Detection and clinical analysis of human coronavirus infection with acute respiratory tract infection in children in the Xiamen area, China, in 2021-2023

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This study investigated human coronavirus (HCoV) infection among 15,283 children hospitalized with acute respiratory tract infections in Xiamen, China from January 2021 to June 2023, using real-time PCR on nasopharyngeal samples for 13 respiratory pathogens and then analyzing clinical features in HCoV-only cases. HCoV positivity was reported for 8,624 children overall, with an HCoV detection rate of 0.96% (147/15,283) and the highest monthly detection in November; among 147 HCoV-positive cases, 80 were HCoV-only and most commonly presented with cough, fever, and wheezing. Compared with RSV-only infections (n=103), wheezing was more frequent in the RSV group, while other manifestations, complication rates, and need for mechanical ventilation did not differ significantly. The paper’s main caveats include its reliance on hospitalized children from a single center and its preprint status (not peer reviewed). This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract Purpose:To investigate human coronavirus (HCoV) infection with acute respiratory tract infection in children in the Xiamen area, China, and to analyze the clinical features of HCoV infection in children. Methods: A total of 15 283 children with acute respiratory tract infection were hospitalized in Xiamen City Children's Hospital from January 2021 to June 2023. Nasopharyngeal swabs from these children were assessed for the presence 13 respiratory tract-associated viruses, namely, Influenza A virus, adenovirus, bocavirus, rhinovirus, human coronavirus, influenza A virus H1N1, parainfluenza virus, chlamydia, metapneumovirus, influenza B virus, Mycoplasma pneumoniae, respiratory syncytial virus (RSV), and seasonal H3N2 virus using real-time fluorescence quantitative PCR. The clinical symptoms and signs of HCoV-positive children were analyzed and compared with those of RSV-infected children hospitalized during the same period. Results: (1) Of the 15 283 children with acute respiratory infections, 8624 were positive for HCoV.(2) The HCoV detection rate was 0.87% (54/6230) during 2021, 0.82% (53/6439) during 2022, and 1.53% (40/2612) during 2023. The HCoV detection rates (%) for January to December were 0.98, 0.86, 0.83, 0.96, 0.67, 0.57, 0.66, 0.98, 1.02, 1.66, 1.89 and 1.23, respectively.(3) Eighty cases of acute respiratory tract infection with HCoV alone were hospitalized, including 33 cases of bronchopneumonia, 23 cases of acute bronchitis, 10 of acute tonsillitis, 10 of acute tonsillitis, and 4 of acute laryngitis.(4) The common clinical manifestations of HCoV-only infection were cough (72 cases), fever (64 cases), and wheezing (23 cases).(5) The proportion of wheezing in the RSV group was significantly higher than that in the HCoV group (P<0.05), but there were no significant differences observed in other clinical manifestations, the incidence of complications, and proportion of cases requiring mechanical ventilation between HCoV group and 103 RSV infected children (P>0.05). Conclusion: Between January 2021 and June 2023, the detection rate of HCoV in Xiamen was 0.96%. The clinical manifestations and severity of acute respiratory tract infections due to HCoV were similar to those with respiratory syncytial virus infection.
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Detection and clinical analysis of human coronavirus infection with acute respiratory tract infection in children in the Xiamen area, China, in 2021-2023 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Detection and clinical analysis of human coronavirus infection with acute respiratory tract infection in children in the Xiamen area, China, in 2021-2023 Dequan Su, Yong jun Xu, Jinqiang Zhang, Pingping Ye, Chunmei Ou, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4183074/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose:To investigate human coronavirus (HCoV) infection with acute respiratory tract infection in children in the Xiamen area, China, and to analyze the clinical features of HCoV infection in children. Methods: A total of 15 283 children with acute respiratory tract infection were hospitalized in Xiamen City Children's Hospital from January 2021 to June 2023. Nasopharyngeal swabs from these children were assessed for the presence 13 respiratory tract-associated viruses, namely, Influenza A virus, adenovirus, bocavirus, rhinovirus, human coronavirus, influenza A virus H1N1, parainfluenza virus, chlamydia, metapneumovirus, influenza B virus, Mycoplasma pneumoniae, respiratory syncytial virus (RSV), and seasonal H3N2 virus using real-time fluorescence quantitative PCR. The clinical symptoms and signs of HCoV-positive children were analyzed and compared with those of RSV-infected children hospitalized during the same period. Results:(1) Of the 15 283 children with acute respiratory infections, 8624 were positive for HCoV.(2) The HCoV detection rate was 0.87% (54/6230) during 2021, 0.82% (53/6439) during 2022, and 1.53% (40/2612) during 2023. The HCoV detection rates (%) for January to December were 0.98, 0.86, 0.83, 0.96, 0.67, 0.57, 0.66, 0.98, 1.02, 1.66, 1.89 and 1.23, respectively.(3) Eighty cases of acute respiratory tract infection with HCoV alone were hospitalized, including 33 cases of bronchopneumonia, 23 cases of acute bronchitis, 10 of acute tonsillitis, 10 of acute tonsillitis, and 4 of acute laryngitis.(4) The common clinical manifestations of HCoV-only infection were cough (72 cases), fever (64 cases), and wheezing (23 cases).(5) The proportion of wheezing in the RSV group was significantly higher than that in the HCoV group (P<0.05), but there were no significant differences observed in other clinical manifestations, the incidence of complications, and proportion of cases requiring mechanical ventilation between HCoV group and 103 RSV infected children (P>0.05). Conclusion: Between January 2021 and June 2023, the detection rate of HCoV in Xiamen was 0.96%. The clinical manifestations and severity of acute respiratory tract infections due to HCoV were similar to those with respiratory syncytial virus infection. Health sciences/Health care/Public health Health sciences/Diseases/Infectious diseases/Influenza virus Figures Figure 1 Introduction Significant threats to human health have been posed by severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and the novel coronavirus (SARS-Cov-2) in 2019.[1-3] In contrast, four other human coronaviruses (HCoVs), namely, 229E, HKU1, NL63, and OC43, have been circulating globally but generally with low mortality rates.