OBJECTIVES:

Understanding the risk factors, predictors, and clinical presentation of coronavirus disease 2019 (COVID-19) in pediatric patients with severe disease.

METHODS:

We conducted a retrospective chart review of pediatric patients admitted between March 1, 2020, and May 31, 2020, to a large health network in New Jersey with positive test results for severe acute respiratory syndrome coronavirus 2 on reverse transcriptase polymerase chain reaction, rapid testing, or serum immunoglobulin G testing; we included demographic characteristics, clinical features, and outcomes.

RESULTS:

A total of 81 patients ≤21 years old were admitted with positive test results for severe acute respiratory syndrome coronavirus 2 on reverse transcriptase polymerase chain reaction and/or serum immunoglobulin testing. Sixty-seven patients (82.7%) were admitted for management of acute COVID-19 infection, whereas 14 (17.3%) were admitted for management of multisystem inflammatory syndrome in children (MIS-C). Of the 81 hospitalized patients, 28 (34.6%) required intensive care. A majority of patients (42 [51.9%]) admitted for both acute COVID-19 infection and MIS-C were Hispanic. Underlying chronic health conditions were not present in most patients. Obesity (mean BMI of 41.1) was noted in the patients with MIS-C requiring ICU care, although not statistically significant. Absolute lymphopenia and elevated levels of inflammatory markers were statistically significant in the patients with MIS-C treated in the ICU.

CONCLUSIONS:

This study adds to the growing literature of potential risk factors for severe disease in pediatric patients due to COVID-19 infection and MIS-C. Patients of Hispanic ethnicity represented the majority of patients with both acute COVID-19 infection and MIS-C, despite only representing 10% to 20% of the population our hospitals serve. Infants and patients with chronic health conditions were not at increased risk for severe disease. Absolute lymphopenia and elevated levels of inflammatory markers were associated with more severe disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly emerged as a worldwide cause of severe respiratory disease in the adult population.1  A large series of >40 000 patients with confirmed coronavirus disease 2019 (COVID-19) in China revealed that only 1% of the patients were <10 years of age.1  Published data suggest that the clinical manifestations in children are less severe compared with those in adults, although fatalities have been described.2,3  Risk factors associated with greater severity of illness in the pediatric age group include the infant age group, Hispanic ethnicity, and the presence of coexisting conditions, such as obesity, asthma, and malignancy.46  In a recent study, authors described critical illness in patients with greater areas of lung involvement.7  Authors of many studies have reported increased levels of inflammatory markers in patients who were critically ill.48  Our study includes patients from a variety of regions in the state of New Jersey, which is one of the most ethnically diverse states in the United States.9  As reported by the US Centers for Disease Control and Prevention (CDC), New Jersey has had the second most COVID-19–related deaths in the United States and has had children and young adults hospitalized for the infection with varying presentations and severities of illness.10  Our objectives are to describe the demographic and clinical characteristics, patient course, and outcomes, thereby assessing risk factors that may lead to more severe illness in children and young adults.

This study was performed in 12 hospitals of varying geographic locations in a large health network in New Jersey. Patients between the ages of 0 and 21 years old who were admitted to any of the network hospitals with laboratory-confirmed SARS-CoV-2 infection via reverse transcriptase polymerase chain reaction (RT-PCR), rapid testing, or serum immunoglobulin G (IgG) testing between March 1, 2020, and May 31, 2020, were included in the study. We included all febrile or symptomatic patients, even if they had coexisting bacterial or viral infections because the presence of SARS-CoV-2 may have also contributed to the severity of illness. We also included patients who presented with acute abdominal pain because children with COVID-19 infection often present with gastrointestinal symptoms; this included patients with final diagnoses of appendicitis or intussusception because we felt there may be an association with COVID-19, which can be further studied for future similar presentations. Patients with positive RT-PCR or rapid testing results who were asymptomatic and admitted for other indications, including orthopedic surgical procedures, trauma, or pregnancy, were not included in this study. Three hospitals within the network spread across the state (northern NJ, central NJ, and coastal area) treated patients 0 to 21 years old in the pediatric units, whereas the other institutions treated patients aged >18 in adult units. For the purpose of this study, patients admitted to the ICU were considered to have severe infection, which included a requirement for high-flow nasal cannula or higher modes of oxygen delivery, neurologic abnormalities, and/or hypotension unresponsive to intravenous fluids. This study was approved by the institutional review board.

During the study period, real-time RT-PCR testing on nasopharyngeal specimens was performed by using one of several platforms adopted by the clinical microbiology laboratory, including an in-house PCR test (Center for Discovery and Innovation, Nutley, NJ, SARS-CoV-2 real-time RT-PCR) and rapid testing diagnostics developed by Abbott Laboratories (ID NOW COVID-19; Abbott Laboratories, Chicago, IL) and Cepheid (Xpert Xpress SARS-CoV-2; Cepheid, Sunnyvale, CA). On April 29, IgG serology testing became available. Throughout the pandemic, standardized COVID-19 treatment guidelines were developed and were readily available to all network hospitals.

During the COVID-19 pandemic, the network established a COVID-19 universal real-time database using Research Electronic Data Capture, which was populated with data extracted from Epic electronic medical record software of all patients hospitalized with COVID-19 infection within our network. Demographic data included age, sex, and ethnicity. Clinical parameters assessed included days of symptoms before presentation, household contacts who were SARS-CoV-2–positive, admission hospital location and patient care area, BMI for children 2 years and older, comorbid conditions, smoking and/or vaping history, presenting symptoms outlined by the CDC for both acute COVID-19 infection and multisystem inflammatory syndrome in children (MIS-C),11,12  laboratory test results, and radiologic findings. The clinical course during hospitalization, including mode of oxygen delivery if required, investigational antiviral treatment or supporting pharmacologic agents, length of stay, and readmissions within 30 days, was also assessed. For categorical variables, the χ2 test or Fisher’s exact test was used to analyze the variables. For continuous variables, the unpaired t test or Wilcoxon rank test was used to analyze the variables. SAS version 9.4 (SAS Institute, Inc, Cary, NC) was used for analysis.

