Complement Hyperactivation Is Mediated by Alternative and Lectin Pathways During Early Phase of Severe Vaccination-Omicron BA.5 Infection.

Complement temporal activation kinetics, activation pathways, and their relationship with thromboinflammation and antibody responses in severe vaccination-COVID-19 remains unclear. Based on a vaccinated-infected cohort, we analyzed complement immune responses across mild to critical COVID-19 cases by a dynamic model. Our results showed that complement activation was earlier (7-14 days post symptom onset), more intense and lasted longer in severe and critical vaccination-COVID-19, mediated by alternative and lectin pathways instead of classical pathway. Moreover, complement activation in severe vaccination-COVID-19 was related to thromboinflammation but not to the virus-specific antibody response. Our study elucidated the kinetics of complement activation in vaccination-COVID-19 infection, revealing that Bb in alternative pathway were crucial in severe vaccination-COVID-19. These findings indicate the optimal timing for implementing complement activation-targeted interventions in the management of severe vaccination-COVID-19 and provide more potential therapeutic targets.