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CORD-19:f29732f07d2e23f950bd01eab12bdb0165e3cc17 JSONTXT 9 Projects

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Id Subject Object Predicate Lexical cue
T1 0-167 Sentence denotes Epidemiological characteristics and phylogenic analysis of human respiratory syncytial virus in patients with respiratory infections during 2011-2016 in southern China
T2 169-177 Sentence denotes Abstract
T3 178-189 Sentence denotes Background:
T4 190-350 Sentence denotes Human respiratory syncytial virus (RSV) is one of the most important pathogens that cause acute respiratory infections in children and immunocompromised adults.
T5 351-477 Sentence denotes This work was conducted to understand the epidemiological and phylogenetic features of RSV in southern China during 2011-2016.
T6 478-486 Sentence denotes Methods:
T7 487-677 Sentence denotes A total of 16 024 nasopharyngeal swabs were collected from patients with respiratory infections in 14 hospitals, and screened for RSV and seven other respiratory viruses using real-time PCR.
T8 678-781 Sentence denotes Six hundred and twenty-three RSV-positive samples from 13 hospitals were further analyzed for subtypes.
T9 782-880 Sentence denotes G gene sequencing and phylogenetic analysis were performed based on 46 RSV-A and 15 RSV-B strains.
T10 881-997 Sentence denotes Results: RSV was detected in 9.5% of the 16 024 specimens, the highest among the eight respiratory viruses screened.
T11 998-1077 Sentence denotes Most of these specimens came from inpatients and children under 3 years of age.
T12 1078-1206 Sentence denotes The incidence of RSV-A (9.4%) was higher than that of RSV-B (4.4%) in children (<15 years), but not in adults (0.64% vs. 0.58%).
T13 1207-1287 Sentence denotes A 2-year RSV-A dominance followed by a 1-year RSV-B dominance pattern was found.
T14 1288-1327 Sentence denotes The co-detection rate of RSV was 25.1%.
T15 1328-1380 Sentence denotes The main prevalent genotypes were NA1, ON1, and BA9.
T16 1381-1571 Sentence denotes The prevalent RSV-A genotype in 2011-2012 was NA1, close to Chongqing and Brazil, but a new Hong Kong ON1 genotype was introduced and became the prevalent genotype in Guangzhou in 2014-2015.
T17 1572-1737 Sentence denotes Deduced amino acid sequence analysis confirmed the ongoing evolution and a high selection pressure of RSV-A and B strains, especially in RSV-A ON1 and NA1 genotypes.
T18 1738-1750 Sentence denotes Conclusions:
T19 1751-1886 Sentence denotes This study demonstrated the molecular epidemiological characteristics of RSV in patients with respiratory infections in southern China.
T20 1888-2121 Sentence denotes Human respiratory syncytial virus (RSV), an Orthopneumovirus belonging to the Pneumoviridae family, is one of the most important pathogens causing severe acute lower respiratory infections (ALRI) in children (Borchers et al., 2013) .
T21 2122-2350 Sentence denotes Studies have shown that RSV is the most common cause of hospitalization among children under 2 years of age and is associated with significant morbidity and mortality (Borchers et al., 2013; Nair et al., 2010; Shi et al, 2017) .
T22 2351-2556 Sentence denotes In elderly and immunocompromised adults or patients with preexisting diseases, the morbidity and mortality rates have been shown to be significantly higher in RSV-infected patients (Colosia et al., 2017) .
T23 2557-2649 Sentence denotes Therefore, RSV-related respiratory tract infection is a major public health issue worldwide.
T24 2650-3060 Sentence denotes The clinical manifestations after RSV infection range from a mild upper respiratory tract infection to severe life-threatening lower respiratory tract involvement such as bronchiolitis, pneumonia, and croup, together with some common symptoms including fever, rhinorrhea, cough, and wheezing (Borchers et al., 2013) , which are not readily distinguished from those of other common respiratory virus infections.
T25 3061-3346 Sentence denotes Although efforts to develop an RSV vaccine for all age groups began in the 1960s, no safe and effective vaccine is yet available, and antiviral treatment for RSV infection is currently also very limited, with treatments usually being supportive and symptomatic (Colosia et al., 2017) .
T26 3347-3520 Sentence denotes Although RSV has only one single serotype, it can be divided into two antigenic groups -RSV-A and RSV-Baccording to the antigenicity of the G protein (Mufson et al., 1985) .
