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Paragraph: 1, 4, 5 Currently, there are no approved vaccines or medications available for most of the respiratory viruses . 1 A better understanding of the epidemiology of viral respiratory tract infections in children plays a key role for the prevention, control and treatment of ARTIs. Studies showed that many viral respiratory infections exhibited predictable seasonal variations. However, the epidemiological profiles of viral respiratory infections from different climate zones or different countries in the same climate zone may be varied. [6] [7] [8] [9] [10] [11] [12] China is a large country crossing three climate zones, and great differences in climate are found from region to region. A better understanding of the epidemiology of ARTIs in different regions could be helpful to develop effective surveillance, prevention and treatment strategies. Although some studies on the epidemiology of ARTIs have recently been reported in big cities such as Beijing, Shanghai and Hong Kong, [13] [14] [15] [16] the epidemic characteristics of viruses in ARTIs are still not well established all around China, especially in other cities and rural areas. Shenzhen is the largest migratory city of China with high population density and population mobility. It is located in southern China at 22°27 0 -22°52 0 N and 113°46 0 -114°37 0 E, immediately north of Hong Kong, with a typical subtropical monsoon climate. The annual average temperature and relative humidity of Shenzhen are about 23°C (12-33°C) and 77%, respectively. The purpose of this study is to investigate the prevalence, seasonality and clinical characteristics of acute viral respiratory infections in hospitalized children in Shenzhen and to provide insights into etiologies of ARTIs in local infants and children. A consecutive 3-year prospective study from July 2007 to June 2010 was conducted in Shenzhen, a coastal city neighboring Hong Kong. Four hospitals including a children's hospital were chosen for the study. Selected patients with ARTIs admitted to the pediatric wards were enrolled. The inclusion criteria were as follows: less than 14 years old, acute fever (T ≥ 38°C), with any one of respiratory symptoms (such as sore throat, cough, wheezing and dyspnoea/ tachypnoea), normal or low leukocyte count, the onset of illness within 3 days before hospitalization. The diagnosis of pneumonia was based on the guideline of the management of childhood community acquired pneumonia (CAP) issued by the Chinese Medical Association in 2006. 17 In the guideline, the clinical symptoms and signs for the diagnosis of childhood CAP include fever, cough, tachypnoea (defined according to different age), difficulty breathing and/or lower chest wall indrawing. X-ray evaluation has been carried out when necessary. The study protocol was approved by the medical ethical committees of the hospitals. Written informed consent was obtained from the parents or legal guardians of the children. Nasopharyngeal aspirates (NPA) were obtained by trained personnel following standard operating procedures within 24 hour after admission. The specimens were transported immediately to the laboratory by sterile viral transport media, then divided into aliquots and immediately frozen at À80°C until further processing. Total viral nucleic acids (DNA and RNA) were extracted from 200 ll of NPA specimen using the AxyPrep Body Fluid DNA/RNA Miniprep Kit (Axygen, Union City, CA, USA), according to the manufacturer's instructions. Purified DNA and RNA were stored at À80°C in aliquots for further PCR analysis. For each specimen, assays for ten common and newly identified viruses were performed. Briefly, WUPoyV and BOV were tested using monoplex PCRs described previously. 18, 19 Other viruses were tested using the Luminex platform and multiplex xTAG TM respiratory viral panel assay (RVP Assay) according to the manufacturer's instructions. 