From March 1, 2020, to May 31, 2020, a total of 81 children and young adults were admitted to the network hospitals with positive SARS-CoV-2 RT-PCR, rapid testing, and/or serum IgG testing results. All patients were tested by using RT-PCR or rapid testing, and once available, starting April 29, 15 patients had SARS-CoV-2 IgG testing obtained. Results of nasopharyngeal RT-PCR or rapid testing alone were positive for 66 (81.5%) patients, all of whom were admitted for acute COVID-19 infection. In those diagnosed with MIS-C, results of serum IgG testing alone were positive for 6 patients, and 8 patients had positive results for both RT-PCR and serum IgG testing. One patient admitted for acute COVID-19 infection also had a positive result for both RT-PCR and serum IgG testing. Twenty-eight of all patients (35%) had a household contact who tested positive for SARS-CoV-2.

Sixty-seven patients (82.7%) were admitted for management of acute COVID-19 infection. Beginning in mid-April, our hospitals began to have a shift in pathophysiology, from patients with acute COVID-19 infection to patients meeting criteria for MIS-C. Fourteen (35.8%) of our 39 patients from April 21 to May 31 met criteria for MIS-C.

The majority of patients (46 [57%]) were admitted to our hospital in northern New Jersey, in proximity to New York City, followed by 17 patients in our coastal location, and 14 patients in central New Jersey. The remainder of the patients, aged 19 to 21 years, were seen in other hospitals. Fifteen patients (18.5%) were initially admitted to an ICU. Of the 66 who were initially admitted to a general pediatric or adult unit, 13 patients were transferred to an ICU during the course of hospitalization for a total of 28 patients (35%) requiring ICU care. Three of our patients who had a diagnosis of MIS-C required ICU care (21% of patients with MIS-C). Forty-one female patients and 40 male patients were admitted to the hospital, with more male patients requiring ICU care in both acute COVID-19 infection and MIS-C; however, this was not statistically significant. Twenty patients admitted for acute COVID-19 infection (29.8%) were <1 year of age; 2 (10%), aged 4 and 10 months, required intensive care. Seven of the 20 patients <1 year of age (35%) were <60 days old and were admitted for evaluation of serious bacterial infections; however, other sources of infection besides SARS-CoV-2 were not detected. For patients with acute COVID-19 infection, the average ages for those in a general unit and an ICU were 15.4 and 14.0 years, respectively. The average age for patients with MIS-C was 8 years for those in a general unit and 11.7 years for those in the ICU. The majority (42 [52%]) of patients admitted for both acute COVID-19 infection (n = 34) and MIS-C (n = 8) were Hispanic. The mean BMI for patients aged 2 years and older with acute COVID-19 infection was 26.7 for those in the general unit and 25.8 for those in the ICU. The mean BMI for patients with MIS-C was 27.1 for those in the general unit and 41.2 for those in the ICU (P = .393). Forty-six of the 67 patients (68.6%) admitted with acute COVID-19 infection had no chronic health conditions, and 7 of them required ICU care. Of those with chronic health conditions, 8 patients had neurologic comorbid diseases, such as cerebral palsy and seizure disorder; 6 patients had a history of asthma; and 1 patient had chronic lung disease. Six patients, of whom 2 required intensive care, were considered immunocompromised hosts with oncologic diagnoses (n = 4), history of bone marrow transplant (n = 1), and/or rheumatologic disease (n = 1). None of the patients admitted for MIS-C had any chronic health conditions (Tables 1 and 2).

TABLE 1

Acute COVID-19 Presentation: Demographics and Comorbidities by General Unit Versus ICU Care