T27 3521-3707 Sentence denotes To date, 14 genotypes of RSV-A and 25 genotypes of RSV-B have been confirmed (Ren et al., 2015; Shobugawa et al., 2009) , suggesting that genetic variability and evolution of RSV exists.
T28 3708-4005 Sentence denotes However, data concerning the molecular epidemiological characteristics of RSV subtypes are limited, and there are few reports about the epidemiological status and genotypic characteristics of RSV prevailing in patients with acute respiratory infections (ARI) in southern China (Liu et al., 2016) .
T29 4006-4156 Sentence denotes This study was, therefore, performed to investigate the presence of RSV in pediatric (<15 years) and adult (!15 years) patients with ARI in Guangzhou.
T30 4157-4288 Sentence denotes Specimens were collected from ARI patients during 2011-2016 and RSV was analyzed along with seven other common respiratory viruses.
T31 4289-4467 Sentence denotes A phylogenetic analysis of RSV-A and RSV-B strains was performed in order to better understand the molecular epidemiological characteristics of RSV circulating in southern China.
T32 4468-4642 Sentence denotes Nasopharyngeal swabs were collected from pediatric and adult patients with ARI from January 2011 to December 2016 in 14 hospitals covering Guangdong Province, southern China.
T33 4643-4822 Sentence denotes Inclusion criteria were as follows: fever (body temperature !37.5 C within 3 days, accompanied by one or more symptoms of ARI including cough, runny nose, sputum, and sore throat.
T34 4823-4953 Sentence denotes Information including demographic data, case history, symptoms, and clinical results of each patient was collected simultaneously.
T35 4954-5192 Sentence denotes RSV and seven common respiratory viruses were screened: influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), human coronavirus (HCoV), human adenovirus (HADV), human rhinovirus (HRV), and human bocavirus (HBoV).
T36 5193-5361 Sentence denotes Viral RNA and DNA were extracted from 200 ml nasopharyngeal swab using a QIAamp MiniElute Virus Spin Kit (Qiagen, Germany) according to the manufacturer's instructions.
T37 5362-5506 Sentence denotes Reverse transcription of viral RNA was performed using the Thermo Scientific RevertAid First Strand cDNA Synthesis Kit (Thermo Scientific, USA).
T38 5507-5681 Sentence denotes Common respiratory viruses and RSV were screened by realtime PCR as described previously (Bonroy et al., 2007; Van de Pol et al., 2007; Xu et al., 2012; Zhang et al., 2018) .
T39 5682-5778 Sentence denotes The primers and probes used in the screening are listed in the Supplementary Material Table S1 .
T40 5779-5900 Sentence denotes The RSV-specific primers and probes (synthesized by Invitrogen, Life Technology, Shanghai, China) are listed in Table 1 .
T41 5901-6164 Sentence denotes To detect RSV, samples were assayed in a 25-ml reaction mixture containing 5 ml of cDNA, 12.5 ml of 2 Â Universal Master Mix (Applied Biosystems, USA), 300 nM of the forward and reverse primers, respectively, and 200 nM of the probe, with the following procedure:
T42 6165-6237 Sentence denotes 10 min at 95 C, followed by 45 cycles of 15 s at 95 C and 1 min at 60 C.
T43 6238-6567 Sentence denotes For detection of the RSV subtypes, samples were assayed in a 20-ml reaction mixture containing 2 ml of cDNA, 10 ml 2 Â LightCycler 480 Probes Master (Roche, Switzerland), 100 nM of forward and reverse primer, respectively, and 100 nM of probe, with the procedure of 95 C for 10 min and 45 cycles of 95 C for 15 s, 55 C for 1 min.
T44 6568-6661 Sentence denotes The RSV-positive samples were selected and further analyzed for genotypes using a nested PCR.
T45 6662-6746 Sentence denotes Four pairs of primers were designed for G gene amplification, as listed in Table 2 .
T46 6747-6834 Sentence denotes The procedure for the first and the second round amplification of RSV-A was as follows:
T47 6835-6969 Sentence denotes 95 C for 2 min, followed by 30 cycles of 94 C for 1 min, 50 C for 1 min, and 72 C for 1 min, and a final extension at 72 C for 10 min.
T48 6970-7057 Sentence denotes The following procedure was used for the first and second round amplification of RSV-B:
T49 7058-7191 Sentence denotes 95 C for 2 min, followed by 30 cycles of 94 C for 1 min, 50 C for 1 min, and 72 C for 2 min, and a final extension at 72 C for 7 min.
