Severe Respiratory Disease Among Children With and Without Medical Complexity During the COVID-19 Pandemic

Key Points Question Did rates and outcomes of severe respiratory illness change during the first 2 years of the pandemic, compared with prepandemic, among children with medical complexity and those without medical complexity? Findings In this repeated cross-sectional study of 139 078 respiratory hospitalizations in Canada, there were more than 45 000 fewer respiratory hospitalizations, more than 4200 fewer respiratory intensive care unit admissions and, among children with medical complexity, 119 fewer deaths during respiratory hospitalizations than expected in the first 2 years of the pandemic. Meaning This study’s results suggest the need for evaluation of the effect of public health interventions in reducing circulating respiratory pathogens during nonpandemic periods.


Introduction
][9][10][11] Children with medical complexity (CMC) are at risk of severe acute illness from respiratory infections (eg, children with cystic fibrosis, 12 congenital heart disease, 13 or sickle cell disease 14 ).In a Canadian evaluation, children who were admitted with SARS-CoV-2 infections during the early pandemic period often had existing comorbidities including obesity and neurologic impairment. 15Children with neurologic impairment (NI), which account for 28% of all Canadian CMC, 16 are at particularly high risk due to a number of factors, including impaired cough and airway clearance, respiratory muscle weakness, bronchial hyperactivity, sleep disordered breathing, and risk of aspiration from oral secretions. 17This may result in CMC having an outsized benefit from this general decrease in burden of circulating viruses. 18Reports from multiple countries have suggested decreased emergency department visits 7,8 and admissions to hospital during the pandemic both for children with and without medical complexity, [9][10][11] but these findings were limited to those reporting solely on children's hospitals, evaluations during the early pandemic period, and were not denominated on a defined at-risk population.The effect of pandemic-era suppressed respiratory viral transmission on hospitalization, intensive care unit (ICU) admission, and mortality among CMC and children without medical complexity (non-CMC) is unknown.
Understanding the association of the pandemic with health care utilization related to respiratory illnesses among CMC and non-CMC in Canada, a country that instituted relatively stringent public health measures over the first 2 years of the pandemic, 19 may inform our understanding of the potential benefits of nonpharmaceutical interventions (such as masking, 20 reducing contacts, 20 social distancing, 21 and air filtration and purification 22 ) aimed at protecting children at risk of respiratory hospitalizations during seasonal respiratory viral surges (eTable 1 in Supplement 1).Our objective was to evaluate changes in respiratory hospitalizations, ICU admission, and mortality among CMC and non-CMC during the pandemic compared with prepandemic.We hypothesized that there would be a larger decrease in severe respiratory hospitalization and ICU admissions among CMC compared with non-CMC, reflecting the use of nonpharmaceutical interventions mitigating illness transmission for those particularly at risk for infections.

Study Design and Population
This cross-sectional study used a repeated, population-based analysis and followed the Reporting of Studies Conducted Using Observational Routinely-Collected Data (RECORD) reporting guideline. 23ing data from the Canadian Institutes for Health Information Discharge Abstract Database (CIHI-DAD) between April 1, 2017, and February 28, 2022, we identified all non-newborn hospitalizations to every acute care hospital in Canada (excluding Québec, which accounts for 21% of Canada's population) among children younger than 18 years of age (eTable 2 in Supplement 1).We included all respiratory hospitalizations using the Pediatric Clinical Classification System (PECCS), which categorizes common reasons for hospitalizations into clinically meaningful groupings [24][25][26] (eTable 3 in Supplement 1).CMC were identified using the CIHI CMC methodology based on the Feudtner complex chronic condition (CCC) list, 14 adapted for use in Canada 16,27 using the

International Statistical Classification of Diseases and Related Health Problems, Tenth Revision,
Canadian Edition (ICD-10-CA) diagnostic codes and supplemented with high-intensity NI codes. 289 Assuming temporal stability in the published proportion of Canadian children with CMC (948 per 100 000), 27 we calculated CMC prevalence based on each year's total pediatric population.
This study received ethics approval from the Hospital for Sick Children research ethics board.
Waiver of consent was granted by the research ethics board due to the use of administrative data.

