Abstract
BACKGROUND: The long-term impact of the COVID-19 pandemic on the distribution pattern of respiratory pathogens in China was unknown. Our study aimed to determine the multipathogen profiles and co-infection characteristics among patients with acute respiratory infections (ARIs) in the post-COVID-19 era in Shenzhen, China. METHODS: This multi-center cross-sectional study was conducted among patients with ARIs from five sentinel hospitals from November 1, 2022 to June 30, 2023 in Shenzhen, China. The collected respiratory samples were subjected to targeted next-generation sequencing for high-throughput screening of 108 respiratory pathogens. Multi-stage logistic regression models were built to infer interactions between pathogens at the individual level. RESULTS: The median [IQR] age of 1890 patients included was 31.8 [23.7, 45.2] years. The proportions of positivity on any pathogen and co-infection were 84.0% (1587/1890) and 41.4% (782/1890). Children < 5 years and school-age children have the highest viral (78.0%, 99/127) and bacterial positive proportion (65.5%, 114/127). Influenza virus (IFV), SARS-CoV-2, and human rhinovirus (HRV) were the three leading viral pathogens, and Haemophilus influenzae (H. influenzae), Staphylococcus aureus (S. aureus), and Streptococcus pneumoniae (S. pneumoniae) were the three leading bacterial pathogens. The three leading co-infection pathogens were S. pneumoniae combined with H. influenzae (4.6%, 86/1890), IFV with S. aureus (4.5%, 85/1890) and with H. influenzae (3.3%, 62/1890). The proportions of positivity on IFV, enterovirus, SARS-CoV-2, H. influenzae, S. aureus, and S. pneumoniae in outpatients were higher than those in inpatients, while the proportions of positivity on human parainfluenza virus (HPIV), human metapneumovirus (HMPV), Pseudomonas aeruginosa, Acinetobacter baumannii, Mycoplasma pneumoniae, and Legionella pneumophila in inpatients were higher than those in outpatients. RSV, IFV, HPIV, human adenovirus, and HRV were the top five viral pathogens among hospitalized children before, during, and after the COVID-19 pandemic in Shenzhen. Virus‒virus interactions, such as IFV combined with SARS-CoV-2 (OR = 20.3 [95% confidence interval (CI): 7.2-57.0]) and with HRV (OR = 7.2 [95% CI: 3.5-15.0]) exhibited competitive effects. Bacteria-bacteria interactions exhibited synergistic effects such as Moraxella catarrhalis combined with S. pneumoniae (OR = 0.3 [95% CI: 0.2-0.5]). CONCLUSIONS: There were differences in the pathogen profiles among patients with different ages, pneumonia groups, and case types. Virus‒virus interactions presented competitive effects, while bacterium‒bacterium interactions exhibited synergistic effects.