T50 7192-7310 Sentence denotes The PCR products were purified by DNA purification kit (Takara, China) and cloned into vector PMD19-T (Takara, China).
T51 7311-7441 Sentence denotes Sequencing was performed using a dideoxy chain termination method in both forward and reverse directions by Invitrogen Co., China.
T52 7442-7529 Sentence denotes All PCR products used for cloning and sequencing were from three independent reactions.
T53 7530-7639 Sentence denotes A total of 61 strains from the years 2011-2015 were selected for G gene sequencing and phylogenetic analysis.
T54 7640-7779 Sentence denotes The selection criteria were (1) the sample was available; (2) the sample was well preserved and the G gene could be successfully amplified.
T55 7780-7963 Sentence denotes The G gene sequences were compared with those of the representative sequences of RSV-A and RSV-B from other countries or regions in GenBank, and were aligned by the Clustal X program.
T56 7964-8107 Sentence denotes The phylogenetic tree of the RSV G gene was constructed by maximum-likelihood method with the Kimura 2-parameter model using MEGA 5.0 software.
T57 8108-8157 Sentence denotes Bootstrap values were decided by 1000 replicates.
T58 8158-8227 Sentence denotes The deduced amino acid sequences were analyzed with Bioedit software.
T59 8228-8395 Sentence denotes Potential N-glycosylation sites (Asn-Xaa-Ser/ Thr, where Xaa is not a proline) were predicted using the NetNGlyc 1.0 Server (http://www.cbs.dtu.dk/services/NetNGlyc/).
T60 8396-8496 Sentence denotes IBM SPSS Statistics version 20.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analysis.
T61 8497-8605 Sentence denotes The incidence was calculated as the percentage of positive samples in the indicated total number of samples.
T62 8606-8745 Sentence denotes The Chi-square test or Fisher's exact test was used to Table 1 Real-time PCR primers and probes used for the detection of the RSV subtypes.
T63 8746-8795 Sentence denotes Sequence ( evaluate the difference between rates.
T64 8796-8887 Sentence denotes The odds ratio was calculated using the risk estimate of crosstabs Chi-square test in SPSS.
T65 8888-8938 Sentence denotes The trend line was drawn by moving average method.
T66 8939-9000 Sentence denotes A p-value of < 0.05 was considered statistically significant.
T67 9001-9142 Sentence denotes Among the 16 024 patients, 5818 (36.3%) were found to be positive for at least one virus and 771 (4.8%) were infected by more than one virus.
T68 9143-9262 Sentence denotes The male to female ratio was 1.63 (9923/6106), and the inpatient to emergency/outpatient ratio was 2.95 (11 964/ 4060).
T69 9263-9400 Sentence denotes Analysis of the RSV subtypes was performed on 623 RSVpositive swabs from 13 hospitals except Guangzhou Institute of Respiratory Diseases.
T70 9401-9519 Sentence denotes The demographic and clinical characteristics of the 16 024 patients are shown in the Supplementary Material Table S2 .
T71 9520-9646 Sentence denotes The patient composition and surveillance results for RSV and the seven other common respiratory viruses are shown in Table 3 .
T72 9647-9733 Sentence denotes The monthly distributions are shown in Figure 1 and Supplementary Material Figure S1 .
T73 9734-9816 Sentence denotes Influenza virus was prevalent mainly in the spring, especially in February to May.
T74 9817-9967 Sentence denotes Similarly, the epidemic of HMPV was mainly in the spring, especially in March to May, but in 2012, the epidemic season appeared earlier in the winter.
T75 9968-10038 Sentence denotes PIV was mainly epidemic in spring and autumn, especially in 2011-2012.
T76 10039-10176 Sentence denotes HRV was epidemic throughout the year; however, as most of the hospitals did not test for HRV in 2011, the incidence in that year was low.
T77 10177-10285 Sentence denotes HBoV was epidemic mainly in summer during 2011-2014, but in 2015-2016, the epidemic peak appeared in autumn.
T78 10286-10335 Sentence denotes HCoV and HADV were prevalent throughout the year.
T79 10336-10467 Sentence denotes RSV was mainly epidemic in winter and spring, but in the summer of 2011 and 2013, the epidemic level was also high ( Figure 1A -H).
T80 10468-10563 Sentence denotes The age of the enrolled patients ranged from 0 days to 103 years, with a median age of 7 years.
T81 10564-10644 Sentence denotes Among them, 33.8% (5419/16 024) were infants (<1 year) and toddlers (1-2 years).
