Abstract
Large-scale serosurveillance of severe acute respiratory syndrome coronavirus type 2 (SARS- CoV-2) will only be possible if serological tests are sufficiently reliable, rapid and inexpensive. Current assays are either labour-intensive and require specialised facilities (e.g. virus neutralization assays), or expensive with suboptimal specificity (e.g. commercial ELISAs). Bead-based assays offer a cost-effective alternative and allow for multiplexing to test for antibodies of other pathogens. Here, we compare the performance of four antigens for the detection of SARS-CoV-2 specific IgG antibodies in a panel of sera that includes both severe (n=40) and mild (n=52) cases, using a neutralization and a Luminex bead-based assay. While we show that neutralising antibody levels are significantly lower in mild than in severe cases, we demonstrate that a combination of recombinant nucleocapsid protein (NP), receptor- binding domain (RBD) and the whole spike protein (S1S2) results in a highly sensitive (96%) and specific (99%) bead-based assay that can detect IgG antibodies in both groups. Although S1-specific IgG levels correlate most strongly with neutralizing antibody levels, they fall below the detection threshold in 10% of the cases in our Luminex assay. In conclusion, our data supports the use of RBD, NP and S1S2 for the development of SARS-CoV-2 serological bead- based assays. Finally, we argue that low antibody levels in mild/asymptomatic cases might complicate the epidemiological assessment of large-scale surveillance studies.
Competing Interest Statement
The authors have declared no competing interest.
Clinical Trial
This is not a clinical trail
Funding Statement
The work was funded by a European & Developing Countries Clinical Trials Partnership (EDCTP) project (Africover: RIA2020EF-3031), the Research Foundation Flanders (FWO) (G0G4229N and G054820N) and intramural funds from the Institute of Tropical Medicine Antwerp. Joachim Marien is a member of the Outbreak Research Team which is funded by the Department of Economy, Science and Innovation of the Flemish government in Belgium (EE145 4150).
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Approval to sample from COVID-19 cases was obtained from the Ethical committee of the University of Ghent (BC-07587), local committees of each participating hospital and all participants provided consent to participate. The use of prepandemic leftover samples was approved by ITMs internal review board.
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Data Availability
Data supporting the conclusions of this article are included in the article and its additional files. The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.