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

Open Forum Infectious Diseases

Léopold Beeker, Thomas Obadia, Emma Bloch, Laura Garcia, Manon Le Fol, Tiffany Charmet, Laurence Arowas, Rémy Artus, Olivia Cheny, Dorian Cheval, Yanis Dahoumane, Maurine Delhaye, Delal Ergen, Mariem Essaidani, Christine Fanaud, Sandrine Fernandes Pellerin, Nathalie Jolly, Hélène Laude, Emmanuel Roux, Marine Samson, Linda Sangari, Marie-Noëlle Ungeheuer, Sophie Vacant, Ayla Zayoud, Françoise Donnadieu, Stéphane Pelleau, Simon Galmiche, Arnaud Fontanet, Michael White

Summary

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.

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.

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.

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.

More information at DOI: https://doi.org/10.1093/ofid/ofaf006