Samir S Shah, MD

The COVID-19 pandemic has led to more than 40 million infections and more than 650,000 deaths in the United States alone.¹ Morbidity and mortality have disproportionately affected older adults.^2-4 However, acute infection and delayed effects, such as multisystem inflammatory syndrome in children (MIS-C), occur and can lead to severe complications, hospitalization, and death in pediatric patients.^5,6 Due to higher clinical disease prevalence and morbidity in the adult population, we have learned much about the clinical factors associated with severe adult COVID-19 disease.^5,7-9 Such clinical factors include older age, concurrent comorbidities, smoke exposure, and Black race or Hispanic ethnicity, among others.^5,7-10 However, there is a paucity of data on severe COVID-19 disease in pediatric patients.^5,11,12 In addition, most immunization strategies and pharmacologic treatments for COVID-19 have not been evaluated or approved for use in children.¹³ To guide targeted prevention and treatment strategies, there is a critical need to identify children and adolescents—who are among the most vulnerable patient populations—at high risk for severe disease.

Identifying the clinical factors associated with severe COVID-19 disease will help with prioritizing and allocating vaccines when they are approved for use in patients younger than 12 years. It also can provide insight for clinicians and families faced with decisions wherein individual risk assessment is crucial (eg, in-person schooling, other group activities). The objective of this study was to determine the clinical factors associated with severe COVID-19 among children and adolescents in the United States.

Study Design

We conducted a multicenter retrospective cohort study of patients presenting for care at pediatric hospitals that report data to the Pediatric Health Information System (PHIS) database. The PHIS administrative database includes billing and utilization data from 45 US tertiary care hospitals affiliated with the Children’s Hospital Association (Lenexa, Kansas). Data quality and reliability are ensured through a joint validation effort between the Children’s Hospital Association and participating hospitals. Hospitals submit discharge data, including demographics, diagnoses, and procedures using International Classification of Diseases, 10th Revision (ICD-10) codes, along with daily detailed information on pharmacy, location of care, and other services.

Study Population

Patients 30 days to 18 years of age discharged from the emergency department (ED) or inpatient setting with a primary diagnosis of COVID-19 (ICD-10 codes U.071 and U.072) between April 1, 2020, and September 30, 2020, were eligible for inclusion.¹⁴ In a prior study, the positive predictive value of an ICD-10–coded diagnosis of COVID-19 among hospitalized pediatric patients was 95.5%, compared with reverse transcription polymerase reaction results or presence of MIS-C.¹⁵ The diagnostic code for COVID-19 (ICD-10-CM) also had a high sensitivity (98.0%) in the hospitalized population.¹⁶ Acknowledging the increasing practice of screening patients upon admission, and in an attempt to minimize potential misclassification, we did not include encounters with secondary diagnoses of COVID-19 in our primary analyses. Pediatric patients with surgical diagnoses and neonates who never left the hospital were also excluded.

Factors Associated With Severe COVID-19 Disease

Exposures of interest were determined a priori based on current evidence in the literature and included patient age (0-4 years, 5-11 years, and 12-18 years), sex, race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, Asian, other non-White race [defined as Pacific Islander, Native American, or other]), payor type, cardiovascular complex chronic conditions (CCC), neuromuscular CCC, obesity/type 2 diabetes mellitus (DM), pulmonary CCC, asthma (defined using ICD-10 codes¹⁷), and immunocompromised CCC. Race and ethnicity were included as covariates based on previous studies reporting differences in COVID-19 outcomes among racial and ethnic groups.⁹ The CCC covariates were defined using the pediatric CCC ICD-10 classification system version 2.¹⁸

Pediatric Complications and Conditions Associated With COVID-19

Based on current evidence and expert opinion of study members, associated diagnoses and complications co-occurring with a COVID-19 diagnosis were defined a priori and identified through ICD-10 codes (Appendix Table 1). These included acute kidney injury, acute liver injury, aseptic meningitis, asthma exacerbation, bronchiolitis, cerebral infarction, croup, encephalitis, encephalopathy, infant fever, febrile seizure, gastroenteritis/dehydration, Kawasaki disease/MIS-C, myocarditis/pericarditis, pneumonia, lung effusion or empyema, respiratory failure, sepsis, nonfebrile seizure, pancreatitis, sickle cell complications, and thrombotic complications.

Outcomes

COVID-19 severity outcomes were assessed as follows: (1) mild = ED discharge; (2) moderate = inpatient admission; (3) severe = intensive care unit (ICU) admission without mechanical ventilation, shock, or death; and (4) very severe = ICU admission with mechanical ventilation, shock, or death.¹⁹ This ordinal ranking system did not violate the proportional odds assumption. Potential reasons for admission to the ICU without mechanical ventilation, shock, or death include, but are not limited to, need for noninvasive ventilation, vital sign instability, dysrhythmias, respiratory insufficiency, or complications arising from concurrent conditions (eg, thrombotic events, need for continuous albuterol therapy). We examined several secondary, hospital-based outcomes, including associated diagnoses and complications, all-cause 30-day healthcare reutilization (ED visit or rehospitalization), length of stay (LOS), and ICU LOS.

Statistical Analysis

Demographic characteristics were summarized using frequencies and percentages for categorical variables and geometric means with SD and medians with interquartile ranges (IQR) for continuous variables, as appropriate. Factors associated with hospitalization (encompassing severity levels 2-4) vs ED discharge (severity level 1) were assessed using logistic regression. Factors associated with increasing severity among hospitalized pediatric patients (severity levels 2, 3, and 4) were assessed using ordinal logistic regression. Covariates in these analyses included race and ethnicity, age, sex, payor, cardiovascular CCC, neurologic/neuromuscular CCC, obesity/type 2 DM, pulmonary CCC, asthma, and immunocompromised CCC. Adjusted odds ratios (aOR) and corresponding 95% CI for each risk factor were generated using generalized linear mixed effects models and random intercepts for each hospital. Given the potential for diagnostic misclassification of pediatric patients with COVID-19 based on primary vs secondary diagnoses, we performed sensitivity analyses defining the study population as those with a primary diagnosis of COVID-19 and those with a secondary diagnosis of COVID-19 plus a concurrent primary diagnosis of a condition associated with COVID-19 (Appendix Table 1).

All analyses were performed using SAS version 9.4 (SAS Institute, Inc), and P < .05 was considered statistically significant. The Institutional Review Board at Vanderbilt University Medical Center determined that this study of de-identified data did not meet the criteria for human subjects research.

Study Population

A total of 19,976 encounters were included in the study. Of those, 15,913 (79.7%) were discharged from the ED and 4063 (20.3%) were hospitalized (Table 1). The most common race/ethnicity was Hispanic (9741, 48.8%), followed by non-Hispanic White (4217, 21.1%). Reference race/ethnicity data for the overall 2019 PHIS population can be found in Appendix Table 2.

The severity distribution among the hospitalized population was moderate (3222, 79.3%), severe (431, 11.3%), and very severe (380, 9.4%). The frequency of COVID-19 diagnoses increased late in the study period (Figure). Among those hospitalized, the median LOS for the index admission was 2 days (IQR, 1-4), while among those admitted to the ICU, the median LOS was 3 days (IQR, 2-5).

Overall, 10.1% (n = 2020) of the study population had an all-cause repeat encounter (ie, subsequent ED encounter or hospitalization) within 30 days following the index discharge. Repeat encounters were more frequent among patients hospitalized than among those discharged from the ED (Appendix Table 3).

Prevalence of Conditions and Complications Associated With COVID-19

Overall, 3257 (16.3%) patients had one or more co-occurring diagnoses categorized as a COVID-19–associated condition or complication. The most frequent diagnoses included lower respiratory tract disease (pneumonia, lung effusion, or empyema; n = 1415, 7.1%), gastroenteritis/dehydration (n = 1068, 5.3%), respiratory failure (n = 731, 3.7%), febrile infant (n = 413, 2.1%), and nonfebrile seizure (n = 425, 2.1%). Aside from nonfebrile seizure, neurological complications were less frequent and included febrile seizure (n = 155, 0.8%), encephalopathy (n = 63, 0.3%), aseptic meningitis (n = 16, 0.1%), encephalitis (n = 11, 0.1%), and cerebral infarction (n = 6, <0.1%). Kawasaki disease and MIS-C comprised 1.7% (n = 346) of diagnoses. Thrombotic complications occurred in 0.1% (n = 13) of patients. Overall, these conditions and complications associated with COVID-19 were more frequent in hospitalized patients than in those discharged from the ED (P < .001) (Table 2).

Factors Associated With COVID-19 Disease Severity

Compared to pediatric patients with COVID-19 discharged from the ED, factors associated with increased odds of hospitalization included private payor insurance; obesity/type 2 DM; asthma; and cardiovascular, immunocompromised, neurologic/neuromuscular, and pulmonary CCCs (Table 3). Factors associated with decreased risk of hospitalization included Black race or Hispanic ethnicity compared with White race; female sex; and age 5 to 11 years and age 12 to 17 years (vs age 0-4 years). Among children and adolescents hospitalized with COVID-19, factors associated with greater disease severity included Black or other non-White race; age 5 to 11 years; age 12 to 17 years; obesity/type 2 DM; immunocompromised conditions; and cardiovascular, neurologic/neuromuscular, and pulmonary CCCs (Table 3).

Sensitivity Analysis

We performed a sensitivity analysis that expanded the study population to include those with a secondary diagnosis of COVID-19 plus a diagnosis of a COVID-19–associated condition or complication. Analyses using the expanded population (N = 21,247) were similar to the primary analyses (Appendix Table 4 and Appendix Table 5).

In this large multicenter study evaluating COVID-19 disease severity in more than 19,000 patients presenting for emergency care at US pediatric hospitals, approximately 20% were hospitalized, and among those hospitalized almost a quarter required ICU care. Clinical risk factors associated with increased risk of hospitalization include private payor status and selected comorbidities (obesity/type 2 DM; asthma; and cardiovascular, pulmonary, immunocompromised, neurologic/neuromuscular CCCs), while those associated with decreased risk of hospitalization include older age, female sex, and Black race or Hispanic ethnicity. Factors associated with severe disease among hospitalized pediatric patients include Black or other non-White race, school age (≥5 years), and certain chronic conditions (cardiovascular disease, obesity/type 2 DM, neurologic or neuromuscular disease). Sixteen percent of patients had a concurrent diagnosis for a condition or complication associated with COVID-19.

While the study population (ie, children and adolescents presenting to the ED) represents a small fraction of children and adolescents in the community with SARS-CoV-2 infection, the results provide important insight into factors of severe COVID-19 in the pediatric population. A report from France suggested ventilatory or hemodynamic support or death were independently associated with older age (≥10 years), elevated C-reactive protein, and hypoxemia.¹² An Italian study found that younger age (0-4 years) was associated with less severe disease, while preexisting conditions were more likely in patients with severe disease.¹¹ A single-center case series of 50 patients (aged ≤21 years) hospitalized at a children’s hospital in New York City found respiratory failure (n = 9) was more common in children older than 1 year, patients with elevated inflammatory markers, and patients with obesity.²⁰

Our study confirms several factors for severe COVID-19 found in these studies, including older age,^11,12,20 obesity,²⁰ and preexisting conditions.¹¹ Our findings also expand on these reports, including identification of factors associated with hospitalization. Given the rate of 30-day re-encounters among pediatric patients with COVID-19 (10.1%), identifying risk factors for hospitalization may aid ED providers in determining optimal disposition (eg, home, hospital admission, ICU). We also identified specific comorbidities associated with more severe disease in those hospitalized with COVID-19, such as cardiovascular disease, obesity/type 2 DM, and pulmonary, neurologic, or neuromuscular conditions. We also found that asthma increased the risk for hospitalization but not more severe disease among those hospitalized. This latter finding also aligns with recent single-center studies,^21,22 whereas a Turkish study of pediatric patients aged 0 to 18 years found no association between asthma and COVID-19 hospitalizations.²³We also examined payor type and racial/ethnic factors in our analysis. In 2019, patients who identified as Black or Hispanic comprised 52.3% of all encounters and 40.7% of hospitalizations recorded in the PHIS database. During the same year, encounters for influenza among Black or Hispanic pediatric patients comprised 58.7% of all influenza diagnoses and 47.0% of pediatric influenza hospitalizations (Appendix Table 2). In this study, patients who identified as Black or Hispanic race represented a disproportionately large share of patients presenting to children’s hospitals (68.5%) and of those hospitalized (60.8%). Hispanic ethnicity, in particular, represented a disproportionate share of patients seeking care for COVID-19 compared to the overall PHIS population (47.7% and 27.1%, respectively). After accounting for other factors, we found Black and other non-White race—but not of Hispanic ethnicity—were independently associated with more disease severity among those hospitalized. This contrasts with findings from a recent adult study by Yehia et al,²⁴ who found (after adjusting for other clinical factors) no significant difference in mortality between Black patients and White patients among adults hospitalized due to COVID-19. It also contrasts with a recent large population-based UK study wherein pediatric patients identifying as Asian, but not Black or mixed race or ethnicity, had an increased risk of hospital admission and admission to the ICU compared to children identifying as White. Children identifying as Black or mixed race had longer hospital admissions.²⁵ However, as the authors of the study note, residual confounders and ascertainment bias due to differences in COVID testing may have influenced these findings.

