Immune response to and virological profile of SARS-CoV-2 before and after symptom onset in individuals vaccinated with inactivated COVID-19 vaccines

China encountered a COVID-19 pandemic shortly after lifting the zero-COVID-19 policy in December 2022. We prospectively investigated the immune responses to SARS-CoV-2 before and after symptom onset of breakthrough infection in individuals vaccinated with inactivated COVID-19 vaccines. Blood samples from 35 vaccinated participants were collected from December 16 to 20, 2022 when they had no symptoms and a second blood sample was collected from each participant from January 4 to 6, 2023. SARS-CoV-2 RNA, anti-SARS-CoV-2 IgG and IgM, interleukin-6 (IL-6), and C-reactive protein (CRP) were measured with commercially available kits respectively. During a period of average 17.0 (±1.6) days, 30 (85.7%) of 35 participants developed toxemia and respiratory symptoms and 34 (97.1%) were defined with SARS-CoV-2 infection based on positive SARS-CoV-2 RNA in pharyngeal swabs (32) and rising titers of anti-SARS-CoV-2 IgG (34). Before symptom onset, 16 (47.1%), 13 (38.2%), and 5 (14.7%) of the infected individuals already had relatively high anti-SARS-CoV-2 IgG titers, elevated IL-6 and CRP respectively. After 17.0 (±1.6) days, the median anti-SARS-CoV-2 IgG level was significantly increased (46.85 vs 359.45 AU/mL, <i>p</i> &lt; .001), whereas the proportions of elevated IL-6 and CRP were each remarkably reduced. None of the participants infected with SARS-CoV-2 had detectable anti-SARS-CoV-2 IgM. In vaccinated individuals infected with SARS-CoV-2, specific anamnestic immune responses may initiate before symptom onset and robust immune response may develop in very early phase, which should be a critical mechanism to lessen the severity of COVID-19 and reduce the mortality by COVID-19 vaccination.