This retrospective study analyzed data from 11,399 hospitalized children (≤ 14 years old) presenting with ARTI in two large municipal hospitals over a 7-year period in Guangzhou, China. Given the present study’s duration and large sample size, our results represent an important addition to the evidence base on the epidemiology and clinical manifestations of HCoV. Of the 11,399 patients tested, we found that 489 (4.3%) were HCoV-positive and that the most prevalent strain of HCoV was OC43 (3.0%), followed by 229E (0.6%), NL63 (0.5%), and HKU1 (0.3%). These findings are consistent with the results of other studies around the world [11, 13, 19]. The most common co-infecting pathogens among HCoV-positive patients were Flu A and RSV (Table 1). Other recent studies have also reported that RSV, Flu A, and rhinoviruses are the most common pathogens that co-occur with HCoV, and that co-infection may influence the clinical presentation of HCoV-positive patients [4, 5, 19,20,21].
Consistent with studies conducted in other contexts, including America and Slovenia [16, 20], our results showed that the prevalence of HCoV was highest among patients aged 7–12 months (Fig. 1). This increased vulnerability to respiratory pathogens may be attributable to increased contact with pathogens as infants begin to explore their environment or the waning of maternal antibody levels in infants while the immune system remains underdeveloped [22,23,24].
HCoV is widespread globally and patterns of outbreaks vary according to locations and seasonal factors [4]. Our study found that HCoV prevalence among patients presenting with ARTI in Guangzhou over a 7-year period was highest in the spring and autumn (Fig. 2). This stands in contrast to other studies which find higher prevalence of HCoV infection in winter and spring [16, 20]. We also found different seasonal prevalence patterns for each of the four HCoV strains, with peak frequencies of 229E, NL63, and OC43 occurring mostly in the spring and autumn in Guangzhou, although OC43 had lower peaks appearing in July 2012 and 2013, however (Fig. 2). Other studies conducted in Hong Kong have shown that, while the highest frequencies of NL63 and OC43 cases occurred in autumn and winter during the period 2005–2007 [25], OC43 and HKU1 cases peaked in winter and NL63 prevalence was highest in summer and autumn during the period 2004–2005 [14]. In the United States, 229E, OC43, and HKU1 have been shown to follow different seasonal patterns, with outbreaks of 229E occurring in winter, OC43 in spring and autumn, and HKU1 in summer [20]. Although these seasonal patterns vary between countries and over time, it is apparent across all studies that the prevalence of HCoV among children is lowest in early summer.
Patients with HCoV infections presented a wide spectrum of respiratory symptoms. When we compared the clinical presentations of patients with a single HCoV infection to those with co-infections, we found that abnormal pulmonary rales occurred more frequently in the former group, while fever was more prevalent in the latter (Table 2). The results, therefore, indicate that patients infected with more than one respiratory pathogen are more likely to develop fever. Furthermore, abnormal pulmonary rales were more frequently detected among patients infected with OC43 than those infected with other strains. This suggests that HCoV-OC43 is more closely associated with LRTI. Patients with HCoV-OC43 also had the highest prevalence of broncho-pneumonia and asthma, although this was not significantly higher than among patients with other strains (Table 2). Our results are consistent with the findings of Lee and Storch [13] that HCoV-NL63 and HCoV-OC43 are associated with LRTI in children. However, Kuypers et al. [5] have found that, although HCoV-OC43 may be associated with asthma and some symptoms related to LRTI, other pathogens such as RSV may be more strongly implicated in cases of severe LRTI [26]. Recent studies have also shown that the most prevalent URTI symptoms among HCoV-positive individuals are fever, cough, sore throat, and headache [1, 19], and that LRTI including pneumonia and bronchiolitis also occasionally co-occur with HCoV [1, 5]. However, influenza-like symptoms were uncommon in our sample of HCoV-positive patients in this study.
Our study has several strengths, including its large sample size and long duration. Furthermore, given that few studies to date have simultaneously tested for all four strains of HCoV in ARTI pediatric patients, the present study addresses an important gap in the literature.
This study had some limitations, however. First, selection bias may have occurred due to the lack of healthy subjects without ARTI. Second, collecting biological samples using oropharyngeal swabs may be less reliable for detecting the presence of HCoV and other pathogens than obtaining bronchoalveolar lavage fluid. One advantage of this method, however, was that it is non-invasive and more suitable for routine analysis.
In conclusion, the four strains of HCoV investigated in the present study are common among pediatric patients with ARTI in Guangzhou, China, and are often found alongside other respiratory pathogens. HCoV infection may cause a broad spectrum of symptoms, ranging from common cold-like symptoms, to influenza-like symptoms, asthma, and even pneumonia. The present study underscores the importance of HCoV infection in the etiology of pediatric ARTI, its relevance in clinical practice, and the pressing need to improve surveillance and detection in developing country contexts.