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Main article: COVID-19

For COVID-19 frequently asked inpatient questions, click here

For COVID-19 frequently asked outpatient questions, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Harmeet Kharoud M.D.[2]; Asra Firdous, M.B.B.S.[3] Neepa Shah, M.B.B.S.[4]; Abdelrahman Ibrahim Abushouk, MD[5]

Synonyms and Keywords: Novel coronavirus, COVID-19, Wuhan coronavirus, coronavirus disease-19, coronavirus disease 2019, SARS-CoV-2, COVID-19, COVID-19, 2019-nCoV, Neonatal COVID-19, Pediatric COVID-19, Multisystem Inflammatory Syndrome in Children.

Overview

Cases of COVID-19 have been reported in children, yet the prevalence is lower than adults. The presentation of COVID-19 in children ranges from asymptomatic and mild cases to the multisystem inflammatory syndrome. Given that asymptomatic patients may not get tested for COVID-19 and are potential carriers for viral transmission, high clinical suspicion is required to prevent such transmissions to a population at risk of developing severe disease. A pediatrician should be cautious to exclude other causes of respiratory illnesses like seasonal influenza before any diagnostic tests. As no effective treatment has been approved by the FDA yet, the goal of managing patients with COVID-19 is to treat the symptoms, prevent and treat complications, and provide supportive care.

Historical Perspective

Classification

  • Asymptomatic presentation
    • Children present with no clinical signs or symptoms with normal chest imaging.
    • Among 2,143 children with COVID-19 infection 4% of children were asymptomatic.
    • According to one study, 14.2% of children were asymptomatic. Another study found 18% of asymptomatic children tested positive for COVID-19.
  • Mild Disease
    • Children present with mild symptoms including fever, fatigue, myalgia, cough.
    • Among 2,143 children with COVID-19 infection 51% of children had a mild disease of COVID-19.
    • According to one study, 36.3% of children present with a mild form of the disease.
  • Moderate
    • Children present with pneumonia and symptoms or subclinical disease with abnormal chest imaging.
    • Among 2,143 children with COVID-19 infection 39% of children had a moderate presentation.[1]
  • Severe
    • Children present with dyspnea, central cyanosis, hypoxia.[1]
    • Among 2,143 children with COVID-19 infection 5% of children had a severe presentation.[1]
    • 2.1% of children present with a severe form of COVID-19 disease.
    • Children with underlying comorbidities are more susceptible to developing severe COVID-19 symptoms.
  • Critical

Pathophysiology

Pathogenesis

Tropism

  • The virus also relies on the ACE-II receptor not only for host cell entry but also for subsequent viral replication.
  • High viral loads have been detected in the lower respiratory tract, suggesting that the virus might have a higher affinity for the epithelium of the lower respiratory tract and indicating a need for repeat testing of the upper or lower respiratory tract samples in the setting of an initial negative result of nasopharyngeal or throat swab in a suspected case.
  • ACE-II receptors' presence in the extrapulmonary tissues (heart, kidney, endothelium, and intestine) could also explain the multi-organ dysfunction observed in patients.
  • ACE-II receptors are also expressed in the oral cavity with a higher level of expression in the tongue than the buccal or gingival tissues. This indicates oral cavity as potentially high risk for SARS-CoV-2 infectious susceptibility.
  • ACE-II receptors' high expression on the luminal surface of intestinal epithelial cells suggests that the intestine might also be a major entry site for the virus and that the infection might have been initiated by consuming food from the Wuhan market (the assumed site of the outbreak).

Activation of Host Immune Reponses

  • SARS-CoV2 is known to cause a delayed-type I interferon response during the initial phases of infection.
  • Infection and viral replication lead to an activation of neutrophils, macrophages, and monocytes. Th1/Th17 induced specific antibodies are produced.
  • RNA viruses such as SARS-CoV and MERS are recognized pathogen associated molecular patterns by endosomal RNA receptors, TLR3 and TLR7 and the cytosolic RNA sensor, RIG-I/MDA5.
  • This leads to downstream activation of NF-KB signaling cascade and nuclear translocation of transcription factors, which in turn leads to the production of type 1 interferon pro-inflammatory cytokines.
  • Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination.

