Abstract
This study explores immune responses in mild Omicron-era COVID-19 breakthrough cases, focusing on cytokine dysregulation, antibody dynamics, and Long COVID. Samples from 114 mild COVID-19 patients across multiple waves were analyzed 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 suggests prolonged low-grade immune activation. Hybrid immunity from Omicron breakthrough infections provided 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 mild COVID-19 cases and highlight the potential of mRNA vaccines in reducing post-COVID-19 complications. Insights into immune alterations and vaccine effects can inform the development of future vaccination strategies and approaches for managing post-COVID-19 conditions.