T82 10645-10762 Sentence denotes The age distributions of the patients with RSV and the seven other common respiratory viruses are shown in Figure 2 .
T83 10763-11046 Sentence denotes For most of the viruses screened, the incidence in young children (3-5 years) was much higher than that in older children (6-14 years) and adults (!15 years), as shown in Fig. 2B -H, except for Flu, which was mostly detected in the 15-35 years group (row percentage 14.9%, Fig. 2A ).
T84 11047-11188 Sentence denotes PIV and RSV mostly infected infants of 0-1 year (6.5% and 27.6%, respectively), and HBoV mostly infected those in the 1-2 years group (3.5%).
T85 11189-11302 Sentence denotes For HADV and HMPV, the group with the highest incidence was 4-6 years (10.6%) and 2-3 years (4.0%), respectively.
T86 11303-11477 Sentence denotes Similarly, HRV and HCoV tended to infect infants, with a high incidence of 7.4% and 4.0% respectively, and also children in the 3-4 years group (5.6% and 4.3%, respectively).
T87 11478-11601 Sentence denotes Among the 16 024 samples, 1514 (9.5%) were found to be RSVpositive, the highest among the eight respiratory viruses tested.
T88 11602-11779 Sentence denotes The RSV-positive patients included 1389 inpatients and 125 outpatients, and the incidence was significantly higher in inpatients (91.7% vs. 8.3%, Chi-square = 257.86, p < 0.01).
T89 11780-11908 Sentence denotes The odds ratio of infection with RSV resulting in severe disease or admission was 4.14 (95% confidence interval (CI) 3.43-4.98).
T90 11909-12061 Sentence denotes Among the 1514 RSV-positive patients, 1039 (68.6%) were male and 475 (31.4%) were female; the difference was significant (Chi-square = 31.84, p < 0.01).
T91 12062-12260 Sentence denotes The common symptoms of RSV infection were cough (94.8%), fever (71.7%), runny nose (35.6%), and sputum (30.5%), which were not distinguishing from those of other common respiratory virus infections.
T92 12261-12433 Sentence denotes Most of the RSV-positive patients (1432 cases, 94.6%) were children, including children not in nursery (59.5%), school Table 2 Primers used for RSV G gene amplification a .
T93 12434-12442 Sentence denotes Sequence
T94 12443-12662 Sentence denotes RSV, respiratory syncytial virus. a Sense primer: RSV-A-F or RSV-B-F; antisense primer: RSV-ABR. nursery children (17.5%), and primary and junior high school students (1.6%); the adult group were mainly retirees (1.3%).
T95 12663-12796 Sentence denotes Infants and toddlers (<3 years) were the population with the highest risk of RSV infection, especially infants <1 year ( Figure 2H ).
T96 12797-12852 Sentence denotes RSV-positive cases were distributed in eight hospitals.
T97 12853-13019 Sentence denotes Guangzhou Institute of Respiratory Health showed the highest incidence in 2011-2013, but a notable epidemic peak appeared in Zhu Jiang Hospital in 2014 ( Figure 3A ).
T98 13020-13107 Sentence denotes The annual distributions of RSV from 2011 to 2016 in Guangzhou are shown in Figure 3B .
T99 13108-13267 Sentence denotes The RSV incidence was significantly lower in 2012 , and higher in 2011 .06, p < 0.01), showing epidemic peaks in 2011 and 2014-2015 in Guangzhou, respectively.
T100 13268-13454 Sentence denotes Among the 1514 RSV-positive samples, 623 from 13 hospitals were further analyzed for RSV-A/RSV-B subtypes; RSV subtyping was not performed at Guangzhou Institute of Respiratory Diseases.
T101 13455-13647 Sentence denotes Among the 623 cases, 394 (63.2%) were RSV-A and 196 (31.5%) were RSV-B; both RSV-A and RSV-B were co-detected in three cases (0.5%), and 30 (4.8%) failed to be determined for specimen reasons.
T102 13648-13815 Sentence denotes Among the 8936 ARI patients from 13 hospitals (excluding samples from Guangzhou Institute of Respiratory Diseases), the incidence of RSV-A was 4.4% and RSV-B was 2.2%.
T103 13816-13957 Sentence denotes The three cases of RSV-A and B co-detection were all children (two were 2 years old and one was 5 months old) who were inpatients with ALRIs.
