also be expected to yield accuracy gains for this problem.…”

Section: Discussionmentioning

confidence: 99%

Group testing for SARS-CoV-2 allows for up to 10-fold efficiency increase across realistic scenarios and testing strategies

Verdun

Fuchs

Harár

et al. 2020

Preprint

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Background: Due to the ongoing COVID-19 pandemic, demand for diagnostic testing has increased drastically, resulting in shortages of necessary materials to conduct the tests and overwhelming the capacity of testing laboratories. The supply scarcity and capacity limits affect test administration: priority must be given to hospitalized patients and symptomatic individuals, which can prevent the identification of asymptomatic and presymptomatic individuals and hence effective tracking and tracing policies. We describe optimized group testing strategies applicable to SARS-CoV-2 tests in scenarios tailored to the current COVID-19 pandemic and assess significant gains compared to individual testing. Methods:We account for biochemically realistic scenarios in the context of dilution effects on SARS-CoV-2 samples and consider evidence on specificity and sensitivity of PCR-based tests for the novel coronavirus. Because of the current uncertainty and the temporal and spatial changes in the prevalence regime, we provide analysis for a number of realistic scenarios and propose fast and reliable strategies for massive testing procedures. Findings:We find significant efficiency gaps between different group testing strategies in realistic scenarios for SARS-CoV-2 testing, highlighting the need for an informed decision of the pooling protocol depending on estimated prevalence, target specificity, and high-vs. low-risk population. For example, using one of the presented methods, all 1·47 million inhabitants of Munich, Germany, could be tested using only around 141 thousand tests if the infection rate is below 0·4% is assumed. Using 1 million tests, the 6·69 million inhabitants from the city of Rio de Janeiro, Brazil, could be tested as long as the infection rate does not exceed 1%.Interpretation: Altogether this work may help provide a basis for efficient upscaling of current testing procedures, taking the population heterogeneity into account and fine grained towards the desired study populations, e.g. cross-sectional versus health-care workers and adapted mixtures thereof.

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Towards the next phase: evaluation of serological assays for diagnostics and exposure assessment

Cited by 59 publications

References 4 publications

Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison

Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison

Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity

Group testing for SARS-CoV-2 allows for up to 10-fold efficiency increase across realistic scenarios and testing strategies

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