Correlates of Protection Against Symptomatic COVID-19: The CORSER 5 Case-Control Study

Overview

Journal Open Forum Infect Dis

Date 2025 Jan 28

PMID 39872812

Authors

Leopold Beeker

Thomas Obadia

Emma Bloch

Laura Garcia

Manon Le Fol

Tiffany Charmet

Laurence Arowas

Remy Artus

Olivia Cheny

Dorian Cheval

Yanis Dahoumane

Maurine Delhaye

Delal Ergen

Mariem Essaidani

Christine Fanaud

Sandrine Fernandes Pellerin

Nathalie Jolly

Helene Laude

Emmanuel Roux

Marine Samson

Linda Sangari

Marie-Noelle Ungeheuer

Sophie Vacant

Ayla Zayoud

Francoise Donnadieu

Stephane Pelleau

Simon Galmiche

Arnaud Fontanet

Michael White

Affiliations

Soon will be listed here.

Abstract

Background: Establishing correlates of protection often requires large cohorts. A rapid and adaptable case-control study design can be used to identify antibody correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in serum and saliva.

Methods: We designed a case-control study to compare antibody levels between cases of SARS-CoV-2 infection within 5 days of symptom onset and uninfected controls. Controls were matched on age, number of coronavirus disease 2019 vaccine doses, time since last dose, and past episodes of infection. We quantified anti-SARS-CoV-2 and seasonal coronavirus immunoglobulin (Ig) G in serum and saliva at inclusion, 1 month, and 6 months.

Results: We included 90 cases and 62 controls between February and September 2022. A boost and decay pattern of serum antibodies was observed in cases at 1 and 6 months, respectively, but not in controls. Anti-SARS-CoV-2 antibody levels were significantly higher in controls at inclusion both in serum (particularly antinucleocapsid IgG: 4.14 times higher compared with cases; 95% CI, 2.46-6.96) and saliva (particularly antispike for Delta variant IgG: 4.89 times higher compared with cases; 95% CI, 2.91-9.89). Saliva antibodies generally outperformed serum antibodies for case/control differentiation.

Conclusions: In this case-control study, we provided evidence of correlates of protection of anti-SARS-CoV-2 IgG in saliva and serum, with saliva antibodies often outperforming serum. The finding that antibodies in saliva are a better correlate of protection than antibodies in serum may inform vaccine development by highlighting the importance of robust induction of mucosal immune responses. This study design may be used during future epidemics for the prompt assessment of correlates of protection.

References

Austin P . Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 2010; 10(2):150-61. PMC: 3120982. DOI: 10.1002/pst.433. View

B Gilbert P, Donis R, Koup R, Fong Y, Plotkin S, Follmann D . A Covid-19 Milestone Attained - A Correlate of Protection for Vaccines. N Engl J Med. 2022; 387(24):2203-2206. DOI: 10.1056/NEJMp2211314. View

Regev-Yochay G, Lustig Y, Joseph G, Gilboa M, Barda N, Gens I . Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study. Lancet Microbe. 2023; 4(5):e309-e318. PMC: 10030121. DOI: 10.1016/S2666-5247(23)00012-5. View

Killingley B, Mann A, Kalinova M, Boyers A, Goonawardane N, Zhou J . Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults. Nat Med. 2022; 28(5):1031-1041. DOI: 10.1038/s41591-022-01780-9. View

Aydillo T, Rombauts A, Stadlbauer D, Aslam S, Abelenda-Alonso G, Escalera A . Immunological imprinting of the antibody response in COVID-19 patients. Nat Commun. 2021; 12(1):3781. PMC: 8213790. DOI: 10.1038/s41467-021-23977-1. View

Yman V, White M, Asghar M, Sundling C, Sonden K, Draper S . Antibody responses to merozoite antigens after natural Plasmodium falciparum infection: kinetics and longevity in absence of re-exposure. BMC Med. 2019; 17(1):22. PMC: 6352425. DOI: 10.1186/s12916-019-1255-3. View

Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez J . pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011; 12:77. PMC: 3068975. DOI: 10.1186/1471-2105-12-77. View

Galmiche S, Charmet T, Rakover A, Schaeffer L, Cheny O, Von Platen C . Risk of SARS-CoV-2 Infection Among Households With Children in France, 2020-2022. JAMA Netw Open. 2023; 6(9):e2334084. PMC: 10504612. DOI: 10.1001/jamanetworkopen.2023.34084. View

Rosado J, Pelleau S, Cockram C, Merkling S, Nekkab N, Demeret C . Multiplex assays for the identification of serological signatures of SARS-CoV-2 infection: an antibody-based diagnostic and machine learning study. Lancet Microbe. 2021; 2(2):e60-e69. PMC: 7837364. DOI: 10.1016/S2666-5247(20)30197-X. View

10.

Anderson E, Goodwin E, Verma A, Arevalo C, Bolton M, Weirick M . Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection. Cell. 2021; 184(7):1858-1864.e10. PMC: 7871851. DOI: 10.1016/j.cell.2021.02.010. View

11.

Puhach O, Bellon M, Adea K, Bekliz M, Hosszu-Fellous K, Sattonnet P . SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses. EBioMedicine. 2023; 98:104893. PMC: 10755109. DOI: 10.1016/j.ebiom.2023.104893. View

12.

Hertz T, Levy S, Ostrovsky D, Oppenheimer H, Zismanov S, Kuzmina A . Correlates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2. Nat Commun. 2023; 14(1):4575. PMC: 10387073. DOI: 10.1038/s41467-023-39816-4. View

13.

Bobrovitz N, Ware H, Ma X, Li Z, Hosseini R, Cao C . Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression. Lancet Infect Dis. 2023; 23(5):556-567. PMC: 10014083. DOI: 10.1016/S1473-3099(22)00801-5. View

14.

Woudenberg T, Pinaud L, Garcia L, Tondeur L, Pelleau S, De Thoisy A . Estimated protection against COVID-19 based on predicted neutralisation titres from multiple antibody measurements in a longitudinal cohort, France, April 2020 to November 2021. Euro Surveill. 2023; 28(25). PMC: 10288827. DOI: 10.2807/1560-7917.ES.2023.28.25.2200681. View

15.

Goldblatt D, Fiore-Gartland A, Johnson M, Hunt A, Bengt C, Zavadska D . Towards a population-based threshold of protection for COVID-19 vaccines. Vaccine. 2021; 40(2):306-315. PMC: 8673730. DOI: 10.1016/j.vaccine.2021.12.006. View

16.

Pelleau S, Woudenberg T, Rosado J, Donnadieu F, Garcia L, Obadia T . Kinetics of the Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response and Serological Estimation of Time Since Infection. J Infect Dis. 2021; 224(9):1489-1499. PMC: 8420633. DOI: 10.1093/infdis/jiab375. View

17.

Borremans B, Gamble A, Prager K, Helman S, McClain A, Cox C . Quantifying antibody kinetics and RNA detection during early-phase SARS-CoV-2 infection by time since symptom onset. Elife. 2020; 9. PMC: 7508557. DOI: 10.7554/eLife.60122. View

18.

Isho B, Abe K, Zuo M, Jamal A, Rathod B, Wang J . Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol. 2020; 5(52). PMC: 8050884. DOI: 10.1126/sciimmunol.abe5511. View

19.

Grimee M, Tacoli C, Sandfort M, Obadia T, Taylor A, Vantaux A . Using serological diagnostics to characterize remaining high-incidence pockets of malaria in forest-fringe Cambodia. Malar J. 2024; 23(1):49. PMC: 10870639. DOI: 10.1186/s12936-024-04859-5. View

20.

Grant R, Charmet T, Schaeffer L, Galmiche S, Madec Y, Von Platen C . Impact of SARS-CoV-2 Delta variant on incubation, transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France. Lancet Reg Health Eur. 2021; 13:100278. PMC: 8616730. DOI: 10.1016/j.lanepe.2021.100278. View