Commercial Serology Assays Predict Neutralization Activity against SARS-CoV-2
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Abstract
Background
It is unknown whether a positive serology result correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value of SARS-CoV-2 serology tests, especially when testing populations with low disease prevalence.
Methods
A neutralization assay was validated in a set of PCR-confirmed positive specimens and in a negative cohort. In addition, 9530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N = 164 individuals) were reanalyzed using the neutralization assay, the Roche total immunoglobin assay, and the Abbott IgG assay. The relationship between the magnitude of a positive SARS-CoV-2 serology result and neutralizing activity was determined. Neutralizing antibody titers (50% inhibitory dilution, ID50) were also longitudinally monitored in patients confirmed to have SARS-CoV-2 by PCR.
Results
The SARS-CoV-2 neutralization assay had a positive percentage agreement (PPA) of 96.6% with a SARS-CoV-2 PCR test and a negative percentage agreement (NPA) of 98.0% across 100 negative control individuals. ID50 neutralization titers positively correlated with all 3 clinical serology platforms. Longitudinal monitoring of hospitalized PCR-confirmed patients with COVID-19 demonstrated they made high neutralization titers against SARS-CoV-2. PPA between the Diazyme IgG assay alone and the neutralization assay was 50.6%, while combining the Diazyme IgG assay with either the Roche or Abbott platforms increased the PPA to 79.2 and 78.4%, respectively.
Conclusions
These 3 clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in patients with COVID-19. All patients confirmed SARS-CoV-2 positive by PCR develop neutralizing antibodies.
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SciScore for 10.1101/2020.07.10.20150946: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The amount of luminescence in HeLa cells that stably expressed the cell surface receptor angiotensin converting enzyme 2 were measured after viral infection. HeLasuggested: CLS Cat# 300194/p772_HeLa, RRID:CVCL_0030)Software and Algorithms Sentences Resources The Abbott platform reports results in the form of an Index value (S/C); Index values ≥ 1.4 S/C are considered positive. Abbottsuggested: (Abbott, RRID:SCR_010477)Box and whisker … SciScore for 10.1101/2020.07.10.20150946: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The amount of luminescence in HeLa cells that stably expressed the cell surface receptor angiotensin converting enzyme 2 were measured after viral infection. HeLasuggested: CLS Cat# 300194/p772_HeLa, RRID:CVCL_0030)Software and Algorithms Sentences Resources The Abbott platform reports results in the form of an Index value (S/C); Index values ≥ 1.4 S/C are considered positive. Abbottsuggested: (Abbott, RRID:SCR_010477)Box and whisker plots were generated in Rstudio. Rstudiosuggested: (RStudio, RRID:SCR_000432)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:The retrospective analysis of only the 164 seropositive SARS-CoV-2 individuals and not the population of 9530 individuals is a limitation of the study, preventing a fair comparison of the Diazyme platform with the Roche and Abbott SARS-CoV-2 serology platforms. This is because these individuals were effectively pre-screened for SARS-CoV-2 seropositivity before analysis on either the Roche or Abbott platforms. Moreover, out of the 9,530 tests performed, the estimated overall false positive rate of the Diazyme IgG assay was between 0.7 - 0.9%, and is equal to or lower than its published value of 0.9% (13). This suggests that our findings would have been similar if either the Roche total Ig or Abbott IgG assays were used as the screening platform and not the confirmatory platform, as both assays have been reported to have specificity that exceeds 99% (14–16); underlining the dangers of using any one single serology platform to screen low prevalence populations for SARS-CoV-2 serology. We report a comprehensive retrospective study of 164 SARS-CoV-2 seropositive samples from 9,530 SARS-CoV-2 serology tests and for the first time demonstrate that serology results correlate with neutralization. Our study demonstrates the risk of using a single serology platform to identify SARS-CoV-2 seropositive individuals in low prevalence populations and highlights the benefits of a two-platform approach. Finally, the inclusion of serology and neutralization activity found in mild and asymptomat...
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.
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- No protocol registration statement was detected.
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