T104 13958-14069 Sentence denotes The RSV-A incidence was 4.7% (258/5467) in males and 4.0% (139/ 3469) in females (Chi-square = 2.54, p > 0.05).
T105 14070-14219 Sentence denotes However, the RSV-B incidence was 2.5% (139/5467) in males and 1.7% (60/3469) in females, with a significant difference (Chi-square = 6.44, p < 0.05).
T106 14220-14495 Sentence denotes Both RSV-A and RSV-B mainly infected infants and toddlers, and the incidence of RSV-A (9.4%) was higher than that of RSV-B (4.4%) in children (Chi-square = 63.46, p < 0.01); however there was no difference in adults (0.64% vs. 0.58%, Chi-square = 0.15, p > 0.05; Figure 3C ).
T107 14496-14660 Sentence denotes The annual distribution trend for RSV-A was similar to that of the total RSV, with epidemic peaks in 2011 and 2014-2015 (Chi-square = 194.03, p < 0.01; Figure 3D ).
T108 14661-14882 Sentence denotes In contrast, RSV-B was predominant in 2013 and 2016 (Chi-square = 168.19, p < 0.01; Figure RSV-A mainly circulated in winter and spring, with a peak in January to April and a lower peak in July to September ( Figure 4A ).
T109 14883-15030 Sentence denotes RSV-B showed a 1-month stagger in epidemic peaks, with a later high peak in March to May and an earlier small peak in June to August ( Figure 4B ).
T110 15031-15143 Sentence denotes RSV-A was the predominant subtype in most of the months except July, when RSV-B slightly exceeded ( Figure 4C ).
T111 15144-15485 Sentence denotes On analysis of the detailed monthly distribution for 2011-2016 ( Figure 5) , it was found that most of the time, RSV-A and RSV-B had dominance alternately, except for January to June in 2014, when both RSV-A and RSV-B were epidemic at a high level. (Table 4) ; 91.1% were double infections (346/380) and 8.9% were triple infections (34/380).
T112 15486-15554 Sentence denotes No correlation was found between co-detection and clinical symptoms.
T113 15555-15735 Sentence denotes Among the 380 patients with co-detection, 232 was diagnosed as ALRI, not statistically higher than RSV single positive patients (232/380 vs. 745/1134, Chi-square = 2.68, p > 0.05).
T114 15736-15800 Sentence denotes The age of patients with co-detection ranged from 0 to 87 years.
T115 15801-15983 Sentence denotes Children <3 years were the most likely population to have RSV as a co-detection, accounting for 77.4% (294/380) of the co-detection cases, and 44.2% (168/380) were infants (<1 year).
T116 15984-16184 Sentence denotes The co-detection rates were 25.6% in inpatients (355/1389) and 20.0% (25/125) in outpatients, with no significant difference between inpatients and emergency/outpatients (Chi-square = 1.88, p > 0.05).
T117 16185-16338 Sentence denotes However, the co-detection rate in females was 28.6% (136/ 475), which was higher than the rate of 23.5% in males (244/1039, Chi-square = 4.59, p < 0.05).
T118 16339-16547 Sentence denotes To better understand the phylogenetic characteristics of RSV in southern China, 61 RSV strains, including 46 RSV-A and 15 RSV-B strains obtained in 2011-2015 in Guangzhou, were selected for G gene sequencing.
T119 16548-16598 Sentence denotes Among the 46 RSV-A strains, 24 were selected 14) .
T120 16599-16736 Sentence denotes Accordingly, two to four of the representative strains for each RSV-A and RSV-B genotype were selected from GenBank as reference strains.
T121 16737-16912 Sentence denotes Phylogenetic analysis showed that among the 46 Guangzhou RSV-A strains, there were 29 genotype NA1, 15 genotype ON1, one genotype NA3, and one genotype GA5 (Figures 6 and 7) .
T122 16913-16989 Sentence denotes The 29 NA1 strains included 24 strains from 2011 and five strains from 2012.
T123 16990-17144 Sentence denotes Among these, 25 were close to Chongqing NA1 strain GU550471, and the remaining four strains were in another cluster, closer to the Brazil strain JX513285.
T124 17145-17309 Sentence denotes The 15 ON1 strains included eight 2015strains, five 2014 strains, one 2012 strain, and one 2013 strain, and all of them were close to Hong Kong ON1 strain KP221572.
T125 17310-17453 Sentence denotes The NA3 strain was a 2015strain which was close to Beijing strain KC297277 and the GA5 strain was a 2014 strain close to Japan strain AB175815.
