Abstract
IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic and associated non-pharmaceutical interventions (NPIs) have significantly altered the epidemiology of respiratory pathogens. Understanding the interactions between non-bacterial respiratory pathogens is crucial for clinical management and surveillance. OBJECTIVE: To investigate how interactions among non-bacterial respiratory pathogens in children changed during and after the COVID-19 pandemic in two cities in eastern China. METHODS: This retrospective study reviewed the data of children hospitalized with acute respiratory tract infections in Wenzhou and Ningbo between March 1, 2021, and February 28, 2024. The SureX 13 respiratory pathogen multiplex kit was used to detect 13 pathogen types/subtypes in the respiratory tract secretion specimens. The chi-square test or Fisher's exact test, virus correlation, and vector autoregressive modelling were employed to evaluate correlations and dynamic changes in the weekly positive detection rates before and after the NPIs. RESULTS: Among the 73 096 children tested, 65.18% had at least one non-bacterial respiratory pathogen, and 11.97% had multiple pathogens. Detection rates declined significantly by 56.65% during NPIs but rebounded by 75.46% afterward, particularly for Mycoplasma pneumoniae, which increased from 5.29% to 34.78%. Post-pandemic, the co-detection of non-bacterial respiratory pathogens increased, with interaction patterns varying by phase. Notably, after the pandemic, the positive and negative correlations among pathogens intensified, with a significant increase in negative associations. Furthermore, a persistent negative correlation existed between the influenza B virus and Mycoplasma pneumoniae (-0.36 to -0.25), suggesting the potential presence of pathogen interference. INTERPRETATION: The interactions between non-bacterial respiratory pathogens markedly changed after COVID-19, showing strengthened correlations, which were primarily negative in nature. These observations underscore the importance of the ongoing surveillance of respiratory pathogens in evolving NPIs and epidemiological patterns.