[4] Infection with these four HCoVs is usually associated with the symptoms of common colds rather gastrointestinal symptoms, and can cause severe disease in both children and adults, requiring hospitalization due to bronchitis, bronchiolitis, and pneumonia.[5] The presence of these four HCoVs is often underestimated due to the relatively mild course of disease in most healthy individuals[6] and thus the current understanding of the epidemiology of HCoV is very limited. We, therefore, assessed the rates of HCoV infection in children with acute respiratory tract infection hospitalized in Xiamen City Children's Hospital between January 2021 and June 2023. The clinical manifestations of HCoV-positive hospitalized cases were analyzed and compared with those of patients hospitalized with RSV infections during the same period to explore the role of HCoV infection in children with acute respiratory tract infection and its clinical characteristics. Subjects and Methods From January 2020 to June 2023, a total of 15 283 children were diagnosed with acute respiratory tract infection, including 8724 males and 6559 females. The youngest was 0.5 months old and the oldest was 15 years old. A total of 6230 cases occurred during 2020, 6439 during 2021, and 2612 during 2023. The criteria for diagnosis followed those of Zhufutang Practical Pediatrics, 7th edition, and included a WBC count of ≤12.0× 10 9/L.[7]. The inclusion criterion for cases of HCoV-only infection was the presence of only HCoV positivity in 13 tests for various respiratory tract pathogens. The exclusion criteria were: (1) children with severe immune deficiency or under treatment with relevant immunosuppressants;(2) children with positive blood or sputum bacterial culture during hospitalization;(3) children with serum antibody titers ≥1∶160, change in successive Mycoplasma pneumoniae IgM antibody tests from negative to positive or a four-fold increase in the antibody titer;(4) patients definitely diagnosed as being infected with other pathogens. The studies involving human participants were reviewed and approved by Ethical committee of Children Hospital of Xiamen(XMSETYY-2022-123). Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.We confrmed that all methods were performed in accordance with the relevant guidelines and regulations. 2. Virus detection Nasopharyngeal aspirates (0.5 ml) were collected either on the day of hospitalization or the following day. Three milliliters of virus carrier solution were added and the samples were refrigerated (4 ℃) and sent to the Institute of Pathogenic Microbiology Laboratory Department for analysis within 12 h. RT-PCR was used to detect HCoV and other common respiratory viruses, including respiratory syncytial virus (RSV), human rhinovirus (HRV), parainfluenza viruses (PIV) 1-4, influenza A virus, influenza B virus, and influenza C virus, adenovirus, enterovirus, human metapneumovirus, and human bocavirus.The PCR products were analyzed by 2% agarose gel electrophoresis and positive products were sequenced. 3. Statistical analysis The data were analyzed by SPSS 19.0 software (IBM Corp., Armonk, NY, USA). The rate of positive HCoV detection in different age groups and different years, the use of mechanical ventilation in children infected with HCoV and those infected with RSV were compared by ꭓ2 tests, and the differences in common clinical manifestations and the incidence of complications between the HCoV-infected and RSV-infected groups were analyzed by Fisher's exact test. Results 1. Of the 15 283 children with acute respiratory infections, 8624 were found to be positive for viruses. Of these, 147 cases were HCoV-positive, indicating a detection rate of 0.96%. The age of the youngest child infected with HCoV was 3 months and the oldest was 14 years old. Eighty of the 147 cases were found to be infected only with HCoV, while 67 were infected with one or more viruses, and 20 with two or more viruses. In terms of age groups, 11 patients with HCoV infection only were between 0 and <1 years old, while 38 cases (25.85%) fell into the 1-<3 year-old group, 76 cases (51.70%) in the 3-6 year-old group. The differences between the different age groups were found to be significant (ꭓ2 = 23.11,P<0.05)(Table 1). Table 1: Age distribution of children with acute respiratory tract infection infected with HCoV Age (years) Number of cases (%) ꭓ2 P <1 11(7.48) 23.11 <0.05 1-<3 38(25.85) 3-<6 76(51.70) >6 22(14.95) 2. The HCoV detection rates in 2021, 2022. and 2023 were 0.87% (54/6230), 0.82% (53/6439), and 1.53% (40/2612), respectively. The detection rates of HCoV from January to December were 0.98, 0.86, 0.83, 0.96, 0.67, 0.57, 0.66, 0.98, 1.02, 1.66, 0.99, 0.09, 0.0 1.89 and 1.23%, respectively. The HCoV detection rate was higher in autumn and winter, with the highest rate of detection observed in November (1.89%). 3.In terms of the specific HCoV viruses, of the 147 HCoV-positive cases, infection with HCoV-OC43, HCoV-NL63, HCoV-229E, and HCoV-HKU1 was detected in 55 of these cases. OvHCoV was detected most frequently in autumn and winter, with the highest detection rate in November (1.89%). HCoV-OC43, HCoV-NL63, and HCoV-HKU1 were detected most frequently in November, while HCoV-229E was detected most frequently in October.(Figure 1) Figure 1: HCoV detection rates per month 4. Overall, 80 of the hospitalized children were found to have acute respiratory tract infection due to HCoV only. These included 33 cases of bronchopneumonia, 23 of acute bronchitis, 10 of acute tonsillitis, 10 of acute tonsillitis, and 4 of acute laryngitis. The most common clinical manifestations were cough (72 cases), fever (64 cases), wheezing (23 cases), hoarseness (4 cases), throat wheezing (2 cases), and dyspnea (2 cases). The proportion of wheezing in the RSV group was higher than that in the HCoV group, and the difference was statistically significant (P0.05). There were 10 cases with myocardial damage and 2 cases with respiratory failure among the children with HCoV infection alone, while there were 15 cases with myocardial damage and 4 cases with respiratory failure in children infected with only RSV. There was no significant difference in the incidence of complications between the two groups (P>0.05) (Table 2) Table 2: Comparison of the clinical characteristics of HCoV and RSV simplex acute respiratory tract infections Clinical features Simple HCov group (n=80)(%) simplex RSV group (n=132)(%) ꭓ2 P cough 72(90.00) 112(84.85) 1.333 0.248 fever 64(80.00) 98(74.24) 0.916 0.338 breathing 23(28.75) 62(46.97) 6.884 0.009 hoarseness 4(5.00) 10(7.58) 0.536 0.464 laryngeal stridor 2(2.50) 6(4.55) 0.574 0.449 dyspnea 2(2.50) 6(4.55) 0.574 0.449 complications 12(15.00) 22(16.67) 0.103 0.749 mechanical ventilation 0(0) 2(1.52) 1.224 0.669 average hospitalization time 5.63(3.56,7.23) 6.23(3.98,8.12) 0.678 Discussion In this study, 8624 (56.43%) of the total of 15 283 children with acute respiratory tract infection were found to be positive for HCoV, indicating the importance of HCoV in the etiology of respiratory tract infections in children. There are few clinical studies on the epidemiology and symptoms of HCoV in children in China. Although the epidemiological and clinical characteristics of HCoV have not been fully clarified, HCoV-NL63 and HCoV-HKU1 represent common viruses causing respiratory tract infections in children.