T126 17454-17559 Sentence denotes All 15 Guangzhou strains of RSV-B belonged to the BA9 genotype and were close to Chengdu strain KT765074.
T127 17560-17705 Sentence denotes Therefore, the main genotypes of RSV-A circulating in Guangzhou from 2011 to 2015 were NA1 and ON1, whereas the prevalent RSV-B genotype was BA9.
T128 17706-17829 Sentence denotes Moreover, the dominant RSV-A genotype in 2011-2012 was NA1, but ON1 became the dominant genotype in 2014-2015 ( Figure 6 ).
T129 17830-18109 Sentence denotes The deduced amino acid sequences (according to the second hypervariable region of the G protein) of the 46 RSV-A and 15 RSV-B Guangzhou strains were aligned and compared with the RSV-A prototype strain A2, representative NA1, ON1, NA3, GA5 strains and ETLHSTTSEGYLSPSQVYTTSGQE) .
T130 18110-18311 Sentence denotes Compared to the A2 prototype, ON1 subtype-specific substitutions (S222P, T253K, and S314L) were observed in all of the ON1 subtypes, and E232G was observed in most of the ON1 strains except GZ/2014/05.
T131 18312-18369 Sentence denotes M286E, P310L, and S314P were observed in all NA1 strains.
T132 18370-18510 Sentence denotes Other commonly observed substitutions for RSV-A strains included L208I, P215S, S222P, N237D/Y, T249I, N251Y, E262K, N297Y, P298L, and P320T.
T133 18511-18575 Sentence denotes There were two deletions (L265 and E308) observed in GZ/2015/16.
T134 18576-18882 Sentence denotes The analysis of potential N-glycosylation sites revealed that due to the N237Y substitution of ON1 and NA3 genotype, GZ/2015/16 and GZ/2015/10 lost potential N-glycosylation sites at residue 237, but interestingly, due to the D237N substitution, 10 Guangzhou NA1 strains regained this N-glycosylation site.
T135 18883-19055 Sentence denotes Moreover, due to N318Y, T319A, or T320S/I/P mutation, eight Guangzhou NA1 and one Guangzhou NA3 strains lost the potential N-glycosylation site at residue 318 ( Figure 8 ).
T136 19056-19227 Sentence denotes Compared to the sequences of the representative BA1 strain (BA4128/99B; Fan et al., 2017; Trento et al., 2003) , all BA9 strains had K218T, L223P, and S247P substitutions.
T137 19228-19335 Sentence denotes I281T and H287Y existed in most of the Guangzhou BA9 strains except GZ2012/03 and GZ/2012/15, respectively.
T138 19336-19453 Sentence denotes Besides the I281A substitution, GZ/ 2012/03 strain showed a loss of amino acids 254-273 (i.e., TTTSKHTERDTSTSQSIALD).
T139 19454-19559 Sentence denotes Other commonly observed substitutions for RSV-B strains included P216S/L, I229T, T254I, T275I, and S304P.
T140 19560-19680 Sentence denotes Due to T312P substitution, three Guangzhou BA9 strains lost potential N-glycosylation sites at residue 310 ( Figure 9 ).
T141 19681-19768 Sentence denotes RSV is one of the most common pathogens that cause ALRI, especially in young children .
T142 19769-20213 Sentence denotes Since there is no specific drug and no effective vaccine for RSV infection, the long-term monitoring of RSV is important for RSV prevention and controlby continuously collecting and analyzing data related to RSV introduction, transmission, distribution, and variation, and by understanding more about RSV epidemic and variation patterns, we can predict the prevalent level and scale of RSV and help to produce control and prevention strategies.
T143 20214-20370 Sentence denotes This study investigated the molecular epidemiological characteristics of RSV and its subtypes in ARI patients during 2011-2016 in Guangzhou, southern China.
T144 20371-20546 Sentence denotes Since RSV usually co-infects with other respiratory viruses, seven common respiratory viruses including Flu, PIV, HCoV, HADV, HBoV, HMPV, and HRV were detected simultaneously.
T145 20547-20766 Sentence denotes The results showed that among the eight common respiratory viruses, RSV was the one most commonly detected, with a detection rate of 9.5% in 16 024 patients with ARI from 14 hospitals during 2011-2016 in southern China.
T146 20767-20836 Sentence denotes Flu was the second most frequently detected respiratory virus (9.3%).