Our findings of differences in hospitalization and disease severity among those hospitalized by race and ethnicity should be interpreted carefully. These may reflect a constellation of factors that are difficult to measure, including differences in healthcare access, inequalities in care (including hospital admission inequalities), and implicit bias—all of which may reflect structural racism. For example, it is possible that children who identify as Black or Hispanic have different access to care compared to children who identify as White, and this may affect disease severity on presentation.² Alternatively, it is possible that White pediatric patients are more likely to be hospitalized as compared to non-White pediatric patients with similar illness severity. Our finding that pediatric patients who identify as Hispanic or Black had a lower risk of hospitalization should be also interpreted carefully, as this may reflect higher utilization of the ED for SARS-CoV-2 testing, increased use of nonemergency services among those without access to primary care, or systematic differences in provider decision-making among this segment of the population.² Further study is needed to determine specific drivers for racial and ethnic differences in healthcare utilization in children and adolescents with COVID-19.²⁶

Complications and co-occurring diagnoses in adults with COVID-19 are well documented.^27-30 However, there is little information to date on the co-occurring diagnoses and complications associated with COVID-19 in children and adolescents. We found that complications and co-occurring conditions occurred in 16.3% of the study population, with the most frequent conditions including known complications of viral infections such as pneumonia, respiratory failure, and seizures. Acute kidney and liver injury, as well as thrombotic complications, occurred less commonly than in adults.^26-29 Interestingly, neurologic complications were also uncommon compared to adult reports^8,31 and less frequent than in other viral illnesses in children and adolescents. For example, neurologic complications occur in approximately 7.5% of children and adolescents hospitalized with influenza.³²

Limitations of the present study include the retrospective design, as well as incomplete patient-level clinical data in the PHIS database. The PHIS database only includes children’s hospitals, which may limit the generalizability of findings to community hospitals. We also excluded newborns, and our findings may not be generalizable to this population. We only included children and adolescents with a primary diagnosis of COVID-19, which has the potential for misclassification in cases where COVID-19 was a secondary diagnosis. However, results of our sensitivity analysis, which incorporated secondary diagnoses of COVID-19, were consistent with findings from our main analyses. Our study was designed to examine associations between certain prespecified factors and COVID-19 severity among pediatric patients who visited the ED or were admitted to the hospital during the COVID-19 pandemic. Thus, our findings must be interpreted in light of these considerations and may not be generalizable outside the ED or hospital setting. For example, it could be that some segments of the population utilized ED resources for testing, whereas others avoided the ED and other healthcare settings for fear of exposure to SARS-CoV-2. We also relied on diagnosis codes to identify concurrent diagnoses, as well as mechanical ventilation in our very severe outcome cohort, which resulted in this classification for some of these diagnoses. Despite these limitations, our findings represent an important step in understanding the risk factors associated with severe clinical COVID-19 disease in pediatric patients.

Our findings may inform future research and clinical interventions. Future studies on antiviral therapies and immune modulators targeting SARS-CoV-2 infection in children and adolescents should focus on high-risk populations, such as those identified in the study, as these patients are most likely to benefit from therapeutic interventions. Similarly, vaccine-development efforts may benefit from additional evaluation in high-risk populations, some of which may have altered immune responses. Furthermore, with increasing vaccination among adults and changes in recommendations, societal mitigation efforts (eg, masking, physical distancing) will diminish. Continued vigilance and COVID-19–mitigation efforts among high-risk children, for whom vaccines are not yet available, are critical during this transition.

Among children with COVID-19 who received care at children’s hospitals and EDs, 20% were hospitalized, and, of those, 21% were admitted to the ICU. Older children and adolescent patients had a lower risk of hospitalization; however, when hospitalized, they had greater illness severity. Those with selected comorbidities (eg, cardiovascular, obesity/type 2 DM, pulmonary and neurologic or neuromuscular disease) had both increased odds of hospitalization and in-hospital illness severity. While there were observed differences in COVID-19 severity by race and ethnicity, additional research is needed to clarify the drivers of such disparities. These factors should be considered when prioritizing mitigation strategies to prevent infection (eg, remote learning, avoidance of group activities, prioritization of COVID-19 vaccine when approved for children aged <12 years).

The COVID-19 pandemic has led to more than 40 million infections and more than 650,000 deaths in the United States alone.¹ Morbidity and mortality have disproportionately affected older adults.^2-4 However, acute infection and delayed effects, such as multisystem inflammatory syndrome in children (MIS-C), occur and can lead to severe complications, hospitalization, and death in pediatric patients.^5,6 Due to higher clinical disease prevalence and morbidity in the adult population, we have learned much about the clinical factors associated with severe adult COVID-19 disease.^5,7-9 Such clinical factors include older age, concurrent comorbidities, smoke exposure, and Black race or Hispanic ethnicity, among others.^5,7-10 However, there is a paucity of data on severe COVID-19 disease in pediatric patients.^5,11,12 In addition, most immunization strategies and pharmacologic treatments for COVID-19 have not been evaluated or approved for use in children.¹³ To guide targeted prevention and treatment strategies, there is a critical need to identify children and adolescents—who are among the most vulnerable patient populations—at high risk for severe disease.

Identifying the clinical factors associated with severe COVID-19 disease will help with prioritizing and allocating vaccines when they are approved for use in patients younger than 12 years. It also can provide insight for clinicians and families faced with decisions wherein individual risk assessment is crucial (eg, in-person schooling, other group activities). The objective of this study was to determine the clinical factors associated with severe COVID-19 among children and adolescents in the United States.

Study Design

We conducted a multicenter retrospective cohort study of patients presenting for care at pediatric hospitals that report data to the Pediatric Health Information System (PHIS) database. The PHIS administrative database includes billing and utilization data from 45 US tertiary care hospitals affiliated with the Children’s Hospital Association (Lenexa, Kansas). Data quality and reliability are ensured through a joint validation effort between the Children’s Hospital Association and participating hospitals. Hospitals submit discharge data, including demographics, diagnoses, and procedures using International Classification of Diseases, 10th Revision (ICD-10) codes, along with daily detailed information on pharmacy, location of care, and other services.

Study Population

Patients 30 days to 18 years of age discharged from the emergency department (ED) or inpatient setting with a primary diagnosis of COVID-19 (ICD-10 codes U.071 and U.072) between April 1, 2020, and September 30, 2020, were eligible for inclusion.¹⁴ In a prior study, the positive predictive value of an ICD-10–coded diagnosis of COVID-19 among hospitalized pediatric patients was 95.5%, compared with reverse transcription polymerase reaction results or presence of MIS-C.¹⁵ The diagnostic code for COVID-19 (ICD-10-CM) also had a high sensitivity (98.0%) in the hospitalized population.¹⁶ Acknowledging the increasing practice of screening patients upon admission, and in an attempt to minimize potential misclassification, we did not include encounters with secondary diagnoses of COVID-19 in our primary analyses. Pediatric patients with surgical diagnoses and neonates who never left the hospital were also excluded.

Factors Associated With Severe COVID-19 Disease

Exposures of interest were determined a priori based on current evidence in the literature and included patient age (0-4 years, 5-11 years, and 12-18 years), sex, race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, Asian, other non-White race [defined as Pacific Islander, Native American, or other]), payor type, cardiovascular complex chronic conditions (CCC), neuromuscular CCC, obesity/type 2 diabetes mellitus (DM), pulmonary CCC, asthma (defined using ICD-10 codes¹⁷), and immunocompromised CCC. Race and ethnicity were included as covariates based on previous studies reporting differences in COVID-19 outcomes among racial and ethnic groups.⁹ The CCC covariates were defined using the pediatric CCC ICD-10 classification system version 2.¹⁸

Pediatric Complications and Conditions Associated With COVID-19

Based on current evidence and expert opinion of study members, associated diagnoses and complications co-occurring with a COVID-19 diagnosis were defined a priori and identified through ICD-10 codes (Appendix Table 1). These included acute kidney injury, acute liver injury, aseptic meningitis, asthma exacerbation, bronchiolitis, cerebral infarction, croup, encephalitis, encephalopathy, infant fever, febrile seizure, gastroenteritis/dehydration, Kawasaki disease/MIS-C, myocarditis/pericarditis, pneumonia, lung effusion or empyema, respiratory failure, sepsis, nonfebrile seizure, pancreatitis, sickle cell complications, and thrombotic complications.

Outcomes

COVID-19 severity outcomes were assessed as follows: (1) mild = ED discharge; (2) moderate = inpatient admission; (3) severe = intensive care unit (ICU) admission without mechanical ventilation, shock, or death; and (4) very severe = ICU admission with mechanical ventilation, shock, or death.¹⁹ This ordinal ranking system did not violate the proportional odds assumption. Potential reasons for admission to the ICU without mechanical ventilation, shock, or death include, but are not limited to, need for noninvasive ventilation, vital sign instability, dysrhythmias, respiratory insufficiency, or complications arising from concurrent conditions (eg, thrombotic events, need for continuous albuterol therapy). We examined several secondary, hospital-based outcomes, including associated diagnoses and complications, all-cause 30-day healthcare reutilization (ED visit or rehospitalization), length of stay (LOS), and ICU LOS.

Statistical Analysis

Demographic characteristics were summarized using frequencies and percentages for categorical variables and geometric means with SD and medians with interquartile ranges (IQR) for continuous variables, as appropriate. Factors associated with hospitalization (encompassing severity levels 2-4) vs ED discharge (severity level 1) were assessed using logistic regression. Factors associated with increasing severity among hospitalized pediatric patients (severity levels 2, 3, and 4) were assessed using ordinal logistic regression. Covariates in these analyses included race and ethnicity, age, sex, payor, cardiovascular CCC, neurologic/neuromuscular CCC, obesity/type 2 DM, pulmonary CCC, asthma, and immunocompromised CCC. Adjusted odds ratios (aOR) and corresponding 95% CI for each risk factor were generated using generalized linear mixed effects models and random intercepts for each hospital. Given the potential for diagnostic misclassification of pediatric patients with COVID-19 based on primary vs secondary diagnoses, we performed sensitivity analyses defining the study population as those with a primary diagnosis of COVID-19 and those with a secondary diagnosis of COVID-19 plus a concurrent primary diagnosis of a condition associated with COVID-19 (Appendix Table 1).

All analyses were performed using SAS version 9.4 (SAS Institute, Inc), and P < .05 was considered statistically significant. The Institutional Review Board at Vanderbilt University Medical Center determined that this study of de-identified data did not meet the criteria for human subjects research.

Study Population

A total of 19,976 encounters were included in the study. Of those, 15,913 (79.7%) were discharged from the ED and 4063 (20.3%) were hospitalized (Table 1). The most common race/ethnicity was Hispanic (9741, 48.8%), followed by non-Hispanic White (4217, 21.1%). Reference race/ethnicity data for the overall 2019 PHIS population can be found in Appendix Table 2.

The severity distribution among the hospitalized population was moderate (3222, 79.3%), severe (431, 11.3%), and very severe (380, 9.4%). The frequency of COVID-19 diagnoses increased late in the study period (Figure). Among those hospitalized, the median LOS for the index admission was 2 days (IQR, 1-4), while among those admitted to the ICU, the median LOS was 3 days (IQR, 2-5).

Overall, 10.1% (n = 2020) of the study population had an all-cause repeat encounter (ie, subsequent ED encounter or hospitalization) within 30 days following the index discharge. Repeat encounters were more frequent among patients hospitalized than among those discharged from the ED (Appendix Table 3).

Prevalence of Conditions and Complications Associated With COVID-19

Overall, 3257 (16.3%) patients had one or more co-occurring diagnoses categorized as a COVID-19–associated condition or complication. The most frequent diagnoses included lower respiratory tract disease (pneumonia, lung effusion, or empyema; n = 1415, 7.1%), gastroenteritis/dehydration (n = 1068, 5.3%), respiratory failure (n = 731, 3.7%), febrile infant (n = 413, 2.1%), and nonfebrile seizure (n = 425, 2.1%). Aside from nonfebrile seizure, neurological complications were less frequent and included febrile seizure (n = 155, 0.8%), encephalopathy (n = 63, 0.3%), aseptic meningitis (n = 16, 0.1%), encephalitis (n = 11, 0.1%), and cerebral infarction (n = 6, <0.1%). Kawasaki disease and MIS-C comprised 1.7% (n = 346) of diagnoses. Thrombotic complications occurred in 0.1% (n = 13) of patients. Overall, these conditions and complications associated with COVID-19 were more frequent in hospitalized patients than in those discharged from the ED (P < .001) (Table 2).