[8-9] The detection rate of HCoV in patients with respiratory tract infection in China is 1-10.3%, with variations due to the detection methods used in different centers and the age composition of patients.[10-11]In this study, 8624 (56.43%) of 15 283 children with acute respiratory tract infection were found to be positive for respiratory tract viruses, of which 147 were positive for HCoV, indicating a detection rate of 0.96%. It was found that the HCoV infection rate in children with respiratory tract infection was lower than that in adults, and that infection was higher in the 0-<1 year-old and 1-<3 year-old groups than that in the 3-6 year-old groups, suggesting that the rate of HCoV detection in children under 3 years old was higher. The findings of the study indicated that the rate of HCoV detection differed according to season, being highest during November (1.89%). This is similar to the results of a study conducted in Beijing between 2007 and 2015. The authors of the study monitored the HCoV infection rates continuously for eight years, finding that infection rates were higher in winter than in in other seasons.[7] A 5-year epidemiological study by Zhou Yanqiu et al. conducted in Shanghai also observed higher rates of HCoV detection in patients with acute respiratory tract infection during the winter.[12] A study found a 70% mixed HCoV infection rate in children under 6 years old [13], while an epidemiological survey in Beijing observed a mixed infection rate of 67.3% [7]. In this study, 67 of 140 children were found to be co-infected with other viruses, with a mixed infection rate of 47.85%. Both domestic and foreign studies found that children with HCoV had a high mixed infection rate, and it is recommended that clinicians should be aware of this. In the present study, the detection rate of HCoV-only infection was 54.42%, while many patients were found to be infected with other viruses or bacteria in addition to HCoV. This makes it difficult to assess the contribution of HCoV to disease severity in these cases. Previous studies have considered that the respiratory tract infection symptoms caused by HCoV infection are relatively mild, and that in the presence of co-infection with other viruses, HCoV does not aggravate the clinical symptoms and final prognosis of the children [14]. In this study, the clinical symptoms and signs of pure HCoV infection were analyzed in detail and compared with those of children with pure RSV respiratory tract infection. In our study, the most common disease associated with pure HCoV infection was bronchopneumonia, followed by bronchitis and acute tonsillitis, indicating that the virus mainly invades the respiratory tract and may cause lower respiratory tract infection. This is similar to the findings of previous studies both at home and abroad [7.15]. The main clinical manifestations of respiratory tract infection caused by HCoV infection were cough and fever, and 23% of patients presented with wheezing, which is also consistent with previous reports [7.15]. RSV is the causative agent of both intestinal and respiratory tract infections in children, especially in infants under 1 year of age. In this study, we compared the clinical characteristics of children infected with HCoV alone with those of children hospitalized with RSV alone during the same period. It was found that the clinical symptoms of patients in the two groups were similar. The proportion of cases with wheezing in the RSV group was higher than that in the HCoV group, while no significant differences were observed in other clinical symptoms. The incidence of dyspnea and mechanical ventilation in the RSV group was lower than that in the RSV group. However, the incidence of laryngeal chirping, hoarseness, and complications in the HCoV group was lower than that in the RSV group, suggesting that HCoV-infected patients were less likely to develop severe respiratory tract infection than those infected with RSV, which may be related to the younger age of patients with RSV infections. Among the 147 HCoV positive cases in this study, HCoV-OC43 accounted for the greatest proportion, namely, 37.42%. A domestic coronavirus epidemiological study in Shanghai also found that HCoV-OC43 was the most common viral strain.[16] HCoV-OC43 infection is mostly manifested as a respiratory tract infection in adults, although some patients can also experience nervous system gastrointestinal symptoms.[17-18] In infants, HCoV-NL63 infection can manifest with severe lower respiratory tract symptoms, and it was reported than an elderly patient in Canada died five days after the onset of infection, suggesting that the virus may be serious in certain populations.[19] In conclusion, HCoV is a common pathogen associated with respiratory tract infections in children. The high proportion of HCoV infection in children under 3 years of age, as well as the high proportion of HCoV co-infection with other viruses or bacteria, and the high HCoV detection rates during the winter all require the attention of clinicians. The clinical symptoms and severity of childhood HCoV infection resemble those of RSV infection, although the incidence of severe disease is lower. Nevertheless, the present study was conducted in a single center, and further multicenter data is needed to fully understand the clinical characteristics of HCoV infection. Declarations Ethics approval and consent to participate The studies involving human participants were reviewed and approved by Ethical committee of Children Hospital of Xiamen(XMSETYY-2022-123). Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.We confrmed that all methods were performed in accordance with the relevant guidelines and regulations. Consent for publication Not applicable. Availability of data and materials All data generated or analysed during this study are included in this published article. Competing interests The authors declare that they have no competing interests. FUNDING Xiamen Children's Hospital Clinical Key Specialized Training Project (No: XE2022-PNPY-B003). AUTHOR CONTRIBUTIONS SD and XY contributed to the data analysis and drafted the manuscript. ZZ and SW contributed to the study design and critically revised the manuscript for important intellectual content. ZJ, YP, OC and LX contributed to the patient follow-up and data collection. All authors have approved the final version of the manuscript to be published. Each author participated sufficiently in the work to be responsible for the content. Acknowledgements Not applicable. References De Groot RJ, Baker SC, Barric RS, et al. Middle East respiratory syndrome coronavirus (MERS CoV): announcement of the Coronavirus Study Group J Virol 2013; 87 (14): 7790–2 Xiong LJ, Zhou MY, He XQ, et al. The Role of Human Coronavirus Infection in Pediatric Acute Gastroenteritis. Pediatr Infect Dis J. 2020;39(7):645–649. Ochani R, Asad A, Yasmin F, et al. COVID-19 panel: from origins to outcomes A comprehensive review of virtual pathologies, clinical presentations, diagnostic evaluation, and management Infez Med. 2021; 29 (1): 20–36 Vabret A, Mourez T, Dina J, et al. Human coronavirus NL63, France Emergency Effect Dis 2005; 11 (8): 1225-9 Talbot HK, Crowe JE Jr, Edwards KM, et al; New Vaccine Surveillance Network. Coronavirus infection and hospitalizations for acute respiratory Illness in young children J Med Virol 2009; 81 (5): 853–6 Esper F, Ou Z, Huang YT. Human coronavirus are uncommon in patients with gastrointestinal illness J Clin Virol 2010; 48 (2): 131–3 Doi: 10.1016/j.jcv.2010.03.007 Epub 2010 Apr 1 Xie Z D, Xiao Y, Liu C Y, et al. Surveillance of viral etiology of acute lower respiratory tract infection in children from 2007 to 2010 [J]. Chinese Journal of Pediatrics, 2011, 49 (10): 745–749. Liu D, Chen C, Chen D, Zhu A, et al. Mouse models suitable to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2 Proc Natl Acad Sci U S A. 2023; 120 (4): e22202820120 Kesheh MM, Hosseini P, Soltani S, et al. An overview on the seven pathogenic human coronaviruses Rev Med Virol 2022; 32 (2): e2282 Xu G, Xiong Y, Gong T, et al. Analysis of human coronavirus NL63 infection and genetic characteristics in Nanchang City from 2010 to 2018 [J]. Journal of Modern Preventive Medicine, 2022, 49 (01):134–137. Wang Y, Huang Y F, Wang Z D, et al. Epidemiological analysis of a cluster epidemic of upper respiratory tract infection caused by human coronavirus NL63 in Shenzhen, Guangdong Province in 2020 [J]. Disease Surveillance, 2021, 36 (11):1212–1216. Zhou Yanqiu, Teng Zheng, Wang Jiayu, et al. Analysis of human coronavirus infection in acute respiratory tract infection cases in Shanghai City from 2015 to 2019 [J]. Disease Surveillance, 2021, 07:653–658. Jeff š Nik M, Ur š I č T, Zigon N, et al Coronavirus infections in hospitalized pediatric patients with acute respiratory tract disease BMC Effect Dis 2012; 12: 365 Shah MM, Winn A, Dahl RM, et al. Seasonality of Common Human Coronavirus, United States, 2014–20211 Emergency Effect Dis 2022; 28 (10): 1970–1976 Alamri KA, Farrag MA, Aziz IM, et al. Prevalence of Human Coronavirus in Children and Physiological Analysis of HCoV-OC43 during 2016–2022 in Riyadh, Saudi Arabia. Viruses 2022; 14 (12): 2592 Yang Yijing, Hu Yunwen. Molecular epidemiology of Shanghai human coronavirus OC43 from 2009 to 2016 [J]. Chinese Journal of Preventive Medicine, 2018, 52 (1): 55–61. Dorendorf A, Bachmann I, Spiegel M, et al., Rapid detection of human coronavirus NL63 by isothermal reverse transcription recombine polymerase amplification J Clin Virol Plus 2022; 2 (4): 100115 Van der Hoek L, Pyrc K, Berkhout B. Human coronavirus NL63, a new respiratory virus FEMS Microbiol Rev. 2006; 30 (5): 760–73 Bastien N, Anderson K, Hart L, et al. Human coronavirus NL63 infection in Canada J Infect Dis 2005; 191 (4): 503–6 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4183074","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":291041401,"identity":"61fb4c44-57f5-42ec-8a34-dd2c6ff43ff3","order_by":0,"name":"Dequan Su","email":"","orcid":"","institution":"Xiamen Children's Hospital/Children's Hospital of Fudan University Xiamen Branch","correspondingAuthor":false,"prefix":"","firstName":"Dequan","middleName":"","lastName":"Su","suffix":""},{"id":291041403,"identity":"94873751-1bec-4043-be24-498684c79969","order_by":1,"name":"Yong jun Xu","email":"","orcid":"","institution":"Xiamen Children's 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08:46:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":511838,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4183074/v1/9d184723-6f6a-482e-b884-c53aa3f62ffb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Detection and clinical analysis of human coronavirus infection with acute respiratory tract infection in children in the Xiamen area, China, in 2021-2023","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSignificant threats to human health have been posed by severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and the novel coronavirus (SARS-Cov-2) in 2019.[1-3] In contrast, four other human coronaviruses (HCoVs), namely, 229E, HKU1, NL63, and OC43, have been circulating globally but generally with low mortality rates.[4]\u003c/p\u003e\n\u003cp\u003eInfection with these four HCoVs is usually associated with the symptoms of common colds rather gastrointestinal symptoms, and can cause severe disease in both children and adults, requiring hospitalization due to bronchitis, bronchiolitis, and pneumonia.[5] The presence of these four HCoVs is often underestimated due to the relatively mild course of disease in most healthy individuals[6] and thus the current understanding of the epidemiology of HCoV is very limited. We, therefore, assessed the rates of HCoV infection in children with acute respiratory tract infection hospitalized in Xiamen City Children\u0026apos;s Hospital between January 2021 and June 2023. The clinical manifestations of HCoV-positive hospitalized cases were analyzed and compared with those of patients hospitalized with RSV infections during the same period to explore the role of HCoV infection in children with acute respiratory tract infection and its clinical characteristics.\u003c/p\u003e"},{"header":"Subjects and Methods","content":"\u003cp\u003eFrom January 2020 to June 2023, a total of 15 283 children were diagnosed with acute respiratory tract infection, including 8724 males and 6559 females. The youngest was 0.5 months old and the oldest was 15 years old. \u0026nbsp;A total of 6230 cases occurred during 2020, 6439 during 2021, and 2612 during 2023. The criteria for diagnosis followed those of Zhufutang Practical Pediatrics, 7th edition, and included a WBC count of \u0026le;12.0\u0026times; 10 9/L.[7].