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Background: Understanding of the early immune response in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) breakthrough infections is limited. Methods: Ninety‐eight patients with coronavirus disease 2019 (COVID‐19) breakthrough infections were divided into two groups, with intervals from receiving the second dose of inactivated vaccine to the onset of illness <60 or ≥60 days. Results: The median lymphocyte count and the median anti‐SARS‐CoV‐2 spike immunoglobulin G (IgG) and immunoglobulin M (IgM) titers were higher in the <60‐day interval group compared with the corresponding medians in the ≥60‐day interval group (p = 0.005, p = 0.001, and p = 0.001, respectively). The median interleukin‐6 (IL‐6) level in the <60‐day interval group was significantly lower than the median IL‐6 level in the ≥60‐day interval group (p < 0.001). Conclusions: Our results highlight the different anti‐SARS‐CoV‐2 spike IgG and IgM antibody titers among patients with different intervals from receiving the second dose of inactivated vaccine to the onset of illness. [ABSTRACT FROM AUTHOR]