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Vox Sang . SARS-CoV-2 immunoassays in a predominantly vaccinated population: Performances and qualitative agreements obtained with two analytical ap

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Editor, Senior Moderator
Vox Sang


. 2024 Apr 5.
doi: 10.1111/vox.13625. Online ahead of print. SARS-CoV-2 immunoassays in a predominantly vaccinated population: Performances and qualitative agreements obtained with two analytical approaches and four immunoassays

Christian Renaud[SUP] 1 [/SUP], Antoine Lewin[SUP] 1 [/SUP], Yves Gregoire[SUP] 1 [/SUP], Nathalie Simard[SUP] 1 [/SUP], Émilie Vallières[SUP] 2 3 [/SUP], Maude Paquette[SUP] 2 3 [/SUP], Steven J Drews[SUP] 4 5 [/SUP], Sheila F O'Brien[SUP] 6 [/SUP], Clara Di Germanio[SUP] 7 [/SUP], Michael P Busch[SUP] 7 [/SUP], Marc Germain[SUP] 1 [/SUP], Renée Bazin[SUP] 1 [/SUP]



Affiliations
Abstract

Background and objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys are typically analysed by applying a fixed threshold for seropositivity ('conventional approach'). However, this approach underestimates the seroprevalence of anti-nucleocapsid (N) in vaccinated individuals-who often exhibit a difficult-to-detect anti-N response. This limitation is compounded by delays between the onset of infection and sample collection. To address this issue, we compared the performance of four immunoassays using a new analytical approach ('ratio-based approach'), which determines seropositivity based on an increase in anti-N levels.
Materials and methods: Two groups of plasma donors and four immunoassays (Elecsys total anti-N, VITROS total anti-N, Architect anti-N Immunoglobulin G (IgG) and in-house total anti-N) were evaluated. First-group donors (N = 145) had one positive SARS-CoV-2 polymerase chain reaction (PCR) test result and had made two plasma donations, including one before and one after the PCR test (median = 27 days post-PCR). Second-group donors (N = 100) had made two plasma donations early in the Omicron wave.
Results: Among first-group donors (97.9% vaccinated), sensitivity estimates ranged from 60.0% to 89.0% with the conventional approach, compared with 94.5% to 98.6% with the ratio-based approach. Among second-group donors, Fleiss's κ ranged from 0.56 to 0.83 with the conventional approach, compared with 0.90 to 1.00 with the ratio-based approach.
Conclusion: With the conventional approach, the sensitivity of four immunoassays-measured in a predominantly vaccinated population based on samples collected ~1 month after a positive test result-fell below regulatory agencies requirement of ≥95%. The ratio-based approach significantly improved the sensitivities and qualitative agreement among immunoassays, to the point where all would meet this requirement.

Keywords: COVID‐19 antibodies; donors; epidemiology; high throughput testing; nucleocapsid immunoassay; ratio‐based approach; sensitivity; serological testing; vaccination.

 
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