Haibo Li, Jing LiuPhD, Qianjiao Fang, Ziyao Li, Chang Ming Guo, Yuanmei Chen, Guohui Fan, Qi Zhang, Zhaolin Hua, Di Lv, Lijuan Tang, Baidong Hou, Bin Cao
BACKGROUND: During the COVID-19 pandemic, prolonged nonpharmaceutical interventions (NPIs) reduced the circulation of respiratory pathogens. The effects of NPIs on "immunity debt" in children are unclear, especially after almost 3 years of NPIs in China. METHODS: Between November 2021 and October 2023, a cross-sectional study of 235 children (age 9 months-5 years) was conducted at the China-Japan Friendship Hospital, Beijing. Serum IgG antibodies against 10 respiratory pathogens, including influenza A, influenza B, respiratory syncytial virus (RSV), parainfluenza virus, adenovirus (types 7 and 55), Mycoplasma pneumoniae, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, were measured using a novel antigen-specific detection platform. Antibody levels were compared between the following three periods: during NPIs (2021-2022), after NPIs (January-June 2023), and during the Mycoplasma pneumoniae epidemic (July-October 2023). In parallel, hospital-based nucleic acid surveillance from 2017 to 2023 was analyzed. FINDINGS: IgG levels exhibited pathogen-specific patterns. Antibody titers against M. pneumoniae and influenza A declined significantly during NPIs and rebounded after the restrictions were lifted, coinciding with increased clinical detection of these two pathogens. In contrast, the antibody levels for influenza B, RSV, parainfluenza virus, and adenovirus were stable across all periods. SARS-CoV-2 antibody titers rose after December 2022, reflecting the introduction of this new pathogen. INTERPRETATION: Our results provide the first multi-pathogen serological evidence that prolonged NPIs led to pathogen-specific immunity debt in young children in China. The effects were most pronounced for pathogens with high pre-pandemic circulation or rapid antigenic drift. Sustained serological surveillance and pathogen-targeted vaccination strategies can mitigate epidemic rebounds after periods of reduced exposure.