Factors Associated With COVID-19 Disease Severity

Compared to pediatric patients with COVID-19 discharged from the ED, factors associated with increased odds of hospitalization included private payor insurance; obesity/type 2 DM; asthma; and cardiovascular, immunocompromised, neurologic/neuromuscular, and pulmonary CCCs (Table 3). Factors associated with decreased risk of hospitalization included Black race or Hispanic ethnicity compared with White race; female sex; and age 5 to 11 years and age 12 to 17 years (vs age 0-4 years). Among children and adolescents hospitalized with COVID-19, factors associated with greater disease severity included Black or other non-White race; age 5 to 11 years; age 12 to 17 years; obesity/type 2 DM; immunocompromised conditions; and cardiovascular, neurologic/neuromuscular, and pulmonary CCCs (Table 3).

Sensitivity Analysis

We performed a sensitivity analysis that expanded the study population to include those with a secondary diagnosis of COVID-19 plus a diagnosis of a COVID-19–associated condition or complication. Analyses using the expanded population (N = 21,247) were similar to the primary analyses (Appendix Table 4 and Appendix Table 5).

In this large multicenter study evaluating COVID-19 disease severity in more than 19,000 patients presenting for emergency care at US pediatric hospitals, approximately 20% were hospitalized, and among those hospitalized almost a quarter required ICU care. Clinical risk factors associated with increased risk of hospitalization include private payor status and selected comorbidities (obesity/type 2 DM; asthma; and cardiovascular, pulmonary, immunocompromised, neurologic/neuromuscular CCCs), while those associated with decreased risk of hospitalization include older age, female sex, and Black race or Hispanic ethnicity. Factors associated with severe disease among hospitalized pediatric patients include Black or other non-White race, school age (≥5 years), and certain chronic conditions (cardiovascular disease, obesity/type 2 DM, neurologic or neuromuscular disease). Sixteen percent of patients had a concurrent diagnosis for a condition or complication associated with COVID-19.

While the study population (ie, children and adolescents presenting to the ED) represents a small fraction of children and adolescents in the community with SARS-CoV-2 infection, the results provide important insight into factors of severe COVID-19 in the pediatric population. A report from France suggested ventilatory or hemodynamic support or death were independently associated with older age (≥10 years), elevated C-reactive protein, and hypoxemia.¹² An Italian study found that younger age (0-4 years) was associated with less severe disease, while preexisting conditions were more likely in patients with severe disease.¹¹ A single-center case series of 50 patients (aged ≤21 years) hospitalized at a children’s hospital in New York City found respiratory failure (n = 9) was more common in children older than 1 year, patients with elevated inflammatory markers, and patients with obesity.²⁰

Our study confirms several factors for severe COVID-19 found in these studies, including older age,^11,12,20 obesity,²⁰ and preexisting conditions.¹¹ Our findings also expand on these reports, including identification of factors associated with hospitalization. Given the rate of 30-day re-encounters among pediatric patients with COVID-19 (10.1%), identifying risk factors for hospitalization may aid ED providers in determining optimal disposition (eg, home, hospital admission, ICU). We also identified specific comorbidities associated with more severe disease in those hospitalized with COVID-19, such as cardiovascular disease, obesity/type 2 DM, and pulmonary, neurologic, or neuromuscular conditions. We also found that asthma increased the risk for hospitalization but not more severe disease among those hospitalized. This latter finding also aligns with recent single-center studies,^21,22 whereas a Turkish study of pediatric patients aged 0 to 18 years found no association between asthma and COVID-19 hospitalizations.²³We also examined payor type and racial/ethnic factors in our analysis. In 2019, patients who identified as Black or Hispanic comprised 52.3% of all encounters and 40.7% of hospitalizations recorded in the PHIS database. During the same year, encounters for influenza among Black or Hispanic pediatric patients comprised 58.7% of all influenza diagnoses and 47.0% of pediatric influenza hospitalizations (Appendix Table 2). In this study, patients who identified as Black or Hispanic race represented a disproportionately large share of patients presenting to children’s hospitals (68.5%) and of those hospitalized (60.8%). Hispanic ethnicity, in particular, represented a disproportionate share of patients seeking care for COVID-19 compared to the overall PHIS population (47.7% and 27.1%, respectively). After accounting for other factors, we found Black and other non-White race—but not of Hispanic ethnicity—were independently associated with more disease severity among those hospitalized. This contrasts with findings from a recent adult study by Yehia et al,²⁴ who found (after adjusting for other clinical factors) no significant difference in mortality between Black patients and White patients among adults hospitalized due to COVID-19. It also contrasts with a recent large population-based UK study wherein pediatric patients identifying as Asian, but not Black or mixed race or ethnicity, had an increased risk of hospital admission and admission to the ICU compared to children identifying as White. Children identifying as Black or mixed race had longer hospital admissions.²⁵ However, as the authors of the study note, residual confounders and ascertainment bias due to differences in COVID testing may have influenced these findings.

Our findings of differences in hospitalization and disease severity among those hospitalized by race and ethnicity should be interpreted carefully. These may reflect a constellation of factors that are difficult to measure, including differences in healthcare access, inequalities in care (including hospital admission inequalities), and implicit bias—all of which may reflect structural racism. For example, it is possible that children who identify as Black or Hispanic have different access to care compared to children who identify as White, and this may affect disease severity on presentation.² Alternatively, it is possible that White pediatric patients are more likely to be hospitalized as compared to non-White pediatric patients with similar illness severity. Our finding that pediatric patients who identify as Hispanic or Black had a lower risk of hospitalization should be also interpreted carefully, as this may reflect higher utilization of the ED for SARS-CoV-2 testing, increased use of nonemergency services among those without access to primary care, or systematic differences in provider decision-making among this segment of the population.² Further study is needed to determine specific drivers for racial and ethnic differences in healthcare utilization in children and adolescents with COVID-19.²⁶

Complications and co-occurring diagnoses in adults with COVID-19 are well documented.^27-30 However, there is little information to date on the co-occurring diagnoses and complications associated with COVID-19 in children and adolescents. We found that complications and co-occurring conditions occurred in 16.3% of the study population, with the most frequent conditions including known complications of viral infections such as pneumonia, respiratory failure, and seizures. Acute kidney and liver injury, as well as thrombotic complications, occurred less commonly than in adults.^26-29 Interestingly, neurologic complications were also uncommon compared to adult reports^8,31 and less frequent than in other viral illnesses in children and adolescents. For example, neurologic complications occur in approximately 7.5% of children and adolescents hospitalized with influenza.³²

Limitations of the present study include the retrospective design, as well as incomplete patient-level clinical data in the PHIS database. The PHIS database only includes children’s hospitals, which may limit the generalizability of findings to community hospitals. We also excluded newborns, and our findings may not be generalizable to this population. We only included children and adolescents with a primary diagnosis of COVID-19, which has the potential for misclassification in cases where COVID-19 was a secondary diagnosis. However, results of our sensitivity analysis, which incorporated secondary diagnoses of COVID-19, were consistent with findings from our main analyses. Our study was designed to examine associations between certain prespecified factors and COVID-19 severity among pediatric patients who visited the ED or were admitted to the hospital during the COVID-19 pandemic. Thus, our findings must be interpreted in light of these considerations and may not be generalizable outside the ED or hospital setting. For example, it could be that some segments of the population utilized ED resources for testing, whereas others avoided the ED and other healthcare settings for fear of exposure to SARS-CoV-2. We also relied on diagnosis codes to identify concurrent diagnoses, as well as mechanical ventilation in our very severe outcome cohort, which resulted in this classification for some of these diagnoses. Despite these limitations, our findings represent an important step in understanding the risk factors associated with severe clinical COVID-19 disease in pediatric patients.

Our findings may inform future research and clinical interventions. Future studies on antiviral therapies and immune modulators targeting SARS-CoV-2 infection in children and adolescents should focus on high-risk populations, such as those identified in the study, as these patients are most likely to benefit from therapeutic interventions. Similarly, vaccine-development efforts may benefit from additional evaluation in high-risk populations, some of which may have altered immune responses. Furthermore, with increasing vaccination among adults and changes in recommendations, societal mitigation efforts (eg, masking, physical distancing) will diminish. Continued vigilance and COVID-19–mitigation efforts among high-risk children, for whom vaccines are not yet available, are critical during this transition.

Among children with COVID-19 who received care at children’s hospitals and EDs, 20% were hospitalized, and, of those, 21% were admitted to the ICU. Older children and adolescent patients had a lower risk of hospitalization; however, when hospitalized, they had greater illness severity. Those with selected comorbidities (eg, cardiovascular, obesity/type 2 DM, pulmonary and neurologic or neuromuscular disease) had both increased odds of hospitalization and in-hospital illness severity. While there were observed differences in COVID-19 severity by race and ethnicity, additional research is needed to clarify the drivers of such disparities. These factors should be considered when prioritizing mitigation strategies to prevent infection (eg, remote learning, avoidance of group activities, prioritization of COVID-19 vaccine when approved for children aged <12 years).

The COVID-19 pandemic has led to more than 40 million infections and more than 650,000 deaths in the United States alone.¹ Morbidity and mortality have disproportionately affected older adults.^2-4 However, acute infection and delayed effects, such as multisystem inflammatory syndrome in children (MIS-C), occur and can lead to severe complications, hospitalization, and death in pediatric patients.^5,6 Due to higher clinical disease prevalence and morbidity in the adult population, we have learned much about the clinical factors associated with severe adult COVID-19 disease.^5,7-9 Such clinical factors include older age, concurrent comorbidities, smoke exposure, and Black race or Hispanic ethnicity, among others.^5,7-10 However, there is a paucity of data on severe COVID-19 disease in pediatric patients.^5,11,12 In addition, most immunization strategies and pharmacologic treatments for COVID-19 have not been evaluated or approved for use in children.¹³ To guide targeted prevention and treatment strategies, there is a critical need to identify children and adolescents—who are among the most vulnerable patient populations—at high risk for severe disease.

Identifying the clinical factors associated with severe COVID-19 disease will help with prioritizing and allocating vaccines when they are approved for use in patients younger than 12 years. It also can provide insight for clinicians and families faced with decisions wherein individual risk assessment is crucial (eg, in-person schooling, other group activities). The objective of this study was to determine the clinical factors associated with severe COVID-19 among children and adolescents in the United States.

Study Design

We conducted a multicenter retrospective cohort study of patients presenting for care at pediatric hospitals that report data to the Pediatric Health Information System (PHIS) database. The PHIS administrative database includes billing and utilization data from 45 US tertiary care hospitals affiliated with the Children’s Hospital Association (Lenexa, Kansas). Data quality and reliability are ensured through a joint validation effort between the Children’s Hospital Association and participating hospitals. Hospitals submit discharge data, including demographics, diagnoses, and procedures using International Classification of Diseases, 10th Revision (ICD-10) codes, along with daily detailed information on pharmacy, location of care, and other services.

Study Population

Patients 30 days to 18 years of age discharged from the emergency department (ED) or inpatient setting with a primary diagnosis of COVID-19 (ICD-10 codes U.071 and U.072) between April 1, 2020, and September 30, 2020, were eligible for inclusion.¹⁴ In a prior study, the positive predictive value of an ICD-10–coded diagnosis of COVID-19 among hospitalized pediatric patients was 95.5%, compared with reverse transcription polymerase reaction results or presence of MIS-C.¹⁵ The diagnostic code for COVID-19 (ICD-10-CM) also had a high sensitivity (98.0%) in the hospitalized population.¹⁶ Acknowledging the increasing practice of screening patients upon admission, and in an attempt to minimize potential misclassification, we did not include encounters with secondary diagnoses of COVID-19 in our primary analyses. Pediatric patients with surgical diagnoses and neonates who never left the hospital were also excluded.

Factors Associated With Severe COVID-19 Disease

Exposures of interest were determined a priori based on current evidence in the literature and included patient age (0-4 years, 5-11 years, and 12-18 years), sex, race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, Asian, other non-White race [defined as Pacific Islander, Native American, or other]), payor type, cardiovascular complex chronic conditions (CCC), neuromuscular CCC, obesity/type 2 diabetes mellitus (DM), pulmonary CCC, asthma (defined using ICD-10 codes¹⁷), and immunocompromised CCC. Race and ethnicity were included as covariates based on previous studies reporting differences in COVID-19 outcomes among racial and ethnic groups.⁹ The CCC covariates were defined using the pediatric CCC ICD-10 classification system version 2.¹⁸

Pediatric Complications and Conditions Associated With COVID-19

Based on current evidence and expert opinion of study members, associated diagnoses and complications co-occurring with a COVID-19 diagnosis were defined a priori and identified through ICD-10 codes (Appendix Table 1). These included acute kidney injury, acute liver injury, aseptic meningitis, asthma exacerbation, bronchiolitis, cerebral infarction, croup, encephalitis, encephalopathy, infant fever, febrile seizure, gastroenteritis/dehydration, Kawasaki disease/MIS-C, myocarditis/pericarditis, pneumonia, lung effusion or empyema, respiratory failure, sepsis, nonfebrile seizure, pancreatitis, sickle cell complications, and thrombotic complications.