T147 20837-21044 Sentence denotes The age characteristics and monthly distribution of RSV and the seven respiratory viruses in Guangzhou during 2011-2016 were consistent with those in previous reports (Liu et al., 2014; Zhang et al., 2014) .
T148 21045-21169 Sentence denotes A total of 1514 patients were RSV-positive, 91.7% of whom were inpatients, significantly higher than outpatients (p < 0.01).
T149 21170-21348 Sentence denotes The odds ratio of hospitalized patients with RSV infection to outpatient/emergency was 4.14, indicating that RSV infection has a considerable risk of resulting in severe disease.
T150 21349-21580 Sentence denotes Infants and toddlers (<3 years) not in nursery (59.5%) seemed to have the highest risk of RSV infection, and the reason may lie in the decrease in maternal protective antibodies and the increase in exposure opportunities to crowds.
T151 21581-21742 Sentence denotes The monthly distribution confirmed that RSV was mainly prevalent in winter and spring, consistent with other regions (Bashir et al., 2017; Slovic et al., 2016) .
T152 21743-21894 Sentence denotes The annual distribution of RSV during 2011-2016 in Guangzhou revealed high epidemic years for 2011, 2014, and 2015, with year 2015 as an epidemic peak.
T153 21895-22099 Sentence denotes There may be a biennial high incidence pattern of RSV in Guangzhou, and surveillance over a longer period will confirm the annual distribution characteristics (Esposito et al., 2015; Xiang et al., 2013) .
T154 22100-22267 Sentence denotes To better understand the epidemiological characteristics of RSV subtypes, RSV-A and RSV-B subtypes were determined based on 623 RSV-positive samples from 13 hospitals.
T155 22268-22449 Sentence denotes The results showed that RSV-A was the dominant subtype circulating in Guangzhou during 2011-2016, consistent with reports from other regions (Hu et al., 2017; Slovic et al., 2016) .
T156 22450-22565 Sentence denotes The three patients with co-detection were all infants and toddlers and inpatients with ALRI, and none of them died.
T157 22566-22675 Sentence denotes It cannot be deduced whether the co-detection of both subtypes exacerbates the disease based on the symptoms.
T158 22676-22927 Sentence denotes Both RSV-A and RSV-B mainly infected young children under 3 years of age, and the incidence of RSV-A was higher than that of RSV-B in children (p < 0.01), but not in adults (p > 0.05), indicating that RSV-A may have a higher pathogenicity to children.
T159 22928-23094 Sentence denotes The annual distribution of RSV subtypes revealed an interesting year distribution, as a 2-year RSV-A dominance followed by a 1-year RSV-B dominance pattern was found.
T160 23095-23283 Sentence denotes A similar year distribution pattern has been reported previously in Beijing and Belgium, among others (Xiang et al., 2013; Coggins et al., 1998; Zlateva et al., 2007; Scott et al., 2004) .
T161 23284-23581 Sentence denotes In addition to this pattern, RSV-A has been reported to show an epidemic for 2-4 years followed by RSV-B for 1 year pattern, as reported in Uruguay (Arbiza et al., 2005) ; and also, an RSV-A epidemic for 4 years followed by RSV-B for 1 year pattern, as reported in Japan (Shobugawa et al., 2009 ).
T162 23582-23709 Sentence denotes It appears that this is the first time such a year distribution characteristic of RSV subtypes has been reported for Guangzhou.
T163 23710-23852 Sentence denotes Most of the time, RSV-A and RSV-B took dominance alternately, but in January to June 2014, both RSV-A and RSV-B were epidemic at a high level.
T164 23853-24008 Sentence denotes The co-detection rate of RSV was as high as 25.1% in Guangzhou from 2011 to 2016, and 91.1% of them were double infections and 8.9% were triple infections.
T165 24009-24186 Sentence denotes Table 4 Cases of co-detection of RSV and seven other common respiratory viruses (Flu, PIV, HMPV, HCoV, HADV, HRV, and HBoV Influenza virus was the most common co-detected virus.
T166 24187-24363 Sentence denotes No correlation was found between clinical symptoms and co-detection (p > 0.05), indicating that co-detection may not aggravate the disease or enhance the mortality of patients.
T167 24364-24581 Sentence denotes However, this finding may be limited by the small sample size and the heterogeneity of co-detected viruses, and more studies will be needed to elucidate the relationships between RSV co-infection and disease severity.
T168 24582-24746 Sentence denotes Of the 46 Guangzhou RSV-A strains, 29 strains belonged to genotype NA1, 15 belonged to genotype ON1, one belonged to genotype NA3, and one belonged to genotype GA5.
