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mission to ICU seems not to be more likely in younger children. The likelihood of being hospitalised was higher when children had an underlying condition, and a severe course was rare (https://covid19-surveillancereport.ecdc.europa.eu). In a cross-sectional study including 48 children with COVID-19 (median age 13 years; admitted to 46 North American pediatric ICUs between March 14 and April 3, 2020), forty patients (83%) had significant pre-existing co-morbidities and 18 (38%) required invasive ventilation. Targeted therapies were used in 28 patients (61%, mainly HCQ). Two patients (4%) died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving ECMO (Shekerdemian 2020). In an observational retrospective cohort study that included 177 children and young adults with clinical symptoms and laboratory confirmed SARS-CoV-2 infection treated between March 15 and April 30, 2020 at the Children’s National Hospital in Washington, 44 were hospitalized and 9 were critically ill. Of these, 6/9 were adolescents and young adults > 15 years of age. Although asthma was the most prevalent underlying condition overall, it was not more common among patients with severe disease (DeBiasi 2020). Although the natural course of COVID-19 is uneventful in most pediatric patients, a very small percentage can develop a potentially fatal severe hyperinflammatory state 2-4 weeks after acute infection with SARS-CoV-2 (Riphagen 2020). This hyperinflammatory state is termed as pediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2 (PIMS-TS) (or synonym Multisystem Inflammatory Syndrome in Children (MIS-C). Of the 570 MIS-C cases reported to the CDC by July 2020, 10 patients had died (1.8% ) and 364 (63.9%) patients required treatment in an intensive care unit. Obesity was the most commonly reported underlying medical condition (GodfredCato 2020).
Pathophysiology and immunopathology It is unclear why COVID-19 in children is associated with a less severe disease course. The tissue expression pattern of the receptor for CoV-2 angiotensin converting enzyme (ACE2) and the transmembrane serine protease TMPRSS2 (essential for CoV-2 cell entry) as well as the tissue tropism of CoV-2 in childhood are unknown but age-dependent differences in ACE2 receptor expression may explain why outcomes differ in children versus adults (Bunyavanich 2020). ACE2 is expressed on cells of the airways, the lungs, mucosal cells (lids, eyelids, nasal cavities), intestines and on immune cells (monocytes, lymphocytes, Kamps – Hoffmann
