Methods
After Institutional Review Board (IRB) approval, we identified all patients (0 to 17 years of age) who were admitted to the Children’s Hospital of Illinois from 01/01/2015 to 12/31/2019 and had a respiratory pathogen array (RPA) sent within 48 hours of admission. Patients were identified using an automated query of the electronic medical records (epic clarity and enterprise explorer). Only the first admission of the patient was included in the study. Patients with pre-existing tracheostomy (ICD 10 code of Z 93.0) and patients with a diagnosis of chronic respiratory failure (ICD code J 96.1) were excluded. From this list of patients, we identified patients who had positive RPA. Patients positive for Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae on RPA were also excluded. Included patients were further categorized as patients who had only one virus identified, and patients who had more than one virus identified for descriptive and comparative analysis.
Children’s Hospital of Illinois is a 138-bed hospital within the hospital system. It is the largest freestanding children’s facility in downtown Illinois and comprise of representation of all pediatric subspecialties including pediatric congenital heart surgery. Pediatric critical care comprises of a 32-bed unit which includes 16 intermediate care beds. Intermediate care beds are “open” and hospital allows for direct admission to the intermediate care unit.
All the study variables were directly extracted by the automated query of the electronic medical records. This included demographics (age, weight, height, race, gender) as well as comorbidities. The comorbidities including the pre-existing diagnosis of prematurity (diagnostic code P07), asthma (diagnostic code J45), congenital heart disease (diagnostic code Q24), oncologic diagnosis (diagnostic code C1-C100) and developmental delay (diagnostic code R 62.5) on any hospital encounter before the index encounter. Body Mass Index (BMI) was calculated based on the patient’s weight, and height and all patients were characterized into BMI categories of underweight (< 18.5), normal (18.5 to 24.9), overweight (25 to 29.9) and obese (>=30). Age was also categorized as < one month, one month to 12 months, 12 months to 5 years and more than five years, and further as less than 12 months and more than 12 months for comparative analysis. Concurrent bacterial superinfection was assessed by the presence of positive culture (blood, respiratory, or urine) within 24 hours of hospital admission. Prescription of antibiotics (oral or intravenous) within six hours of admission was assessed based on electronic order start time within six hours of hospital admission time. The antibiotic duration was calculated as the difference in days between antibiotic ordered start time, and antibiotic ordered end time. We also identified patients who received antibiotics for more than five days. In this search, “antibiotic” was defined as a therapeutic class of “anti-infective” and antiviral agents like Tamiflu was included in the category. We also assessed patient management and resource utilization variables such as intermediate care unit admission, intensive care unit admission, intubation (placement of endotracheal tube during the encounter), chest x-ray, escalation of care (Transfer from lower acuity to a higher acuity unit) and total direct cost of care. Outcome variables included total ICU length of stay (total time in days patients spent in the ICU, if the patient was in ICU on two separate occasions during the hospital encounter, cumulative ICU days were calculated), hospital length of stay, ventilator duration (difference in days between endotracheal tube placement time and endotracheal tube removal time) and mortality (death date on the encounter).
All the variables were extracted in an excel file. The subtypes of viruses (Coronavirus 229E, HKU1, NL63, OC43, Influenza A, AH1, AH3, A2009H1, Influenza B, and Parainfluenza 1, 2, 3 and 4) were combined as Coronavirus, Influenza virus, and parainfluenza virus. Comparative analysis was then performed for patients who had single viral infection versus patients who had more than one virus infection. Patients with different strains of the single virus were counted as a single viral infection. The statistical analysis included a comparative analysis of the various demographic and outcome variables. We calculated the mean and standard deviation or median with an interquartile range (IQR) for continuous variables as appropriate, and proportions for categorical variables. Comparative analysis was performed by student t-test or Wilcoxon test for nonparametric data and chi-square test as appropriate. Outcome factors significant on univariate comparison were analyzed by multivariable regression after accounting for age (in months), comorbidities (prematurity, asthma, congenital heart disease, developmental delay and cancer) and bacterial coinfection is (blood, urine and respiratory). Length of stay and costs were log transformed and parameters were exponentiated. Standard least square model was used for linear regression. P value of less than 0.05 was considered significant. All statistical analyses were performed using JMP version 12.4 (SAS Institute, Cary, NC).