Sensitivity of commercial Anti-SARS-CoV-2 serological assays in a high-prevalence setting

Mueller, Lisa; Ostermann, Philipp Niklas; Walker, Andreas; Wienemann, Tobias; Mertens, Alexander; Adams, Ortwin; Andrée, Marcel; Hauka, Sandra; Luebke, Nadine; Keitel, Verena; Drexler, Ingo; Cristanziano, Veronica Di; Hermsen, Derik; Kaiser, Rolf; Boege, Friedrich; Klein, Florian; Schaal, Heiner; Timm, Joerg; Senff, Tina

doi:10.1101/2020.06.11.20128686

Cited by 22 publications

(22 citation statements)

References 15 publications

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“…However, it should be noted that the PNA reported herein is based on only two isolates and thus requires further validation. These findings are in overall agreement with those of Müller et al, who compared four commercially available serological assays for SARS-CoV-2 (the Elecsys Anti-SARS-CoV-2 immunoassay, EuroImmun anti-SARS-CoV-2 IgA and IgG enzyme-linked immunosorbent assay [ELISA], Abbott SARS-CoV-2 IgG chemiluminescent microparticle immunoassay [CMIA], and Liaison SARS-CoV-2 S1/S2 IgG chemiluminescent immunoassay [CLIA]) with a neutralization assay and observed good PPA (65.4%), PNA (100%), and POA (78.6%) for the Elecsys Anti-SARS-CoV-2 immunoassay ( 23 ). Our results also align with those of Kohmer et al, who compared six commercially available serological assays for SARS-CoV-2 (the Elecsys Anti-SARS-CoV-2 immunoassay, EuroImmun anti-SARS-CoV-2 IgG ELISA, Abbott SARS-CoV-2 IgG CMIA, Liaison SARS-CoV-2 S1/S2 IgG CLIA, VirClia COVID-19 IgG Monotest CLIA, and Virotech SARS-CoV-2 IgG ELISA) with an in-house plaque reduction neutralization test and observed good PPA (75.6%), PNA (97.1%), and POA (84.8%) ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…High-affinity nAbs are critical for the control of infection, since they can recognize and bind to specific viral epitopes, thereby "neutralizing" the virus and rendering it nonpathogenic (20,22). Previous studies involving commercially available anti-SARS-CoV-2 immunoassays have found a positive correlation between antibody titration results from pseudoneutralization assays and SARS-CoV-2 nAbs; however, further investigation is warranted (23,24).…”

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confidence: 99%

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Development and Validation of the Elecsys Anti-SARS-CoV-2 Immunoassay as a Highly Specific Tool for Determining Past Exposure to SARS-CoV-2

et al. 2020

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The Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics) was developed to provide accurate, reliable detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated sensitivity, specificity, cross-reactivity, and agreement with a vesicular stomatitis virus-based pseudo-neutralisation assay for the Elecsys Anti-SARS-CoV-2 immunoassay. Sensitivity and agreement between the Elecsys Anti-SARS-CoV-2 immunoassay and pseudo-neutralisation assay measurements were evaluated using samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection, a majority of whom were hospitalised. Specificity was evaluated using samples from routine diagnostic testing/blood donors collected pre-December 2019 and thus deemed negative for SARS-CoV-2-specific antibodies. Cross-reactivity was evaluated using samples containing a wide range of potentially cross-reacting analytes, purchased from commercial vendors. For sensitivity and specificity, point estimates and 95% confidence intervals (CIs) were calculated. Agreement between the Elecsys Anti-SARS-CoV-2 immunoassay and pseudo-neutralisation assay was calculated. Sensitivity of the Elecsys Anti-SARS-CoV-2 immunoassay in patients with prior PCR-confirmed SARS-CoV-2 infection was 99.5% (95% CI 97.0–100.0) at ≥14 days post-PCR confirmation. Overall specificity (n=10,453) was 99.80% (99.69–99.88). Only 4/792 samples containing potential cross-reacting analytes were reactive with the Elecsys Anti-SARS-CoV-2 immunoassay, resulting in an overall specificity in this cohort of 99.5% (98.6–99.9). Positive, negative and overall agreement (n=46) between Elecsys Anti-SARS-CoV-2 immunoassay and a pseudo-neutralisation assay were 86.4% (73.3–93.6), 100% (34.2–100) and 87.0% (74.3–93.9), respectively. The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated high sensitivity (99.5% at ≥14 days post-PCR confirmation) and specificity (99.80%), supporting its use as a tool for identification of past SARS-CoV-2 infection, including in populations with low disease prevalence.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Development and Validation of the Elecsys Anti-SARS-CoV-2 Immunoassay as a Highly Specific Tool for Determining Past Exposure to SARS-CoV-2