\u003c/p\u003e\n\u003cp\u003eThe inclusion criterion for cases of HCoV-only infection was the presence of only HCoV positivity in 13 tests for various respiratory tract pathogens. The exclusion criteria were: (1) children with severe immune deficiency or under treatment with relevant immunosuppressants;(2) children with positive blood or sputum bacterial culture during hospitalization;(3) children with serum antibody titers \u0026ge;1∶160, change in successive Mycoplasma pneumoniae IgM antibody tests from negative to positive or a four-fold increase in the antibody titer;(4) patients definitely diagnosed as being infected with other pathogens.\u003c/p\u003e\n\u003cp\u003eThe studies involving human participants were reviewed and approved by Ethical committee of Children Hospital of Xiamen(XMSETYY-2022-123). Written informed consent to participate in this study was provided by the participants\u0026rsquo; legal guardian/next of kin.We confrmed that all methods were performed in accordance with the relevant guidelines and regulations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. Virus detection\u003c/p\u003e\n\u003cp\u003eNasopharyngeal aspirates (0.5 ml) were collected either on the day of hospitalization or the following day. Three milliliters of virus carrier solution were added and the samples were refrigerated (4 ℃) and sent to the Institute of Pathogenic Microbiology Laboratory Department for analysis within 12 h. RT-PCR was used to detect HCoV and other common respiratory viruses, including respiratory syncytial virus (RSV), human rhinovirus (HRV), parainfluenza viruses (PIV) 1-4, influenza A virus, influenza B virus, and influenza C virus, adenovirus, enterovirus, human metapneumovirus, and human bocavirus.The PCR products were analyzed by 2% agarose gel electrophoresis and positive products were sequenced.\u003c/p\u003e\n\u003cp\u003e3. Statistical analysis\u003c/p\u003e\n\u003cp\u003eThe data were analyzed by SPSS 19.0 software (IBM Corp., Armonk, NY, USA). The rate of positive HCoV detection in different age groups and different years, the use of mechanical ventilation in children infected with HCoV and those infected with RSV were compared by ꭓ2 tests, and the differences in common clinical manifestations and the incidence of complications between the HCoV-infected and RSV-infected groups were analyzed by Fisher\u0026apos;s exact test.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e1. Of the 15 283 children with acute respiratory infections, 8624 were found to be positive for viruses. Of these, 147 cases were HCoV-positive, indicating a detection rate of 0.96%. The age of the youngest child infected with HCoV was 3 months and the oldest was 14 years old. Eighty of the 147 cases were found to be infected only with HCoV, while 67 were infected with one or more viruses, and 20 with two or more viruses. In terms of age groups, 11 patients with HCoV infection only were between 0 and \u0026lt;1 years old, while 38 cases (25.85%) fell into the 1-\u0026lt;3 year-old group, 76 cases (51.70%) in the 3-\u0026lt;6 year-old group, and 22 cases (14.97%) in the \u0026gt;6 year-old group. The differences between the different age groups were found to be significant (ꭓ2 = 23.11,P\u0026lt;0.05)(Table 1).\u003c/p\u003e\n\u003cp\u003eTable 1: Age distribution of children with acute respiratory tract infection infected with HCoV\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"468\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.83511777301927%\" valign=\"top\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.1220556745182%\" valign=\"top\"\u003e\n \u003cp\u003eNumber of cases (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.130620985010708%\" valign=\"top\"\u003e\n \u003cp\u003eꭓ2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.91220556745182%\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.83511777301927%\" valign=\"top\"\u003e\n \u003cp\u003e<1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.1220556745182%\" valign=\"top\"\u003e\n \u003cp\u003e11(7.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.130620985010708%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e23.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.91220556745182%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e<0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.42857142857143%\" valign=\"top\"\u003e\n \u003cp\u003e1-<3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.57142857142857%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;38(25.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.42857142857143%\" valign=\"top\"\u003e\n \u003cp\u003e3-<6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.57142857142857%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;76(51.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.42857142857143%\" valign=\"top\"\u003e\n \u003cp\u003e>6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.57142857142857%\" valign=\"top\"\u003e\n \u003cp\u003e22(14.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. The HCoV detection rates in 2021, 2022. and 2023 were 0.87% (54/6230), 0.82% (53/6439), and 1.53% (40/2612), respectively. The detection rates of HCoV from January to December were 0.98, 0.86, 0.83, 0.96, 0.67, 0.57, 0.66, 0.98, 1.02, 1.66, 0.99, 0.09, 0.0 1.89 and 1.23%, respectively. The HCoV detection rate was higher in autumn and winter, with the highest rate of detection observed in November (1.89%).\u003c/p\u003e\n\u003cp\u003e3.In terms of the specific HCoV viruses, of the 147 HCoV-positive cases, infection with HCoV-OC43, HCoV-NL63, HCoV-229E, and HCoV-HKU1 was detected in 55 of these cases. OvHCoV was detected most frequently in autumn and winter, with the highest detection rate in November (1.89%). HCoV-OC43, HCoV-NL63, and HCoV-HKU1 were detected most frequently in November, while HCoV-229E was detected most frequently in October.(Figure 1)\u003c/p\u003e\n\u003cp\u003eFigure 1: HCoV detection rates per month\u003c/p\u003e\n\u003cp\u003e4. Overall, 80 of the hospitalized children were found to have acute respiratory tract infection due to HCoV only. These included 33 cases of bronchopneumonia, 23 of acute bronchitis, 10 of acute tonsillitis, 10 of acute tonsillitis, and 4 of acute laryngitis. The most common clinical manifestations were cough (72 cases), fever (64 cases), wheezing (23 cases), hoarseness (4 cases), throat wheezing (2 cases), and dyspnea (2 cases). The proportion of wheezing in the RSV group was higher than that in the HCoV group, and the difference was statistically significant (P\u0026lt;0.05). No significant differences were found for other clinical manifestations (P\u0026gt;0.05). There were 10 cases with myocardial damage and 2 cases with respiratory failure among the children with HCoV infection alone, while there were 15 cases with myocardial damage and 4 cases with respiratory failure in children infected with only RSV. There was no significant difference in the incidence of complications between the two groups (P\u0026gt;0.05) (Table 2)\u003c/p\u003e\n\u003cp\u003eTable 2: Comparison of the clinical characteristics of HCoV and RSV simplex acute respiratory tract infections\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"552\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003eClinical features\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.71014492753623%\" valign=\"top\"\u003e\n \u003cp\u003eSimple HCov group\u003c/p\u003e\n \u003cp\u003e(n=80)(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003esimplex RSV group\u003c/p\u003e\n \u003cp\u003e(n=132)(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.22463768115942%\" valign=\"top\"\u003e\n \u003cp\u003eꭓ2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.94927536231884%\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003ecough\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.71014492753623%\" valign=\"top\"\u003e\n \u003cp\u003e72(90.