CharacteristicGeneral Unit (n = 55)ICU Care (n = 12)P
Sex, n (%)   .321 
 Male 28 (50.9) 8 (66.7)  
 Female 27 (49.1) 3 (33.3)  
Ethnicity, n (%)   .431 
 White 14 (25.4) 2 (16.7)  
 African American 3 (5.5) 2 (16.7)  
 Hispanic 27 (49.1) 7 (58.3)  
 Asian 2 (3.6) 0 (0)  
 Other 9 (16.4) 1 (8.3)  
Patients >1 y old, n 37 11 .434 
 Age, y, mean (range) 15.4 (1–21) 14.0 (1–21)  
Infants <1 y old, n 18  
 Age, mo, mean (range) 2.1 (0–10) 5.0 (5)  
Smoking history, n (%)   .989 
 None 49 (89.0) 10 (83.3)  
 Cigarettes 0 (0) 0 (0)  
 Vaping 3 (5.5) 0 (0)  
 Unknown 3 (5.5) 2 (16.7)  
BMI for patients ≥2 y old, mean (range) 26.7 (15.6–56) 25.8 (11–41.8) .989 
Chronic health conditions, n (%)    
 None 39 (70.1) 7 (58.3) .283 
 Asthma 4 (7.3) 2 (16.7) .509 
 Chronic lung disease 1 (1.8) 0 (0) .99 
 Oncologic diagnoses 3 (5.5) 1 (8.3) .555 
 Cardiac disease 0 (0) 0 (0) — 
 Diabetes 0 (0) 0 (0) — 
 Neurologic disorders 6 (12.7) 2 (16.7) .448 
 Rheumatologic disease 1 (1.8) 0 (0) .99 
 Transplant, stem cell 1 (1.8) 0 (0) .99 
CharacteristicGeneral Unit (n = 55)ICU Care (n = 12)P
Sex, n (%)   .321 
 Male 28 (50.9) 8 (66.7)  
 Female 27 (49.1) 3 (33.3)  
Ethnicity, n (%)   .431 
 White 14 (25.4) 2 (16.7)  
 African American 3 (5.5) 2 (16.7)  
 Hispanic 27 (49.1) 7 (58.3)  
 Asian 2 (3.6) 0 (0)  
 Other 9 (16.4) 1 (8.3)  
Patients >1 y old, n 37 11 .434 
 Age, y, mean (range) 15.4 (1–21) 14.0 (1–21)  
Infants <1 y old, n 18  
 Age, mo, mean (range) 2.1 (0–10) 5.0 (5)  
Smoking history, n (%)   .989 
 None 49 (89.0) 10 (83.3)  
 Cigarettes 0 (0) 0 (0)  
 Vaping 3 (5.5) 0 (0)  
 Unknown 3 (5.5) 2 (16.7)  
BMI for patients ≥2 y old, mean (range) 26.7 (15.6–56) 25.8 (11–41.8) .989 
Chronic health conditions, n (%)    
 None 39 (70.1) 7 (58.3) .283 
 Asthma 4 (7.3) 2 (16.7) .509 
 Chronic lung disease 1 (1.8) 0 (0) .99 
 Oncologic diagnoses 3 (5.5) 1 (8.3) .555 
 Cardiac disease 0 (0) 0 (0) — 
 Diabetes 0 (0) 0 (0) — 
 Neurologic disorders 6 (12.7) 2 (16.7) .448 
 Rheumatologic disease 1 (1.8) 0 (0) .99 
 Transplant, stem cell 1 (1.8) 0 (0) .99 

—, not applicable.

TABLE 2

MIS-C Presentation: Demographics and Comorbidities by General Unit Versus ICU Care

CharacteristicGeneral Unit (n = 11)ICU Care (n = 3)P
Sex, n (%)   .505 
 Male 3 (27.2) 2 (66.7)  
 Female 8 (72.7) 1 (33.3)  
Ethnicity, n (%)   .428 
 White 1 (9.1) 2 (66.7)  
 African American 1 (9.1) 0 (0)  
 Hispanic 8 (72.7) 0 (0)  
 Asian 1 (9.1) 0 (0)  
 Other 0 () 1 (33.3)  
Patients >1 y old, n 10 .428 
 Age, y, mean (range) 8.0 (1–21) 11.7 (5–18)  
Infants <1 y old, n — 
 Mean age, mo 10 — — 
Smoking history, n (%)   .033 
 None 10 (90.9) 1 (33.3)  
 Cigarettes 1 (9.1) 0 (0)  
 Vaping 0 (0) 0 (0)  
 Unknown 0 (0) 2 (66.7)  
BMI for patients ≥2 y old, mean (range) 27.1 (14.1–73) 41.1 (19–71.7) .392 
Chronic health conditions, n (%)    
 None 11 (100) 3 (100) .99 
 Asthma 0 (0) 0 (0) — 
 Chronic lung disease 0 (0) 0 (0) — 
 Oncologic diagnoses 0 (0) 0 (0) — 
 Cardiac disease 0 (0) 0 (0) — 
 Diabetes 0 (0) 0 (0) — 
 Neurologic disorders 0 (0) 0 (0) — 
 Rheumatologic disease 0 (0) 0 (0) — 
 Transplant 0 (0) 0 (0) — 
CharacteristicGeneral Unit (n = 11)ICU Care (n = 3)P
Sex, n (%)   .505 
 Male 3 (27.2) 2 (66.7)  
 Female 8 (72.7) 1 (33.3)  
Ethnicity, n (%)   .428 
 White 1 (9.1) 2 (66.7)  
 African American 1 (9.1) 0 (0)  
 Hispanic 8 (72.7) 0 (0)  
 Asian 1 (9.1) 0 (0)  
 Other 0 () 1 (33.3)  
Patients >1 y old, n 10 .428 
 Age, y, mean (range) 8.0 (1–21) 11.7 (5–18)  
Infants <1 y old, n — 
 Mean age, mo 10 — — 
Smoking history, n (%)   .033 
 None 10 (90.9) 1 (33.3)  
 Cigarettes 1 (9.1) 0 (0)  
 Vaping 0 (0) 0 (0)  
 Unknown 0 (0) 2 (66.7)  
BMI for patients ≥2 y old, mean (range) 27.1 (14.1–73) 41.1 (19–71.7) .392 
Chronic health conditions, n (%)    
 None 11 (100) 3 (100) .99 
 Asthma 0 (0) 0 (0) — 
 Chronic lung disease 0 (0) 0 (0) — 
 Oncologic diagnoses 0 (0) 0 (0) — 
 Cardiac disease 0 (0) 0 (0) — 
 Diabetes 0 (0) 0 (0) — 
 Neurologic disorders 0 (0) 0 (0) — 
 Rheumatologic disease 0 (0) 0 (0) — 
 Transplant 0 (0) 0 (0) — 

—, not applicable.

For the 67 patients admitted for acute COVID-19 infection, the mean time from development of symptoms to admission was 4.0 days. The most common presenting symptoms included fever (49 [73.1%]) and cough (38 [56.7%]). Seventeen patients (25.4%) reported gastrointestinal symptoms. Six of these patients were found to have acute appendicitis, and 1 patient had intussusception. Mental status changes and other neurologic symptoms were reported in 7 patients (10.4%). An atypical presentation of acute COVID-19 infection included atrial fibrillation in 1 patient. Of the 14 patients admitted for MIS-C, the mean time from development of symptoms to admission was 4.9 days. The most common presenting symptoms included fever (14 [100%]), gastrointestinal symptoms (9 [64.3%]), and conjunctivitis (7 [50%]). Rash was reported in 3 patients (4%) with acute COVID-19 infection presentation and in 5 patients (35.7%) with MIS-C presentation.