et al. 2020

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“…These are standard methods for coronavirus serology in blood serum 105 , 106 and can function as reference methods to evaluate the diagnostic performance of binding antibody tests. 107 Plaque reduction neutralization tests (PRNT) take advantage of virus–antibody interactions in a test tube or microtiter plate to measure antibody effects on viral infectivity in virus-susceptible cells. Briefly, serial dilutions of serum sample or antibody solution to be tested are incubated with a standardized amount of virus.…”

Section: Antibody Testsmentioning

confidence: 99%

COVID-19 Antibody Tests and Their Limitations

2021

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COVID-19, caused by the SARS-CoV-2 virus, has developed into a global health crisis, causing over 2 million deaths and changing people’s daily life the world over. Current main-stream diagnostic methods in the laboratory include nucleic acid PCR tests and direct viral antigen tests for detecting active infections, and indirect human antibody tests specific to SARS-CoV-2 to detect prior exposure. In this Perspective, we briefly describe the PCR and antigen tests and then focus mainly on existing antibody tests and their limitations including inaccuracies and possible causes of unreliability. False negatives in antibody immunoassays can arise from assay formats, selection of viral antigens and antibody types, diagnostic testing windows, individual variance, and fluctuation in antibody levels. Reasons for false positives in antibody immunoassays mainly involve antibody cross-reactivity from other viruses, as well as autoimmune disease. The spectrum bias has an effect on both the false negatives and false positives. For assay developers, not only improvement of assay formats but also selection of viral antigens and isotopes of human antibodies need to be carefully considered to improve sensitivity and specificity. For clinicians, the factors influencing the accuracy of assays must be kept in mind to test patients using currently imperfect but available tests with smart tactics and realistic interpretation of the test results.

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“…For the detection of IgG isotype antibodies, our data suggest that the use of the S protein should be su cient to identify positive patients. However, there is evidence that the use of the S1 domain instead of the full-length S protein leads to less cross-reactivity [21] .…”

Section: Discussionmentioning

confidence: 99%

Analysis of IgM, IgA, and IgG Isotype Antibodies Directed Against SARS‑CoV‑2 Spike Glycoprotein and ORF8 in the Course of COVID‑19.

Meinberger

Koch

Roth

et al. 2020

Preprint

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Immunoassays are a standard diagnostic tool assessing immunity in severe acute respiratory syndrome coronavirus type 2 (SARS‑CoV‑2) infection. However, immunoassays do not provide information about contaminating antigens or cross‑reactions and might exhibit inaccurately high sensitivity and low specificity. We aimed to gain insight into the serological immune response of SARS‑CoV‑2 patients by immunoblot analysis.We analyzed serum immunoglobulins IgM, ‑A, and ‑G directed against SARS‑CoV‑2 proteins by immunoblot analysis from 12 infected patients. We determined IgG isotype antibodies by commercially available ELISA and assessed the clinical parameters of inflammation status and kidney and liver injury.We found evidence for antibody cross‑reactivity, which calls into question a reliable assessment of serum samples tested negative for anti‑SARS‑CoV‑2 antibodies by immunoassays. Nevertheless, for the detection of IgG anti‑SARS‑CoV‑2 antibodies, our data suggest that the use of the spike glycoprotein in immunoassays should be sufficient to identify positive patients. Using a combination of the spike glycoprotein and the open reading frame 8 protein could prove to be the best for the detection of patients positive for anti‑SARS‑CoV‑2 IgM antibodies. We found that the antibody response alone is not decisive for the course of the disease, but inflammation parameters are promising indicators.

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Sensitivity of commercial Anti-SARS-CoV-2 serological assays in a high-prevalence setting

Cited by 22 publications

References 15 publications

Development and Validation of the Elecsys Anti-SARS-CoV-2 Immunoassay as a Highly Specific Tool for Determining Past Exposure to SARS-CoV-2

Development and Validation of the Elecsys Anti-SARS-CoV-2 Immunoassay as a Highly Specific Tool for Determining Past Exposure to SARS-CoV-2

COVID-19 Antibody Tests and Their Limitations

Analysis of IgM, IgA, and IgG Isotype Antibodies Directed Against SARS‑CoV‑2 Spike Glycoprotein and ORF8 in the Course of COVID‑19.

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