Vacharathit V.Pluempreecha M.Manopwisedjaroen S.Srisaowakarn C.Srichatrapimuk S.Sritipsukho P.Sritipsukho N.Thitithanyanont A.Mahidol University2025-05-202025-05-202025-09-01Clinical Immunology Vol.278 (2025)15216616https://repository.li.mahidol.ac.th/handle/123456789/110242This study explores immune responses in mild Omicron-era COVID-19 breakthrough cases, focusing on cytokine dysregulation, antibody dynamics, and Long COVID. We analyzed samples from 114 mild symptomatic COVID-19 patients across multiple pandemic waves, each dominated by different SARS-CoV-2 variants, at three timepoints: (T1: 2–4 weeks, T2: 3–4 months, T3: 6–8 months post-infection). Persistent IP-10 elevation up to 8 months post–Omicron breakthrough infection suggests sustained low-grade immune activation that appears unique to this wave. Hybrid immunity from Omicron breakthrough infections elicited broad cross-variant antibody recognition but showed declining neutralization over time. Among vaccination regimens, mRNA-inclusive combinations were associated with lower Long COVID scores. CoV-229E antibody levels correlated with Long COVID scores. These findings underscore the need for extended monitoring of even mild COVID-19 cases and highlight the potential of mRNA vaccines in reducing post-COVID-19 complications. Insights into post-infection immune alterations and vaccine effects can inform the development of future vaccination strategies and approaches for managing post-COVID-19 conditions.MedicineImmunology and MicrobiologyArticleSCOPUS10.1016/j.clim.2025.1105072-s2.0-1050049261631521703540306350