Of the total 81 patients, 42 patients (51.9%) were tested for other viral pathogens. Coinfection with other respiratory viruses (enterovirus, parainfluenza virus type 3) was found in 2 patients with acute COVID-19 infection; 1 required intensive care. Bacterial coinfections were identified in the patients with acute COVID-19 infection and included suspected bacterial pneumonia (17 [25.4%]) and urinary tract infections (2 [2.9%]). None of the patients had bacteremia. Tables 3 and 4 reveal the laboratory findings in our population, with patients with acute COVID-19 infection compared separately with those with MIS-C. Patients with acute COVID-19 infection requiring intensive care management during their admission had a higher mean white blood cell (WBC) count of 29.3 × 109/L, as opposed to a WBC count of 8.8 × 109/L for those admitted to the general unit (P = .009). The mean WBC count was not statistically significant for the patients with MIS-C. For the patients with acute COVID-19 infection, the mean C-reactive protein (CRP) level was higher in the ICU group (131 mg/L for patients in the ICU versus 66 mg/L for patients in the general unit; P = .132). The mean CRP level in the patients with MIS-C treated in the ICU was significantly higher than the mean CRP level in the patients treated in the general unit (343 vs 144 mg/L; P = .005). For the MIS-C subgroup, patients who were treated in the ICU had more significant lymphopenia (lymphocyte count of 0.7 × 109/L for patients in the ICU versus 2.2 × 109/L for patients in the general unit; P = .048). Admission creatinine levels were also significantly higher for patients with MIS-C treated in the ICU (141.4 vs 53.0 µmol/L; P < .0001). Those with higher D-dimer values were more likely to require ICU admission in the MIS-C group as well (P = .042). Table 5 reveals the radiologic findings in the patients with acute COVID-19 infection. Our patients were more likely to have pulmonary infiltrates seen on imaging in both the ICU and the general unit (P = .852). Patients with pleural effusions (P = .033) or ground-glass opacities (P = .011) were more often treated in the ICU.