Outcomes

COVID-19 severity outcomes were assessed as follows: (1) mild = ED discharge; (2) moderate = inpatient admission; (3) severe = intensive care unit (ICU) admission without mechanical ventilation, shock, or death; and (4) very severe = ICU admission with mechanical ventilation, shock, or death.¹⁹ This ordinal ranking system did not violate the proportional odds assumption. Potential reasons for admission to the ICU without mechanical ventilation, shock, or death include, but are not limited to, need for noninvasive ventilation, vital sign instability, dysrhythmias, respiratory insufficiency, or complications arising from concurrent conditions (eg, thrombotic events, need for continuous albuterol therapy). We examined several secondary, hospital-based outcomes, including associated diagnoses and complications, all-cause 30-day healthcare reutilization (ED visit or rehospitalization), length of stay (LOS), and ICU LOS.

Statistical Analysis

Demographic characteristics were summarized using frequencies and percentages for categorical variables and geometric means with SD and medians with interquartile ranges (IQR) for continuous variables, as appropriate. Factors associated with hospitalization (encompassing severity levels 2-4) vs ED discharge (severity level 1) were assessed using logistic regression. Factors associated with increasing severity among hospitalized pediatric patients (severity levels 2, 3, and 4) were assessed using ordinal logistic regression. Covariates in these analyses included race and ethnicity, age, sex, payor, cardiovascular CCC, neurologic/neuromuscular CCC, obesity/type 2 DM, pulmonary CCC, asthma, and immunocompromised CCC. Adjusted odds ratios (aOR) and corresponding 95% CI for each risk factor were generated using generalized linear mixed effects models and random intercepts for each hospital. Given the potential for diagnostic misclassification of pediatric patients with COVID-19 based on primary vs secondary diagnoses, we performed sensitivity analyses defining the study population as those with a primary diagnosis of COVID-19 and those with a secondary diagnosis of COVID-19 plus a concurrent primary diagnosis of a condition associated with COVID-19 (Appendix Table 1).

All analyses were performed using SAS version 9.4 (SAS Institute, Inc), and P < .05 was considered statistically significant. The Institutional Review Board at Vanderbilt University Medical Center determined that this study of de-identified data did not meet the criteria for human subjects research.

Study Population

A total of 19,976 encounters were included in the study. Of those, 15,913 (79.7%) were discharged from the ED and 4063 (20.3%) were hospitalized (Table 1). The most common race/ethnicity was Hispanic (9741, 48.8%), followed by non-Hispanic White (4217, 21.1%). Reference race/ethnicity data for the overall 2019 PHIS population can be found in Appendix Table 2.

The severity distribution among the hospitalized population was moderate (3222, 79.3%), severe (431, 11.3%), and very severe (380, 9.4%). The frequency of COVID-19 diagnoses increased late in the study period (Figure). Among those hospitalized, the median LOS for the index admission was 2 days (IQR, 1-4), while among those admitted to the ICU, the median LOS was 3 days (IQR, 2-5).

Overall, 10.1% (n = 2020) of the study population had an all-cause repeat encounter (ie, subsequent ED encounter or hospitalization) within 30 days following the index discharge. Repeat encounters were more frequent among patients hospitalized than among those discharged from the ED (Appendix Table 3).

Prevalence of Conditions and Complications Associated With COVID-19

Overall, 3257 (16.3%) patients had one or more co-occurring diagnoses categorized as a COVID-19–associated condition or complication. The most frequent diagnoses included lower respiratory tract disease (pneumonia, lung effusion, or empyema; n = 1415, 7.1%), gastroenteritis/dehydration (n = 1068, 5.3%), respiratory failure (n = 731, 3.7%), febrile infant (n = 413, 2.1%), and nonfebrile seizure (n = 425, 2.1%). Aside from nonfebrile seizure, neurological complications were less frequent and included febrile seizure (n = 155, 0.8%), encephalopathy (n = 63, 0.3%), aseptic meningitis (n = 16, 0.1%), encephalitis (n = 11, 0.1%), and cerebral infarction (n = 6, <0.1%). Kawasaki disease and MIS-C comprised 1.7% (n = 346) of diagnoses. Thrombotic complications occurred in 0.1% (n = 13) of patients. Overall, these conditions and complications associated with COVID-19 were more frequent in hospitalized patients than in those discharged from the ED (P < .001) (Table 2).

Factors Associated With COVID-19 Disease Severity

Compared to pediatric patients with COVID-19 discharged from the ED, factors associated with increased odds of hospitalization included private payor insurance; obesity/type 2 DM; asthma; and cardiovascular, immunocompromised, neurologic/neuromuscular, and pulmonary CCCs (Table 3). Factors associated with decreased risk of hospitalization included Black race or Hispanic ethnicity compared with White race; female sex; and age 5 to 11 years and age 12 to 17 years (vs age 0-4 years). Among children and adolescents hospitalized with COVID-19, factors associated with greater disease severity included Black or other non-White race; age 5 to 11 years; age 12 to 17 years; obesity/type 2 DM; immunocompromised conditions; and cardiovascular, neurologic/neuromuscular, and pulmonary CCCs (Table 3).

Sensitivity Analysis

We performed a sensitivity analysis that expanded the study population to include those with a secondary diagnosis of COVID-19 plus a diagnosis of a COVID-19–associated condition or complication. Analyses using the expanded population (N = 21,247) were similar to the primary analyses (Appendix Table 4 and Appendix Table 5).

In this large multicenter study evaluating COVID-19 disease severity in more than 19,000 patients presenting for emergency care at US pediatric hospitals, approximately 20% were hospitalized, and among those hospitalized almost a quarter required ICU care. Clinical risk factors associated with increased risk of hospitalization include private payor status and selected comorbidities (obesity/type 2 DM; asthma; and cardiovascular, pulmonary, immunocompromised, neurologic/neuromuscular CCCs), while those associated with decreased risk of hospitalization include older age, female sex, and Black race or Hispanic ethnicity. Factors associated with severe disease among hospitalized pediatric patients include Black or other non-White race, school age (≥5 years), and certain chronic conditions (cardiovascular disease, obesity/type 2 DM, neurologic or neuromuscular disease). Sixteen percent of patients had a concurrent diagnosis for a condition or complication associated with COVID-19.

While the study population (ie, children and adolescents presenting to the ED) represents a small fraction of children and adolescents in the community with SARS-CoV-2 infection, the results provide important insight into factors of severe COVID-19 in the pediatric population. A report from France suggested ventilatory or hemodynamic support or death were independently associated with older age (≥10 years), elevated C-reactive protein, and hypoxemia.¹² An Italian study found that younger age (0-4 years) was associated with less severe disease, while preexisting conditions were more likely in patients with severe disease.¹¹ A single-center case series of 50 patients (aged ≤21 years) hospitalized at a children’s hospital in New York City found respiratory failure (n = 9) was more common in children older than 1 year, patients with elevated inflammatory markers, and patients with obesity.²⁰

Our study confirms several factors for severe COVID-19 found in these studies, including older age,^11,12,20 obesity,²⁰ and preexisting conditions.¹¹ Our findings also expand on these reports, including identification of factors associated with hospitalization. Given the rate of 30-day re-encounters among pediatric patients with COVID-19 (10.1%), identifying risk factors for hospitalization may aid ED providers in determining optimal disposition (eg, home, hospital admission, ICU). We also identified specific comorbidities associated with more severe disease in those hospitalized with COVID-19, such as cardiovascular disease, obesity/type 2 DM, and pulmonary, neurologic, or neuromuscular conditions. We also found that asthma increased the risk for hospitalization but not more severe disease among those hospitalized. This latter finding also aligns with recent single-center studies,^21,22 whereas a Turkish study of pediatric patients aged 0 to 18 years found no association between asthma and COVID-19 hospitalizations.²³We also examined payor type and racial/ethnic factors in our analysis. In 2019, patients who identified as Black or Hispanic comprised 52.3% of all encounters and 40.7% of hospitalizations recorded in the PHIS database. During the same year, encounters for influenza among Black or Hispanic pediatric patients comprised 58.7% of all influenza diagnoses and 47.0% of pediatric influenza hospitalizations (Appendix Table 2). In this study, patients who identified as Black or Hispanic race represented a disproportionately large share of patients presenting to children’s hospitals (68.5%) and of those hospitalized (60.8%). Hispanic ethnicity, in particular, represented a disproportionate share of patients seeking care for COVID-19 compared to the overall PHIS population (47.7% and 27.1%, respectively). After accounting for other factors, we found Black and other non-White race—but not of Hispanic ethnicity—were independently associated with more disease severity among those hospitalized. This contrasts with findings from a recent adult study by Yehia et al,²⁴ who found (after adjusting for other clinical factors) no significant difference in mortality between Black patients and White patients among adults hospitalized due to COVID-19. It also contrasts with a recent large population-based UK study wherein pediatric patients identifying as Asian, but not Black or mixed race or ethnicity, had an increased risk of hospital admission and admission to the ICU compared to children identifying as White. Children identifying as Black or mixed race had longer hospital admissions.²⁵ However, as the authors of the study note, residual confounders and ascertainment bias due to differences in COVID testing may have influenced these findings.

Our findings of differences in hospitalization and disease severity among those hospitalized by race and ethnicity should be interpreted carefully. These may reflect a constellation of factors that are difficult to measure, including differences in healthcare access, inequalities in care (including hospital admission inequalities), and implicit bias—all of which may reflect structural racism. For example, it is possible that children who identify as Black or Hispanic have different access to care compared to children who identify as White, and this may affect disease severity on presentation.² Alternatively, it is possible that White pediatric patients are more likely to be hospitalized as compared to non-White pediatric patients with similar illness severity. Our finding that pediatric patients who identify as Hispanic or Black had a lower risk of hospitalization should be also interpreted carefully, as this may reflect higher utilization of the ED for SARS-CoV-2 testing, increased use of nonemergency services among those without access to primary care, or systematic differences in provider decision-making among this segment of the population.² Further study is needed to determine specific drivers for racial and ethnic differences in healthcare utilization in children and adolescents with COVID-19.²⁶

Complications and co-occurring diagnoses in adults with COVID-19 are well documented.^27-30 However, there is little information to date on the co-occurring diagnoses and complications associated with COVID-19 in children and adolescents. We found that complications and co-occurring conditions occurred in 16.3% of the study population, with the most frequent conditions including known complications of viral infections such as pneumonia, respiratory failure, and seizures. Acute kidney and liver injury, as well as thrombotic complications, occurred less commonly than in adults.^26-29 Interestingly, neurologic complications were also uncommon compared to adult reports^8,31 and less frequent than in other viral illnesses in children and adolescents. For example, neurologic complications occur in approximately 7.5% of children and adolescents hospitalized with influenza.³²

Limitations of the present study include the retrospective design, as well as incomplete patient-level clinical data in the PHIS database. The PHIS database only includes children’s hospitals, which may limit the generalizability of findings to community hospitals. We also excluded newborns, and our findings may not be generalizable to this population. We only included children and adolescents with a primary diagnosis of COVID-19, which has the potential for misclassification in cases where COVID-19 was a secondary diagnosis. However, results of our sensitivity analysis, which incorporated secondary diagnoses of COVID-19, were consistent with findings from our main analyses. Our study was designed to examine associations between certain prespecified factors and COVID-19 severity among pediatric patients who visited the ED or were admitted to the hospital during the COVID-19 pandemic. Thus, our findings must be interpreted in light of these considerations and may not be generalizable outside the ED or hospital setting. For example, it could be that some segments of the population utilized ED resources for testing, whereas others avoided the ED and other healthcare settings for fear of exposure to SARS-CoV-2. We also relied on diagnosis codes to identify concurrent diagnoses, as well as mechanical ventilation in our very severe outcome cohort, which resulted in this classification for some of these diagnoses. Despite these limitations, our findings represent an important step in understanding the risk factors associated with severe clinical COVID-19 disease in pediatric patients.

Our findings may inform future research and clinical interventions. Future studies on antiviral therapies and immune modulators targeting SARS-CoV-2 infection in children and adolescents should focus on high-risk populations, such as those identified in the study, as these patients are most likely to benefit from therapeutic interventions. Similarly, vaccine-development efforts may benefit from additional evaluation in high-risk populations, some of which may have altered immune responses. Furthermore, with increasing vaccination among adults and changes in recommendations, societal mitigation efforts (eg, masking, physical distancing) will diminish. Continued vigilance and COVID-19–mitigation efforts among high-risk children, for whom vaccines are not yet available, are critical during this transition.