Pre-COVID-19 and COVID-19 Periods
A prepandemic period (April 1, 2017, to March 1, 2020) was used to derive expected hospitalizations, accounting for time trends and seasonality.The pandemic period was divided into two 12-month periods corresponding with the public sector fiscal year (FY) in Canada (April 1 to March 31).We excluded a 1-month washout period (March 2020) at the start of the pandemic, defining the pandemic period as April 1, 2020, to February 28, 2022.Hospitalization data at CIHI is only captured at discharge, so we excluded the last month (March) of FY 2022 to minimize right-censoring.

Variables
We identified all hospitalizations among CMC, which we further described based on

Statistical Analysis
We evaluated changes in CMC and non-CMC respiratory hospitalizations, ICU admission, and in-hospital mortality, using a negative binomial regression model comparing prepandemic observed vs pandemic expected weekly event counts, and summarized as rate ratios (RR) by FY 2020 and 2021 offset by the total pediatric population each year.We conducted a sensitivity analysis limiting respiratory hospitalizations for CMC and non-CMC and mortality for CMC to those with PECCS codes corresponding to a clear infectious etiology (eg, bronchiolitis).As sex and age of the child can be associated with illness severity, 30,31 we completed an additional analysis stratified on these variables.
We assumed that nonoverlapping 95% CIs for group estimates indicated significant differences.All analyses were completed using SAS studio version 9.4 (SAS Institute) from October 2022 to April 2023.

Results
There

Respiratory Hospitalizations
A comparison of observed and expected respiratory hospitalizations among CMC and non-CMC is summarized in Figure 1. 32Among CMC, compared with prepandemic annual respiratory hospitalization rates of 1385.6 per 10 000, hospitalizations in FY 2020 decreased to 611.4 per 10 000 CMC, corresponding to an annual rate difference of 774.2 per 10 000 CMC and a rate ratio (RR) of 0.44 (95% CI, 0.42-0.46)(Table 2).In FY 2021, hospitalizations decreased to 774 per 10 000 CMC, which corresponded to an annual rate difference of 611 per 10 000 CMC and an RR of 0.56 (95% CI, 0.51-0.62).Among non-CMC, there was an even larger relative reduction in respiratory hospitalizations in FY 2020 compared with prepandemic, decreasing from 52.9 per 10 000 in the prepandemic period to 9.7 per 10 000 in FY 2020, corresponding to an annual rate difference of 43.2 per 10 000 non-CMC, and a RR of 0.18 (95% CI, 0.17-0.among CMC and reported a 20% decline in all-cause hospitalizations but did not observe a decline in ICU use. 10 Our study focused specifically on respiratory hospitalizations which may have been associated with greater pandemic-era declines than hospitalizations overall, and extended evaluation to a longer pandemic period, focused on broader groups of CMC, and included all hospital admissions, not just those in children's hospitals. The findings of greater relative mitigation of respiratory hospitalizations in non-CMC compared with CMC in FY 2020 was surprising as we expected greater declines among CMC due to their elevated risk.Potential explanations for this observation include the ongoing circulation of other respiratory viruses during the pandemic for which CMC are at particular risk for hospitalization (eg, enterovirus), 34 unavoidable respiratory admissions unrelated to an infection (eg, noninfectious triggers for asthma or aspiration), and the use of nonpharmacologic infection-prevention strategies to reduce infection risk prepandemic among families of CMC.These explanations may also be relevant in understanding why older children who have a baseline lower risk of respiratory hospitalizations 35 were also observed to have greater relative decreases in respiratory admissions during the pandemic.It is important to emphasize that despite the larger attenuation of respiratory hospitalizations among non-CMC in the first pandemic year, given the much higher baseline prevalence of CMC respiratory hospitalizations, the decline observed among CMC is clinically important and was associated with decreased mortality.