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003e112(84.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.22463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e1.333\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.94927536231884%\" valign=\"top\"\u003e\n \u003cp\u003e0.248\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003efever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.71014492753623%\" valign=\"top\"\u003e\n \u003cp\u003e64(80.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003e98(74.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.22463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e0.916\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.94927536231884%\" valign=\"top\"\u003e\n \u003cp\u003e0.338\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003ebreathing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.71014492753623%\" valign=\"top\"\u003e\n \u003cp\u003e23(28.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003e62(46.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.22463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e6.884\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.94927536231884%\" valign=\"top\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003ehoarseness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.71014492753623%\" valign=\"top\"\u003e\n \u003cp\u003e4(5.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003e10(7.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.22463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e0.536\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.94927536231884%\" valign=\"top\"\u003e\n \u003cp\u003e0.464\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003elaryngeal stridor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.71014492753623%\" valign=\"top\"\u003e\n \u003cp\u003e2(2.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003e6(4.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.22463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.94927536231884%\" valign=\"top\"\u003e\n \u003cp\u003e0.449\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003edyspnea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.71014492753623%\" valign=\"top\"\u003e\n \u003cp\u003e2(2.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003e6(4.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.22463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.94927536231884%\" valign=\"top\"\u003e\n \u003cp\u003e0.449\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003ecomplications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.71014492753623%\" valign=\"top\"\u003e\n \u003cp\u003e12(15.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003e22(16.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.22463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e0.103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.94927536231884%\" valign=\"top\"\u003e\n \u003cp\u003e0.749\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003emechanical ventilation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.71014492753623%\" valign=\"top\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003e2(1.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.22463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e1.224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.94927536231884%\" valign=\"top\"\u003e\n \u003cp\u003e0.669\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003eaverage hospitalization time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.71014492753623%\" valign=\"top\"\u003e\n \u003cp\u003e5.63(3.56,7.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.557971014492754%\" valign=\"top\"\u003e\n \u003cp\u003e6.23(3.98,8.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.22463768115942%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.94927536231884%\" valign=\"top\"\u003e\n \u003cp\u003e0.678\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, 8624 (56.43%) of the total of 15 283 children with acute respiratory tract infection were found to be positive for HCoV, indicating the importance of HCoV in the etiology of respiratory tract infections in children. There are few clinical studies on the epidemiology and symptoms of HCoV in children in China. Although the epidemiological and clinical characteristics of HCoV have not been fully clarified, HCoV-NL63 and HCoV-HKU1 represent common viruses causing respiratory tract infections in children.[8-9] The detection rate of HCoV in patients with respiratory tract infection in China is 1-10.3%, with variations due to the detection methods used in different centers and the age composition of patients.[10-11]In this study, 8624 (56.43%) of 15 283 children with acute respiratory tract infection were found to be positive for respiratory tract viruses, of which 147 were positive for HCoV, indicating a detection rate of 0.96%. It was found that the HCoV infection rate in children with respiratory tract infection was lower than that in adults, and that infection was higher in the 0-\u0026lt;1 year-old and 1-\u0026lt;3 year-old groups than that in the 3-\u0026lt;6 year-old and \u0026gt;6 year-old groups, suggesting that the rate of HCoV detection in children under 3 years old was higher.\u003c/p\u003e\n\u003cp\u003eThe findings of the study indicated that the rate of HCoV detection differed according to season, being highest during November (1.89%). This is similar to the results of a study conducted in Beijing between 2007 and 2015. The authors of the study monitored the HCoV infection rates continuously for eight years, finding that infection rates were higher in winter than in in other seasons.