International Analysis of Electronic Health Records of Children and Youth Hospitalized With COVID-19 Infection in 6 Countries

Abstract

Importance: Additional sources of pediatric epidemiological and clinical data are needed to efficiently study COVID-19 in children and youth and inform infection prevention and clinical treatment of pediatric patients.

Objective: To describe international hospitalization trends and key epidemiological and clinical features of children and youth with COVID-19.

Design, setting, and participants: This retrospective cohort study included pediatric patients hospitalized between February 2 and October 10, 2020. Patient-level electronic health record (EHR) data were collected across 27 hospitals in France, Germany, Spain, Singapore, the UK, and the US. Patients younger than 21 years who tested positive for COVID-19 and were hospitalized at an institution participating in the Consortium for Clinical Characterization of COVID-19 by EHR were included in the study.

Main outcomes and measures: Patient characteristics, clinical features, and medication use.

Results: There were 347 males (52%; 95% CI, 48.5-55.3) and 324 females (48%; 95% CI, 44.4-51.3) in this study's cohort. There was a bimodal age distribution, with the greatest proportion of patients in the 0- to 2-year (199 patients [30%]) and 12- to 17-year (170 patients [25%]) age range. Trends in hospitalizations for 671 children and youth found discrete surges with variable timing across 6 countries. Data from this cohort mirrored national-level pediatric hospitalization trends for most countries with available data, with peaks in hospitalizations during the initial spring surge occurring within 23 days in the national-level and 4CE data. A total of 27 364 laboratory values for 16 laboratory tests were analyzed, with mean values indicating elevations in markers of inflammation (C-reactive protein, 83 mg/L; 95% CI, 53-112 mg/L; ferritin, 417 ng/mL; 95% CI, 228-607 ng/mL; and procalcitonin, 1.45 ng/mL; 95% CI, 0.13-2.77 ng/mL). Abnormalities in coagulation were also evident (D-dimer, 0.78 ug/mL; 95% CI, 0.35-1.21 ug/mL; and fibrinogen, 477 mg/dL; 95% CI, 385-569 mg/dL). Cardiac troponin, when checked (n = 59), was elevated (0.032 ng/mL; 95% CI, 0.000-0.080 ng/mL). Common complications included cardiac arrhythmias (15.0%; 95% CI, 8.1%-21.7%), viral pneumonia (13.3%; 95% CI, 6.5%-20.1%), and respiratory failure (10.5%; 95% CI, 5.8%-15.3%). Few children were treated with COVID-19-directed medications.

Conclusions and relevance: This study of EHRs of children and youth hospitalized for COVID-19 in 6 countries demonstrated variability in hospitalization trends across countries and identified common complications and laboratory abnormalities in children and youth with COVID-19 infection. Large-scale informatics-based approaches to integrate and analyze data across health care systems complement methods of disease surveillance and advance understanding of epidemiological and clinical features associated with COVID-19 in children and youth.

Figure 1.. Age and Race/Ethnicity Distribution by Country

The race/ethnicity variable was based on the categories as defined by the US National Institutes of Health. For Singapore, the term Asian includes Chinese, Asian Indian, and Malaysian and the term other was used for Eurasian and other races and ethnicities. For patients in the UK and the US, the term other represents other races and ethnicities, mixed races, and missing information on race. Information on race and ethnicity were not collected in France, Germany, and Spain.

Figure 2.. Hospitalized Pediatric Case Counts by Country

For France, daily pediatric hospitalization data were obtained from Santé Publique France. For Germany, weekly pediatric hospitalization data were obtained from the German Society for Pediatric Infectious Diseases. National pediatric hospitalization data were not available for Singapore. For Spain, weekly pediatric hospitalization data were obtained from the Spanish National Epidemiological Surveillance Network, which lacks hospitalization counts between May 11 and July 15, 2020. For the UK, daily pediatric hospitalization data were obtained from the Royal College of Paediatrics and Child Health and represent pediatric hospitalizations in England. For the US, weekly pediatric hospitalization data between July 31, 2020, and October 9, 2020, were obtained from the Department of Health and Human Services. The y-axis scales for country-level data are independent to compare country-level trends with Consortium for Clinical Characterization of COVID-19 by EHR (4CE) trends. The plots in Figure 2A display the counts with a 14-day (centered) rolling mean.

Figure 3.. Trajectories for Laboratory Values During Hospitalization

Mean daily values across sites were calculated using random-effects meta-analysis. Values in parenthesis represent the minimum and maximum numbers of patients contributing data on any single day during the 14-day observation period. The shaded areas represent 95% CIs. SI conversion factors: To convert alanine aminotransferase to microkatal per liter, multiply by 0.0167; albumin to g/L, multiply by 10; aspartate aminotransferase to microkatal per liter, multiply by 0.0167; C-reactive protein to milligrams per liter; creatinine to micromoles per liter, multiply by 76.25; ferritin to micrograms per liter, multiply by 1; D-dimer to nanomoles per liter, multiply by 5.476; fibrinogen to grams per liter, multiply by .01; lactate dehydrogenase to microkatal per liter, multiply by 0.0167; lymphocyte count to proportion of 1.0, multiply by 0.01; neutrophil to proportion of 1.0, multiply by 0.01; total bilirubin to micromoles per liter, multiply by 17.104; troponin to milligrams per liter, multiply by 1.0, white blood cell count to proportion of 1.0, multiply by 0.01.