Infection and co-infection patterns of community-acquired pneumonia in patients of different ages in China from 2009 to 2020: a national surveillance study

Abstract

Background: Severe community-acquired pneumonia (SCAP) is associated with a substantial number of hospitalisations and deaths worldwide. Infection or co-infection patterns, along with their age dependence and clinical effects are poorly understood. We aimed to explore the causal and epidemiological characteristics by age, to better describe patterns of community-acquired pneumonia (CAP) and their association with severe disease.

Methods: National surveillance of CAP was conducted through a network of hospitals in 30 provinces in China from 2009-20 inclusive. Patients with CAP were included if they had evidence of acute respiratory tract, had evidence of pneumonia by chest radiography, diagnosis of pneumonia within 24 h of hospital admission, and resided in the study catchment area. For the enrolled patients with CAP, nasopharyngeal and oral swabs were taken and tested for eight viral pathogens; and blood, urine, or expectorated sputum was tested for six bacterial pathogens. Clinical outcomes, including SCAP, were investigated with respect to age and patterns of infections or co-infections by performing binary logistic regression and multivariate analysis.

Findings: Between January, 2009, and December, 2020, 18 807 patients with CAP (3771 [20·05%] with SCAP) were enrolled. For both children (aged ≤5 years) and older adults (aged >60 years), a higher overall rate of viral and bacterial infections, as well as viral-bacterial co-infections were seen in patients with SCAP than in patients with non-SCAP. For adults (aged 18-60 years), however, only a higher rate of bacterial-bacterial co-infection was observed. The most frequent pathogens associated with SCAP were respiratory syncytial virus (RSV; 21·30%) and Streptococcus pneumoniae (12·61%) among children, and influenza virus (10·94%) and Pseudomonas aeruginosa (15·37%) among older adults. Positive rates of detection of most of the tested pathogens decreased during 2020 compared with the 2009-19 period, except for RSV, P aeruginosa, and Klebsiella pneumoniae. Multivariate analyses showed SCAP was significantly associated with infection with human adenovirus, human rhinovirus, K pneumoniae, or co-infection of RSV and Haemophilus influenzae or RSV and Staphylococcus aureus in children and adolescents (aged <18 years), and significantly associated with infection with P aeruginosa, K pneumoniae, or S pneumoniae, or co-infection with P aeruginosa and K pneumoniae in adults (aged ≥18 years).

Interpretation: Both prevalence and infection pattern of respiratory pathogens differed between patients with SCAP and patients with non-SCAP in an age-dependent manner. These findings suggest potential advantages to age-related strategies for vaccine schedules, as well as clinical diagnosis, treatment, and therapy.

Funding: China Mega-Project on Infectious Disease Prevention and The National Natural Science Funds of China.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.

Figure 1:. Comparison of the positive rates of eight viral and six bacterial pathogens in patients with SCAP and non-SCAP in mainland China, 2009‒20

The positive rate of each pathogen among 13 009 patients with pneumonia (2695 SCAP and 10 314 non-SCAP) tested for all the eight viral pathogens and among 5178 patients with pneumonia (1405 SCAP and 3773 non-SCAP) tested for all the six bacterial pathogens was compared for different age groups. The length of the red bar indicates the positive rate of SCAP and the length of the blue bar indicates the positive rate of non-SCAP. Positive rate was calculated by taking the positive number of each pathogen as the numerator and the number of CAP tested as denominator. The significant difference of the positive rate (χ² test or Fisher’s exact test) is indicated. HAdV=human adenovirus. HBoV=human bocavirus. HCoV=seasonal human coronavirus. HMPV=human metapneumovirus. HPIV=human parainfluenza virus. HRV=human rhinovirus. IFV=influenza virus. RSV=respiratory syncytial virus. SCAP=severe community acquired pneumonia. *p<0·05. †p<0·01.

Figure 2:. Prevalence of pathogens in mono infection and co-infection in patients with SCAP and non-SCAP in mainland China, 2009‒20

(A) Positive proportion of viruses, viral-viral co-infections, viral-bacteria co-infections, bacterial-bacterial co-infections, and bacteria in different age groups. (B) Heatmap of the co-infection rate of respiratory pathogens. The grid colour represents the co-infection rate of respiratory pathogens among patients with non-SCAP, and the dot colour represents the co-infection rate of respiratory pathogens among patients with SCAP. Bigger size and darker colour of the circles indicates higher co-infection rates between the pair of pathogens. HAdV=human adenovirus. HBoV=human bocavirus. HCoV=seasonal human coronavirus. HMPV=human metapneumovirus. HPIV=human parainfluenza virus. HRV=human rhinovirus. IFV=influenza virus. SCAP=severe community acquired pneumonia.

Figure 3:. Adjusted OR for SCAP

The numbers next to the bars represent the number of patients with SCAP in each group. The lengths of the bars indicate the incidence rate of SCAP, with blue bar representing the reference groups. The black points are the adjusted ORs for SCAP and the black error bars are the 95% CIs, and the arrow indicates that the 95% CI is out of the graph. (A) Incidence and adjusted OR for SCAP in children and adolescents younger than 18 years. (B) Incidence and adjusted OR for SCAP in adults aged 18 years or older. HAdV=human adenovirus. HBoV=human bocavirus. HCoV=seasonal human coronavirus. HMPV=human metapneumovirus. HPIV=human parainfluenza virus. HRV=human rhinovirus. IFV=influenza virus. RSV=respiratory syncytial virus. SCAP=severe community acquired pneumonia.

Figure 4:. Comparison of age-standardised test positive rates of pathogens and their percent changes between the pre-pandemic years (2009‒19) and the first COVID-19 pandemic year (2020)

(A) Age-standardised positive rates of eight viruses detected in patients with CAP during pre-pandemic years and the first COVID-19 pandemic year in mainland China. (B) Percent change of test positive rates of eight viruses detected. (C) Age-standardised positive rates of six bacteria detected in patients with CAP during pre-pandemic years and the first COVID-19 pandemic year. (D) Percent change of test positive rate of six bacteria detected. Statistical significance was based on χ² test or Fisher’s exact test. HAdV=human adenovirus. HBoV=human bocavirus. HCoV=seasonal human coronavirus. HMPV=human metapneumovirus. HPIV=human parainfluenza virus. HRV=human rhinovirus. IFV=influenza virus. RSV=respiratory syncytial virus. CAP=community acquired pneumonia. *p<0·01.