T169 24747-24857 Sentence denotes The genome of RSV encodes 11 proteins, including NS1, NS2, N, P, M, SH, G, F, M2-1, M2-2, and L (Cane, 2001) .
T170 24858-25010 Sentence denotes According to the genetic diversity, RSV is genotyped mainly by the second highvariant region of the G protein C-terminal (HVR2) (Schobel et al., 2016) .
T171 25011-25224 Sentence denotes Therefore, to better understand the phylogenetic characteristics of RSV in southern China and to gain more insight into RSV variation, we further analyzed the sequences of the G genes of the Guangzhou RSV strains.
T172 25225-25358 Sentence denotes Most of the RSV-A genotypes from Guangzhou were close to Chongqing and Hong Kong strains and the RSV-B was close to a Chengdu strain.
T173 25359-25483 Sentence denotes The prevalent RSV-B genotype in Guangzhou during 2011-2016 was BA9, whereas the prevalent RSV-A genotypes were more diverse.
T174 25484-25559 Sentence denotes Among the 30 strains from the years 2011-2012, 29 were NA1 and one was ON1.
T175 25560-25668 Sentence denotes Among the 15 strains from the years 2014-2015, 13 were ON1 and the other two were GA5 and BA9, respectively.
T176 25669-25701 Sentence denotes The 2013 strain belonged to ON1.
T177 25702-25888 Sentence denotes It can be seen that the NA1 genotype of RSV-A was prevalent in 2011-2012, while ON1 became the prevalent genotype in 2014-2015, which is consistent with the report of Fan et al. (2017) .
T178 25889-26024 Sentence denotes Deduced amino acid sequence analysis confirmed the ongoing evolution of RSV-A and B strains, especially in RSV-A ON1 and NA1 genotypes.
T179 26025-26240 Sentence denotes Multiple highly variable substitutions were observed, and moreover, three Guangzhou ON1 strains showed the loss of a 24-amino acid fragment in the duplication region, and one BA9 strain had a 20-amino acid deletion.
T180 26241-26560 Sentence denotes N-glycosylation site changes were also commonly observed in Guangzhou RSV-A strains, including the loss of the 251 and 318 glycosylation sites and regain of the 237 glycosylation site in most of the NA1 strains, and the loss of the 237 glycosylation site and two single amino acid deletions in an ON1 strain GZ/2015/16.
T181 26561-26634 Sentence denotes Glycosylation site changes were also observed in three RSV-B BA9 strains.
T182 26635-26687 Sentence denotes These mutations indicated a high selection pressure.
T183 26688-26986 Sentence denotes Since 2014-2015 was also the highest epidemic year for RSV-A, it was deduced that before 2012, the prevalent RSV genotype was NA1 from Chongqing, but in 2014, due to staff turnover, a new Hong Kong strain of ON1 genotype was introduced (Song et al., 2017) , evolved, and became the dominant strain.
T184 26987-27148 Sentence denotes Furthermore, because the population lacked antibody protection, the new genotype spread rapidly and caused the high incidence of RSV-A in 2014-2015 in Guangzhou.
T185 27149-27355 Sentence denotes Combined with the monthly distribution by site, we believe that the epidemic peaks in Zhu Jiang Hospital and Guangzhou Institute of Respiratory Diseases in 2014 reflected the prevalence of the new genotype.
T186 27356-27608 Sentence denotes Although Zou et al. (2016) also investigated the evolution and transmission of RSV-A in Guangdong in 2008-2015, the present study is the first to report the introduction, evolution, and transmission of the new ON1 genotype in Guangzhou, southern China.
T187 27609-27725 Sentence denotes Further studies should be conducted to reveal the mechanisms behind the emergence of new genotypes and RSV epidemic.
T188 27726-27911 Sentence denotes In conclusion, this study investigated the molecular epidemiological characteristics of RSV and its genotypes in children and adult patients with ARI in southern China during 2011-2016.
T189 27912-28068 Sentence denotes The findings may have significance in guiding policy-making for RSV prevention and control, and may provide important information for RSV variation studies.
T190 28069-28287 Sentence denotes All studies involving human participants were approved by the Medical Ethics Review Board of Zhongshan School of Medicine, Sun Yat-sen University, in accordance with the guidelines for the protection of human subjects.
T191 28288-28472 Sentence denotes Written informed consent was obtained from all participants or their guardians after being informed about the aims of the research and the right to keep their information confidential.