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).