Background
Respiratory virus is well known to cause significant morbidity and mortality in pediatric populations [
1‐
3]; especially in neonates or very young infants; in patients with chronic heart or lung disease; and in the immunosuppressed [
4]. Numerous studies have described viral respiratory infection (VRI) as a leading cause of illness and death in people of all ages [
5]. The most frequent community-acquired respiratory viruses are respiratory syncytial virus (RSV), parainfluenza virus (PIV), human influenza virus (IV), human metapneumovirus (HMPV), and human rhinovirus (HRV) in the respiratory infection patients, hematopoietic cell transplant recipients, and hematologic malignancy patients with an immunocompromised status [
3,
6‐
9].
Most observations of human respiratory virus carriage are derived from medical surveillance. As VRIs can often be mild or asymptomatic and typically go undocumented, individuals may not seek medical care because either the infection is mild or it elicits symptoms not severe enough to warrant contacting a medical professional [
10]. Asymptomatic viral shedding in the nasopharynx in asymptomatic populations and immunocompetent hosts is relatively common [
11‐
13]. Asymptomatic shedding among pediatric surgery patients (PSPs) could potentially play an key role in propagating outbreaks of respiratory diseases if subclinical VRI is transmissible and leads to progression of symptomatic disease [
13]. However, the infections reported by the surveillance showed only the symptomatic fraction of the total infected population [
14]. The role of asymptomatic infection in respiratory virus transmission is still largely unknown and the rates of asymptomatic shedding are not well studied.
The issue of preoperative VRI screening among children undergoing surgery is unclear and complex. If children with VRI presented with obvious symptoms (fever, cough), it would be an easy decision for the surgeon or anesthesiologist to delay surgery if appropriate. In cases of children with mild or no symptoms, it becomes very difficult for doctors to make the right decision. A few studies have investigated VRI associated with a limited number of respiratory viruses and have demonstrated an increased length of stay (LOS) and increased postoperative complication rates in pediatric cardiac surgical patients [
15,
16]. The data for VRI among the PSPs is not performed systematically recorded and thus detailed etiologic data are lacking. To better estimate the current state of VRI in PSPs and to improve clinical management, this study aims to investigate the incidence of VRI in the mild symptomatic and asymptomatic pediatric surgery population after surgical procedures and to evaluate the impact of VRI on postoperative outcomes. We analyzed detailed symptom data using a standardized symptom survey and quantitative viral load using multiple qRT-PCR to determine the associations between viruses, symptoms and viral quantity.
Discussion
VIR has the potential to result in serious respiratory disease in postoperative recovery. In previous studies, the significance of VIR in postoperative recovery patients was questioned, as previous studies reported low positive PCR results for common respiratory viruses in 4.2 and 1.7% of pediatric cardiac surgical patients [
15,
16]. These reported studies were limited to RSV, HRV/EV, and IV, possibly missing the other majority of respiratory viruses. In addition, these studies lacked quantitative analysis of viral pathogens in the PSPs. Though the frequency of symptomatic VRI was low, presence of VRI significantly prolonged postoperative recovery in children following surgery, as evidenced by longer LOS periods in hospitalization. In the present study, we aimed to investigate the infection rates and outcomes of both asymptomatic and symptomatic PSPs leading to VRI after surgery using qRT-PCR. As samples were taken not only from patients with symptoms of infection, but also from asymptomatic patients in this study, we were therefore able to explore the impact of viral testing in asymptomatic patients, which could help improve estimates of VRI in PSPs and further study of disease transmission modeling and forecasting.
A total of 171 out of 1629 children (10.50%) were confirmed to have VRI with laboratory results, which is a considerably higher proportion than previous studies have identified. HRV/EV was the most common pathogen detected in 42.19% of PSPs, who had either mild symptoms or were asymptomatic, compared to previously reported 17% of asymptomatic controls and 22% of children with pneumonia enrolled at the same study sites during the same time period [
19]. This might be owing to the high sensitivity of the proposed qRT-PCR assays identifying more viral pathogens. In this study, we also observed that HRV/EV were associated with prolonged shedding and the most commonly found coinfections were PIV3 and HRV/EV. These results are consistent with previous findings that HRV/EV co-infection or different HRV species co-infection were associated with acute respiratory illness hospitalization and that prolonged viral shedding over the course of 30 days was more commonly associated with respiratory viruses [
9,
20‐
23]. Because shedding of HRV can occur more than two weeks after infection [
19], it could be interpreted that HRV was the most commonly found co-infection pathogen in this study.
RSV and IV infections with higher Ct values and high proportion of symptoms were detected in 9.90 and 5.20% of the PSPs, respectively. RSV was the main pathogen detected in children with pneumonia younger than two years of age. RSV and IV caused more severe clinical symptoms, potentially causing patient transfers to the department of respiratory infection or surgery delays in the preoperative period, suggesting lower detection of RSV and IV than other viruses in this study.
In our study, PIV3 infection with a higher viral load was frequently found in PSPs with mild symptoms, and caused pneumonia with radiographic evidence after surgery. These results were consistent with previous reports that PIV3 was frequently detected in patients with bronchiolitis and pneumonia less than one year of age and was the second pathogen to cause VRIs in neonates and young infants. PIV3 infections were most common in the spring and summer in this study, which is similar to previous report [
24]. Additionally, PIV3 infections were also found in 29 patients with no symptoms, this result is different from a previous study in which many viruses (ADV, IV, RSV, HMPV, COV and HRV/EV) but no PIV was identified in hospitalized children without symptoms of respiratory viral illness [
11]. Our findings suggested that PIV3 is a new risk factor for VRI in PSPs. The PIV3-infected PSPs with mild symptoms or without obviously clinical respiratory symptoms should strictly adhere to the VRI isolation procedures when undergoing elective surgery. In order to prevent and control VRI, further study of PIV3 infections in the perioperative period is needed.
In a previous study, CoVOC43 was the most commonly detected coronavirus [
25], followed by CoV (NL63 HKU1), with similarly moderate detection frequencies. CoV 229E was detected with a comparatively lower frequency [
26,
27]. Similar to previous study, CoV OC43 (
n = 13, 6.77%) and CoV HKU1 (
n = 8, 4.17%) infections with relatively lower Ct values and less serious illnesses or radiographic findings, were recognized. However, CoV (OC43, HKU1) infections with a higher viral load were also observed in asymptomatic PSPs progressing to alveolar or interstitial infiltration. CoV 229E was not discovered in PSPs in this study.
This observational study has several limitations: 1) The small subgroup numbers may lead to differences in detection rates, making it worthwhile to consider a multicenter study with greater numbers of surgical cases to further examine the impact of VRI on postoperative outcomes; 2) The possible bacterial pathogens in the PSP were not considered; 3) no information was available about the vaccination and immunological status of eligible patients.
In conclusion, our findings indicate that VRI is associated with prolonged postoperative recovery in children following surgery. In addition, PIV3 is a new risk factor for VRI in PSPs. Employing a more sensitive and quantitative method, such as qRT-PCR, should be considered for preoperative testing of respiratory viruses. Further prospective studies are required to define the risk stratification and to guide optimal surgical timing.