Respiratory viruses in pediatric emergency department patients and their family members

Abstract Background Respiratory viral infections account for a substantial fraction of pediatric emergency department (ED) visits. We examined the epidemiological patterns of seven common respiratory viruses in children presenting to EDs with influenza‐like illness (ILI). Additionally, we examined the co‐occurrence of viral infections in the accompanying adults and risk factors associated with the acquisition of these viruses. Methods Nasopharyngeal swab were collected from children seeking medical care for ILI and their accompanying adults (Total N = 1315). Study sites included New York Presbyterian, Bellevue, and Tisch hospitals in New York City. PCR using a respiratory viral panel was conducted, and data on symptoms and medical history were collected. Results Respiratory viruses were detected in 399 children (62.25%) and 118 (17.5%) accompanying adults. The most frequent pathogen detected was human rhinovirus (HRV) (28.81%). Co‐infection rates were 14.79% in children and 8.47% in adults. Respiratory syncytial virus (RSV) and parainfluenza infections occurred more often in younger children. Influenza and HRV occurred more often in older children. Influenza and coronavirus were mostly isolated in winter and spring, RSV in fall and winter and HRV in fall and spring. Children with HRV were more likely to have history of asthma. Adults with the same virus as their child often accompanied ≤ 2‐year‐old‐positive children and were more likely to be symptomatic compared to adults with different viruses. Conclusions Respiratory viruses, while presenting the same suite of symptoms, possess distinct seasonal cycles and affect individuals differently based on a number of identifiable factors, including age and history of asthma.


| INTRODUC TI ON
Respiratory infections account for a substantial fraction of emergency department (ED) visits, 1 particularly among the pediatric population. 2 Respiratory diseases were among the most common reasons for pediatric ED visits in the US during 2015, of which acute upper respiratory tract infections (RTI) were the most common. 3 Despite major public health efforts, epidemics of viral RTI continue to be highly prevalent among healthy populations with potential lethal consequences in susceptible individuals. 4 Advances in laboratory testing for RTI have become widely available. 5 However, clinical decision regarding RTI is usually based on presumptive diagnosis, which can be challenging due to the similarity of symptoms exhibited by different respiratory viruses. 6 Identifying epidemiological characteristics of respiratory viral infections may therefore help clinicians better manage their patients. 7 Infection rates for different respiratory viruses vary across age groups in children. 8 Although there is consistency in the literature about higher risk of respiratory syncytial virus (RSV) 9  Taylor, et al 11 reported that influenza infection rates increase in children older than 5 years. More research is thus needed to capture the distribution of common respiratory viruses across different age groups. Ultimately, this may help advance targeted control and prevention of RTI. 12 Most respiratory viruses possess distinct seasonal cycles. 13,14 For example, influenza and coronavirus are known to be prominent in the winter. [13][14][15] Peak prevalence for HRV has been observed in the spring and fall. 16 Identification of the seasonality of common respiratory viruses may aid in determining appropriate precautions that can curb the morbidity and mortality rates during peak transmission months. 17 Children often carry respiratory viruses to their homes and spread infection to their families. Alternatively, family members occasionally expose their child to viruses. 18 Influenza-like illness has been reported in 12% of the adult family members of the children with a laboratory-detected viral pathogen and viral pathogens have been detected in 42.3% of symptomatic family members. 19 In the current study, we analyzed swab specimens from children seeking medical care in pediatric EDs for acute respiratory illness, as well as from adults who accompanied these children and were living in the same household. We examined the prevalence trends of seven common respiratory viruses, which often produce a suite of non-specific respiratory symptoms-commonly referred to as influenza-like illness (ILI), including influenza, coronavirus, human metapneumovirus (hMPV), HRV, PIV, RSV, and adenovirus. Additionally, we examined the age and seasonal distribution of these respiratory viral infections in children, the co-occurrence of viral infections in accompanying adults, and potential risk factors for viral RTIs.

| Sample collection and clinical data
Participants were recruited at three Pediatric EDs, New York Presbyterian (NYP), Bellevue, and Tisch hospitals in New York, NY, from August 2016 to May 2018. Nasopharyngeal swabs were collected from children and teenagers aged 0-19 years old who were brought to the ED with an ILI-defined as a fever of 100°F or greater and a cough or sore throat in the absence of other diagnosis. 20 Additionally, adults who accompanied children to the ED visit and were living in the same household were recruited and swabbed, regardless of symptoms. A detailed epidemiological questionnaire was obtained that included information on demographics, clinical presentation, medical history, immunizations (including influenza vaccination history for the previous 5 years), and living situation.
Parents provided informed consent and completed the survey for children under 13. The study protocol was approved by Institutional Review Board of Columbia University Medical Center (Protocol AAAQ4358). Participants were asked whether they had experienced symptoms commonly associated with respiratory virus infection during the 48 hours prior to completing the survey, and to rate those symptoms as mild, moderate, or severe. These symptoms included fever, chills, muscle paints, watery eyes, runny nose, sneezing, sore throat, cough, and chest pain.