Strengths and Limitations
To our knowledge, this study is the longest evaluation (2-year pandemic period) comparing CMC with non-CMC respiratory hospitalizations using population-level data published to date.Nevertheless, the study has limitations.First, although we used an algorithm for ascertaining CMC that has been used extensively in Canadian health services research, 27 administrative data are unable to capture important domains of complexity such as family and/or caregiver needs, psychosocial complexity, and functional status; and administrative data were limited to those with previous hospitalization data.Second, we used PECCS respiratory codes that excluded admissions for underlying respiratory conditions that are likely unrelated to viral infections (eg, bronchopulmonary dysplasia).Among the included codes were diagnoses for which hospitalization may or may not be attributed to a viral respiratory infection (eg, asthma exacerbations by infectious or noninfectious triggers), 19 although hospitalization and ICU admission rates did not change when these codes were excluded.Third, we limited capture of COVID-19 diagnoses to those with an additional PECCS respiratory code (eg, pneumonia).Although we may have missed some cases that were misclassified, at the time, 43.2% of Canadian children admitted to hospital with SARS-CoV-2 infections were not admitted because of COVID-19 (they typically had incidental SARS-CoV-2 infection detected during universal screening at hospital admission). 15Fourth, the data sets used did not include out-of-hospital mortality from respiratory illnesses; however, more than 80% of CMC deaths occur in hospital. 16Fifth, this study was conducted in Canada, which had less severe outcomes related to COVID-19 than the United States 36 ; this may be due in part to more widespread adoption of public health measures or other factors.For instance, in Ontario, Canada's most populous province, mandatory masking, daily symptom checks, social distancing, and cohorting were instituted in schools at the start of the 2020 to 2021 school year. 37Findings may differ in other jurisdictions.Additionally, this study cannot identify causative factors related to the reduction of hospitalization, ICU admissions, and mortality between CMC and non-CMC.

Conclusions
In this cross-sectional study, we observed decreased hospitalizations and ICU admissions related to respiratory illnesses for both CMC and non-CMC during the COVID- Abbreviations: CCC, complex chronic condition; ICU intensive care unit; NA, not applicable; NI neurologic impairment.a Excludes newborn admissions.

at the JAMA Network Open | Pediatrics Severe
The population of children in Canada (excluding Québec) Respiratory Disease Among Children With and Without Medical Complexity During the COVID-19 Pandemic

Table 1 .
Respiratory Admissions for Children With and Without Medical Complexity by Year were 139 078 respiratory hospitalizations (29 461 for CMC and 109 617 for non-CMC) from March 1, 2017, to February 28, 2022 (Table 1).Children younger than 2 years of age were hospitalized most frequently, accounting for 10 271 (34.8%) of CMC and 56 652 (51.7%) of non-CMC hospitalizations.Male children accounted for the majority of respiratory hospitalizations for both of all CMC hospitalizations).Overall, 11 717 (39.8%) of CMC hospitalizations were among children assisted by a medical technology.

Table 2 .
Severe Respiratory Disease Among Children With and Without Medical Complexity During the COVID-19 Pandemic Serious Respiratory Illnesses in Children With and Without Medical Complexity Comparing Pandemic (2020-2021) to Prepandemic (2017-2019) Periods in Canadian Hospitals (Excluding Quebec) Severe Respiratory Disease Among Children With and Without Medical Complexity During the COVID-19 PandemicFigure 2. Relative Rate Ratios of Respiratory Hospitalization, Intensive Care Unit Admission, and Mortality Comparing Pandemic and Prepandemic Periods by Sex and Age Severe Respiratory Disease Among Children With and Without Medical Complexity During the COVID-19 Pandemic Downloaded from jamanetwork.comby guest on 11/17/2023 pandemic reported a 14.4% decrease in all-cause hospitalizations among children with NI. 11 Another multicenter study of children's hospitals in the United States evaluated the first year of the pandemic Figure 1.Observed vs Expected Respiratory Hospitalizations in Children With Medical Complexity (CMC) and Children Without Medical Complexity (Non-CMC) a Observed Expected Weekly observed and expected counts based on children with and without medical complexity aged 0 to 17 years of age during prepandemic (April 1, 2017, to February 28, 2020) and pandemic (April 1, 2020 to February 28, 2022) periods.Shaded region indicates 1-month washout period (March 2020).aVariant of concern emergence (Alpha, Delta, Omicron) based on first case in Canada. 32AMA Network Open | Pediatrics JAMA Network Open.2023;6(11):e2343318. doi:10.1001/jamanetworkopen.2023.43318(Reprinted)November 14, 2023 5/12 Downloaded from jamanetwork.combyguest on 11/17/2023 a Cell sizes too small to provide stable estimates.JAMA Network Open | Pediatrics 19pandemic and decreasedJAMA Network Open | PediatricsSevere Respiratory Disease Among Children With and Without Medical Complexity During the COVID-19 Pandemic hospital mortality among CMC.This study's results suggest that the outcomes of public health interventions are not always equal across population groups.Groups of people with greater risk require special attention and monitoring when crafting population-level recommendations.Future evaluations of the effect of nonpharmaceutical interventions during subsequent periods in the pandemic when the infection rate in children was higher (eg, Omicron) and during nonpandemic periods of increased respiratory illness may be warranted.