Introduction

Intensive care has played a pivotal role during the COVID-19 pandemic as many patients developed severe pulmonary complications. The availability of information in pediatric intensive care (PICUs) remains limited. The purpose of this study is to characterize COVID-19 positive admissions (CPAs) in the United States and to determine factors that may impact those admissions.

Materials and Methods

This is a retrospective cohort study using data from the COVID-19 dashboard virtual pediatric system) containing information regarding respiratory support and comorbidities for all CPAs between March and April 2020. The state level data contained 13 different factors from population density, comorbid conditions and social distancing score. The absolute CPAs count was converted to frequency using the state’s population. Univariate and multivariate regression analyses were performed to assess the association between CPAs frequency and endpoints.

Results

A total of 205 CPAs were reported by 167 PICUs across 48 states. The estimated CPAs frequency was 2.8 per million children. A total of 3,235 tests were conducted with 6.3% positive tests. Children above 11 years of age comprised 69.7% of the total cohort and 35.1% had moderated or severe comorbidities. The median duration of a CPA was 4.9 days [1.25-12.00 days]. Out of the 1,132 total CPA days, 592 [52.2%] were for mechanical ventilation. The inpatient mortalities were 3 [1.4%]. Multivariate analyses demonstrated an association between CPAs with greater population density [beta-coefficient 0.01, p<0.01] and increased percent of children receiving the influenza vaccination [beta-coefficient 0.17, p=0.01].

Conclusions

Inpatient mortality during PICU CPAs is relatively low at 1.4%. CPA frequency seems to be impacted by population density while characteristics of illness severity appear to be associated with ultraviolet index, temperature, and comorbidities such as Type 1 diabetes. These factors should be included in future studies using patient-level data.

This study utilized only publicly available, deidentified, state-level data. As such, no institutional review board review or approval was sought.

Endpoint identification and data collection

The following data was identified for collection regarding the CPAs themselves: number, duration, need for various ventilatory support measures, severity of comorbidities, and the total number of COVID-19 tests conducted. The following data was collected regarding US states: pediatric population, state population (pediatric and adult) density, air and drinking water quality, average temperature, average ultraviolet index, prevalence of pediatric obesity, type 1 diabetes mellitus (DM) and asthma, the proportion of children who smoke cigarettes, received the influenza vaccine, had health insurance, and received home health care, race, percent of households with children below the poverty line, highest education level of adults in homes with children, and the social distancing score by global positional satellite data (Supplementary Table 1).

The data regarding the CPAs themselves was collected from the publicly available COVID-19 dashboard provided by the Virtual Pediatric System (VPS), which collects data from several PICUs in the US. COVID-19 data was collected from March 14^th through April 14^th, 2020, in order to represent one full month of data. Data regarding number of centers, number of tests, and number of CPAs was captured in absolute counts. Data regarding CPAs duration was collected in days. The respiratory support modalities for which data was available were room air (RA), nasal cannula (NC) and for the advanced respiratory support modalities (i.e. other than RA and NC) there was available data for high flow nasal cannula (HFNC), non-invasive positive pressure ventilation (NIPPV), conventional mechanical ventilation (MCV), high frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation (ECMO), and was captured in duration (days) of their use. Data regarding severity of comorbidities is reported in the VPS dashboard and the percentage of CPAs with moderate or severe degree of comorbidities was collected.

State-wide data for the analyses were collected from a variety of sources with the complete list of sources provided as Supplementary Material 1. Children’s population data and pediatric comorbidity data was obtained from 2018, as these were the most recent and comprehensive data available. The sources for these other data points were generally US government-based efforts to capture state-level data on various medical issues, however, not all states reported data for all the endpoints (Supplementary Table 2).

Endpoints were assigned to the authors for collection. One author was responsible for collecting data for each state for the variables assigned. Once these data were collected a different author, who did not primarily collect data for that specific endpoint, verified the numbers for accuracy. Finally, values in the top and bottom 10^th percentile were identified and verified by a third author.

Statistical analyses

As the data was collected for each state and intended for state-level analyses, and each state has a different pediatric population, the absolute numbers of CPAs for each state were not directly comparable. Thus, the absolute CPAs count for each state was first converted to a frequency of CPAs per 1,000,000 children using the specific state’s population. This CPAs frequency was then used as the dependent variable in a series of single-independent variable linear regressions to determine the univariate association between CPAs frequency and the other endpoints. Multivariate regression was conducted with CPAs frequency as the dependent variable and with other variables entered as independent variables. Forward stepwise regression was utilized with the model with greatest R-squared value being used for the analyses.

Next, a composite endpoint called “percent of PICUs days requiring advanced respiratory support” was created. This consisted of the total duration of HFNC, NIPPV, MCV, HFOV, and ECMO divided by the total PICUs admission duration. This was then modeled similarly to CPAs frequency. Next, a composite outcome called “percent of PICU days requiring intubation” was created. This consisted of the total duration of MCV and HFOV divided by the total PICU admission duration. This, too, was then modeled similarly as CPA frequency. Lastly, an endpoint called “PICUs duration per admission” was created for each state and consisted of the total CPAs PICUs duration for that specific state divided by the number of CPAs reported by that state. This was also then modeled similarly to CPA frequency.

All statistical analyses were done using the user-coded, syntax-based interface of SPSS Version 23.0. A p-value of 0.05 was considered statistically significant. All statistical analyses were done at the state-level with state-level data. Analyses were not conducted at a patient-level with patient-level data. Any use of the word significant here-on in the manuscript refers to “statistically significant” unless explicitly specified otherwise.