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Comment & Response
October 26, 2020

Additional Concerns Regarding Children With Coronavirus Disease 2019

Author Affiliations
  • 1Pediatric Department, Hospital “F. Del Ponte,” University of Insubria, Varese, Italy
JAMA Pediatr. 2020;174(12):1217-1218. doi:10.1001/jamapediatrics.2020.2922

To the Editor We read with great interest “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review” by Castagnoli et al.1 This analysis of 18 studies and 1065 children and adolescents, all from China except one from Singapore, updated to March 3, 2020, showed that coronavirus disease 2019 (COVID-19) affects all ages. Children often present with fatigue, nasal congestion, fever and cough, but severe pneumonia is less common and deaths are extremely rare.1 Castagnoli et al1 stated that defining the clinical characteristics and severity of the disease in large cohorts of patients is an urgent need. Italian,2 European,3 and US4 reports all have confirmed that few cases (<3%) were among children and adolescents who appeared the least at-risk population for critical disease in all countries. We consider that interpreting these data and understanding the varied susceptibility of children to SARS-CoV-2 are particularly important to figure out the protective factors in patients of all ages. Resistance to COVID-19 is highly likely to be multifactorial. Preexisting health conditions, including cardiovascular and chronic respiratory diseases, obesity, diabetes, cancer, and immune suppression, have been associated with severe illness and lethality in adult patients and elderly patients.2-4 Data on comorbidities in pediatric COVID-19 were not available in this systematic review1 but need to be fully analyzed in the next large case series to better identify key risk factors in children and potential individual protective and therapeutic strategies. Antigen sequencing of SARS-CoV-2 could also clarify whether cross-immunity with other respiratory viruses or infant vaccinations may occur in different populations. The mechanistic role of angiotensin-converting enzyme 2 receptors in the pathogenesis of severe COVID-19 and its variation according to age still need to be studied. Next, immune senescence and inflammaging include decreased number of naive T cells, impaired phagocytosis, restricted T-cell antigen receptor repertoire, reduced B-cell and T-cell functional responses, and persistent inflammatory molecules, thus predisposing to increased risk of infections and tissue fibrosis.5 Exploring nasopharyngeal and systemic innate and adaptive immunity in pediatric cases is crucial for understanding children’s resistance to SARS-CoV-2, viral transmission, and plausible therapeutic approaches. Anosmia and dysgeusia are reported in many adult patients with COVID-19; the prevalence and importance of these symptoms in children is uncertain. Finally, SARS-CoV-2 antibody tests will reveal whether children were less tested or less exposed to the virus or whether they contracted the infection and expressed mild illness owing to multiple protective mechanisms.

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Article Information

Corresponding Author: Silvia Salvatore, MD, PhD, Pediatric Department, Hospital “F. Del Ponte,” University of Insubria, Varese, Italy (

Published Online: October 26, 2020. doi:10.1001/jamapediatrics.2020.2922

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank Sara Trabanelli, MD, who provided us great immunologic insights and precious help to critically interpret the data.

Castagnoli  R, Votto  M, Licari  A,  et al.  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Infection in children and adolescents: a systematic review.   JAMA Pediatr. 2020;174(9):882-889. doi:10.1001/jamapediatrics.2020.1467PubMedGoogle Scholar
Task force COVID-19 del Dipartimento Malattie Infettive e Servizio di Informatica, Istituto Superiore di Sanità. Epidemia COVID-19, Aggiornamento nazionale: 16 aprile 2020.
European Center for Disease Prevention and Control. Coronavirus disease 2019 (COVID-19) in the EU/EEA and the UK: ninth update, 23 April 2020. Accessed September 22, 2020.
CDC COVID-19 Response Team.  Coronavirus disease 2019 in children: United States, February 12-April 2, 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(14):422-426. doi:10.15585/mmwr.mm6914e4PubMedGoogle ScholarCrossref
Nikolich-Žugich  J.  The twilight of immunity: emerging concepts in aging of the immune system.   Nat Immunol. 2018;19(1):10-19. doi:10.1038/s41590-017-0006-xPubMedGoogle ScholarCrossref