20 All multiple infection samples were retested. If there was discordance between two tests, the sample was confirmed by monoplex PCR. Statistical Package for the Social Sciences (SPSS) for Windows version 11.0 (SPSS Inc. Chicago, IL, USA) was used. For comparison of categorical data, chi-square or Fisher's exact test was used. All tests were two-tailed, and a P value below 0Á05 was considered statistically significant. A total of 2025 specimens were obtained from 2025 eligible patients ranging from 15 days to 14 years old with a median age of 12 months, in which 89Á6% of patients were < 4 years old. There were 964 (47Á6%) females and 1061 (52Á4%) males included. Of all hospitalized children enrolled in this study, 84Á0% involved lower respiratory infection and 16Á0% had upper respiratory tract infection (Table 1) . Among 971 positive cases, 572 (58Á9%) were diagnosed as pneumonia. About 971 of the 2025 cases (48Á0%) were positive for at least one viral pathogen. Among them, IAV, RSV, HRV and PIVs were detected in 348 (35Á8%), 296 (30Á5%), 209 (21Á5%) and 169 (17Á4%) cases, respectively. Single infection was observed in 669 (68Á9%) cases, and multiple infection was found in 302 (31Á1%). Our results also showed that RSV, IAV and HRV were the main pathogens in single viral infection cases ( Table 1) . The monthly positive rates varied from 32Á5% to 75Á0% with a mean of 45Á1% ( Figure 1 ). In the year 2009, when influenza A (H1N1) was pandemic worldwide, the positive rate started to increase in March and the highest positive rate 75Á0% was observed in May. Among the 971 positive cases, a total of 1335 viral pathogens were detected. The most frequently detected pathogen was IAV (26Á1%, 348/1335), followed by RSV (22Á2%, 296/1335), HRV (15Á7%, 209/1335), PIV1 and PIV3 (12Á7%, 169/1335) ( 

About 302 co-infection cases were identified, accounting for 14Á9% of all 2025 hospitalized children. During the H1N1 outbreak from March to August 2009, co-infection cases and co-infection rate increased significantly ( Figure 2 ). 143 of 302 (47Á4%) co-infection cases were detected during that time. Among them, 121 cases were involved in IAV infection, including 90 dual infection cases. Of all co-infection cases, 247 (81Á8%), 49 (16Á2%) and 5 (1Á7%) were infected with two, three and four potential viral pathogens, respectively. One multiple infection with five viruses was detected in a RSV  IAV  HRV  BOV  PIV3  ADV  HMPV  WUPoyV  PIV1  IBV  Total   A  Total cases  163  172  85  55  51  49  37  26  24  7  669  Bronchitis  12  19  7  7  5  2  2  3  5  0  62  Bronchiolitis  45  19  20  7  13  9  8  2  5  0  128  Pneumonia  93  97  55  28  24  28  25  18  14  5  387  URTI  13  37  3  13  9  10  2  3  0  2 *Case number and percentage in all enrolled children. **Incidence rate in this age group significantly higher than the other age groups. ***No significant difference between these three age groups. †No significant differences between these two age groups, but significantly lower than the other age groups. 6-month-old infant. IAV, RSV and HRV were the three most frequently found viruses in co-infection and detected in 176, 133 and 124 cases with co-infection rates of 50Á6%, 44Á9% and 59Á3%, respectively ( Table 2) . Various multiple infection patterns were observed in the study. A total of 152 (50Á3%) co-infection cases involved at least two viruses of RSV, HRV and IAV. Co-infection rate of each individual virus detected varied significantly. The lowest and highest co-infection rates were observed in WUPoyV (33Á3%) and IBV (66Á7%), respectively. 91Á4% (276/302) of co-infection cases were tested in the age group of 4 years old or younger ( Table 2) , but among all age groups, no statistical difference in co-infection rate was found (v 2 = 1Á83, P = 0Á8721). Gender-specific difference in co-infection rate was not observed (v 2 = 2Á17, P = 0Á1404). There was no significant difference in co-infection rates between PICU and non-PICU cases. Similarly, no significant difference in clinical symptoms was observed between co-infection and single cases (data not shown). In general, respiratory viruses were detected more often in the period of March to May than in other months (55Á4% and 40Á6%, respectively, v 2 = 28Á06, P = 0Á0000), and obvious seasonal peaks were observed during those months with peak strength varying from 1 year to another. A weaker seasonal peak could also be distinguished in some winter months in different years ( Figure 1) . The seasonality profile of each individual virus detected was diversified. A seasonal distribution of IAV can be observed from late spring to summer (mainly March to May) and sometimes in fall (October, November or December). A wide seasonal peak of IAV infection was detected from March to August 2009 ( Figure 3A ). Although RSV was tested almost a whole year, two yearly peaks were identified. One was found in November and/or December and the other stronger one was found in March to May of the year. The