Among children with COVID-19 who received care at children’s hospitals and EDs, 20% were hospitalized, and, of those, 21% were admitted to the ICU. Older children and adolescent patients had a lower risk of hospitalization; however, when hospitalized, they had greater illness severity. Those with selected comorbidities (eg, cardiovascular, obesity/type 2 DM, pulmonary and neurologic or neuromuscular disease) had both increased odds of hospitalization and in-hospital illness severity. While there were observed differences in COVID-19 severity by race and ethnicity, additional research is needed to clarify the drivers of such disparities. These factors should be considered when prioritizing mitigation strategies to prevent infection (eg, remote learning, avoidance of group activities, prioritization of COVID-19 vaccine when approved for children aged <12 years).

In the United States, respiratory illnesses are the most common cause of emergency department (ED) visits and hospitalizations in children.¹ In response to the ongoing COVID-19 pandemic, several public health interventions, including school and business closures, stay-at-home orders, and mask mandates, were implemented to limit transmission of SARS-CoV-2.^2,3 Studies have shown that children can contribute to the spread of SARS-CoV-2 infections, especially within households.^4-6 Recent data suggest that COVID-19, and the associated public health measures enacted to slow its spread, may have affected the transmission of other respiratory pathogens.⁷ Similarly, the pandemic has likely affected healthcare utilization for nonrespiratory illnesses through adoption of social distancing recommendations, suspension and delays in nonemergent elective care, avoidance of healthcare settings, and the effect of decreased respiratory disease on exacerbation of chronic illness.⁸ The objective of this study was to examine associations between the COVID-19 pandemic and healthcare utilization for pediatric respiratory and nonrespiratory illnesses at US pediatric hospitals.

Study Design

This is a multicenter, cross-sectional study of encounters at 44 pediatric hospitals that reported data to the Pediatric Health Information System (PHIS) database maintained by the Children’s Hospital Association (Lenexa, Kansas).

Study Population

Children 2 months to 18 years of age discharged from ED or inpatient settings with a nonsurgical diagnosis from January 1 to September 30 over a 4-year period (2017-2020) were included.

Exposure

The primary exposure was the 2020 COVID-19 pandemic time, divided into three periods: pre-COVID-19 (January-February 2020, the period prior to the pandemic in the United States), early COVID-19 (March-April 2020, coinciding with the first reported US pediatric case of COVID-19 on March 2, 2020), and COVID-19 (May-September 2020, marked by the implementation of at least two of the following containment measures in every US state: stay-at-home/shelter orders, school closures, nonessential business closures, restaurant closures, or prohibition of gatherings of more than 10 people).²

Outcomes

Respiratory illness diagnoses were classified into mutually exclusive subgroups following a prespecified hierarchy: influenza, pneumonia, croup, bronchiolitis, asthma, unspecified influenza-like illness, and “other respiratory diagnoses” (Appendix Table 1). To assess the impact of COVID-19 after its International Classification of Diseases, Tenth Revision code was established on March 25, 2020, the “other respiratory” subgroup was divided into other respiratory illnesses with and without COVID-19. Nonrespiratory illness diagnoses were defined as all diagnoses not included in the respiratory illness cohort.

Statistical Analysis

Categorical variables were summarized using frequencies and percentages and compared using chi-square tests. Continuous variables were summarized as median and interquartile range (IQR) and compared using Wilcoxon rank sum tests. Weekly observed-to-expected (O:E) ratios were calculated for each hospital by dividing the number of observed respiratory illness and nonrespiratory illness encounters in a given week in 2020 (observed) by the average number of encounters for that same week during 2017-2019 (expected). O:E ratios were then aggregated over the three COVID-19 study periods, and 95% confidence intervals were established around mean O:E ratios across individual hospitals. Outcomes were then stratified by respiratory illness subgroups, geographic region, and age. Additional details can be found in the Supplemental Methods in the Appendix.

Study Population

A total of 9,051,980 encounters were included in the study, 6,811,799 with nonrespiratory illnesses and 2,240,181 with respiratory illnesses. Median age was 5 years (IQR, 1-11 years), and 52.7% of the population was male (Appendix Table 2 and Appendix Table 3).

Respiratory vs Nonrespiratory Illness During the COVID-19 Pandemic

Over the study period, fewer respiratory and nonrespiratory illness encounters were observed than expected, with a larger decrease in respiratory illness encounters (Table, Appendix Table 4).

Respiratory Subgroup Analyses

The O:E ratio decreased for all respiratory subgroups over the study period (Table, Appendix Table 4). There were significant differences in specific respiratory subgroups, including asthma, bronchiolitis, croup, influenza, and pneumonia (Appendix Figure 1A). Temporal trends in respiratory encounters were consistent across hospital settings, ages, and geographic regions (Appendix Figure 1B-D). When comparing the with and without COVID-19 subgroups in the “other respiratory illnesses” cohort, other respiratory illness without COVID-19 decreased and remained lower than expected over the rest of the study period, while other respiratory illness with COVID-19 increased markedly during the summer months and declined thereafter (Appendix Figure 2).

All age groups had reductions in respiratory illness encounters during the early COVID-19 and COVID-19 periods, although the decline was less pronounced in the 12- to 17-year-old group (Appendix Figure 1B). Similarly, while all age groups experienced increases in encounters for respiratory illnesses during the summer months, only children in the 12- to 17-year-old group experienced increases beyond pre-COVID-19 levels. Importantly, this increase in respiratory encounters was largely driven by COVID-19 diagnoses (Appendix Figure 3). The trend in nonrespiratory illness encounters stratified by age is shown in Appendix Figure 4.

When patients were stratified by hospital setting, there were no differences between those hospitalized and those discharged from the ED (Appendix Figure 1C). Patterns in respiratory illnesses by geographic location were qualitatively similar until the beginning of the summer 2020, after which geographical variation became more evident (Appendix Figure 1D).

In this large, multicenter study evaluating ED visits and hospitalizations for respiratory and nonrespiratory illnesses at US pediatric hospitals during the 2020 COVID-19 pandemic, we found a significant and substantial decrease in healthcare encounters for respiratory illnesses. A rapid and marked decline in encounters for respiratory illness in a relatively short period of time (March 12-April 2) was observed across all hospitals and US regions. Declines were consistent across common respiratory illnesses. More modest, yet still substantial, declines were also observed for nonrespiratory illnesses.

There are likely multiple underlying reasons for the observed reductions. Social distancing measures almost certainly played an important role in interrupting respiratory infection transmission. Rapid reduction in influenza transmission during the early COVID-19 period has been attributed to social distancing measures,³ and influenza transmission in children decreases with school closures.⁹ It is also possible that some families delayed seeking care at hospitals due to COVID-19, leading to less frequent encounters but more severe illness. The similar decrease in O:E ratio for ED visits and hospitalizations, however, is inconsistent with this explanation. It is also possible that nonurgent conditions cared for in the hospital settings were diverted to other care settings. For example, during this pandemic, telehealth and telephone visits for pediatric asthma increased by 61% and 19%, respectively, while ED and outpatient visits decreased concurrently.¹⁰Similar changes in location of care may also contribute to the decline in nonrespiratory illness encounters. Decreased use of hospital resources for nonurgent care diagnoses during the pandemic would suggest that, prior to COVID-19, there was overutilization of ambulatory services at children’s hospitals. Therefore, the pandemic may be driving care to more appropriate settings.

We also found relative differences in changes in encounters for respiratory illness by age. Adolescents’ levels of respiratory healthcare use declined less and recovered at a faster rate than those of younger children, returning to pre-COVID-19 levels by the end of the study period. The reason for this age differential is likely multifaceted. Infections, such as bronchiolitis and pneumonia, are more likely to be a source of respiratory illness in younger than in older children. It is also likely that disproportionate relaxation of social distancing measures among adolescents, who are known to have a stronger pattern of social interaction, contributed to the faster rise in respiratory illness–related encounters in this age group.¹¹ Adolescents have been reported to be more susceptible to, and more likely to transmit, SARS-CoV-2 compared to younger age groups.¹² More modest, albeit similar, age-based changes were observed in encounters for nonrespiratory illnesses. It is possible that pandemic-related stressors resulted in a subsequent increase in mental health encounters among this age group.¹³ While the reason for this also is likely multifactorial, adolescent behavior, as well as transmission of infectious illness that can exacerbate nonrespiratory conditions, may be a factor.

Emerging evidence suggests that school-age children may play an important role in SARS-CoV-2 transmission in the community.^4,14 Our finding that, compared to younger children, adolescents had significantly fewer reductions in respiratory illness encounters is concerning. These findings suggest that community-based efforts to help prevent respiratory illnesses, especially COVID-19, should focus on adolescents, who are most likely to maintain social interactions and transmit respiratory infections in the school setting and their households.

This study is limited by the inclusion of only tertiary care children’s hospitals, which may not be nationally representative, and the inability to assess the precise timing of when specific public health interventions were introduced. Moreover, previous studies suggest that social distancing behaviors may have changed even before formal recommendations were enacted.¹⁵ Future studies should investigate the local impact of state- and municipality-specific mandates on the burden of COVID-19 and other respiratory illnesses.

The COVID-19 pandemic was associated with substantial reductions in encounters for respiratory diseases, and also with more modest but still sizable reductions in encounters for nonrespiratory diseases. These reductions varied by age. Encounters among adolescents declined less and returned to previous levels faster compared with those of younger children.

This publication is dedicated to the memory of our coauthor, Dr. Michael Bendel-Stenzel. Dr. Bendel-Stenzel was dedicated to bettering the lives of children and advancing our knowledge of pediatrics through his research.

In the United States, respiratory illnesses are the most common cause of emergency department (ED) visits and hospitalizations in children.¹ In response to the ongoing COVID-19 pandemic, several public health interventions, including school and business closures, stay-at-home orders, and mask mandates, were implemented to limit transmission of SARS-CoV-2.^2,3 Studies have shown that children can contribute to the spread of SARS-CoV-2 infections, especially within households.^4-6 Recent data suggest that COVID-19, and the associated public health measures enacted to slow its spread, may have affected the transmission of other respiratory pathogens.⁷ Similarly, the pandemic has likely affected healthcare utilization for nonrespiratory illnesses through adoption of social distancing recommendations, suspension and delays in nonemergent elective care, avoidance of healthcare settings, and the effect of decreased respiratory disease on exacerbation of chronic illness.⁸ The objective of this study was to examine associations between the COVID-19 pandemic and healthcare utilization for pediatric respiratory and nonrespiratory illnesses at US pediatric hospitals.

Study Design

This is a multicenter, cross-sectional study of encounters at 44 pediatric hospitals that reported data to the Pediatric Health Information System (PHIS) database maintained by the Children’s Hospital Association (Lenexa, Kansas).

Study Population

Children 2 months to 18 years of age discharged from ED or inpatient settings with a nonsurgical diagnosis from January 1 to September 30 over a 4-year period (2017-2020) were included.

Exposure

The primary exposure was the 2020 COVID-19 pandemic time, divided into three periods: pre-COVID-19 (January-February 2020, the period prior to the pandemic in the United States), early COVID-19 (March-April 2020, coinciding with the first reported US pediatric case of COVID-19 on March 2, 2020), and COVID-19 (May-September 2020, marked by the implementation of at least two of the following containment measures in every US state: stay-at-home/shelter orders, school closures, nonessential business closures, restaurant closures, or prohibition of gatherings of more than 10 people).²

Outcomes

Respiratory illness diagnoses were classified into mutually exclusive subgroups following a prespecified hierarchy: influenza, pneumonia, croup, bronchiolitis, asthma, unspecified influenza-like illness, and “other respiratory diagnoses” (Appendix Table 1). To assess the impact of COVID-19 after its International Classification of Diseases, Tenth Revision code was established on March 25, 2020, the “other respiratory” subgroup was divided into other respiratory illnesses with and without COVID-19. Nonrespiratory illness diagnoses were defined as all diagnoses not included in the respiratory illness cohort.

Statistical Analysis

Categorical variables were summarized using frequencies and percentages and compared using chi-square tests. Continuous variables were summarized as median and interquartile range (IQR) and compared using Wilcoxon rank sum tests. Weekly observed-to-expected (O:E) ratios were calculated for each hospital by dividing the number of observed respiratory illness and nonrespiratory illness encounters in a given week in 2020 (observed) by the average number of encounters for that same week during 2017-2019 (expected). O:E ratios were then aggregated over the three COVID-19 study periods, and 95% confidence intervals were established around mean O:E ratios across individual hospitals. Outcomes were then stratified by respiratory illness subgroups, geographic region, and age. Additional details can be found in the Supplemental Methods in the Appendix.

Study Population

A total of 9,051,980 encounters were included in the study, 6,811,799 with nonrespiratory illnesses and 2,240,181 with respiratory illnesses. Median age was 5 years (IQR, 1-11 years), and 52.7% of the population was male (Appendix Table 2 and Appendix Table 3).

Respiratory vs Nonrespiratory Illness During the COVID-19 Pandemic

Over the study period, fewer respiratory and nonrespiratory illness encounters were observed than expected, with a larger decrease in respiratory illness encounters (Table, Appendix Table 4).

