A total of 3480 children who diagonsed with CAP from 13 hospitals in Chinese mainland during November 2014 to June 2016 were screened in this study. Of 3480 children, 2721 (78.2%) patients were recruited finally, and the other patients (21.8%) were exculded because of rejection of guardians (82.2%) or no respiratory specimen (17.4%) (Fig. 1). The demographic and clinical characteristics of recruited cases were list in Table 1.
Characteristics n (%) Gender Male 1698 (60.7) Female 1092 (39.3) Age Median 2.17 y Age group <6 m 413 (15.2) 6–12 m 362 (13.3) 1–3 y 824 (30.2) 3–5 y 511 (18.8) 5–18 y 611 (22.5) Symptom Fever 2043 (75.1) Cough 2664 (97.9) Expectoration 1012 (37.2) Wheeze 985 (36.2) Hemoptysis 16 (0.6) The major complications of severe pneumonia case 240 (8.8) Acute respiratory failure 77 (32.1) Pleural effusion 42 (17.5) Atelectasis 26 (10.8) Cardiac damage 9 (3.8) CAP: community-acquired pneumonia
Table 1. Demographic and clinical data of children with CAP
Viral pathogens were detected in 56.6% (1539/2721) of the cases, with 39.8% (1082/2721) single virus infection and 16.8% (457/2721) multiple virus infection. HEV/HRV (73.1%, 334/457) was the most common virus associated with co-infection, followed by RSV (47.9%, 219/457), HMPV (30.0%, 137/457), HPIVs (26.5%, 121/457), HBoV (20.8%, 95/457) and HAdV (14.2%, 65/457). In north China, viral pathogen was detected in 54.6% (616/1128) of the cases: single virus infection in 35.5% (401/1128) of the cases and multiple virus infection in 19.1% (215/1128) of the cases. In south China, viral pathogen was detected in 57.9% (923/1593) of the cases: single virus in 42.7% (681/1593) of the cases and multiple viruses in 15.2% of the case (242/1593) (Fig. 2). There was no statistic difference in detection rate of recruited children between north China and south China (χ2 = 2.98, P = 0.0843).
Figure 2. Detection rate of viral pathogens in children with CAP. CAP: community-acquired pneumonia.
The most frequently detected viral pathogen was RSV (15.2%, 413/2721), followed by HEV (13.4%), HRV (10.2%) [The HEV/HRV was detected in 23.6% (643/2721) of the cases by using Luminex RVP Fast V2 kit. To further classify the HEV or HRV infection, real-time RT-PCR (Taqman probe) assay were performed in 180 available HEV/HRV-positive samples. The HEV- and HRV-positive samples accounted for 56.7% (102/180) and 43.3% (78/180), respectively. According to the proportion, the detection rate of HEV and HRV should be 13.4% and 10.2%, respectively], HPIVs (9.0%, 244/2721), HBoV (8.7%, 238/2721), HMPV (7.8%, 213/2721), HAdV (5.7%, 154/2721), Flu A (2.5%, 75/2721), HCoVs (2.6%, 71/2721), Flu B (2.5%, 69/2721) (Fig. 3). For HPIVs, the detection rate of HPIV1–4 was 1.6% (44/2721), 1.4% (37/2721), 5.2% (141/2721), 1.1% (31/2721), respectively. For HCoVs, the most common detected virus was HCoV-OC43 (1.3%, 36/2721), and the positive rate of other three HCoVs, 229E, NL63, HKU1, was 0.6% (15/2721), 0.1% (4/2721), 0.7% (18/2721), respectively. In 75 Flu A-positive samples, the 2009 pandemic H1N1 influenza A virus accounted for 20% (15/75), H3 subtype influenza A virus accounted for 22.7% (17/75), while the rest part was unsubtyped Flu A (57.3%, 43/75). The detection rate of HPIVs, HBoV and Flu B in north China were significantly higher than that in south China (HPIVs: χ2 = 8.735, P = 0.0031, HBoV: χ2 = 14.99, P = 0.0001 and Flu B: χ2 = 25.28, P < 0.0001). However, the detection rate of RSV and HMPV in north China were significantly lower than that in south China (RSV: χ2 = 11.67, P = 0.0006 and HMPV: χ2 = 8.735, P = 0.0031). There were no statistic differences in detection rate of HEV/HRV, HAdV, Flu A and HCoVs between cases in north and south China.
