Analytical and clinical evaluation of antibody tests for SARS-CoV-2 serosurveillance studies used in Finland in 2020
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Abstract
Background
Sensitive and highly specific antibody tests are critical for detection of SARS-CoV-2 antibodies especially in populations where seroprevalence is low.
Aim
To set up, optimize and evaluate the analytical and clinical performance of a new in-house microsphere immunoassay for measurement of IgG antibodies to SARS-CoV-2 nucleoprotein for assessment of population seroprevalence in Finland.
Methods
We set up a new in-house microsphere immunoassay (FMIA) with SARS-CoV-2 nucleoprotein and optimized its analytical performance. For evaluation of clinical performance, we tested sera collected in a well-characterized cohort of PCR positive-confirmed SARS-CoV-2 patients (n=89) with mostly mild symptoms, and before the COVID-19 pandemic (n=402), for nucleoprotein specific IgG concentrations by FMIA and a commercial chemiluminescent immunoassay and for neutralizing antibodies by the microneutralization test.
Results
The analytical performance of FMIA was established in terms of sensitivity, linearity and precision. FMIA discriminated between COVID-19 patient and control samples with high specificity (100%) and sensitivity (100%). We generated FMIA seropositivity cut-offs, 0.46 and 1.71 U/ml, for low- and high-seroprevalence settings, respectively. In addition, we obtained high level of agreement between FMIA results and results by the microneutralization test.
Conclusion
The fluorescent microsphere immunoassay showed excellent analytical and clinical performance and is well suited for serosurveillance studies of SARS-CoV-2. However, to optimize analytical sensitivity and clinical specificity of the assay, different seropositivity thresholds depending on the intended use of the assay and the target population, may be needed.
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SciScore for 10.1101/2021.01.21.21250207: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Altogether 129 subjects from 39 households participated and gave written consent between March and June 2020. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Evaluation and comparison of the clinical performances of FMIA, Abbott test and MNT: The ability of FMIA to discriminate PCR-positive confirmed COVID-19 patients and controls was assessed for IgG concentrations by analysis of receiver operating characteristic (ROC) curve and area under curve (AUC, 95% CI) with GraphPad Prism v7 (San Diego, USA). GraphPad Prismsuggested: …SciScore for 10.1101/2021.01.21.21250207: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: Altogether 129 subjects from 39 households participated and gave written consent between March and June 2020. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Evaluation and comparison of the clinical performances of FMIA, Abbott test and MNT: The ability of FMIA to discriminate PCR-positive confirmed COVID-19 patients and controls was assessed for IgG concentrations by analysis of receiver operating characteristic (ROC) curve and area under curve (AUC, 95% CI) with GraphPad Prism v7 (San Diego, USA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of this study include that the sample size, especially for assessment of sensitivity by days post onset of symptoms, was relatively small. Another limitation was that because only few patients had been hospitalized, we could not assess differences in performance that depend on disease severity. On the other hand, as the majority of the samples used in assessment of performance were from COVID-19 patients with mild symptoms, they well reflect the general population in seroprevalence studies. Furthermore, testing potentially cross-reactive sera from patients with recent infection of endemic human coronaviruses or other respiratory pathogens was not done due to lack of suitable sera. In the future, the capacity of the FMIA-based assays can be utilized in antibody testing within SARS-CoV-2 vaccine evaluation. The flexibility of FMIA will allow several additional SARS-CoV-2 antigens to be incorporated easily into a single multiplex assay. Importantly, by measuring antibodies to the SARS-CoV-2 nucleoprotein, immune responses induced by infection and potential circulation of the virus can be assessed also in vaccinated populations.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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