Aetiology of Community-Acquired Pneumonia and the Role of Genetic Host Factors in Hospitalized Patients in Cyprus

Abstract

Community-acquired pneumonia (CAP) remains the leading cause of hospitalization among infectious disease in Europe, and a major cause of morbidity and mortality. In order to determine and characterize the aetiology of CAP in hospitalized adults in Cyprus, respiratory and blood samples were obtained from hospitalized patients with CAP, and analyzed using Multiplex Real-Time PCR/RT-PCR, and ID/AMR enrichment panel (RPIP) analysis. Probe-based allelic discrimination was used to investigate genetic host factors in patients. The aetiology could be established in 87% of patients. The most prevalent viral pathogens detected were influenza A, SARS-CoV-2, and human rhinovirus. The most common bacterial pathogens detected were Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. Antimicrobial resistance genes were identified in 23 patients. S. aureus was the most common AMR correlated strain in our study. A positive correlation was detected between bacterial infections and the NOS3 rs1799983 G allele and the FCGR2A rs1801274 G allele. A positive correlation was also detected between the TNF-α rs1800629 A allele and sepsis, while a negative correlation was detected with the ACE rs1799752 insertion genotype and the severity of pneumonia. In conclusion, the targeted NGS panel approach applied provides highly sensitive, comprehensive pathogen detection, in combination with antimicrobial resistance AMR insights that can guide treatment choices. In addition, several host factors have been identified that impact the disease progression and outcome.

Keywords: clinical microbiology; community-acquired pneumonia; genomics; microorganism detection and analysis; next-generation sequencing; real-time PCR/RT-PCR.

Figure 1

Study flowchart. * Patients with a past medical history of congestive heart failure (CHF) and pneumonia were included; in patients with pulmonary oedema and CHF, without signs of infection, the pulmonary infiltrates were considered noninfectious, and were excluded.

Figure 2

Microbial pathogens detected in CAP patients. Microbial findings in 100 cases, with the proportion of co-infections. Single pathogen refers to cases where only one pathogen was identified in a CAP patient. Multiple pathogens refer to cases where multiple pathogens, viral–bacterial co-infection, multiple bacterial infections, or multiple viral infections were identified in a CAP patient.

Figure 3

Association of genetic host factors with CAP severity and disease. Logarithmic scale of odds ratios of genetic host factors, with the error bars representing confidence intervals of 95%. Viral infection represents the incidence of single viral infections in the patient population. Bacterial infection represents the incidence of single bacterial infections in the patient population. ARDS represents the number of patients with acute respiratory distress syndrome. Sepsis represents the number of patients diagnosed as septic during hospitalization. * Indicates that the logistic regression was statistically significant (p value ≤ 0.05).