Respiratory Subgroup Analyses

The O:E ratio decreased for all respiratory subgroups over the study period (Table, Appendix Table 4). There were significant differences in specific respiratory subgroups, including asthma, bronchiolitis, croup, influenza, and pneumonia (Appendix Figure 1A). Temporal trends in respiratory encounters were consistent across hospital settings, ages, and geographic regions (Appendix Figure 1B-D). When comparing the with and without COVID-19 subgroups in the “other respiratory illnesses” cohort, other respiratory illness without COVID-19 decreased and remained lower than expected over the rest of the study period, while other respiratory illness with COVID-19 increased markedly during the summer months and declined thereafter (Appendix Figure 2).

All age groups had reductions in respiratory illness encounters during the early COVID-19 and COVID-19 periods, although the decline was less pronounced in the 12- to 17-year-old group (Appendix Figure 1B). Similarly, while all age groups experienced increases in encounters for respiratory illnesses during the summer months, only children in the 12- to 17-year-old group experienced increases beyond pre-COVID-19 levels. Importantly, this increase in respiratory encounters was largely driven by COVID-19 diagnoses (Appendix Figure 3). The trend in nonrespiratory illness encounters stratified by age is shown in Appendix Figure 4.

When patients were stratified by hospital setting, there were no differences between those hospitalized and those discharged from the ED (Appendix Figure 1C). Patterns in respiratory illnesses by geographic location were qualitatively similar until the beginning of the summer 2020, after which geographical variation became more evident (Appendix Figure 1D).

In this large, multicenter study evaluating ED visits and hospitalizations for respiratory and nonrespiratory illnesses at US pediatric hospitals during the 2020 COVID-19 pandemic, we found a significant and substantial decrease in healthcare encounters for respiratory illnesses. A rapid and marked decline in encounters for respiratory illness in a relatively short period of time (March 12-April 2) was observed across all hospitals and US regions. Declines were consistent across common respiratory illnesses. More modest, yet still substantial, declines were also observed for nonrespiratory illnesses.

There are likely multiple underlying reasons for the observed reductions. Social distancing measures almost certainly played an important role in interrupting respiratory infection transmission. Rapid reduction in influenza transmission during the early COVID-19 period has been attributed to social distancing measures,³ and influenza transmission in children decreases with school closures.⁹ It is also possible that some families delayed seeking care at hospitals due to COVID-19, leading to less frequent encounters but more severe illness. The similar decrease in O:E ratio for ED visits and hospitalizations, however, is inconsistent with this explanation. It is also possible that nonurgent conditions cared for in the hospital settings were diverted to other care settings. For example, during this pandemic, telehealth and telephone visits for pediatric asthma increased by 61% and 19%, respectively, while ED and outpatient visits decreased concurrently.¹⁰Similar changes in location of care may also contribute to the decline in nonrespiratory illness encounters. Decreased use of hospital resources for nonurgent care diagnoses during the pandemic would suggest that, prior to COVID-19, there was overutilization of ambulatory services at children’s hospitals. Therefore, the pandemic may be driving care to more appropriate settings.

We also found relative differences in changes in encounters for respiratory illness by age. Adolescents’ levels of respiratory healthcare use declined less and recovered at a faster rate than those of younger children, returning to pre-COVID-19 levels by the end of the study period. The reason for this age differential is likely multifaceted. Infections, such as bronchiolitis and pneumonia, are more likely to be a source of respiratory illness in younger than in older children. It is also likely that disproportionate relaxation of social distancing measures among adolescents, who are known to have a stronger pattern of social interaction, contributed to the faster rise in respiratory illness–related encounters in this age group.¹¹ Adolescents have been reported to be more susceptible to, and more likely to transmit, SARS-CoV-2 compared to younger age groups.¹² More modest, albeit similar, age-based changes were observed in encounters for nonrespiratory illnesses. It is possible that pandemic-related stressors resulted in a subsequent increase in mental health encounters among this age group.¹³ While the reason for this also is likely multifactorial, adolescent behavior, as well as transmission of infectious illness that can exacerbate nonrespiratory conditions, may be a factor.

Emerging evidence suggests that school-age children may play an important role in SARS-CoV-2 transmission in the community.^4,14 Our finding that, compared to younger children, adolescents had significantly fewer reductions in respiratory illness encounters is concerning. These findings suggest that community-based efforts to help prevent respiratory illnesses, especially COVID-19, should focus on adolescents, who are most likely to maintain social interactions and transmit respiratory infections in the school setting and their households.

This study is limited by the inclusion of only tertiary care children’s hospitals, which may not be nationally representative, and the inability to assess the precise timing of when specific public health interventions were introduced. Moreover, previous studies suggest that social distancing behaviors may have changed even before formal recommendations were enacted.¹⁵ Future studies should investigate the local impact of state- and municipality-specific mandates on the burden of COVID-19 and other respiratory illnesses.

The COVID-19 pandemic was associated with substantial reductions in encounters for respiratory diseases, and also with more modest but still sizable reductions in encounters for nonrespiratory diseases. These reductions varied by age. Encounters among adolescents declined less and returned to previous levels faster compared with those of younger children.

This publication is dedicated to the memory of our coauthor, Dr. Michael Bendel-Stenzel. Dr. Bendel-Stenzel was dedicated to bettering the lives of children and advancing our knowledge of pediatrics through his research.

In the United States, respiratory illnesses are the most common cause of emergency department (ED) visits and hospitalizations in children.¹ In response to the ongoing COVID-19 pandemic, several public health interventions, including school and business closures, stay-at-home orders, and mask mandates, were implemented to limit transmission of SARS-CoV-2.^2,3 Studies have shown that children can contribute to the spread of SARS-CoV-2 infections, especially within households.^4-6 Recent data suggest that COVID-19, and the associated public health measures enacted to slow its spread, may have affected the transmission of other respiratory pathogens.⁷ Similarly, the pandemic has likely affected healthcare utilization for nonrespiratory illnesses through adoption of social distancing recommendations, suspension and delays in nonemergent elective care, avoidance of healthcare settings, and the effect of decreased respiratory disease on exacerbation of chronic illness.⁸ The objective of this study was to examine associations between the COVID-19 pandemic and healthcare utilization for pediatric respiratory and nonrespiratory illnesses at US pediatric hospitals.

Study Design

This is a multicenter, cross-sectional study of encounters at 44 pediatric hospitals that reported data to the Pediatric Health Information System (PHIS) database maintained by the Children’s Hospital Association (Lenexa, Kansas).

Study Population

Children 2 months to 18 years of age discharged from ED or inpatient settings with a nonsurgical diagnosis from January 1 to September 30 over a 4-year period (2017-2020) were included.

Exposure

The primary exposure was the 2020 COVID-19 pandemic time, divided into three periods: pre-COVID-19 (January-February 2020, the period prior to the pandemic in the United States), early COVID-19 (March-April 2020, coinciding with the first reported US pediatric case of COVID-19 on March 2, 2020), and COVID-19 (May-September 2020, marked by the implementation of at least two of the following containment measures in every US state: stay-at-home/shelter orders, school closures, nonessential business closures, restaurant closures, or prohibition of gatherings of more than 10 people).²

Outcomes

Respiratory illness diagnoses were classified into mutually exclusive subgroups following a prespecified hierarchy: influenza, pneumonia, croup, bronchiolitis, asthma, unspecified influenza-like illness, and “other respiratory diagnoses” (Appendix Table 1). To assess the impact of COVID-19 after its International Classification of Diseases, Tenth Revision code was established on March 25, 2020, the “other respiratory” subgroup was divided into other respiratory illnesses with and without COVID-19. Nonrespiratory illness diagnoses were defined as all diagnoses not included in the respiratory illness cohort.

Statistical Analysis

Categorical variables were summarized using frequencies and percentages and compared using chi-square tests. Continuous variables were summarized as median and interquartile range (IQR) and compared using Wilcoxon rank sum tests. Weekly observed-to-expected (O:E) ratios were calculated for each hospital by dividing the number of observed respiratory illness and nonrespiratory illness encounters in a given week in 2020 (observed) by the average number of encounters for that same week during 2017-2019 (expected). O:E ratios were then aggregated over the three COVID-19 study periods, and 95% confidence intervals were established around mean O:E ratios across individual hospitals. Outcomes were then stratified by respiratory illness subgroups, geographic region, and age. Additional details can be found in the Supplemental Methods in the Appendix.

Study Population

A total of 9,051,980 encounters were included in the study, 6,811,799 with nonrespiratory illnesses and 2,240,181 with respiratory illnesses. Median age was 5 years (IQR, 1-11 years), and 52.7% of the population was male (Appendix Table 2 and Appendix Table 3).

Respiratory vs Nonrespiratory Illness During the COVID-19 Pandemic

Over the study period, fewer respiratory and nonrespiratory illness encounters were observed than expected, with a larger decrease in respiratory illness encounters (Table, Appendix Table 4).

Respiratory Subgroup Analyses

The O:E ratio decreased for all respiratory subgroups over the study period (Table, Appendix Table 4). There were significant differences in specific respiratory subgroups, including asthma, bronchiolitis, croup, influenza, and pneumonia (Appendix Figure 1A). Temporal trends in respiratory encounters were consistent across hospital settings, ages, and geographic regions (Appendix Figure 1B-D). When comparing the with and without COVID-19 subgroups in the “other respiratory illnesses” cohort, other respiratory illness without COVID-19 decreased and remained lower than expected over the rest of the study period, while other respiratory illness with COVID-19 increased markedly during the summer months and declined thereafter (Appendix Figure 2).

All age groups had reductions in respiratory illness encounters during the early COVID-19 and COVID-19 periods, although the decline was less pronounced in the 12- to 17-year-old group (Appendix Figure 1B). Similarly, while all age groups experienced increases in encounters for respiratory illnesses during the summer months, only children in the 12- to 17-year-old group experienced increases beyond pre-COVID-19 levels. Importantly, this increase in respiratory encounters was largely driven by COVID-19 diagnoses (Appendix Figure 3). The trend in nonrespiratory illness encounters stratified by age is shown in Appendix Figure 4.

When patients were stratified by hospital setting, there were no differences between those hospitalized and those discharged from the ED (Appendix Figure 1C). Patterns in respiratory illnesses by geographic location were qualitatively similar until the beginning of the summer 2020, after which geographical variation became more evident (Appendix Figure 1D).

In this large, multicenter study evaluating ED visits and hospitalizations for respiratory and nonrespiratory illnesses at US pediatric hospitals during the 2020 COVID-19 pandemic, we found a significant and substantial decrease in healthcare encounters for respiratory illnesses. A rapid and marked decline in encounters for respiratory illness in a relatively short period of time (March 12-April 2) was observed across all hospitals and US regions. Declines were consistent across common respiratory illnesses. More modest, yet still substantial, declines were also observed for nonrespiratory illnesses.

There are likely multiple underlying reasons for the observed reductions. Social distancing measures almost certainly played an important role in interrupting respiratory infection transmission. Rapid reduction in influenza transmission during the early COVID-19 period has been attributed to social distancing measures,³ and influenza transmission in children decreases with school closures.⁹ It is also possible that some families delayed seeking care at hospitals due to COVID-19, leading to less frequent encounters but more severe illness. The similar decrease in O:E ratio for ED visits and hospitalizations, however, is inconsistent with this explanation. It is also possible that nonurgent conditions cared for in the hospital settings were diverted to other care settings. For example, during this pandemic, telehealth and telephone visits for pediatric asthma increased by 61% and 19%, respectively, while ED and outpatient visits decreased concurrently.¹⁰Similar changes in location of care may also contribute to the decline in nonrespiratory illness encounters. Decreased use of hospital resources for nonurgent care diagnoses during the pandemic would suggest that, prior to COVID-19, there was overutilization of ambulatory services at children’s hospitals. Therefore, the pandemic may be driving care to more appropriate settings.

We also found relative differences in changes in encounters for respiratory illness by age. Adolescents’ levels of respiratory healthcare use declined less and recovered at a faster rate than those of younger children, returning to pre-COVID-19 levels by the end of the study period. The reason for this age differential is likely multifaceted. Infections, such as bronchiolitis and pneumonia, are more likely to be a source of respiratory illness in younger than in older children. It is also likely that disproportionate relaxation of social distancing measures among adolescents, who are known to have a stronger pattern of social interaction, contributed to the faster rise in respiratory illness–related encounters in this age group.¹¹ Adolescents have been reported to be more susceptible to, and more likely to transmit, SARS-CoV-2 compared to younger age groups.¹² More modest, albeit similar, age-based changes were observed in encounters for nonrespiratory illnesses. It is possible that pandemic-related stressors resulted in a subsequent increase in mental health encounters among this age group.¹³ While the reason for this also is likely multifactorial, adolescent behavior, as well as transmission of infectious illness that can exacerbate nonrespiratory conditions, may be a factor.

Emerging evidence suggests that school-age children may play an important role in SARS-CoV-2 transmission in the community.^4,14 Our finding that, compared to younger children, adolescents had significantly fewer reductions in respiratory illness encounters is concerning. These findings suggest that community-based efforts to help prevent respiratory illnesses, especially COVID-19, should focus on adolescents, who are most likely to maintain social interactions and transmit respiratory infections in the school setting and their households.

