Pediatric Guide to COVID-19 Part 2
Pediatric Guide to COVID-19 Part 2
February 9, 2021 by eMedEvents

Welcome to the second installment of the pediatric Guide to COVID-19, where we will be illustrating the anatomy, pathogenesis of the SARS-CoV-2 virus, and concurrent symptom manifestations in children aged below 21 years.

ANATOMY

The positive-sense single-stranded RNA virus encodes for four structural proteins; surface spike (S), small protein (E), matrix (M), and nucleocapsid (N).2 The S protein is a type 1 fusion protein made up of two subunits, S1 and S2.  S1 utilizes angiotensin-converting enzyme 2 (ACE2) to gain entry into cells while S2 facilitates membrane fusion to type 2 alveolar epithelial, ciliated, and goblet cells of the airways. The presence of ACE2 expression in intestinal epithelia, myocardial and vascular endothelial cells indicates and could explain variable organ involvement.3

PATHOGENESIS

The SARS-CoV-2 virus shares approximately 80% of its RNA sequence within SARS-CoV and 50% with MERS-CoV. The infection mechanisms involved in these coronaviruses are similar to those exhibited by SARS-CoV-2. The infection mechanisms involved in these coronaviruses are similar to those exhibited by SARS-CoV-2. However, additional maneuvers, such as phagocytosis of function virions within immune complexes, may be present. The infection of monocytes/macrophages and T-cells have also been reported in COVID-19 infected patients.

“The SARS-CoV-2 virus evades the early innate immune response through suppressing Toll-like receptor (TLR3 and 7) and/or cytosolic RNA receptor (RIG-I, MDA5) mediated type I interferon signaling, which results in spreading of the infection. When a threshold is reached, cells become necrotic and virus particles are released together with nuclear and cytosolic components, both of which can form immune complexes. Virus containing IC infect monocytes/macrophages (Mφ) and induce massive pro-inflammatory cytokine expression (IL-1, IL-6, TNF-α) in a process named antibody dependent enhancement. IC also activate the complement and clotting cascades, contributing to inflammation and deranged coagulation. Further (uninfected) monocytes/macrophages invade the area and produce type I interferons and pro-inflammatory cytokines, further contributing to inflammation and tissue damage.”3

CLINICAL MANIFESTATIONS

Symptomatic Presentation:

The clinical indicators in Children with COVID-19 are diverse, but fever or chills, and cough are the most commonly reported symptoms.4,5,6,7

A study surveilling 17,877 children, 5188 aged 0 through 9 and 12689 aged 10 through 19, within the United States (till May 30, 2020), provided statistical data to map the frequency of symptoms in pre- and post-adolescent age groups. The findings are depicted below:4

  • 9 Years or Younger:
    • Fever, cough, or shortness of breath – 63 %
      • Fever – 46 %
      • Cough – 37 %
      • Shortness of breath – 7 %
    • Myalgia – 10 %
    • Rhinorrhea – 7 %
    • Sore throat – 13 %
    • Headache – 15 %
    • Nausea/vomiting – 10 %
    • Abdominal pain – 7 %
    • Diarrhea – 14 %
    • Loss of smell or taste – 1 %

 

  • 10 Years and Older:
    • Fever, cough, or shortness of breath – 60 percent
      • Fever – 35 percent
      • Cough – 41 percent
      • Shortness of breath – 16 percent
    • Myalgia – 30 percent
    • Rhinorrhea – 8 percent
    • Sore throat – 29 percent
    • Headache – 42 percent
    • Nausea/vomiting – 10 percent
    • Abdominal pain – 8 percent
    • Diarrhea – 14 percent
    • Loss of smell or taste – 10 percent

By bifurcating symptoms exhibited by infected and non-infected children and eliminating commonalities, a Canadian cohort study managed to identify anosmia/ageusia, nausea/vomiting, headache, and fever as the most substantial signs associated with positive SARS-CoV-2 swab results.8 In terms of cutaneous findings, “COVID toes,” reddish-purple nodules on the distal digits (chilblains) are predominantly present in children and young adults.

A new and rare condition, called Multisystem Inflammatory Syndrome (MIS-C), has also started to manifest in youngsters. This malady’s clinical characteristics appear to be similar to Kawasaki Disease, Kawasaki disease shock syndrome and toxic shock syndrome. Sever cases exhibit persistent fever, hypotension, gastrointestinal symptoms, rash, myocarditis.9

Laboratory Presentations:

A systematic review of COVID-19 cases in children aged less than 18 years has illuminated some common biochemical elevations in infected patients.5

  • Approximately 33% showed increased C-reactive protein or procalcitonin levels
  • 15% showed a rise in creatine kinase levels.
  • 12% showed elevated serum aminotransferases.

