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COVID-19

COVID-19 Brief: How does SARS-CoV-2 cause serious illness in children?

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Children represent only a very small portion of reported COVID-19 patients, with most experiencing fewer symptoms, less severe disease, and a much lower case fatality rate than adults.



In the U.S., only 1.7% of reported COVID-19 cases occur in those younger than 18 years of age, with similar numbers in China (2%) and Italy (1%). However, with symptoms often being mild or not apparent in children, there is a potential for reduced testing and underdiagnosis. Most childhood and adolescent cases are acquired by familial transmission within households.

An understanding of how the host and the environment interact in coronavirus infection provides an explanation for some of the differences in childhood and adult outcomes. Notably, children generally do not carry the comorbidity burden often associated with older age.

Coronavirus Review


There are four known common human coronavirus strains which, having an affinity for the upper airway, cause benign seasonal respiratory tract illnesses such as the common cold. While antibodies to various human coronavirus antigens are found in 90-100% of adults, these seropositive rates are not mimicked in children who have not had exposure to community infections.

Three novel coronavirus strains have now been described in humans (SARS-CoV, MERS-CoV and SARS-CoV-2), having migrated from animals to humans in the current century. Novel viruses have a higher affinity for the lower airway, potentially causing pneumonia and severe acute respiratory syndrome (SARS).

Immune Response Considerations


COVID-19 cases with the most profound systemic inflammatory responses usually present with more severe disease and exhibit the highest mortality. Various hypotheses have emerged as to how age-specific immunological factors might influence this response.

Given the antigenic commonalities among all coronaviruses, exposure to novel viruses in those already possessing antibodies might generate an enhanced antibody-mediated, proinflammatory response by existing immune memory cells that is detrimental to the outcome. While being inadequate for the purposes of killing novel viruses, this type of response may provide a hyperinflammatory environment that promotes severe systemic disease. This process of antibody-dependent enhancement and the resultant “cytokine storm” explain some of the differences in disease behavior in children compared to older individuals.

The innate immune system provides the first line of defense against pathogens in humans, and this protective barrier is particularly active in children as they begin to interact with their environment. Early recognition of foreign antigens by this enhanced innate system in children and the mounting of a prompt and effective immune response contribute to an advantageous outcome.

Clinical Manifestations of COVID-19 in Children


Although childhood COVID-19 differs from adult COVID-19 – lower infection rates, milder symptoms, lower case fatality rates, and a SARS-sparing pattern – children remain vulnerable. The most common, life-threatening manifestations in children include pneumonia, cardiac injury, kidney injury, and coagulation dysfunction. In addition to these complications, there are now reports of an emerging “Multisystem Inflammatory Syndrome in Children and Adolescents,” which seems at least temporally associated with COVID-19 and occurs days or weeks after an acute COVID-19 infection.

Affected children have features shared with other pediatric inflammatory syndromes, including Kawasaki disease and toxic shock syndrome. These children usually present with a protracted fever and rash and may develop cardiac inflammation, multiorgan failure, and shock. They also may be critically ill, and deaths have now been reported.

While many children with this syndrome have detectable viral RNA, they may be RT-PCR negative. Positive serology in children without any detectable residual virus supports the notion that these manifestations reflect a post-viral, immune-mediated consequence of infection and might represent many phenotypes on a spectrum.

Summary


It is now becoming clear that COVID-19 can indeed cause serious illness in children. Though these critical manifestations remain relatively rare, they can be devastating for those affected when they do occur.


References:

  1. Zimmermann, Peter et al. Coronavirus Infections in Children Including COVID-19. The Pediatric Infectious Disease Journal, 39 (5) 2020. Pages 355-368.
  2. World Health Organization 2020. Report of the WHO-China Joint Mission on Corona Virus Disease.
  3. Gorse, GJ et al. Prevalence of antibodies to four human coronaviruses is lower in nasal secretions than in serum. Clin Vaccine Immunol. 2010 Dec: 17(12): 1875-1880.
  4. Kadkhoda, K COVID-19 An Immunopathological View. American Science for Microbiology 5 (2) 2020.
  5. Prill, MM et al. Pediatric Infectious Disease Journal. 29 Feb 2012, 31(3):235-240.
  6. Liccardi, F et al. COVID-19 and What Pediatric Rheumatologists Should Know: A Review from a Highly Infected Country. Pediatr Rheumatol 18, 35 (2020).
  7. Rothan HA, Byrareddy SN. The Epidemiology and Pathogenesis of Coronavirus Disease (COVID-19. J Autoimmun. 2020;109:102433.
  8. Harapan, H et al. Coronavirus Disease (COVID-19): A Literature Review. Journal of Infection and Public Health. Vol 13, Issue 5, May 2020, Pages 667-673.
  9. Huang, C et al. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan China. Lancet February 15, 2020, Vol 395, pages 497-506.
  10. Hedrich, CM. COVID-19 - Considerations for the Paediatric Rheumatologist. Clin Immunol. 2020;214:108420.
  11. Chang, Luan-Yin et al. Viral Infections Associated with Kawasaki Disease. J Formos Med Assoc. 2014 Mar; 113(3): 148-154.
  12. Cao, X. COVID-19: Immunopathology and Its Implications for Therapy. Nat Rev Immunol 20, 269-270 (2020).
  13. Multisystem inflammatory syndrome in children and adolescents with COVID-19. https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19 (accessed 16 May 2020)

 

The Author

  • Dr. Paul Davis
    MB.BS (Hons), FRACP
    Chief Medical Officer

    RGA Australia
    Send email >
     

Summary

Although childhood COVID-19 differs from adult COVID-19, the virus can indeed cause serious illness in children. RGA's Dr. Paul Davis identifies emerging research into links between the virus and pediatric inflammatory syndromes and discusses rare, life-threatening manifestations in children. 
 

  • coronavirus
  • COVID
  • covid19
  • COVID-19
  • Davis
  • hyperinflammatory
  • immune response
  • Kawasaki
  • Paul Davis
  • Pediatric
  • pediatric inflammatory syndrome
  • SARS-CoV
  • SARS-CoV-2
  • toxic shock syndrome