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

Mucosal immunity constitutes the first line of defense against respiratory viruses. We characterized serum and salivary SARS-CoV-2-specific and polyreactive antibodies in 784 Dutch healthcare workers at two timepoints (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, was 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. Salivary polyreactive IgA levels changed over time, which may reflect repeated mucosal immune stimulation, and were associated with greater symptom burden.