[7] A 5-year epidemiological study by Zhou Yanqiu et al. conducted in Shanghai also observed higher rates of HCoV detection in patients with acute respiratory tract infection during the winter.[12]\u003c/p\u003e\n\u003cp\u003eA study found a 70% mixed HCoV infection rate in children under 6 years old [13], while an epidemiological survey in Beijing observed a mixed infection rate of 67.3% [7]. In this study, 67 of 140 children were found to be co-infected with other viruses, with a mixed infection rate of 47.85%. Both domestic and foreign studies found that children with HCoV had a high mixed infection rate, and it is recommended that clinicians should be aware of this.\u003c/p\u003e\n\u003cp\u003eIn the present study, the detection rate of HCoV-only infection was 54.42%, while many patients were found to be infected with other viruses or bacteria in addition to HCoV. This makes it difficult to assess the contribution of HCoV to disease severity in these cases. Previous studies have considered that the respiratory tract infection symptoms caused by HCoV infection are relatively mild, and that in the presence of co-infection with other viruses, HCoV does not aggravate the clinical symptoms and final prognosis of the children [14]. In this study, the clinical symptoms and signs of pure HCoV infection were analyzed in detail and compared with those of children with pure RSV respiratory tract infection. In our study, the most common disease associated with pure HCoV infection was bronchopneumonia, followed by bronchitis and acute tonsillitis, indicating that the virus mainly invades the respiratory tract and may cause lower respiratory tract infection. This is similar to the findings of previous studies both at home and abroad [7.15]. The main clinical manifestations of respiratory tract infection caused by HCoV infection were cough and fever, and 23% of patients presented with wheezing, which is also consistent with previous reports [7.15].\u003c/p\u003e\n\u003cp\u003eRSV is the causative agent of both intestinal and respiratory tract infections in children, especially in infants under 1 year of age. In this study, we compared the clinical characteristics of children infected with HCoV alone with those of children hospitalized with RSV alone during the same period. It was found that the clinical symptoms of patients in the two groups were similar. The proportion of cases with wheezing in the RSV group was higher than that in the HCoV group, while no significant differences were observed in other clinical symptoms. The incidence of dyspnea and mechanical ventilation in the RSV group was lower than that in the RSV group. However, the incidence of laryngeal chirping, hoarseness, and complications in the HCoV group was lower than that in the RSV group, suggesting that HCoV-infected patients were less likely to develop severe respiratory tract infection than those infected with RSV, which may be related to the younger age of patients with RSV infections.\u003c/p\u003e\n\u003cp\u003eAmong the 147 HCoV positive cases in this study, HCoV-OC43 accounted for the greatest proportion, namely, 37.42%. A domestic coronavirus epidemiological study in Shanghai also found that HCoV-OC43 was the most common viral strain.[16] HCoV-OC43 infection is mostly manifested as a respiratory tract infection in adults, although some patients can also experience nervous system gastrointestinal symptoms.[17-18] In infants, HCoV-NL63 infection can manifest with severe lower respiratory tract symptoms, and it was reported than an elderly patient in Canada died five days after the onset of infection, suggesting that the virus may be serious in certain populations.[19]\u003c/p\u003e\n\u003cp\u003eIn conclusion, HCoV is a common pathogen associated with respiratory tract infections in children. The high proportion of HCoV infection in children under 3 years of age, as well as the high proportion of HCoV co-infection with other viruses or bacteria, and the high HCoV detection rates during the winter all require the attention of clinicians. The clinical symptoms and severity of childhood HCoV infection resemble those of RSV infection, although the incidence of severe disease is lower. Nevertheless, the present study was conducted in a single center, and further multicenter data is needed to fully understand the clinical characteristics of HCoV infection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving human participants were reviewed and approved by Ethical committee of Children Hospital of Xiamen(XMSETYY-2022-123). Written informed consent to participate in this study was provided by the participants\u0026rsquo; legal guardian/next of kin.We confrmed that all methods were performed in accordance with the relevant guidelines and regulations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXiamen Children\u0026apos;s Hospital Clinical Key Specialized Training Project\u0026nbsp;(No: XE2022-PNPY-B003).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSD\u0026nbsp;and\u0026nbsp;XY\u0026nbsp;contributed to the data analysis and drafted the manuscript.\u0026nbsp;ZZ\u0026nbsp;and\u0026nbsp;SW\u0026nbsp;contributed to the study design and critically revised the manuscript for important intellectual content.\u0026nbsp;ZJ,\u0026nbsp;YP,\u0026nbsp;OC\u0026nbsp;and\u0026nbsp;LX\u0026nbsp;contributed to the patient follow-up and data collection. All authors have approved the final version of the manuscript to be published. Each author participated sufficiently in the work to be responsible for the content.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDe Groot RJ, Baker SC, Barric RS, et al. Middle East respiratory syndrome coronavirus (MERS CoV): announcement of the Coronavirus Study Group J Virol 2013; 87 (14): 7790\u0026ndash;2\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiong LJ, Zhou MY, He XQ, et al. The Role of Human Coronavirus Infection in Pediatric Acute Gastroenteritis. Pediatr Infect Dis J. 2020;39(7):645\u0026ndash;649.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOchani R, Asad A, Yasmin F, et al. COVID-19 panel: from origins to outcomes A comprehensive review of virtual pathologies, clinical presentations, diagnostic evaluation, and management Infez Med. 2021; 29 (1): 20\u0026ndash;36\u003c/li\u003e\u003cli\u003eVabret A, Mourez T, Dina J, et al. Human coronavirus NL63, France Emergency Effect Dis 2005; 11 (8): 1225-9\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTalbot HK, Crowe JE Jr, Edwards KM, et al; New Vaccine Surveillance Network. Coronavirus infection and hospitalizations for acute respiratory Illness in young children J Med Virol 2009; 81 (5): 853\u0026ndash;6\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEsper F, Ou Z, Huang YT. Human coronavirus are uncommon in patients with gastrointestinal illness J Clin Virol 2010; 48 (2): 131\u0026ndash;3 Doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jcv.2010.03.007\u003c/span\u003e\u003cspan address=\"10.1016/j.jcv.2010.03.