This study is limited by the inclusion of only tertiary care children’s hospitals, which may not be nationally representative, and the inability to assess the precise timing of when specific public health interventions were introduced. Moreover, previous studies suggest that social distancing behaviors may have changed even before formal recommendations were enacted.¹⁵ Future studies should investigate the local impact of state- and municipality-specific mandates on the burden of COVID-19 and other respiratory illnesses.

The COVID-19 pandemic was associated with substantial reductions in encounters for respiratory diseases, and also with more modest but still sizable reductions in encounters for nonrespiratory diseases. These reductions varied by age. Encounters among adolescents declined less and returned to previous levels faster compared with those of younger children.

This publication is dedicated to the memory of our coauthor, Dr. Michael Bendel-Stenzel. Dr. Bendel-Stenzel was dedicated to bettering the lives of children and advancing our knowledge of pediatrics through his research.

For severe asthma exacerbations unresponsive to initial treatment, expert consensus guidelines from 2007 recommend consideration for adjunct treatments (magnesium or heliox) to decrease the likelihood of intubation.¹ Over the last decade, data have emerged suggesting that intravenous (IV) magnesium may be more effective for reduction of hospital admission rates.² Pooled meta-analyses have demonstrated improved pulmonary function and reduction of hospital admission by as much as 68% in children when IV magnesium is administered in the emergency department (ED), although the evidence is extremely limited because of a small number of studies (three) and small sample size (115 children).^2-5

Though these data suggest that use of IV magnesium may reduce admission rates, a study of pediatric emergency medicine (PEM) physicians in US and Canada reported reluctance regarding use for this purpose. While PEM physicians reported awareness of the literature on admission prevention, they estimated that fewer than 5% of their patients receiving IV magnesium were discharged home.⁶ Their practice was generally limited to using IV magnesium in children with impending respiratory failure for the purpose of reducing intensive care unit (ICU) admission and not hospitalization.⁶ PEM physicians’ reluctance to use IV magnesium was related to the lack of strong available evidence supporting the impact of IV magnesium on outcomes, such as admission, and gaps in the literature about its dosing and safety profile.

The goal of this study was to assess the prevailing trends in IV magnesium use across US children’s hospitals and to assess the relationship of IV magnesium use to admission rate, length of stay (LOS), readmission rate, and ICU admission rate. We hypothesized that IV magnesium use might have increased following publication of studies demonstrating an association between IV magnesium use and fewer admissions.

Study Design, Setting, and Participants

This is a retrospective cohort study of asthma (All Patient Refined Diagnosis Related Group 141) hospitalizations for patients less than 18 years old presenting to 35 tertiary care children’s hospitals from January 1, 2010, to December 31, 2017, included in the Pediatric Health Information System (PHIS; Children’s Hospital Association, Lenexa, Kansas) database. The PHIS database is an administrative database that contains demographics, International Classification of Diseases 9th and 10th Revision diagnoses and procedures, and daily billing records for all inpatient, observation, ED, and ambulatory surgery encounters. All data were deidentified prior to inclusion in the database and tracking of patients across ED and inpatient visits was achieved through an encrypted and unique patient identifier. Children transferred from other hospitals were excluded because we could not verify IV magnesium use prior to transfer. For hospitals to be included, they were required to provide continuous data throughout the study period.

Main Outcome Measure

The main outcome was exposure to IV magnesium as determined by billing information available in the PHIS database.

Patient Demographics

We assessed patients’ demographic characteristics, including age (younger than 5 years, 5-11 years, and 12-17 years), sex, race/ethnicity, and insurance status.

Healthcare Utilization and Hospital Characteristics

We assessed healthcare utilization using geometric mean LOS, proportion of patients admitted to the hospital and to the ICU, and the proportion of patients with a 7-day all-cause readmission. In addition, we divided hospitals into three equal groups based on their annual inpatient asthma volume (<300, 300-850, >850 cases per year).

Statistical Analysis

We compared demographic and clinical characteristics across patients receiving IV magnesium with those who did not receive it with use of chi-square tests for categorical variables and Wilcoxon rank sum test for continuous variables. We calculated annual IV magnesium use rates for each hospital and modeled the average annual rate with a general linear model in order to assess change over time. We used Pearson product moment correlation to compare the annual proportion of magnesium use and healthcare utilization measures, including geometric mean LOS, the proportion of patients using the inpatient wards or the ICU, and the proportion of cases with a 7-day all-cause readmission. Geometric mean LOS was used to normalize the compounding effect of non–normally distributed arithmetic mean LOS. A sensitivity analysis was performed stratifying IV magnesium use over time by hospital inpatient volume. Data were analyzed using SAS version 9.4 (SAS Institute, Cary, North Carolina), and P values < .05 were considered statistically significant.

Study Population

A total of 878,188 encounters with acute asthma exacerbation met the inclusion criteria, with 65,558 (7.5%) receiving IV magnesium (Table). Of those receiving IV magnesium, 90% were admitted to the hospital. There were statistically significant differences in IV magnesium use when compared by age, race/ethnicity, and payer type, but not gender. IV magnesium use was significantly associated with older age (more than 5 years old), non-Hispanic black race, ED visit in the year prior to admission, longer hospital LOS, and higher ICU admission rate.

Trends in Intravenous Magnesium Use

IV magnesium use among hospitalized children more than doubled from 2010 to 2017 (17% vs 36%). Low-volume hospitals had a lower frequency of IV magnesium use, compared with the moderate- and high-volume hospitals. The growth rate per year of IV magnesium use was greater in high- and moderate-volume hospitals (3.4% and 2.9% per year, respectively), compared with the low-volume hospitals (1.2% per year; P = .04).

Trends in Intravenous Magnesium Use and Hospital Outcomes

The trend in IV magnesium use was not associated with a statistically significant change in the inpatient and ICU admission rate or in the 7-day all-cause readmission rate (Figure and Appendix Figure). Although IV magnesium use increased over time, LOS decreased significantly during the same period (1.6 days in 2010 vs 1.4 days in 2017; P < .001). When analyzed by hospital volume, no significant associations were found in the inpatient admission, ICU admission, and 7-day readmission rate.

The use of IV magnesium has significantly increased in US children’s hospitals over the last 8 years, especially among those hospitalized following an ED evaluation. Over this interval, trends in inpatient and ICU admission rate, as well as 7-day all-cause readmission rate, for asthma did not change, while LOS decreased. These findings contrast with a recent Cochrane review that summarized the efficacy of IV magnesium for reducing admission rate in few small trials.²

Our study findings are more consistent with prior survey findings that IV magnesium does not reduce hospitalization and that ED physicians tend to use IV magnesium in severe asthma exacerbation for its potential therapeutic benefits because of bronchodilator and anti-inflammatory effect.^6,7 Similar to PEM physicians’ estimates, only 10% of patients receiving IV magnesium were discharged home in our study.

IV magnesium use is higher in high-volume hospitals than in moderate- and low-volume ones. One potential explanation is that high- and moderate-volume hospitals may see a higher volume of children with severe or impending respiratory failure and, therefore, are more likely to use IV magnesium than the low-volume hospitals are. Alternatively, physician adoption of magnesium use for lower-acuity asthma exacerbations could vary by hospital volume.

Trend analyses of outcomes suggest that increase in IV magnesium use was not associated with an increase in inpatient and ICU admission rate or with 7-day all-cause readmission rate, although LOS reduced. LOS might be reduced because of various quality improvement initiatives (eg, discharging patients after every 3 hours albuterol treatments or respiratory therapist–driven protocols) and might not be related to IV magnesium use.^8,9 To this point, a recent study of a respiratory assessment score–matched cohort did not find any therapeutic benefit of IV magnesium with severe asthma exacerbation when receiving continuous albuterol therapy on a pediatric ward.⁵ Perhaps future studies could explore estimating the outcome by performing comparative effectiveness studies between those with severe asthma exacerbation who did or did not receive IV magnesium. Additionally, randomized controlled trials comparing IV magnesium and standard therapy and its effects on outcomes, such as hospitalization, LOS, association with asthma chronicity, and previous oral steroid use, might provide further insight to inform clinical practice.

Certain study limitations should be noted. The study cohort included children’s hospitals only, and it is possible that care at nonchildren’s hospitals for asthma differs. PHIS dataset used in this study does not allow determination of where and when IV magnesium was given, the severity of asthma exacerbation, or the chronicity of baseline disease. Moreover, PHIS hospitals include centers in large cities, and other competing children’s hospitals may provide other tertiary care that could affect the readmission data calculation. Lastly, the temporal associations between IV magnesium use and outcomes reported in this study should not be used as evidence or lack of evidence for the effectiveness of magnesium given the limitations of the observational study design and dataset used.

In conclusion, IV magnesium use in management of asthma exacerbation in children across the United States has significantly increased. The increase occurred disproportionately in high-volume hospitals and was not associated with changes in admission rate, ICU admission rate, or 7-day all-cause readmission rate, although LOS has decreased over time.

The authors have no financial relationships relevant to this article or conflicts of interest to disclose. 

This paper was a platform presentation at annual meetings of Pediatric Academic Societies 2019; accepted for presentation at annual meeting of Pediatric Hospital Medicine, July 2019.

No funding was secured for this study. 

For severe asthma exacerbations unresponsive to initial treatment, expert consensus guidelines from 2007 recommend consideration for adjunct treatments (magnesium or heliox) to decrease the likelihood of intubation.¹ Over the last decade, data have emerged suggesting that intravenous (IV) magnesium may be more effective for reduction of hospital admission rates.² Pooled meta-analyses have demonstrated improved pulmonary function and reduction of hospital admission by as much as 68% in children when IV magnesium is administered in the emergency department (ED), although the evidence is extremely limited because of a small number of studies (three) and small sample size (115 children).^2-5

Though these data suggest that use of IV magnesium may reduce admission rates, a study of pediatric emergency medicine (PEM) physicians in US and Canada reported reluctance regarding use for this purpose. While PEM physicians reported awareness of the literature on admission prevention, they estimated that fewer than 5% of their patients receiving IV magnesium were discharged home.⁶ Their practice was generally limited to using IV magnesium in children with impending respiratory failure for the purpose of reducing intensive care unit (ICU) admission and not hospitalization.⁶ PEM physicians’ reluctance to use IV magnesium was related to the lack of strong available evidence supporting the impact of IV magnesium on outcomes, such as admission, and gaps in the literature about its dosing and safety profile.

The goal of this study was to assess the prevailing trends in IV magnesium use across US children’s hospitals and to assess the relationship of IV magnesium use to admission rate, length of stay (LOS), readmission rate, and ICU admission rate. We hypothesized that IV magnesium use might have increased following publication of studies demonstrating an association between IV magnesium use and fewer admissions.

Study Design, Setting, and Participants

This is a retrospective cohort study of asthma (All Patient Refined Diagnosis Related Group 141) hospitalizations for patients less than 18 years old presenting to 35 tertiary care children’s hospitals from January 1, 2010, to December 31, 2017, included in the Pediatric Health Information System (PHIS; Children’s Hospital Association, Lenexa, Kansas) database. The PHIS database is an administrative database that contains demographics, International Classification of Diseases 9th and 10th Revision diagnoses and procedures, and daily billing records for all inpatient, observation, ED, and ambulatory surgery encounters. All data were deidentified prior to inclusion in the database and tracking of patients across ED and inpatient visits was achieved through an encrypted and unique patient identifier. Children transferred from other hospitals were excluded because we could not verify IV magnesium use prior to transfer. For hospitals to be included, they were required to provide continuous data throughout the study period.

Main Outcome Measure

The main outcome was exposure to IV magnesium as determined by billing information available in the PHIS database.

Patient Demographics

We assessed patients’ demographic characteristics, including age (younger than 5 years, 5-11 years, and 12-17 years), sex, race/ethnicity, and insurance status.

Healthcare Utilization and Hospital Characteristics

We assessed healthcare utilization using geometric mean LOS, proportion of patients admitted to the hospital and to the ICU, and the proportion of patients with a 7-day all-cause readmission. In addition, we divided hospitals into three equal groups based on their annual inpatient asthma volume (<300, 300-850, >850 cases per year).

Statistical Analysis

We compared demographic and clinical characteristics across patients receiving IV magnesium with those who did not receive it with use of chi-square tests for categorical variables and Wilcoxon rank sum test for continuous variables. We calculated annual IV magnesium use rates for each hospital and modeled the average annual rate with a general linear model in order to assess change over time. We used Pearson product moment correlation to compare the annual proportion of magnesium use and healthcare utilization measures, including geometric mean LOS, the proportion of patients using the inpatient wards or the ICU, and the proportion of cases with a 7-day all-cause readmission. Geometric mean LOS was used to normalize the compounding effect of non–normally distributed arithmetic mean LOS. A sensitivity analysis was performed stratifying IV magnesium use over time by hospital inpatient volume. Data were analyzed using SAS version 9.4 (SAS Institute, Cary, North Carolina), and P values < .05 were considered statistically significant.