A sequential study that was not included in systemic review also depicted heightened lactate dehydrogenase (LDH) as a common abnormality.10

Potential markers of severe COVID-19 have also been identified in children on or during hospitalization. Elevated inflammatory markers, such as CRP, procalcitonin, interleukin 6, ferritin, and D-dimer, and gastrointestinal symptoms have been observed and are associated with severe disease in children.11,12,13,14,15

Imaging Presentations

Findings appear to be variable and may be present before symptom manifestation. One meta-analysis of 674 laboratory-confirmed pediatric cases revealed that approximately 50% of children had abnormalities. Another systematic review found that out of 1026 SARS-CoV-2 positive children who underwent tomography imaging, 36% were normal, and 28% had bilateral lesions.16 Ground glass opacities and pneumonic infiltrates also seem to present and are commonly reported. However, none showed typical signs of viral respiratory infections. Lastly, one study found subpleural consolidations and individual or confluent B lines on conducting lung ultrasonography. These overlap with radiological findings seen in adult patients with COVID-19.17

In conclusion, children are either asymptomatic or show mild symptoms, so increased vigilance to correctly identify potential markers is crucial in pediatric patients. We hope this article clears some doubts you may have had and helps you diagnose your patients better. Our next installation will cover emerging variants of the SARS-CoV-2 and surprising discoveries in pediatric patients.

STAY INFORMED! STAY SAFE!


Works Cited

1Cascella, Marco, et al. “Features, Evaluation, and Treatment of Coronavirus.” StatPearls, StatPearls Publishing, 4 October 2020.

2Chan, J. F.-W., Kok, K.-H., Zhu, Z., Chu, H., To, K. K.-W., Yuan, S., & Yuen, K.-Y. (2020). Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting wuhan. Emerging Microbes & Infections, 9(1), 221–236. https://doi.org/10.1080/22221751.2020.1719902

3Felsenstein, Susanna, and Christian M Hedrich. “SARS-CoV-2 infections in children and young people.” Clinical immunology (Orlando, Fla.) vol. 220 (2020): 108588. doi:10.1016/j.clim.2020.108588

4Stokes, Erin K et al. “Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020.” MMWR. Morbidity and mortality weekly report vol. 69,24 759-765. 19 Jun. 2020, doi:10.15585/mmwr.mm6924e2

5Liguoro, Ilaria et al. “SARS-COV-2 infection in children and newborns: a systematic review.” European journal of pediatrics vol. 179,7 (2020): 1029-1046. doi:10.1007/s00431-020-03684-7

6Otto, William R et al. “The Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in a Pediatric Healthcare Network in the United States.” Journal of the Pediatric Infectious Diseases Society vol. 9,5 (2020): 523-529. doi:10.1093/jpids/piaa074

7Hoang, Ansel et al. “COVID-19 in 7780 pediatric patients: A systematic review.” EClinicalMedicine vol. 24 100433. 26 Jun. 2020, doi:10.1016/j.eclinm.2020.100433

8King, James A et al. “Symptoms associated with a positive result for a swab for SARS-CoV-2 infection among children in Alberta.” CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne vol. 193,1 (2021): E1-E9. doi:10.1503/cmaj.202065

9Aguilera, E. (2021, January 21). COVID-19 cases, new syndrome on the rise among children, especially Latino children. CalMatters. https://calmatters.org/health/coronavirus/2021/01/covid-new-syndrome-children/

10Wu, Huan et al. “Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China.” JAMA network open vol. 3,6 e2010895. 1 Jun. 2020, doi:10.1001/jamanetworkopen.2020.10895

11Kainth, Mundeep K et al. “Early Experience of COVID-19 in a US Children's Hospital.” Pediatrics vol. 146,4 (2020): e2020003186. doi:10.1542/peds.2020-003186

12Giacomet, Vania et al. “Gastrointestinal Symptoms in Severe COVID-19 Children.” The Pediatric infectious disease journal vol. 39,10 (2020): e317-e320. doi:10.1097/INF.0000000000002843

13Gonzalez Jimenez, David et al. “COVID-19 Gastrointestinal Manifestations Are Independent Predictors of PICU Admission in Hospitalized Pediatric Patients.” The Pediatric infectious disease journal vol. 39,12 (2020): e459-e462. doi:10.1097/INF.0000000000002935

14Zachariah, Philip et al. “Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York.” JAMA pediatrics vol. 174,10 (2020): e202430. doi:10.1001/jamapediatrics.2020.2430

15Chao, Jerry Y et al. “Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 at a Tertiary Care Medical Center in New York City.” The Journal of pediatrics vol. 223 (2020): 14-19.e2. doi:10.1016/j.jpeds.2020.05.006

16Nino, Gustavo et al. “Pediatric lung imaging features of COVID-19: A systematic review and meta-analysis.” Pediatric pulmonology vol. 56,1 (2021): 252-263. doi:10.1002/ppul.25070

17Denina, Marco et al. “Lung Ultrasound in Children With COVID-19.” Pediatrics vol. 146,1 (2020): e20201157. doi:10.1542/peds.2020-1157

 

 

 

 

 

 

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