Streptococcus pyogenes causes acute pharyngitis or asymptomatic carriage by subverting salivary/mucus clearance and attaching to tonsillar cells. Adherence is well studied, but host susceptibility and infection transitions remain poorly understood. We previously showed the M protein N-terminus binds sialic acid on salivary mucin and sialylated pharyngeal cell surface proteins, both essential for infection. To further assess the contribution of sialic acid, we received ~8000 salivary samples from 125 school-aged children from a longitudinal streptococcal prevalence study. Children were categorized as: i) negative throat culture without symptoms (no infection), ii) two or more consecutive positive cultures without symptoms (carrier), or iii) positive culture with symptoms (acute infection). High-performance anion exchange chromatography (HPAEC) quantitated sialic acid from 57 children (292 samples across 164 days). Infection status changes over time (e.g., no infection to acute), so we also analyzed samples between consecutive time points, stratifying results by all possible transitions. A linear mixed-effects model, adjusted for covariates (age, gender, sampling intervals), accounting for normal sialic acid variations, established a significant correlation between total salivary sialic acid and infection state. Carriers/acutely infected individuals had significantly higher concentrations than throat culture-negative individuals, with notable increases during transitions to, and decreases from, infection. These patterns were repeatable, predictable, and highly significant. To assess the role of emm-type in infection states, isolates were purified from saliva, emm-typed, and subjected to WGS. We present pairwise comparative analyses of emm-matched strains from different infection outcomes, their genetic differences, and preliminary identification of signatures correlating with infection state shifts.