AbstractBackgroundSerological surveys are used to ascertain influenza infection and immunity, but evidence for the utility of mucosal immunoglobulin A (IgA) as a correlate of infection or protection is limited.MethodsWe performed influenza-like illness (ILI) surveillance on 220 individuals living or working in a retirement community in Gainesville, Florida from January to May 2018, and took pre- and postseason nasal samples of 11 individuals with polymerase chain reaction (PCR)-confirmed influenza infection and 60 randomly selected controls. Mucosal IgA against 10 strains of influenza was measured from nasal samples.ResultsOverall, 28.2% and 11.3% of individuals experienced a 2-fold and 4-fold rise, respectively, in mucosal IgA to at least 1 influenza strain. Individuals with PCR-confirmed influenza A had significantly lower levels of preseason IgA to influenza A. Influenza-associated respiratory illness was associated with a higher rise in mucosal IgA to influenza strains of the same subtype, and H3N2-associated respiratory illness was associated with a higher rise in mucosal IgA to other influenza A strains.ConclusionsBy comparing individuals with and without influenza illness, we demonstrated that mucosal IgA is a correlate of influenza infection. There was evidence for cross-reactivity in mucosal IgA across influenza A subtypes.