TABLE 3

Laboratory Values for Acute COVID-19 Infection by General Unit Versus ICU Care

CharacteristicGeneral Unit (n = 55)ICU Care (n = 12)P
Initial WBC count   0.009 
n 53 12  
 Mean ± SD, ×109/L 8.8 ± 4.60 29.3 ± 52.48  
 Range, ×109/L 1.2–23.8 5.6–194.2  
 Median, ×109/L 7.9 12.8  
Initial absolute neutrophil count   .011 
n 52 12  
 Mean ± SD, ×109/L 5.67 ± 4.40 10 ± 7.80  
 Range, ×109/L 0.7–14.3 0.0–25.7  
 Median, ×109/L 4.3 8.1  
Initial absolute lymphocyte count   .964 
n 52 12  
 Mean ± SD, ×109/L 2.46 ± 2.84 2.5 ± 2.36  
 Range, ×109/L 0.1–9.2 0.7–7.8  
 Median, ×109/L 1.3 1.6  
Initial platelet count   .137 
n 53 12  
 Mean ± SD, ×109/L 276.0 ± 118.0 338.0 ± 144.0  
 Range, ×109/L 88.0–656.0 62.0–583.0  
 Median, ×109/L 250.0 372.5  
Initial hemoglobin level   .449 
n 53 12  
 Mean ± SD, g/L 126 ± 23.5 115 ± 33.6  
 Range, g/L 53–186 40–154  
 Median, g/L 126 122  
Initial LDH level   .239 
n 25  
 Mean ± SD, U/L 454.7 ± 318.4 956.7 ± 1151.9  
 Range, U/L 0.2–1584.0 277.0–3277.0  
 Median, U/L 351.0 593.0  
Initial CRP level   .132 
n 34  
 Mean ± SD, mg/L 66 ± 101 131 ± 146  
 Range, mg/L 0.0–470 0.1–443  
 Median, mg/L 26.0 67.0  
Initial D-dimer level   .168 
n  
 Mean ± SD, mg/L 1.65 ± 1.53 5.04 ± 5.95  
 Range, mg/L 0.21–5.14 0.54–20  
 Median, mg/L 1.11 2.03  
Initial ferritin level   .624 
n 21  
 Mean ± SD, pmol/L 1991 ± 3120 2052 ± 3176  
 Range, pmol/L 18.2–10 555 288.3–8471  
 Median, pmol/L 739 782  
Initial sodium level   .634 
n 52 12  
 Mean ± SD, mmol/L 136.2 ± 2.74 135.1 ± 5.55  
 Range, mmol/L 129.0–144.0 124.0–143.0  
 Median, mmol/L 136.0 136.0  
Initial ALT level   .585 
n 44 12  
 Mean ± SD, U/L 38.4 ± 61.4 27 ± 19.7  
 Range, U/L 7.0–312.0 10–81.0  
 Median, U/L 21.5 20.0  
Initial albumin level   .110 
n 49 12  
 Mean ± SD, g/L 11 ± 48 36 ± 7  
 Range, g/L 28–34 23–49  
 Median, g/L 39 36  
Initial creatinine level   .397 
n 49 12  
 Mean ± SD, µmol/L 61.9 ± 79.6 61.9 ± 17.7  
 Range, µmol/L 17.7–627.7 35.4–88.4  
 Median, µmol/L 53 53  
Initial procalcitonin level   .523 
n 15  
 Mean ± SD, µg/L 0.2 ± 0.25 0.3 ± 0.25  
 Range, µg/L 0.1–1.1 0.1–0.5  
 Median, µg/L 0.1 0.5  
Initial IL-6 level   .885 
n  
 Mean ± SD, pg/mL 24.4 ± 34.0 30.3 ± 22.3  
 Range, pg/mL 5.0–85.0 5.0–47.0  
 Median, pg/mL 10.0 39.0  
CharacteristicGeneral Unit (n = 55)ICU Care (n = 12)P
Initial WBC count   0.009 
n 53 12  
 Mean ± SD, ×109/L 8.8 ± 4.60 29.3 ± 52.48  
 Range, ×109/L 1.2–23.8 5.6–194.2  
 Median, ×109/L 7.9 12.8  
Initial absolute neutrophil count   .011 
n 52 12  
 Mean ± SD, ×109/L 5.67 ± 4.40 10 ± 7.80  
 Range, ×109/L 0.7–14.3 0.0–25.7  
 Median, ×109/L 4.3 8.1  
Initial absolute lymphocyte count   .964 
n 52 12  
 Mean ± SD, ×109/L 2.46 ± 2.84 2.5 ± 2.36  
 Range, ×109/L 0.1–9.2 0.7–7.8  
 Median, ×109/L 1.3 1.6  
Initial platelet count   .137 
n 53 12  
 Mean ± SD, ×109/L 276.0 ± 118.0 338.0 ± 144.0  
 Range, ×109/L 88.0–656.0 62.0–583.0  
 Median, ×109/L 250.0 372.5  
Initial hemoglobin level   .449 
n 53 12  
 Mean ± SD, g/L 126 ± 23.5 115 ± 33.6  
 Range, g/L 53–186 40–154  
 Median, g/L 126 122  
Initial LDH level   .239 
n 25  
 Mean ± SD, U/L 454.7 ± 318.4 956.7 ± 1151.9  
 Range, U/L 0.2–1584.0 277.0–3277.0  
 Median, U/L 351.0 593.0  
Initial CRP level   .132 
n 34  
 Mean ± SD, mg/L 66 ± 101 131 ± 146  
 Range, mg/L 0.0–470 0.1–443  
 Median, mg/L 26.0 67.0  
Initial D-dimer level   .168 
n  
 Mean ± SD, mg/L 1.65 ± 1.53 5.04 ± 5.95  
 Range, mg/L 0.21–5.14 0.54–20  
 Median, mg/L 1.11 2.03  
Initial ferritin level   .624 
n 21  
 Mean ± SD, pmol/L 1991 ± 3120 2052 ± 3176  
 Range, pmol/L 18.2–10 555 288.3–8471  
 Median, pmol/L 739 782  
Initial sodium level   .634 
n 52 12  
 Mean ± SD, mmol/L 136.2 ± 2.74 135.1 ± 5.55  
 Range, mmol/L 129.0–144.0 124.0–143.0  
 Median, mmol/L 136.0 136.0  
Initial ALT level   .585 
n 44 12  
 Mean ± SD, U/L 38.4 ± 61.4 27 ± 19.7  
 Range, U/L 7.0–312.0 10–81.0  
 Median, U/L 21.5 20.0  
Initial albumin level   .110 
n 49 12  
 Mean ± SD, g/L 11 ± 48 36 ± 7  
 Range, g/L 28–34 23–49  
 Median, g/L 39 36  
Initial creatinine level   .397 
n 49 12  
 Mean ± SD, µmol/L 61.9 ± 79.6 61.9 ± 17.7  
 Range, µmol/L 17.7–627.7 35.4–88.4  
 Median, µmol/L 53 53  
Initial procalcitonin level   .523 
n 15  
 Mean ± SD, µg/L 0.2 ± 0.25 0.3 ± 0.25  
 Range, µg/L 0.1–1.1 0.1–0.5  
 Median, µg/L 0.1 0.5  
Initial IL-6 level   .885 
n  
 Mean ± SD, pg/mL 24.4 ± 34.0 30.3 ± 22.3  
 Range, pg/mL 5.0–85.0 5.0–47.0  
 Median, pg/mL 10.0 39.0  

ALT, alanine aminotransferase; LDH, lactate dehydrogenase.