| Virus detection and identification
Samples were stored at −4°C for no more than 30 days, then separated into two 1 mL aliquots, placed in 1. 5

| Statistical analysis
Data were statistically evaluated using IBM SPSS Statistics (SPSS Inc, Version 26.0). Analyses focused only on viral types and were not broken down by subtype due to the low numbers for many subtypes. Comparison of demographic and clinical characteristics was performed using two-tailed t-tests for continuous variables and chi-square analyses for categorical variables. For the seasonality analysis, samples collected from December to February were designated as winter, March to May as spring, June to August as summer, and September to November as fall. For the age-wise distribution analysis, children were divided into four age groups: <2 years old, 2-4 years old, 5-12 years old, and 13-19 years old.

| Sample characteristics
A total of 1315 samples were collected from the three Pediatric EDs.
These included 641 children and 674 accompanying family members. Table 1 shows detailed characteristics of the study participants.

| Characteristics of positively tested children
Three hundred and ninety nine positive samples were collected from children in the three pediatric EDs. Out of these, 50.12% were males, 49.6% were females, and one child was transgender. No significant gender differences were observed among all respiratory viruses. (χ 2 = 17.94, P < .001) and (χ 2 = 16.01, P < .001), respectively.
Significant differences across age groups were not observed for other viral infections (Figure 1). Because the 13-19-year-old age group included only 27 children, the above analyses were repeated excluding this age group and yielded similar findings. (χ 2 = 14.44, P = .00014) and (χ 2 = 8.15, P = .003), respectively.
Further, children infected with HRV were less likely to have fever compared with children with other viruses (χ 2 = 5.52, P = .02).

| Differences among infections in children with and without asthma
Given the difficulty in making a definitive diagnosis of asthma in children under five years of age, 21

| Symptomology of accompanying adults
Among 674 accompanying adults in the 3 pediatric EDs, 118 (17.50%) were positive for at least one respiratory virus. Accompanying adults were subdivided into two groups: those with the same virus type Families with a household number of ≥ 5 were more likely to have a child and/or accompanying adult test positive for one or more respiratory viruses, compared to families with households of < 5 (χ 2 = 4.08, P = .04). There was no effect of smoking or presence

| D ISCUSS I ON
Respiratory viral infections are one of the leading causes of pediatric ED visits. 23,24 Understanding their underlying epidemiology is crucial for promoting preparedness to tackle this public health problem. 25 In the current study, we report on the viral etiology that commonly affect children seeking ED with ILI symptoms, as well as addressing their epidemiological features.
We detected at least one of the tested respiratory viruses in two- have also been reported, probably due to different methodological approaches and geographical distribution among these studies. HRV and PIV were detected in co-infected patients more frequently than other viruses, probably because the incidence of both viruses was higher than that of the other respiratory viruses. Further, infections from both of these viruses were abundant during autumn, which may also have contributed to this finding. Among all co-infecting viruses, HRV was the most prevalent virus, consistent with some prior studies. 30,32 We found that RSV and PIV infection rates are significantly higher in younger children, a trend that has been seen in other studies. 10,[33][34][35] RSV and PIV infect cells in the epithelium lining of the trachea and intrapulmonary airways, and cause croup, bronchitis, bronchiolitis, and/or bronchopneumonia. 36 Young infants have small airways, which make them susceptible to obstruction, and, in turn, increase risk for RSV and PIV infection specifically. 37,38 Additionally, we found that HRV and influenza infection rates We found a high rate of adenovirus infection in families with an adenovirus-positive child. This is consistent with one prior study that showed a high secondary attack rate for adenovirus. 57 However, our sample size of adenovirus-positive cases was modest and studies with larger sample size are needed to draw a definitive conclusion.

| Limitations
The current study has some limitations. First, due to the low number of viral subtypes in the current sample, we conducted analyses only on viral types without breakdown by subtype. Additionally, we studied the rate of viral infections in adults who accompanied children seeking care for ILI symptoms at the time of ED visit. This did not allow for calculation of the secondary attack rate per index child.
We also did not have data on whether the children were attending childcare centers, which represent a common source of infection.

| CON CLUS IONS
The epidemiological data on common circulating respiratory viruses in this study could provide helpful information for clinical decision-making. Findings can inform guidelines for clinicians by enabling reasonable estimates of etiologic diagnoses and identification of individuals who are more susceptible to a particular virus and when they are at greatest risk.