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Serological signatures of SARS-CoV-2 infection: Implications for antibody-based diagnostics

Jason Rosado 1, 2 Stéphane Pelleau 1 Charlotte Cockram 3 Sarah Hélène Merkling 4 Narimane Nekkab 1 Caroline Demeret 5 Annalisa Meola 6 Solen Kernéis 7 Benjamin Terrier 8, 9 Samira Fafi-Kremer 10 Jérome De Sèze 11 François Déjardin Stéphane Petres 12 Rhea J Longley 13 Marija Backovic 6 Ivo Mueller 1, 13, 14 Michael T White 1, * 
Abstract : Background The antibody response generated following infection with SARS-CoV-2 is expected to decline over time. This may cause individuals with confirmed SARS-CoV-2 infection to test negative according to serological diagnostic tests in the months and years following symptom onset. Methods A multiplex serological assay was developed to measure IgG and IgM antibody responses to four SARS-CoV-2 Spike (S) antigens: spike trimeric ectodomain (Stri), its receptor-binding domain (RBD), spike subunit 1 (S1), and spike subunit 2 (S2). Antibody responses were measured in serum samples from patients in French hospitals with RT-qPCR confirmed infection (n = 259), and negative control serum samples collected before the start of the SARS-CoV-2 epidemic in 2019 (n = 335). The multiplex antibody data was used to train a random forests algorithm for classifying individuals with previous SARS-CoV-2 infection. A mathematical model of antibody kinetics informed by prior information from other coronaviruses was used to estimate time-varying antibody responses and assess the potential sensitivity and classification performance of serological diagnostics during the first year following symptom onset. Results IgG antibody responses to one S antigen identified individuals with previous RT-qPCR confirmed SARS-CoV-2 infection with 90.3% sensitivity (95% confidence interval (CI); 86.1%, 93.4%) and 99.1% specificity (95% CI; 97.4%, 99.7%). Using a serological signature of IgG to four antigens, it was possible to identify infected individuals with 96.1% sensitivity (95% CI; 93.0%, 97.9%) and 99.1% specificity (95% CI; 97.4%, 99.7%). Antibody responses to SARS-CoV-2 increase rapidly 1-2 weeks after symptom onset, with antibody responses predicted to peak within 2-4 weeks. Informed by prior data from other coronaviruses, one year following symptom onset antibody responses are predicted to decay by approximately 60% from the peak response. Depending on the selection of sero-positivity cutoff, we estimate that the sensitivity of serological diagnostics may reduce to 56% – 97% after six months, and to 49% – 93% after one year. Conclusion Serological signatures based on antibody responses to multiple antigens can provide more accurate and robust serological classification of individuals with previous SARS-CoV-2 infection. Changes in antibody levels over time may cause reductions in the sensitivity of serological diagnostics leading to an underestimation of sero-prevalence. It is essential that data continue to be collected to evaluate this potential risk.
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Submitted on : Friday, June 26, 2020 - 3:28:47 PM
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Jason Rosado, Stéphane Pelleau, Charlotte Cockram, Sarah Hélène Merkling, Narimane Nekkab, et al.. Serological signatures of SARS-CoV-2 infection: Implications for antibody-based diagnostics. 2020. ⟨pasteur-02569149v2⟩



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