Associated Conditions

Causes

Differentiating COVID-19 in Children from other Diseases

COVID-19 disease in children should be differentiated from the following conditions:

Epidemiology and Demographics

  • Less than 2% of the confirmed positive cases of COVID-19 comprise of children less than 19 years of age[3]

Incidence

  • Among the 1,761,503 aggregate cases reported to CDC from January 22–May 30, the incidence of confirmed cases was 403.6 cases per 100,000 population [3].
  • Lowest cumulative incidence being in the group of children less than 9 years. (51.1) per 100,000 population.
  • To accurately calculate the incidence of COVID-19 in children, a study called Human Epidemiology and Response to SARS-CoV-2 HEROS led by Dr. Hartet is under process and has started enrolling 6000 healthy children as well as children with asthma, allergies from 2000 U.S families across 11 states.

Prevalence

Prevalence of coronavirus in children is less compared to adults as the number of cases are less and most of the cases are with the mild presentation.

Age

  • According to the data published by CDC for a period of January 22 to May 30 [3]
    • The cumulative incidence of COVID-19 cases in children age 0-9 is 51.1 from 20,458 cases.
    • The cumulative incidence of COVID-19 cases in children age 10-19 is 117.3 from 49,245 cases.

Race

Non-Hispanic American Indian or Alaska Native persons have an age-adjusted hospitalization rate approximately 5 times that of non-Hispanic White persons, while non-Hispanic Black persons and Hispanic or Latino persons each have a rate approximately 4.5 times that of non-Hispanic White persons

Gender

  • According to the data published by CDC for a period of January 22 to May 30[3]
    • The cumulative incidence of COVID-19 cases:
      • Boys age 0-9 years is 52.5 (1.7%) out of 10,743
      • Boys age 10-19 years is 113.4 (3.8%) out of 24,302
      • Girls age 0-9 years is 49.7 (1.4%) out of 9,715
      • Girls age 10-19 years is 121 (3.7%)out of 24,943

Region

Risk Factors

Breastfeeding

Vertical transmission

  • A study by Marzieh Zamaniyan et all discusses about a pregnant women who developed severe pneumonia with 32 weeks of gestation delivered a healthy pre-term baby without COVID-19 symptoms.
    • The first neonatal nasal swab, vaginal secretion and umbilical cord RT-PCR was negative.
    • However, the second neonate and amniotic sample for RT-PCR tested positive for COVID-19. This study shows more research needs to be done to identify more cases with possible intrauterine infection.
  • Another study documented a possible vertical transmission as increased levels of neonatal Ig M antibodies were found in 3 cases.
    • Seropositivity with IgM antibodies found in neonates needs reflex testing for example - virus neutralization, IgG avidity index, molecular and immunoblotting. A study by Dong E et all discussed decreasing levels of neonatal IgM antibodies in the serum 2 weeks later. So far RT-PCR is the preferred test to docuement for possible vertical transmission.
  • Pregnant women with severe COVID-19 pneumonia were found to have placental inflammation which increases the risk for transplacental infection and pre-term births.[5]
  • Detection of IgM and IL-6 in neonates serum is used as one of the markers for possible transplacental transmission.
  • Some studies which detected the virus hours to days after birth in the nasopharyngeal samples and hence those newborns could have been exposed to the virus after birth via the nosocomial infection.

Screening

Natural History, Complications, and Prognosis

Complications

A. Multisystem Inflammatory Syndrome in Children (MIS-C)

  • To view detailed information on multisystem inflammatory syndrome in children, click here.

B. Acute Heart Failure

C. Negative effects of lockdown in children

Prognosis

Most children recover fully from the infection. Few children, however, require hospitalization and ICU admission.

  • <9 years of age among 20,458 children[3]
  • 10-19 years of age among 49,245 children[3]
Data of children with hospitalized children and ICU admissions as reported by CDC for a period of January 22 to May 30[3]
Age All admissions in the hospital and ICU divided according to associated comorbidity
<9 years (20458 cases) All patients (20458) Among all patients with reported underlying disease (619) Among all patients with no reported underlying disease (2277)
All admissions in the hospital including ICU ICU admissions All admissions in the hospital including ICU ICU admissions All admissions in the hospital including ICU ICU admissions
848/20458 (4.1%) 141/20458 (0.7%) 138/619 (22.3%) 31/619 (5%) 84/2277(3.7%) 116/2277 (0.7%)
10-19 years (49245 cases) All patients (49245) Among all patients with reported

underlying disease (2076)