peak duration in 2009 was longer than those in other years. The seasonal trends of HRV and PIVs were similar to that of RSV, but the peaks of these three viruses fluctuated and shifted mildly ( Figure 3B ). Although IBV and ADV had a low detection rate in the study, similar seasonality was observed and their infection peaks were mainly in midwinter. Peaks in spring and summer were also observed in some years ( Figure 3C ). Our investigation did not find regular seasonality in BOV infections. A sudden increase in BOV infection was recorded in April and May 2010. Although the positive rate of HMPV infection was only 4Á8%, regular seasonality was observed from March to May of each year. Of 39 patients with WUPoyV infection, 36 were detected after July 2008. Our data implied that peak months of WUPoyV infection were from March to May ( Figure 3D ). The positive rates of viral infections in male and female were 52Á5% and 47Á5%, respectively. No significant gender difference was revealed (v 2 = 0Á012, P = 0Á9118). The distribution of viral agents and infection patterns in different age groups are shown in Table 2 . Of all 971 positive children, 890 (91Á7%) were 4 years old or younger. The positive rate in this age group was significantly higher than that in children more than 4 years old (v 2 = 8Á26, P = 0Á0041). Children under 6 months were the most susceptible to respiratory viral pathogens with a positive rate of 14Á8% (Table 2) . Very few long-term prospective studies were performed for viral etiologies of ARTIs among hospitalized children. In this present study, the infection frequency, seasonality, co-infection pattern and clinical features of viral respiratory infections were investigated based on prospective analysis of three consecutive year's data from hospitalized children with ARTIs. Our results provided a distinctive epidemiological profile of viral respiratory infections in hospitalized children with ARTIs in the study areas, which was different from those in the big cities in northern China such as Beijing and Shanghai and also different from that in adjacent Hong Kong. Overall, 48Á0% of our cases were positive for respiratory virus infections, which resembled the latest study in the same city. 21 A similar incidence rate has been obtained in neighboring regions 13, 22 and other cities such as Rome 23 and Milan, 24 but it was different from other studies. [10] [11] [12] In China, the overall positive rate reported varied from 27Á3 to 74Á8% depending on different areas and detection methods. 15, 16, [25] [26] [27] [28] [29] [30] [31] The rate of respiratory viral infections varied worldwide, and many factors such as geographic distribu-tion, study design and detection protocols could lead to these variations. 1, 7, 8, 32 In our study, leukocyte count was used as an indicator of inclusion criteria and it probably affected the positive rate. Viruses not considered in the study, for example coronaviruses, would underestimate the positive rate. Most studies showed that RSV or HRV was the most prevalent viruses in children with viral respiratory tract infection. 1 In this study, IAV was the most frequently detected respiratory virus, followed by RSV and HRV. IAV (H1N1) outbreak in 2009 could explain this shift. Data showed that about 60% of IAV infections were detected during the outbreak period. Studies showed that the H1N1 outbreak could change viral distribution patterns. 24, 29, 33 Regardless of the IAV (H1N1) outbreak, RSV and HRV were the two most common viral pathogens in ARTIs, which was consistent with most previous studies. 1, 10, 15, 16, 22, [25] [26] [27] [28] [29] Our study further confirmed the importance of RSV and HRV in children with ARTIs, especially in children < 4 years of age. 10, 14, 23 Our results also showed that 12Á7% of viral pathogens detected were PIV1 and PIV3, which implied that PIVs played an important role in children with ARTIs. Similar findings were obtained in the studies conducted in Shanghai, 14, 34 Changsha, 26 Harbin, 30 Hong Kong 13 and Rome. 23 The prevalence of PIV3 was twofold higher than that of PIV1, particularly in infants, which was similar with other reports, 25, 26, 30, 35 implying that infants could be more vulnerable to infection with PIV3 than PIV1.

Question: Are there any vaccines against to protect against respiratory viral infections?
Currently, there are no approved vaccines or medications available for most of the respiratory viruses