As of August 31, 2021, over four million cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have been documented in US children aged <18 years.¹ Although children have lower rates of hospitalization for coronavirus disease 2019 (COVID-19) compared with adults,^{2, 3} severe illness and death have occurred.^4–8 Children with SARS-CoV-2 infection may develop serious complications, including acute respiratory distress syndrome, myocarditis, acute renal failure, multisystem organ failure, and multisystem inflammatory syndrome in children (MIS-C).^{3–6, 8–14} Among children hospitalized with COVID-19, approximately 28–40% were admitted to an intensive care unit (ICU), 6–18% required invasive mechanical ventilation, and up to 3% have died.^{3, 4, 6, 10–12}

As of September 2021, the Food and Drug Administration has approved the Pfizer-BioNTech vaccine for use in children aged ≥16 years and has authorized two vaccines for emergency use in children aged 12–17 years.^15–17 Multiple clinical trials testing vaccine efficacy for preventing severe illness and death in the pediatric population are ongoing.^18–22 However, until these vaccines are authorized for use in younger age groups, children may continue to be at risk of severe illness. Information about the demographic and medical characteristics associated with severe COVID-19 in this population can be used to inform clinical decision-making, risk communication, and recommendations for vaccination and other preventive measures. Although several descriptive investigations have characterized the demographic and clinical characteristics of pediatric COVID-19-associated hospitalizations^{3, 10, 11} and ICU admissions,^{5, 9} most studies that have identified risk factors for severe COVID-19 among children have been conducted among geographically limited populations during the initial months of the pandemic.^{4, 6, 12, 23} Additionally, population-based rates of severe COVID-19 in children are needed to establish a baseline for monitoring trends as COVID-19 vaccines are approved for use in younger age groups, to compare with rates of severe adverse vaccine reactions, and as new SARS-CoV-2 variants emerge.

The objectives of this investigation were to identify demographic characteristics and underlying medical conditions associated with increased relative risk of severe COVID-19 among children hospitalized with SARS CoV-2 infection and to calculate population-based rates of severe COVID-19 among children during March 2020–May 2021.

As described previously,^{2, 24} the Coronavirus Disease 2019-Associated Hospitalizations Surveillance Network (COVID-NET) conducts population-based surveillance of laboratory-confirmed COVID-19-associated hospitalizations in 250 acute-care hospitals located in a defined catchment area that includes approximately 10% of the U.S. population. COVID-NET conducts surveillance in 99 counties across 14 states (California, Colorado, Connecticut, Georgia, Iowa, Maryland, Michigan, Minnesota, New Mexico, New York, Ohio, Oregon, Tennessee, and Utah) located in each of the 10 Health and Human Services Department (HHS) regions.

Hospitalizations that meet the case definition of a COVID-19-associated hospitalization are included in surveillance if the patient resided in the catchment area and had a positive molecular or rapid antigen SARS-CoV-2 test during hospitalization or up to 14 days before admission. COVID-NET cases can include patients with acute COVID-19, MIS-C, or incidental SARS-CoV-2 infections. Trained surveillance officers identify cases using notifiable disease and laboratory databases as well as hospital admission and infection control practitioner logs. Medical chart abstraction is completed for all COVID-19-associated hospitalizations among children aged <18 years using a standard case report form; hospitalizations are then reported to COVID-NET. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.1 Participating sites obtained approval from their respective state and local Institutional Review Boards, as required.

Of 2,293 pediatric hospitalizations, 745 (32.5%) were infants and children aged <2 years; 1,548 (67.5%) were children aged 2‒17 years (Table 1). Half (53.4%) were male, and the median age was 7 years (IQR: 1–14). Most were Hispanic (33.7%) or non-Hispanic Black (32.1%), followed by non-Hispanic White (22.9%) or non-Hispanic Asian/PI (5.2%). Over half (55.0%) had ≥1 underlying medical conditions, though the prevalence varied by age group (28.7% among infants and children <2 years, 67.7% among children 2‒17 years). The most common underlying conditions were obesity, chronic lung disease, neurologic disorders, cardiovascular disease, and blood disorders. Within the latter categories, asthma, developmental delay, congenital heart disease, and sickle cell disease were the most common conditions respectively.