Among all patients with no reported underlying disease (5047)
All admissions in the hospital including ICU ICU admissions All admissions in the hospital including ICU (2076) ICU admissions All admissions in the hospital including ICU (5047) ICU admissions
1234/49245 (2.5%) 216/49245 (0.4%) 309/2076 (14.9%) 72/2076 (3.5%) 115/5047 (2.3%) 17/5047 (0.3%)

Diagnosis

Diagnostic Study of Choice

In case of clinical suspicion, the best diagnostic test to diagnose COVID-19 infection in children is Reverse-Transcriptase Polymerase Chain Reaction

History and Symptoms

  • Presentation of COVID-19 is less severe in children as compared to adults. Most of the children are asymptomatic.
  • According to CDC, as of April 2, 2020, 1.7% confirmed cases of COVID-19 were reported in children aged <18 years age among the total number of confirmed cases of COVID-19.
  • Illness severity of COVID-19 in children ranges from asymptomatic to critical.
  • The incubation period of SARS-CoV-2 varies from 2 to 14 days with most patients developing symptoms 3 to 7 days after exposure.[7]

The common symptoms of COVID-19 infection in children are:

  • Fever and Cough are one of the most common symptoms reported in children. One study showed fever is prevalent in 47.5% of children and cough in 41.5% among the 1124 children with COVID-19.According to the CDC, fever, and cough was reported in 56% and 54% of children with COVID 19
  • Dyspnea, nasal congestion, pharyngeal erythema, and sore throat are also common presentations in children.
  • Gastrointestinal symptoms: The gastrointestinal manifestation in COVID-19 positive children are diarrhea, vomiting, abdominal pain, nausea, and anorexia. Children can present with gastrointestinal symptoms in the absence of respiratory symptoms.
  • Cutaneous Findings: The cutaneous findings in COVID-19 positive children range from petechiae to papulovesicular rash and diffuse urticaria. These appear early in the course of COVID-19 due to to viral replication or circulating cytokines. Many patients with COVID-19 present with chilblain-like lesions unrelated to cold (COVID toes). Chilblains are painful or itchy swellings of the toes and fingers, caused by small-vessel inflammation from repeated exposure to cold. A retrospective case series presented 22 children and adolescents with COVID-19 who presented with chillblains.
  • Neurological manifestation: The presentation of neurological manifestation in children is rare. However, a case report described a rare case of a 6-week old infant with COVID-19 who had 10-15 seconds episodes of upward gaze and bilateral leg stiffening.
  • Neonates and Infants with COVID-19 are often asymptomatic or present with fever with or without mild cough and congestion.

Physical Examination

The physical examination findings of COVID-19 in children are similar to those in adults. To view physical examination findings in COVID-19, click here.

Laboratory Findings

Studies reportedly showed following lab abnormalities in pediatric patients with COVID-19

Electrocardiogram

There are no current, evidence-based information on electrocardiographic changes in children with COVID-19.

X-ray

CT scan

CT chest is an important diagnostic modality in pediatric patients with COVID-19. Chest CT scans has reportedly shown higher positive rates in suspected patients than RT-PCR. It has better sensitivity. CT chest and a series of chest X-rays can be used to monitor the progression of the disease. Imaging findings reported in the studies are[8][9][10]

Children are at increased risk of radiation and its effects, so CT scans and X-rays should be judiciously used in them. It is advised to perform Pulmonary Ultrasonography (USG) in newborns. It has better sensitivity and is safer than CT scans and Chest X-rays.

MRI

Other Imaging Findings

  • To view other imaging findings on COVID-19, click here.

Other Diagnostic Studies

  • To view other diagnostic studies for COVID-19, click here.

Treatment

Management of COVID-19 in pediatric patients depends on the severity of symptoms.