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e Epub 2010 Apr 1\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXie Z D, Xiao Y, Liu C Y, et al. Surveillance of viral etiology of acute lower respiratory tract infection in children from 2007 to 2010 [J]. Chinese Journal of Pediatrics, 2011, 49 (10): 745\u0026ndash;749.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu D, Chen C, Chen D, Zhu A, et al. Mouse models suitable to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2 Proc Natl Acad Sci U S A. 2023; 120 (4): e22202820120\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKesheh MM, Hosseini P, Soltani S, et al. An overview on the seven pathogenic human coronaviruses Rev Med Virol 2022; 32 (2): e2282\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu G, Xiong Y, Gong T, et al. Analysis of human coronavirus NL63 infection and genetic characteristics in Nanchang City from 2010 to 2018 [J]. Journal of Modern Preventive Medicine, 2022, 49 (01):134\u0026ndash;137.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Huang Y F, Wang Z D, et al. Epidemiological analysis of a cluster epidemic of upper respiratory tract infection caused by human coronavirus NL63 in Shenzhen, Guangdong Province in 2020 [J]. Disease Surveillance, 2021, 36 (11):1212\u0026ndash;1216.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou Yanqiu, Teng Zheng, Wang Jiayu, et al. Analysis of human coronavirus infection in acute respiratory tract infection cases in Shanghai City from 2015 to 2019 [J]. Disease Surveillance, 2021, 07:653\u0026ndash;658.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeff š Nik M, Ur š I č T, Zigon N, et al Coronavirus infections in hospitalized pediatric patients with acute respiratory tract disease BMC Effect Dis 2012; 12: 365\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShah MM, Winn A, Dahl RM, et al. Seasonality of Common Human Coronavirus, United States, 2014\u0026ndash;20211 Emergency Effect Dis 2022; 28 (10): 1970\u0026ndash;1976\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlamri KA, Farrag MA, Aziz IM, et al. Prevalence of Human Coronavirus in Children and Physiological Analysis of HCoV-OC43 during 2016\u0026ndash;2022 in Riyadh, Saudi Arabia. Viruses 2022; 14 (12): 2592\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang Yijing, Hu Yunwen. Molecular epidemiology of Shanghai human coronavirus OC43 from 2009 to 2016 [J]. Chinese Journal of Preventive Medicine, 2018, 52 (1): 55\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDorendorf A, Bachmann I, Spiegel M, et al., Rapid detection of human coronavirus NL63 by isothermal reverse transcription recombine polymerase amplification J Clin Virol Plus 2022; 2 (4): 100115\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan der Hoek L, Pyrc K, Berkhout B. Human coronavirus NL63, a new respiratory virus FEMS Microbiol Rev. 2006; 30 (5): 760\u0026ndash;73\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBastien N, Anderson K, Hart L, et al. Human coronavirus NL63 infection in Canada J Infect Dis 2005; 191 (4): 503\u0026ndash;6\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4183074/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4183074/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePurpose:To investigate human coronavirus (HCoV) infection with acute respiratory tract infection in children in the Xiamen area, China, and to analyze the clinical features of HCoV infection in children.\u003c/p\u003e\n\u003cp\u003eMethods: A total of 15 283 children with acute respiratory tract infection were hospitalized in Xiamen City Children's Hospital from January 2021 to June 2023. Nasopharyngeal swabs from these children were assessed for the presence 13 respiratory tract-associated viruses, namely, Influenza A virus, adenovirus, bocavirus, rhinovirus, human coronavirus, influenza A virus H1N1, parainfluenza virus, chlamydia, metapneumovirus, influenza B virus, Mycoplasma pneumoniae, respiratory syncytial virus (RSV), and seasonal H3N2 virus using real-time fluorescence quantitative PCR. The clinical symptoms and signs of HCoV-positive children were analyzed and compared with those of RSV-infected children hospitalized during the same period.\u003c/p\u003e\n\u003cp\u003eResults:(1) Of the 15 283 children with acute respiratory infections, 8624 were positive for HCoV.(2) The HCoV detection rate was 0.87% (54/6230) during 2021, 0.82% (53/6439) during 2022, and 1.53% (40/2612) during 2023. The HCoV detection rates (%) for January to December were 0.98, 0.86, 0.83, 0.96, 0.67, 0.57, 0.66, 0.98, 1.02, 1.66, 1.89 and 1.23, respectively.(3) Eighty cases of acute respiratory tract infection with HCoV alone were hospitalized, including 33 cases of bronchopneumonia, 23 cases of acute bronchitis, 10 of acute tonsillitis, 10 of acute tonsillitis, and 4 of acute laryngitis.(4) The common clinical manifestations of HCoV-only infection were cough (72 cases), fever (64 cases), and wheezing (23 cases).(5) The proportion of wheezing in the RSV group was significantly higher than that in the HCoV group (P\u0026lt;0.05), but there were no significant differences observed in other clinical manifestations, the incidence of complications, and proportion of cases requiring mechanical ventilation between HCoV group and 103 RSV infected children (P\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003eConclusion: Between January 2021 and June 2023, the detection rate of HCoV in Xiamen was 0.96%. The clinical manifestations and severity of acute respiratory tract infections due to HCoV were similar to those with respiratory syncytial virus infection.\u003c/p\u003e","manuscriptTitle":"Detection and clinical analysis of human coronavirus infection with acute respiratory tract infection in children in the Xiamen area, China, in 2021-2023","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-19 17:30:34","doi":"10.21203/rs.3.rs-4183074/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0373c45c-6679-4b42-b583-580f91ef4b6b","owner":[],"postedDate":"April 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":30656075,"name":"Health sciences/Health care/Public health"},{"id":30656076,"name":"Health sciences/Diseases/Infectious diseases/Influenza virus"}],"tags":[],"updatedAt":"2024-08-16T08:38:12+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-19 17:30:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4183074","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4183074","identity":"rs-4183074","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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