Background The overall global impact of COVID-19 in children and regional variability in pediatric outcomes are presently unknown. Methods To evaluate the magnitude of global COVID-19 death and intensive care unit (ICU) admission in children aged 0–19 years, a systematic review was conducted for articles and national reports as of December 7, 2020. This systematic review is registered with PROSPERO (registration number: CRD42020179696). Results We reviewed 16,027 articles as well as 225 national reports from 216 countries. Among the 3,788 global pediatric COVID-19 deaths, 3,394 (91.5%) deaths were reported from low- and middle-income countries (LMIC), while 83.5% of pediatric population from all included countries were from LMIC. The pediatric deaths/1,000,000 children and case fatality rate (CFR) were significantly higher in LMIC than in high-income countries (HIC) (2.77 in LMIC vs 1.32 in HIC; p < 0.001 and 0.24% in LMIC vs 0.01% in HIC; p < 0.001, respectively). The ICU admission/1,000,000 children was 18.80 and 1.48 in HIC and LMIC, respectively (p < 0.001). The highest deaths/1,000,000 children and CFR were in infants < 1 year old (10.03 and 0.58% in the world, 5.39 and 0.07% in HIC and 10.98 and 1.30% in LMIC, respectively). Conclusions The study highlights that there may be a larger impact of pediatric COVID-19 fatality in LMICs compared to HICs.

Drotrecogin alfa (activated) demonstrated significant improvements in organ function compared with placebo in a large phase 3 clinical trial that has shown a mortality benefit in patients with severe sepsis.