  • Hospital admission and level of care depend on the clinical presentation, supportive care requirement, underlying comorbidities, and availability of health care facilities at home
  • Suspected patients must be isolated at a hospital or home until the diagnosis is excluded
  • After confirming the diagnosis, they should be hospitalized and isolated in the wards maintained for pediatric patients with COVID-19
  • Critical and severe cases require Intensive Care Unit (ICU) admission and management

As no effective treatment has been approved by the FDA yet, the main goal of managing patients with COVID-19 is to treat the symptoms, provide supportive care, prevent and treat complications, treat underlying diseases and secondary infections, and provide organ function support. Following measures are reported to be crucial in the management of COVID-19

Symptomatic treatment and Supportive Care

Fever should be treated with physical cooling and antipyretics. If the body temperature exceeds 38.5C, antipyretic drugs should be started. Drugs that can be used in children are acetaminophen 10-15 mg/kg and ibuprofen 5-10 mg/kg orally.[11]

Respiratory support

Mechanical Ventilation

Low tidal volume mechanical ventilation is preferred to prevent ventilation related lung injury. Criteria for starting mechanical ventilation[11]

OR

OR

Antibiotics

Antibiotics and antifungals help in reducing symptoms and preventing complications of secondary infections[10]

Corticosteroids

Steroids are used in severe cases and to prevent complications[10]. Any of the following criteria must be met before starting corticosteroid therapy in patients with COVID-19[11]. Intravenous methylprednisolone 1-2mg/kg/day used for 3-5 days. Long-term usage is highly discouraged.

  • Rapid progression of the disease as documented from chest imaging and development of ARDS

OR

OR

OR

Anticoagulation therapy

Convalescent plasma therapy

Evidence suggests the use of plasma therapy in children with exacerbations and severe and critical disease.

Immunoglobulin therapy

  • Intravenous immunoglobulins (IVIG) can be used in severe cases[10]
  • Dose of 1g/kg/day for 2days or 400mg/kg/day for 8 days is recommended for children
  • More studies are required to support its efficacy and safety in children with COVID-19

Antiviral therapy

Following are the experimental drugs that are being considered to treat children with COVID-19. Various clinical trials are being conducted on the efficacy and safety of these drugs in children with COVID-19.

Interferon-alpha

Inhaled interferon-alpha was the most commonly used antiviral in patients with COVID-19. Reports suggest that it helps in decreasing the viral load, alleviating symptoms and shortening the disease course.

Remdesivir

  • It is a nucleotide analogue that inhibits viral RNA polymerase
  • It was effectively used during Ebola, SARS, and MERS outbreaks
  • It was effective in-vitro against SARS-CoV-2
  • No adverse effects were reported in a newborn treated for Ebola
  • Phase III clinical trial is being conducted on the effectiveness of Remdesivir in treating COVID-19 in adults and children above 12 years of age
  • FDA has approved the emergency use of Remdesivir in treating hospitalized children with severe disease"Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment | FDA".

Favipiravir

Prevention

Re-opening of schools

  • The pandemic which started in China in January 2020 and now is all over the world has had a tremendous effect on the everyday life of many however children are the most affected.
  • With the peak of the coronavirus cases being over in many countries like the USA and Europe, there is a dilemma for the school officials about when to reopen schools for children.
  • According to the data collected by the CDC[3] and other articles children are affected less compared to adults with asymptomatic to mild COVID-19 symptoms.
  • The challenge faced by the school committees around the world is to decide between the pros and cons of whether to reopen the school with children facing the emotional toll of the lockdown and quarantine.

The CDC guidelines for re-opening schools are as follows

  • These guidelines are to be followed by schools by coordinating with the local health department to know the level of mitigation in your community as the coronavirus cases are increasing.
  • Educate the teachers and the parents on signs of coronavirus like dry cough, cold, high fever, and other flu-like symptoms.
  • If the child has the above-mentioned symptoms or is in contact with an adult at home having these symptoms or the adult at home has tested positive the child should stay home.
  • Teachers, children, and other staff members with the immunocompromised state should be given the option to work from home virtually as they are in the high-risk group.
  • Hand hygiene- Soap and water should be provided by the school for students to wash hands frequently for 20 seconds
  • If soap and water are not available provide hand sanitizer with at least 60% alcohol.
  • Use a tissue to cover cough/sneeze and wash hands after discarding the tissue safely.
  • Cloth face mask is advised for all the school staff and the children except kids younger than 2 years of age or kids with a breathing problem who needs assistance in removing the face mask.
  • Signs about COVID 19 should be placed in places frequently visited like the school entrance, cafeteria, and the bathroom.
  • Avoid sharing objects and if possible give kids individual supplies.
  • Ensure proper ventilation systems are in place, open windows when it's safe and possible.
  • Identify small groups of children and try to keep them together with the same teacher.
  • Food brought from home is advisable. If not then food should be distributed in the classroom, not the cafeteria.
  • Advise students and teachers to limit their exposure to the news stories. It can be overwhelming for the students.
  • Encourage the students to talk to anyone they trust or to reach out to teachers to talk when overwhelmed.
  • If a child tests positive or is suspected to have COVID-19 the school should arrange special transport for the student separately.
  • Inform the local health care department and close contacts if the student tests positive.
  • Proper contact tracing, isolation, disinfecting the common places frequently used by the students should be made a priority.

