Year-round infectome profiling of acute febrile respiratory illness unveiled complex epidemiological dynamics post-lifting of COVID-19 restrictions.

Objective: Following the lifting of COVID-19 non-pharmaceutical interventions in China, respiratory infections surged, though the specific causes remained unclear. This study provided a comprehensive overview of the infectome in patients with acute febrile respiratory illness (AFRI) to inform disease surveillance.

Methods: Between March 2023 and February 2024, 1,163 oropharyngeal swabs from AFRI patients and 338 from healthy individuals were collected in Shenzhen. Meta-transcriptomic sequencing was employed for microbial analysis.

Results: We identified 14 viruses and 10 bacteria species known to cause human disease. Influenza virus, SARS-CoV-2, Streptococcus pneumoniae, and redondovirus were the most common, with a negative correlation between H3N2 and SARS-CoV-2. Notably, we detected certain enterovirus subtypes (e.g., Coxsackievirus A6 and Echovirus 30), previously overlooked pathogens (e.g., redondovirus), and rare pathogens like Streptococcus pseudopneumoniae. Comparisons revealed five pathogens showed significantly higher abundance in patients than in controls, despite no significant differences for others probably due to their limited number of positive pools. Seasonal shifts in microbial diversity and composition were observed, with climate factors like temperature and precipitation playing a role. Phylogenetic analysis revealed changes in genotype diversity and dominant pathogen lineages.

Conclusions: This study highlighted complex pathogen infections in AFRI patients following COVID-19 restrictions, demonstrating the value of meta-transcriptomics over PCR-based methods for more detailed pathogen surveillance.