Utilization of Saliva for Anti-SARS-CoV-2 Antibody Detection in the General Population

Similar to how salivary cortisol reflects serum cortisol as a stress biomarker, saliva by its easy, non-invasive collection, holds promise for mucosal antibody testing to assess systemic humoral immunity. In this study, we aimed to determine the prevalence of SARS-CoV-2 antibodies in saliva during the COVID-19 pandemic.

Between February and December 2022, paired saliva and serum specimens were collected twice per participant with the history of infection. SARS-CoV-2 antibodies were measured by Roche Elecsys anti-N and Abbott anti-S1-RBD assays. Cortisol was also quantified in serum-saliva paired samples using Elecsys Cortisol II. Saliva antibody results with manufacturer's serum cutoff were compared with those of the serum.

Out of the 166 participants enrolled, the first and second visits showed serum anti-S1-RBD Ab in 162 (97.6%) and anti-N Ab in 79 (47.5%) and 97 (58.4%) participants. At the first and second visits, 14 (8.4%) and 13 (7.8%) participants had salivary anti-S1-RBD Ab, while 4 (2.4%) and 5 (3.0%) participants had anti-N Ab. Agreement between serum and saliva was slight for anti-S1-RBD (κ = 0.004) and poor for anti-N (κ < 0). The mean serum cortisol was 7.52 μg/dL (visit 1) and 7.97 μg/dL (visit 2) versus 0.19 μg/dL and 0.18 μg/dL in saliva. Saliva cortisol levels were ~ 95.5 - 97.6% lower than serum.

Salivary SARS-CoV-2 antibody levels and serologic results are poorly concordant, preventing saliva as a direct substitute without assay-specific cutoffs. Salivary cortisol correlates predictably with serum levels but consistently underestimates them. Further work is needed to establish standardized saliva thresholds for both antibodies and cortisol.