Domestic violence in children

References

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  2. 2.0 2.1 Velavan, Thirumalaisamy P.; Meyer, Christian G. (2020). "The COVID‐19 epidemic". Tropical Medicine & International Health. 25 (3): 278–280. doi:10.1111/tmi.13383. ISSN 1360-2276.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S; et al. (2020). "Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020". MMWR Morb Mortal Wkly Rep. 69 (24): 759–765. doi:10.15585/mmwr.mm6924e2. PMC 7302472 Check |pmc= value (help). PMID 32555134 Check |pmid= value (help).
  4. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X; et al. (2020). "High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa". Int J Oral Sci. 12 (1): 8. doi:10.1038/s41368-020-0074-x. PMC 7039956 Check |pmc= value (help). PMID 32094336 Check |pmid= value (help).
  5. 5.0 5.1 Mahyuddin AP, Kanneganti A, Wong J, Dimri PS, Su LL, Biswas A; et al. (2020). "Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2". Prenat Diagn. doi:10.1002/pd.5765. PMC 7307070 Check |pmc= value (help). PMID 32529643 Check |pmid= value (help).
  6. Belhadjer, Zahra; Méot, Mathilde; Bajolle, Fanny; Khraiche, Diala; Legendre, Antoine; Abakka, Samya; Auriau, Johanne; Grimaud, Marion; Oualha, Mehdi; Beghetti, Maurice; Wacker, Julie; Ovaert, Caroline; Hascoet, Sebastien; Selegny, Maëlle; Malekzadeh-Milani, Sophie; Maltret, Alice; Bosser, Gilles; Giroux, Nathan; Bonnemains, Laurent; Bordet, Jeanne; Di Filippo, Sylvie; Mauran, Pierre; Falcon-Eicher, Sylvie; Thambo, Jean-Benoît; Lefort, Bruno; Moceri, Pamela; Houyel, Lucile; Renolleau, Sylvain; Bonnet, Damien (2020). "Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic". Circulation. doi:10.1161/CIRCULATIONAHA.120.048360. ISSN 0009-7322.
  7. Chen ZM, Fu JF, Shu Q, Chen YH, Hua CZ, Li FB; et al. (2020). "Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus". World J Pediatr. 16 (3): 240–246. doi:10.1007/s12519-020-00345-5. PMC 7091166 Check |pmc= value (help). PMID 32026148 Check |pmid= value (help).
  8. Du H, Dong X, Zhang JJ, Cao YY, Akdis M, Huang PQ; et al. (2020). "Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status". Allergy. doi:10.1111/all.14452. PMC 7307120 Check |pmc= value (help). PMID 32524611 Check |pmid= value (help).
  9. de Souza TH, Nadal JA, Nogueira RJN, Pereira RM, Brandão MB (2020). "Clinical manifestations of children with COVID-19: A systematic review". Pediatr Pulmonol. doi:10.1002/ppul.24885. PMC 7300659 Check |pmc= value (help). PMID 32492251 Check |pmid= value (help).
  10. 10.0 10.1 10.2 10.3 Zhang L, Peres TG, Silva MVF, Camargos P (2020). "What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases". Pediatr Pulmonol. doi:10.1002/ppul.24869. PMC 7300763 Check |pmc= value (help). PMID 32519809 Check |pmid= value (help).
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  12. Bouazza N, Treluyer JM, Foissac F, Mentré F, Taburet AM, Guedj J; et al. (2015). "Favipiravir for children with Ebola". Lancet. 385 (9968): 603–604. doi:10.1016/S0140-6736(15)60232-X. PMID 25706078.
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