TABLE 4

Laboratory Values for MIS-C by General Unit Versus ICU Care

CharacteristicGeneral Unit (n = 11)ICU Care (n = 3)P
Initial WBC count   .323 
n 11  
 Mean ± SD, ×109/L 10.3 ± 3.9 12.9 ± 2.89  
 Range, ×109/L 5.5–16.1 10.6–16.0  
 Median, ×109/L 9.0 12.3  
Initial absolute neutrophil count   .084 
n 11  
 Mean ± SD, ×109/L 7.5 ± 3.1 11.5 ± 3.38  
 Range, ×109/L 3.9–14.5 8.5–15.2  
 Median, ×109/L 6.9 10.8  
Initial absolute lymphocyte count   .048 
n 11  
 Mean ± SD, ×109/L 2.2 ± 1.75 0.7 ± 0.21  
 Range, ×109/L 0.6–6.7 0.4–0.8  
 Median, ×109/L 1.3 0.8  
Initial platelet count   .508 
n 11  
 Mean ± SD, ×109/L 181.5 ± 105.2 137.0 ± 68.1  
 Range, ×109/L 17.1–351.0 63.0–197.0  
 Median, ×109/L 164.0 151.0  
Initial hemoglobin level   .131 
n 11  
 Mean ± SD, g/L 108 ± 19.4 128 ± 13.9  
 Range, g/L 68–132 118–144  
 Median, g/L 107 122  
Initial LDH level   .598 
n  
 Mean ± SD, U/L 283.7 ± 80.8 317.0 ± 18.4  
 Range, U/L 190.0–439.0 304.0–330.0  
 Median, U/L 265.0 317.0  
Initial CRP level   .005 
n 11  
 Mean ± SD, mg/L 144 ± 88.6 343 ± 94  
 Range, mg/L 4.0–277 270–449  
 Median, mg/L 137.0 310.0  
Initial D-dimer level   .042 
n  
 Mean ± SD, mg/L 2.28 ± 1.49 5.33 ± 3.22  
 Range, mg/L 0.43–4.73 3.24–9.78  
 Median, mg/L 2.1 3.49  
Initial ferritin level   .095 
n 10  
 Mean ± SD, pmol/mL 892 ± 1119 3845 ± 1646  
 Range, pmol/mL 13.5–3901.8 2682–5009  
 Median, pmol/mL 630 3845  
Initial sodium level   .009 
n 11  
 Mean ± SD, mmol/L 134.5 ± 3.6 127.7 ± 1.53  
 Range, mmol/L 131.0–141.0 126.0–129.0  
 Median, mmol/L 133.0 128.0  
Initial BNP level   .124 
n  
 Mean ± SD, pmol/L 51.6 ± 74.7 220.3 ± 102  
 Range, pmol/L 2.8–226.6 148.2–292.4  
 Median, pmol/L 21.9 220.3  
Initial troponin level   .402 
n  
 Mean± SD, µg/L 0.2 ± 0.3 2.4 ± 2.3  
 Range, µg/L 0.0–0.7 0.8–4.1  
 Median, µg/L 0.1 2.4  
Initial ALT level   .474 
n 11  
 Mean ± SD, U/L 28.5 ± 6.0 57 ± 56.4  
 Range, U/L 10.0–61.0 20–122  
 Median, U/L 27.0 29.0  
Initial albumin level   .391 
n 11  
 Mean ± SD, g/L 36 ± 6 33 ± 6  
 Range, g/L 26–46 26–38  
 Median, g/L 36 35  
Initial creatinine level, µmol/L   <.0001 
n 11  
 Mean ± SD, µmol/L 53.0 ± 17.7 141.4 ± 35.4  
 Range, µmol/L 26.5–79.6 114.9–185.6  
 Median, µmol/L 44.2 132.6  
Initial IL-6 level, pg/mL   .512 
n  
 Mean ± SD 11.1 ± 9.1 17.0 ± 23.3  
 Range 4.6–17.5 5.0–33.5  
 Median 11.1 17.0  
Initial procalcitonin level   .512 
n  
 Mean ± SD, ng/mL 6.4 ± 8.3 40.5 ± 0  
 Range, ng/mL 0.5–12.3 —  
 Median, ng/mL 6.4 40.5  
CharacteristicGeneral Unit (n = 11)ICU Care (n = 3)P
Initial WBC count   .323 
n 11  
 Mean ± SD, ×109/L 10.3 ± 3.9 12.9 ± 2.89  
 Range, ×109/L 5.5–16.1 10.6–16.0  
 Median, ×109/L 9.0 12.3  
Initial absolute neutrophil count   .084 
n 11  
 Mean ± SD, ×109/L 7.5 ± 3.1 11.5 ± 3.38  
 Range, ×109/L 3.9–14.5 8.5–15.2  
 Median, ×109/L 6.9 10.8  
Initial absolute lymphocyte count   .048 
n 11  
 Mean ± SD, ×109/L 2.2 ± 1.75 0.7 ± 0.21  
 Range, ×109/L 0.6–6.7 0.4–0.8  
 Median, ×109/L 1.3 0.8  
Initial platelet count   .508 
n 11  
 Mean ± SD, ×109/L 181.5 ± 105.2 137.0 ± 68.1  
 Range, ×109/L 17.1–351.0 63.0–197.0  
 Median, ×109/L 164.0 151.0  
Initial hemoglobin level   .131 
n 11  
 Mean ± SD, g/L 108 ± 19.4 128 ± 13.9  
 Range, g/L 68–132 118–144  
 Median, g/L 107 122  
Initial LDH level   .598 
n  
 Mean ± SD, U/L 283.7 ± 80.8 317.0 ± 18.4  
 Range, U/L 190.0–439.0 304.0–330.0  
 Median, U/L 265.0 317.0  
Initial CRP level   .005 
n 11  
 Mean ± SD, mg/L 144 ± 88.6 343 ± 94  
 Range, mg/L 4.0–277 270–449  
 Median, mg/L 137.0 310.0  
Initial D-dimer level   .042 
n  
 Mean ± SD, mg/L 2.28 ± 1.49 5.33 ± 3.22  
 Range, mg/L 0.43–4.73 3.24–9.78  
 Median, mg/L 2.1 3.49  
Initial ferritin level   .095 
n 10  
 Mean ± SD, pmol/mL 892 ± 1119 3845 ± 1646  
 Range, pmol/mL 13.5–3901.8 2682–5009  
 Median, pmol/mL 630 3845  
Initial sodium level   .009 
n 11  
 Mean ± SD, mmol/L 134.5 ± 3.6 127.7 ± 1.53  
 Range, mmol/L 131.0–141.0 126.0–129.0  
 Median, mmol/L 133.0 128.0  
Initial BNP level   .124 
n  
 Mean ± SD, pmol/L 51.6 ± 74.7 220.3 ± 102  
 Range, pmol/L 2.8–226.6 148.2–292.4  
 Median, pmol/L 21.9 220.3  
Initial troponin level   .402 
n  
 Mean± SD, µg/L 0.2 ± 0.3 2.4 ± 2.3  
 Range, µg/L 0.0–0.7 0.8–4.1  
 Median, µg/L 0.1 2.4  
Initial ALT level   .474 
n 11  
 Mean ± SD, U/L 28.5 ± 6.0 57 ± 56.4  
 Range, U/L 10.0–61.0 20–122  
 Median, U/L 27.0 29.0  
Initial albumin level   .391 
n 11  
 Mean ± SD, g/L 36 ± 6 33 ± 6  
 Range, g/L 26–46 26–38  
 Median, g/L 36 35  
Initial creatinine level, µmol/L   <.0001 
n 11  
 Mean ± SD, µmol/L 53.0 ± 17.7 141.4 ± 35.4  
 Range, µmol/L 26.5–79.6 114.9–185.6  
 Median, µmol/L 44.2 132.6  
Initial IL-6 level, pg/mL   .512 
n  
 Mean ± SD 11.1 ± 9.1 17.0 ± 23.3  
 Range 4.6–17.5 5.0–33.5  
 Median 11.1 17.0  
Initial procalcitonin level   .512 
n  
 Mean ± SD, ng/mL 6.4 ± 8.3 40.5 ± 0  
 Range, ng/mL 0.5–12.3 —  
 Median, ng/mL 6.4 40.5  

