Etiological landscape and co-infection dynamics in Acute Respiratory Infections (ARIs): insights from a multicenter outpatient study in Yunnan, China

ARIs pose significant health risks, especially among children, elderly, and immunocompromised populations. This study investigated the etiological spectrum and epidemiological features of ARIs in Yunnan Province from December 2023 to February 2025. Throat swab samples and demographic information of ARI patients were collected from fever clinics of 23 sentinel hospitals in Yunnan Province every two weeks during the study period. Twenty-eight respiratory pathogens (13 viruses, 13 bacteria and 2 fungi) were detected by real-time PCR, and their overall detection rate, age distribution, seasonal variation and pathogen interactions were analyzed. From the 2,386 patient samples tested, the overall detection rate for viruses and Mycoplasma pneumoniae (MP) was 33.86%, while bacteria and fungi were detected in 63.16% of samples. The most frequently detected pathogens varied by age group. Influenza A virus (IAV) and Human rhinovirus (HRV) were among the three most frequently detected viral pathogens across four age groups. Respiratory syncytial virus (RSV) showed the highest positivity rate (12.61%) in the 5–14 years age group and the second-highest rate (14.29%) in children under 5 years. Integrated modeling data revealed distinct temporal patterns among five respiratory pathogens: IAV exhibited bimodal winter peaks, Severe acute respiratory syndrome coronavirus (SARS-CoV-2) a single spring peak, while RSV and HRV showed dispersed low-intensity activity. The cross-correlation analysis indicates a significant short-term temporal correlation between IAV and SARS-CoV-2, limited to lags within ± 0.42 months. Among cases positive for IAV, SARS-CoV-2, or MP, co-infection rates with other tested pathogens (including a panel of respiratory viruses and MP) were 13.26%, 10.88%, and 18.88%, respectively. In the pairwise logistic regression analysis of pathogen co-detection, both IAV and SARS-CoV-2 were significant positively correlated with Aspergillus (False Discovery Rate (FDR)-adjusted p < 0.05). Pathogens of ARI patients across Yunnan since late 2023 exhibited distinct seasonal fluctuations, diverse population susceptibility, and widespread co-infections. Statistically significant positive correlations with Aspergillus were observed for both SARS-CoV-2 and IAV. Therefore, we recommend the establishment of a seasonal, multi-pathogen surveillance and early warning system, coupled with enhanced clinical protocols for the management of coinfections, particularly among vulnerable populations.