Salivary polyreactive and SARS-CoV-2-specific antibody responses following SARS-CoV-2 infection and vaccination in healthcare workers

Mucosal immunity constitutes the first defense against respiratory viruses. We characterized serum and salivary SARS-CoV-2-specific and polyreactive antibodies in 784 Dutch healthcare workers at two time points (2020-2021). SARS-CoV-2-specific antibodies and salivary polyreactive IgA were quantified using multiplex immunoassays. Associations with infection, vaccination, and symptom burden were analyzed using multivariable regression, Cox proportional hazard models, and mixed-effects models. SARS-CoV-2 infection induced systemic SARS-CoV-2-specific IgG and salivary IgA responses, whereas vaccination increased serum and salivary anti-Spike-1 IgG. Salivary polyreactive IgA increased over time, were associated with smoking (p = 0.022) and asthma (p = 0.021), and higher levels were associated with an increased hazard of subsequent SARS-CoV-2 infection (HR 1.15 [1.01-1.31]). Polyreactive IgA levels declined more rapidly in participants with a higher symptom burden (p = 0.081). SARS-CoV-2 infection, but not vaccination, induces distinct changes in the salivary IgA compartment, including polyreactive antibodies, which may reflect repeated mucosal immune stimulation and is associated with greater symptom burden.