Study Population

A total of 878,188 encounters with acute asthma exacerbation met the inclusion criteria, with 65,558 (7.5%) receiving IV magnesium (Table). Of those receiving IV magnesium, 90% were admitted to the hospital. There were statistically significant differences in IV magnesium use when compared by age, race/ethnicity, and payer type, but not gender. IV magnesium use was significantly associated with older age (more than 5 years old), non-Hispanic black race, ED visit in the year prior to admission, longer hospital LOS, and higher ICU admission rate.

Trends in Intravenous Magnesium Use

IV magnesium use among hospitalized children more than doubled from 2010 to 2017 (17% vs 36%). Low-volume hospitals had a lower frequency of IV magnesium use, compared with the moderate- and high-volume hospitals. The growth rate per year of IV magnesium use was greater in high- and moderate-volume hospitals (3.4% and 2.9% per year, respectively), compared with the low-volume hospitals (1.2% per year; P = .04).

Trends in Intravenous Magnesium Use and Hospital Outcomes

The trend in IV magnesium use was not associated with a statistically significant change in the inpatient and ICU admission rate or in the 7-day all-cause readmission rate (Figure and Appendix Figure). Although IV magnesium use increased over time, LOS decreased significantly during the same period (1.6 days in 2010 vs 1.4 days in 2017; P < .001). When analyzed by hospital volume, no significant associations were found in the inpatient admission, ICU admission, and 7-day readmission rate.

The use of IV magnesium has significantly increased in US children’s hospitals over the last 8 years, especially among those hospitalized following an ED evaluation. Over this interval, trends in inpatient and ICU admission rate, as well as 7-day all-cause readmission rate, for asthma did not change, while LOS decreased. These findings contrast with a recent Cochrane review that summarized the efficacy of IV magnesium for reducing admission rate in few small trials.²

Our study findings are more consistent with prior survey findings that IV magnesium does not reduce hospitalization and that ED physicians tend to use IV magnesium in severe asthma exacerbation for its potential therapeutic benefits because of bronchodilator and anti-inflammatory effect.^6,7 Similar to PEM physicians’ estimates, only 10% of patients receiving IV magnesium were discharged home in our study.

IV magnesium use is higher in high-volume hospitals than in moderate- and low-volume ones. One potential explanation is that high- and moderate-volume hospitals may see a higher volume of children with severe or impending respiratory failure and, therefore, are more likely to use IV magnesium than the low-volume hospitals are. Alternatively, physician adoption of magnesium use for lower-acuity asthma exacerbations could vary by hospital volume.

Trend analyses of outcomes suggest that increase in IV magnesium use was not associated with an increase in inpatient and ICU admission rate or with 7-day all-cause readmission rate, although LOS reduced. LOS might be reduced because of various quality improvement initiatives (eg, discharging patients after every 3 hours albuterol treatments or respiratory therapist–driven protocols) and might not be related to IV magnesium use.^8,9 To this point, a recent study of a respiratory assessment score–matched cohort did not find any therapeutic benefit of IV magnesium with severe asthma exacerbation when receiving continuous albuterol therapy on a pediatric ward.⁵ Perhaps future studies could explore estimating the outcome by performing comparative effectiveness studies between those with severe asthma exacerbation who did or did not receive IV magnesium. Additionally, randomized controlled trials comparing IV magnesium and standard therapy and its effects on outcomes, such as hospitalization, LOS, association with asthma chronicity, and previous oral steroid use, might provide further insight to inform clinical practice.

Certain study limitations should be noted. The study cohort included children’s hospitals only, and it is possible that care at nonchildren’s hospitals for asthma differs. PHIS dataset used in this study does not allow determination of where and when IV magnesium was given, the severity of asthma exacerbation, or the chronicity of baseline disease. Moreover, PHIS hospitals include centers in large cities, and other competing children’s hospitals may provide other tertiary care that could affect the readmission data calculation. Lastly, the temporal associations between IV magnesium use and outcomes reported in this study should not be used as evidence or lack of evidence for the effectiveness of magnesium given the limitations of the observational study design and dataset used.

In conclusion, IV magnesium use in management of asthma exacerbation in children across the United States has significantly increased. The increase occurred disproportionately in high-volume hospitals and was not associated with changes in admission rate, ICU admission rate, or 7-day all-cause readmission rate, although LOS has decreased over time.

The authors have no financial relationships relevant to this article or conflicts of interest to disclose. 

This paper was a platform presentation at annual meetings of Pediatric Academic Societies 2019; accepted for presentation at annual meeting of Pediatric Hospital Medicine, July 2019.

No funding was secured for this study. 

For severe asthma exacerbations unresponsive to initial treatment, expert consensus guidelines from 2007 recommend consideration for adjunct treatments (magnesium or heliox) to decrease the likelihood of intubation.¹ Over the last decade, data have emerged suggesting that intravenous (IV) magnesium may be more effective for reduction of hospital admission rates.² Pooled meta-analyses have demonstrated improved pulmonary function and reduction of hospital admission by as much as 68% in children when IV magnesium is administered in the emergency department (ED), although the evidence is extremely limited because of a small number of studies (three) and small sample size (115 children).^2-5

Though these data suggest that use of IV magnesium may reduce admission rates, a study of pediatric emergency medicine (PEM) physicians in US and Canada reported reluctance regarding use for this purpose. While PEM physicians reported awareness of the literature on admission prevention, they estimated that fewer than 5% of their patients receiving IV magnesium were discharged home.⁶ Their practice was generally limited to using IV magnesium in children with impending respiratory failure for the purpose of reducing intensive care unit (ICU) admission and not hospitalization.⁶ PEM physicians’ reluctance to use IV magnesium was related to the lack of strong available evidence supporting the impact of IV magnesium on outcomes, such as admission, and gaps in the literature about its dosing and safety profile.

The goal of this study was to assess the prevailing trends in IV magnesium use across US children’s hospitals and to assess the relationship of IV magnesium use to admission rate, length of stay (LOS), readmission rate, and ICU admission rate. We hypothesized that IV magnesium use might have increased following publication of studies demonstrating an association between IV magnesium use and fewer admissions.

Study Design, Setting, and Participants

This is a retrospective cohort study of asthma (All Patient Refined Diagnosis Related Group 141) hospitalizations for patients less than 18 years old presenting to 35 tertiary care children’s hospitals from January 1, 2010, to December 31, 2017, included in the Pediatric Health Information System (PHIS; Children’s Hospital Association, Lenexa, Kansas) database. The PHIS database is an administrative database that contains demographics, International Classification of Diseases 9th and 10th Revision diagnoses and procedures, and daily billing records for all inpatient, observation, ED, and ambulatory surgery encounters. All data were deidentified prior to inclusion in the database and tracking of patients across ED and inpatient visits was achieved through an encrypted and unique patient identifier. Children transferred from other hospitals were excluded because we could not verify IV magnesium use prior to transfer. For hospitals to be included, they were required to provide continuous data throughout the study period.

Main Outcome Measure

The main outcome was exposure to IV magnesium as determined by billing information available in the PHIS database.

Patient Demographics

We assessed patients’ demographic characteristics, including age (younger than 5 years, 5-11 years, and 12-17 years), sex, race/ethnicity, and insurance status.

Healthcare Utilization and Hospital Characteristics

We assessed healthcare utilization using geometric mean LOS, proportion of patients admitted to the hospital and to the ICU, and the proportion of patients with a 7-day all-cause readmission. In addition, we divided hospitals into three equal groups based on their annual inpatient asthma volume (<300, 300-850, >850 cases per year).

Statistical Analysis

We compared demographic and clinical characteristics across patients receiving IV magnesium with those who did not receive it with use of chi-square tests for categorical variables and Wilcoxon rank sum test for continuous variables. We calculated annual IV magnesium use rates for each hospital and modeled the average annual rate with a general linear model in order to assess change over time. We used Pearson product moment correlation to compare the annual proportion of magnesium use and healthcare utilization measures, including geometric mean LOS, the proportion of patients using the inpatient wards or the ICU, and the proportion of cases with a 7-day all-cause readmission. Geometric mean LOS was used to normalize the compounding effect of non–normally distributed arithmetic mean LOS. A sensitivity analysis was performed stratifying IV magnesium use over time by hospital inpatient volume. Data were analyzed using SAS version 9.4 (SAS Institute, Cary, North Carolina), and P values < .05 were considered statistically significant.

Study Population

A total of 878,188 encounters with acute asthma exacerbation met the inclusion criteria, with 65,558 (7.5%) receiving IV magnesium (Table). Of those receiving IV magnesium, 90% were admitted to the hospital. There were statistically significant differences in IV magnesium use when compared by age, race/ethnicity, and payer type, but not gender. IV magnesium use was significantly associated with older age (more than 5 years old), non-Hispanic black race, ED visit in the year prior to admission, longer hospital LOS, and higher ICU admission rate.

Trends in Intravenous Magnesium Use

IV magnesium use among hospitalized children more than doubled from 2010 to 2017 (17% vs 36%). Low-volume hospitals had a lower frequency of IV magnesium use, compared with the moderate- and high-volume hospitals. The growth rate per year of IV magnesium use was greater in high- and moderate-volume hospitals (3.4% and 2.9% per year, respectively), compared with the low-volume hospitals (1.2% per year; P = .04).

Trends in Intravenous Magnesium Use and Hospital Outcomes

The trend in IV magnesium use was not associated with a statistically significant change in the inpatient and ICU admission rate or in the 7-day all-cause readmission rate (Figure and Appendix Figure). Although IV magnesium use increased over time, LOS decreased significantly during the same period (1.6 days in 2010 vs 1.4 days in 2017; P < .001). When analyzed by hospital volume, no significant associations were found in the inpatient admission, ICU admission, and 7-day readmission rate.

The use of IV magnesium has significantly increased in US children’s hospitals over the last 8 years, especially among those hospitalized following an ED evaluation. Over this interval, trends in inpatient and ICU admission rate, as well as 7-day all-cause readmission rate, for asthma did not change, while LOS decreased. These findings contrast with a recent Cochrane review that summarized the efficacy of IV magnesium for reducing admission rate in few small trials.²

Our study findings are more consistent with prior survey findings that IV magnesium does not reduce hospitalization and that ED physicians tend to use IV magnesium in severe asthma exacerbation for its potential therapeutic benefits because of bronchodilator and anti-inflammatory effect.^6,7 Similar to PEM physicians’ estimates, only 10% of patients receiving IV magnesium were discharged home in our study.

IV magnesium use is higher in high-volume hospitals than in moderate- and low-volume ones. One potential explanation is that high- and moderate-volume hospitals may see a higher volume of children with severe or impending respiratory failure and, therefore, are more likely to use IV magnesium than the low-volume hospitals are. Alternatively, physician adoption of magnesium use for lower-acuity asthma exacerbations could vary by hospital volume.

Trend analyses of outcomes suggest that increase in IV magnesium use was not associated with an increase in inpatient and ICU admission rate or with 7-day all-cause readmission rate, although LOS reduced. LOS might be reduced because of various quality improvement initiatives (eg, discharging patients after every 3 hours albuterol treatments or respiratory therapist–driven protocols) and might not be related to IV magnesium use.^8,9 To this point, a recent study of a respiratory assessment score–matched cohort did not find any therapeutic benefit of IV magnesium with severe asthma exacerbation when receiving continuous albuterol therapy on a pediatric ward.⁵ Perhaps future studies could explore estimating the outcome by performing comparative effectiveness studies between those with severe asthma exacerbation who did or did not receive IV magnesium. Additionally, randomized controlled trials comparing IV magnesium and standard therapy and its effects on outcomes, such as hospitalization, LOS, association with asthma chronicity, and previous oral steroid use, might provide further insight to inform clinical practice.

Certain study limitations should be noted. The study cohort included children’s hospitals only, and it is possible that care at nonchildren’s hospitals for asthma differs. PHIS dataset used in this study does not allow determination of where and when IV magnesium was given, the severity of asthma exacerbation, or the chronicity of baseline disease. Moreover, PHIS hospitals include centers in large cities, and other competing children’s hospitals may provide other tertiary care that could affect the readmission data calculation. Lastly, the temporal associations between IV magnesium use and outcomes reported in this study should not be used as evidence or lack of evidence for the effectiveness of magnesium given the limitations of the observational study design and dataset used.

In conclusion, IV magnesium use in management of asthma exacerbation in children across the United States has significantly increased. The increase occurred disproportionately in high-volume hospitals and was not associated with changes in admission rate, ICU admission rate, or 7-day all-cause readmission rate, although LOS has decreased over time.

The authors have no financial relationships relevant to this article or conflicts of interest to disclose. 

This paper was a platform presentation at annual meetings of Pediatric Academic Societies 2019; accepted for presentation at annual meeting of Pediatric Hospital Medicine, July 2019.

No funding was secured for this study.