Figure 3. Detection rate of different viruses or virus subtypes in children with CAP. CAP: community-acquired pneumonia; RSV: respiratory syncytial virus; HEV/HRV: human enterovirus/human rhinovirus; HPIVs: human parainfluenza viruses (including HPIV1–4); HBoV: human bocavirus; HMPV: human metapneumovirus; HAdV: human adenovirus; Flu A: influenza A virus (including 2009 pandemic H1N1 influenza A virus, H3 subtype influenza A virus); HCoVs: human coronavirus (including HCoV-229E, -OC43, -NL63 and -HKU1); Flu B: influenza B virus. The symbol "*" indicated that there was statistic difference in the detection rate between north and south China using the chi-square test or the Fisher's exact test. A P < 0.05 was considered statistically significant.
Severe pneumonia patients accounted for 8.8% (240/2721) in children with CAP. The major complications included acute respiratory failure (32.1%, 77/240), pleural effusion (17.5%, 42/240), atelectasis (10.8%, 26/240), cardiac damage (3.8%, 9/240) (Table 1). Of all severe pneumonia cases, 40.8% (98/240) patients were infected with single virus, while 19.2% (46/240) patients were co-infected with multiple viruses. However, 40.0% (96/240) severe pneumonia cases were viral pathogen-negative. HEV/HRV (27.6%, 27/98), HBoV (18.4%, 18/98), RSV (16.3%, 16/98) and HMPV (14.3%, 14/98) were the most common detected viral pathogens in patients with single virus infection (Fig. 4).
Figure 4. Spectrum of viral pathogens in severe CAP cases. CAP: community-acquired pneumonia; RSV: respiratory syncytial virus; HEV/HRV: human enterovirus/human rhinovirus; HPIVs: human parainfluenza viruses (including HPIV1–4); HBoV: human bocavirus; HMPV: human metapneumovirus, HAdV: human adenovirus; Flu A: influenza A virus (including 2009 pandemic H1N1 influenza A virus, H3 subtype influenza A virus); HCoVs: human coronavirus (including HCoV-229E, -OC43, -NL63 and -HKU1); Flu B: influenza B virus.
The detection rates of viral pathogen decreased gradually with the increase of age. The detection rate of virus was the highest in children younger than six months old (70.7%, 292/413). There were significantly difference among five age groups (χ2 = 207.89, P < 0.001) (Fig. 5). RSV and HRV/HEV were the most frequently detected viruses in < 6 months, 6–12 months and 1–3 years groups. HBoV, HPIVs and HAdV were more commonly detected in children aged between 1–3 years. HMPV showed more often in children younger than five years. And similar detection rates were found among < 6 months, 6–12 months, 1–3 years and 3–5 years age groups. Flu A and Flu B showed the highest detection rate in cases between 1–3 years old and 3–5 years old, respectively. HCoVs were the most common pathogens appeared in < 6 months group (Supplementary Table 1).
RSV, HMPV and Flu B infection peaked in winter both in north and south China. Infection of Flu A reached the peak in winter and spring in north China, while peaked in summer in south China. HPIV infection was most frequently detected in summer both in north and south China. HEV/HRV infection circulated all year round, which showed higher detection rate from spring to summer. HBoV were more prevalent in summer in north China, but the peak of HBoV infection occurred in winter and summer in south China. Though HAdV was detected more often during winter than other seasons in north China, it kept lower prevalence in south China. The detection rate of HCoVs ascended in spring and summer in north China, which showed lower level in south China all year round (Fig. 6A, 6B).