Almost one-third of hospitalized children with SARS-CoV-2 infection required ICU admission or invasive mechanical ventilation and children with specific underlying medical conditions were at greater risk of severe COVID-19. A strength of this investigation was the large, geographically diverse sample of children hospitalized with SARS-CoV-2 infection, which enabled the identification of demographic and medical characteristics associated with severe COVID-19 among pediatric subgroups, including by age and race/ethnicity. These results provide needed descriptive information about COVID-19 severity in children prior to widespread availability of pediatric COVID-19 vaccination and can serve as a baseline to assess changes in trends as COVID-19 vaccines are approved for use in younger age groups, to compare with severe adverse vaccine reactions, and as new SARS-CoV-2 variants emerge. Additionally, information about pediatric risk factors for severe COVID-19 can inform clinical decision making by identifying children who may benefit from closer monitoring following hospitalization. These results may also guide other prevention measures, including health education and risk communication campaigns and recommendations for vaccination^26–28 once COVID-19 vaccines are approved for use among younger children.

Similar to previous investigations,^{29, 30} we found that the presence of one or more underlying medical conditions was associated with increased risk of severe COVID-19 and identified the specific underlying conditions associated with severe COVID-19 within pediatric subgroups. Results underscore the importance of obesity and diabetes, which have previously been documented as risk factors for severe COVID-19 among both adults and children,^{4, 12, 24, 30–33} and identify additional risk factors, including neurologic and cardiovascular disease, feeding tube dependence, airway abnormality, and prematurity among specific pediatric subgroups. These results highlight the potential importance of neurologic disorders (including developmental delay), which were reported in over half of the 12 in-hospital pediatric deaths and were associated with increased risk of severe COVID-19 across several pediatric population subgroups, including children 2–17 years of age without a discharge diagnosis of MIS-C and infants and children <2 years. Neurologic disorders have been shown to increase risk of severe illness in other respiratory diseases, potentially through decreased muscle tone and strength, impaired mobility, or structural conditions that diminish pulmonary function.^34–36 Consistent with findings from influenza-associated hospitalizations,³⁷ we found that some underlying medical conditions, including immunocompromised conditions and blood disorders, were not associated with increased risk of severe COVID-19, which may be explained by lower thresholds for hospital admission among children with conditions, such as sickle cell disease.

When we examine population-based rates, which have not been calculated in most other studies, infants <12 months had the highest rates of hospitalization and severe COVID-19 compared to all other pediatric age groups, an important finding when assessing infant risk from COVID-19 disease.³ However, similar to other studies,^{4, 12, 29} we found that once hospitalized with SARS-CoV-2 infection, infants were not at significantly increased risk of severe COVID-19 relative to older children. Young infants may have a lower threshold for admission compared with older children and therefore some hospitalized infants may not be as seriously ill from SARS-CoV-2 disease as hospitalized older children, potentially obscuring the true risk to infants compared with older children. More research is needed to evaluate the risk of severe COVID-19 among infants relative to older children.

Consistent with other studies,^{2, 3} Hispanic and non-Hispanic Black children had higher population-based rates of hospitalization and severe disease relative to non-Hispanic White children. However, as reported elsewhere,^{6, 12, 23, 29} once hospitalized with SARS-CoV-2 infection, Hispanic and Black children aged 2–17 years were not at increased risk of severe COVID-19 relative to White children after controlling for the presence of ≥1 underlying medical conditions. These results may suggest that Hispanic and non-Hispanic Black children may be at greater risk of SARS-CoV-2 infection, COVID-19 illness, and associated hospitalization, but are not necessarily at greater risk of severe disease outcomes after accounting for variation in the prevalence of underlying medical conditions. Hispanic and non-Hispanic Black children may be at greater risk of SARS-CoV-2 infection relative to non-Hispanic White children by, for example, increased risk of infection with SARS-CoV-2 among household members who may be disproportionately represented among essential occupations, structural barriers to accessing health care, or other mechanisms.^38–40

Limitations of this investigation include geographic and temporal variability in testing availability, capacity, and performance across contributing sites. Additionally, this investigation may have had limited statistical power to detect differences in severe COVID-19, particularly by less prevalent underlying medical conditions or among pediatric subgroups. In addition, ICU admission and invasive mechanical ventilation may not be proxies for disease severity for all children, particularly if the threshold for admission to the ICU for monitoring varied by pediatric subgroup. Also, children could have been misclassified if underlying conditions were not noted on their electronic medical records or case report form. Finally, these results are from a network of acute care hospitals in 14 states and may not generalize to all hospitalized children with SARS-CoV-2 infection in the US.

Children experience severe COVID-19 and, in hospitalized children, the presence of specific underlying medical conditions may be associated with greater risk of severe COVID-19 outcomes. Results provide baseline information about disease severity among children prior to widespread pediatric COVID-19 vaccination and can be used to inform clinical decision-making, monitor population-based trends over time, and improve risk communication.