ALT, alanine aminotransferase; BNP, brain-type natriuretic peptide; LDH, lactate dehydrogenase; —, not applicable.

TABLE 5

Chest Imaging Characteristics for Acute COVID-19 Infection by General Unit Versus ICU

CharacteristicaGeneral Unit (n = 31), n (%)ICU Care (n = 21), n (%)P
Chest imaging findings: ground-glass opacities 2 (6) 7 (33) .0116 
Chest imaging findings: infiltrates 18 (58) 16 (76) .8527 
Chest imaging findings: pleural effusion 0 (0.0) 3 (14) .0337 
Chest imaging findings: clear lung fields 14 (45) 5 (24) .1264 
CharacteristicaGeneral Unit (n = 31), n (%)ICU Care (n = 21), n (%)P
Chest imaging findings: ground-glass opacities 2 (6) 7 (33) .0116 
Chest imaging findings: infiltrates 18 (58) 16 (76) .8527 
Chest imaging findings: pleural effusion 0 (0.0) 3 (14) .0337 
Chest imaging findings: clear lung fields 14 (45) 5 (24) .1264 
a

Chest radiograph or CT scan.

Respiratory failure was not the most common presenting symptom of acute COVID-19 infection, and most of the patients did not require ICU care. Of the 67 patients with acute COVID-19 infection, 37 (55.2%) did not require any oxygen supplementation during their admission. For those who received oxygen supplementation, 17 patients (25.4%) required simple nasal cannula, 7 patients (10.4%) required high-flow nasal cannula, 3 patients (4.5%) required a non-rebreather mask, and 3 patients (4.5%) required mechanical ventilation. Of the 14 patients with MIS-C, 10 (71.4%) did not require oxygen supplementation, 3 (21.4%) required simple nasal cannula, and 1 (7.2%) required high-flow nasal cannula.

Nine patients (11%) required vasoactive substances (eg, dopamine, norepinephrine, milrinone); 5 of these were patients with an MIS-C diagnosis. Six of the patients with MIS-C (42.8%) had abnormal echocardiogram findings revealing decreased myocardial function.

Other complications in the patients with acute COVID-19 infection included acute respiratory distress syndrome (3 [4.5%]) and acute kidney injury (2 [3%]). Three of the patients with MIS-C (21%) had acute kidney injury. Six thrombotic events occurred in all patients combined (6 [7.4%]). These thrombotic events included 1 deep vein thrombosis, 1 atrial thrombus, 2 pulmonary emboli, and 2 sinus venous thrombi. Acute COVID-19 infection presentation was more likely to be associated with thromboses in our population because only 1 patient with a diagnosis of MIS-C had a thrombotic event. All of these patients were treated with enoxaparin.

Several patients received investigational agents meant to target viral activity and/or provide supportive care for the management of acute coronavirus disease on the basis of network clinical practice guidelines. These were created on the basis of treatment experience and limited evidence available for management. Hydroxychloroquine was administered to 15 patients. Remdesivir was administered to 6 patients (5 patients obtained through compassionate use and 1 patient enrolled in a clinical trial). Sarilumab, an interleukin 6 (IL-6) receptor antagonist being studied as a supportive care agent in a clinical trial, was administered to 1 patient. Additional therapies included convalescent plasma for 2 patients through compassionate use and corticosteroids in 15 patients with acute COVID-19 infection. There were no adverse events attributable to the medications observed in our study.

For the 14 patients admitted with criteria of MIS-C, 4 patients were treated with supportive care only. Two patients received only corticosteroids, whereas 6 patients received intravenous immune globulin in combination with corticosteroids and aspirin therapy. Two patients were transferred to another institution for further management of MIS-C because of subspecialist availability and parental request. Both of these patients recovered fully.

Most patients (71 [88%]) were discharged from the hospital with no limitations. We had one mortality in a newly diagnosed oncology patient with acute COVID-19 infection and respiratory failure. The mean length of stay was 5.0 days for patients with acute COVID-19 infection and 3.8 days for patients with MIS-C (P = .91). There were no readmissions within 30 days.

