Community-acquired pneumonia with Staphylococcus aureus and viral co-infection: clinical characteristics and pathogen...

Bacterial-viral co-infection in pneumonia has attracted significant attention owing to its complex pathogenesis and poor prognosis. The incidence of severe pneumonia caused by Staphylococcus aureus (SA) is on the rise, and the transmission of respiratory viruses further aggravates the burden of infectious diseases, exerting a synergistic pathogenic effect. However, research on the clinical characteristics and interaction mechanisms of SA-viral co-infection pneumonia remains insufficient. This study was designed to investigate the clinical and pathogen genomic characteristics of patients with community-acquired pneumonia (CAP) caused by co-infection with SA and respiratory viruses, and to preliminarily assess the potential impact of SA-viral co-infection on prognosis.

A multicenter retrospective cohort study was conducted, enrolling 118 hospitalized SA-CAP patients from two hospitals between November 2022 and April 2025. Differences in clinical manifestations, laboratory parameters, complications, and in-hospital mortality were compared between survivors and non-survivors. The Holm-Bonferroni correction was applied to mitigate the Type I error. Only the variables that were statistically significant after Holm-Bonferroni correction and had clear clinical significance were finally included in the subsequent random forest. The random forest method was employed to screen for potential key variables, followed by multivariate logistic regression analysis to identify factors associated with in-hospital mortality. Whole-genome sequencing (WGS) was performed on 30 SA strains and 6 influenza A virus (IAV) strains isolated from 20 SA-CAP patients to characterize their virulence and drug resistance-related genetic profiles.

A total of 118 hospitalized SA-CAP patients were enrolled, among whom 36 experienced in-hospital mortality, resulting in a mortality rate of 30.5%. Multivariate analysis revealed that platelet count (PLT) <100×10⁹/L [odds ratio (OR) =9.864; 95% confidence interval (CI): 1.237-18.656; P=0.007], high-sensitive troponin T (hs-TnT) >14 pg/mL (OR =11.120; 95% CI: 1.644-15.199; P=0.005), and the development of acute kidney injury (AKI) (OR =11.944; 95% CI: 1.868-26.368; P=0.006) were independently associated with an increased risk of in-hospital mortality. Compared to the SA monoinfection group, the SA-IAV co-infection group had a significantly higher mortality rate (80.0% vs. 31.3%, P=0.001). WGS results indicated that SA strains from the co-infection group more frequently carried the lukF-PV/lukS-PV virulence genes. SA strains from deceased patients showed higher expression of the sak and fnbB genes. The tested IAV strains exhibited adaptive mutations, with no definitive highly pathogenic mutations identified.

This study identified PLT <100×10⁹/L, hs-TnT >14 pg/mL, and AKI as independent risk factors for in-hospital mortality. Co-infection with SA and influenza virus may exacerbate CAP severity and is associated with poorer prognosis. The enhanced expression of certain SA virulence genes (e.g., lukF-PV, sak, fnbB) in the context of viral co-infection suggests their potential value in clinical risk assessment.