We report epidemiology, clinical manifestations, and outcomes of pediatric patients hospitalized with COVID-19 infection at 12 hospitals in New Jersey. In a large study of >2000 pediatric patients, the authors reported that 10.6% of children <1 year of age in their study had severe or critical illness, although some of these cases were associated with other coexisting viral infections.2  This is similar to our cohort, in which 10% of children <1 year of age required intensive care, suggesting that children <1 year of age do not have more severe illness compared with other age groups. In the Washington, District of Columbia metropolitan area, it was reported that older patients >15 years old were more likely to require critical care and that obesity was the most prevalent comorbidity.4  Our study revealed no statistically significant age difference between patients admitted to the general unit and those admitted to the ICU. Similar to other centers in the New York City area, a majority of our patients were Hispanic.5,6  Contrary to those studies, people who identify as Hispanic make up 10% to 20% of the population of the counties our hospitals serve, thereby suggesting that this population may be more vulnerable to the infection than other ethnicities. In these New York City area studies, researchers also described that histories of obesity and asthma were highly prevalent in patients with acute COVID-19 infection but not significantly associated with ICU admission. Most of our patients with either acute COVID-19 infection or MIS-C did not have preexisting conditions, but obesity did predict a more severe course in the patients with MIS-C. The mean BMI for those requiring MIS-C care in the ICU was 41.2. This difference, although not statistically significant in our population, was clinically notable. In addition, the majority of our patients with a history of asthma and/or an immunocompromised state did not require ICU management.

Our population did show that lymphopenia may be an indicator of more severe disease. In general, most of our patients diagnosed with COVID-19 infection had lymphopenia, with an overall average absolute lymphocyte count of 2.5 × 109/L in all patients combined. In patients with MIS-C, lymphopenia was more profound in those requiring ICU care and was statistically significant. Authors of several studies reported elevated levels of inflammatory markers, including procalcitonin, CRP, and IL-6, in patients requiring respiratory support.48  In our population, patients requiring intensive care, including respiratory or blood pressure support, had higher levels of inflammatory markers as well. CRP levels were higher for patients in the ICU who presented with both acute COVID-19 infection and MIS-C, and this difference was statistically significant in those admitted for MIS-C, which is noted in other studies.1214  Many of our patients did not have evaluated levels of other inflammatory markers (such as procalcitonin or IL-6), but of those who did, there was a trend of higher values in patients requiring intensive care.

Chest computed tomography (CT) findings commonly seen in pediatric cases includes ground-glass opacities and consolidation with halo signs.7,8  Involvement of >3 lung segments has been identified as a risk factor for severe illness.7  As expected, on the basis of previous citations, patients who required intensive care in our network generally had more pathologic findings on radiologic studies, including ground-glass opacities and pleural effusions, compared with those in the general unit.

Another observation of our study is that a large proportion of our patients met criteria for MIS-C. Of the 81 patients, 14 (17.3%) were diagnosed with MIS-C. One patient had acute COVID-19 infection and 4 weeks later, while still hospitalized, developed and was treated for MIS-C. The condition itself is believed to be a rare manifestation of the virus, with the CDC reporting <600 cases nationwide, yet in our network, it was a significant presentation of SARS-CoV-2 infection in the pediatric population. The prevalence of MIS-C patients increased to 35.9% of all those admitted with SARS-CoV-2 disease after April 21, which supports the theory of a postviral immunologic response seen in the pediatric population and supports the hypothesis that peak severity in children may occur after the peak of admissions in the adult population.

Limitations of this study include a small sample size, with patients from a single network of hospitals in New Jersey. However, the hospitals are geographically dispersed throughout the state of New Jersey, and they care for patients of various ethnic backgrounds and socioeconomic statuses, which we consider a strength of our study. It is worth noting that we were unable to explore the relationship between social determinants of health and COVID-19 infection in our population. The patient population recorded in our study may not be representative of that in other states in the United States. Additionally, given the widespread community transmission, SARS-CoV-2 detection may also be coincidental with other diagnoses. This may be the case for our patients with acute appendicitis, intussusception, and atrial fibrillation. However, intussusception has been reported in association with COVID-19 infection.15  It is unclear if atrial fibrillation can definitively be linked causatively to acute COVID-19 infection, but this condition was temporally associated with a positive RT-PCR test result in a patient with no previous cardiac history. Furthermore, our presentation of the experimental therapies provided in these hospitalized children and young adults with COVID-19 infection is purely descriptive and does not imply any possible benefit from these therapies. Safe and effective treatments of COVID-19 in pediatric patients remains to be revealed by rigorous clinical trials.

This study adds to the growing literature of potential risk factors, patterns, and likely predictors for severe disease in pediatric patients with COVID-19 infection. Unlike other published studies from urban hospitals in the United States, this study provides further information on patients from both urban and suburban communities of New Jersey with diverse socioeconomic, geographic, and ethnic backgrounds. It is also unique in that the study period includes the time frame shift from acute COVID-19 infection to MIS-C presentation. Despite our diverse communities, patients of Hispanic ethnicity represented the majority of patients admitted to our hospitals with both acute COVID-19 infection and MIS-C. Infants and patients with chronic health conditions in our network hospitals were not at increased risk for severe disease.

We are grateful for the incredible work of the entire health care team within the Hackensack Meridian Health network hospitals, in particular, the members of the divisions of pediatric emergency medicine, pediatric intensive care, hospital medicine, pediatric infectious diseases, pediatric cardiology, and pediatric rheumatology; the departments of infection prevention and pharmacy; and the diagnostics laboratory at each hospital. We also thank Michelle Secic, MS, for her assistance with statistics.

Drs Bhavsar and Clouser drafted the initial manuscript and participated in data collection and analysis; Dr Gadhavi participated in data collection and analysis; Drs Anene and Ballance, Ms Chen, and Drs Kaur, Lewis, Michalak, Naganathan, Shah, and Siu participated in data collection; and all authors reviewed and revised the manuscript and approved the final manuscript as submitted.

FUNDING: No external funding.

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.