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Basic Information ⬇

AUTHORS: Daniel Chilcote, MD and Margaret Priestley, MD

Definition

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a coronavirus discovered in 2019 named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Synonyms

Multisystem inflammatory syndrome in children (MIS-C)

ICD10-CM CODES
U07.1COVID-19
J12.82Pneumonia due to coronavirus disease 2019
M35.81Multisystem inflammatory syndrome (MIS)
Z20.822Contact with and (suspected) exposure to COVID-19
Z86.16Personal history of COVID-19
Epidemiology & Demographics

  • The emergence of COVID-19 is the third coronavirus outbreak in humans since 2000; included are the 2002 severe acute respiratory syndrome coronavirus (SARS-CoV) and 2012 Middle East respiratory syndrome coronavirus (MERS-CoV).
  • The incubation period of COVID-19 ranges from 2 to 14 days with a median of 5 days.
  • Acute pneumonia caused by SARS-CoV-2 was first identified in December 2019. The primary cluster was connected with a seafood and live animal market in Wuhan City, the capital of Hubei Province, in China.
  • In March 2020, COVID-19 was declared a pandemic by the World Health Organization (WHO).
  • In late April/early May 2020, the United Kingdom National Health Service and the Centers for Disease Control and Prevention (CDC) issued public health advisories highlighting a multisystem inflammatory syndrome in children (MIS-C).
  • Throughout the COVID-19 pandemic, many variants are known to cause disease globally. Significant variants of interest include the delta and omicron (including BA.5) variants.
  • As of August 2022, over 14 million children had tested positive for COVID-19 in the U.S., representing 18.4% of all cases.
  • Approximately 150,000 pediatric admissions with confirmed COVID-19 were reported from August 2020 to August 2022. Similar to the adult population, a third of children hospitalized for COVID-19 require intensive care unit (ICU) admission. Up to 0.1% of COVID-19 cases in children result in mortality.
Route of Transmission

  • Exposure to COVID-19 occurs via three primary mechanisms:
    1. Airborne inhalation of fine droplets and aerosol particles (including during medical “aerosol-generating procedures”).
    2. Deposition of droplets and particles on exposed mucous membranes (mouth, nose, eyes).
    3. Touching mucous membranes with contaminated (virus-containing) hands.
  • Transmission may occur through fomites, but this is markedly less efficient than the primary mechanisms described earlier.
  • Vertical transmission of COVID-19 is thought to be rare. Data suggest that neonates born to people with COVID-19 are at increased risk for admission to the neonatal intensive care unit. Current evidence suggests that breast milk is not a source of COVID-19 infection.
Incidence

  • Children of all ages can get COVID-19. Males and females are equally affected.
  • By February 2022, approximately 75% of children and adolescents (ages 0 to 17 yr) in the U.S. were seropositive for SARS-CoV-2.
  • Children from underrepresented racial and ethnic groups appear to be disproportionately affected by acute COVID-19 and COVID-19-associated hospitalizations and deaths, perhaps related to social determinants of health.
Risk Factors

  • Underlying conditions are associated with higher rates of hospitalization and ICU admission.
  • The most common underlying conditions are obesity, chronic lung disease/asthma, developmental delay, congenital heart disease, and sickle cell disease.
  • Almost one third of hospitalized children with SARS-CoV-2 infection required ICU admission or invasive mechanical ventilation.
Physical Findings & Clinical Presentation
Acute COVID-19 Infection

  • The clinical spectrum of SARS-CoV-2 infections in children ranges from asymptomatic to life-threatening.
  • Signs/symptoms include:
    1. Most frequent: Fever and/or cough.
    2. Less frequent: Fatigue, headache, myalgia, nasal congestion, rhinorrhea, anosmia, ageusia (loss of taste), sore throat, stridor, shortness of breath, abdominal pain, diarrhea, nausea, vomiting, or decreased oral intake.
  • Children with severe COVID-19 may present with acute respiratory failure, myocarditis, shock, acute renal failure, coagulopathy, and multisystem organ failure.
  • Laboratory evidence: Lymphocytosis or lymphopenia, mildly elevated inflammatory markers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], procalcitonin), mildly elevated liver enzymes.
  • Radiographic evidence:
    1. Chest x-ray: Unilateral or bilateral opacities.
    2. Chest computed tomography (CT): Unilateral or bilateral ground-glass opacities and consolidation with surrounding halo sign.
Multisystem Inflammatory Syndrome in Children (MIS-C)

  • MIS-C is a serious delayed complication of COVID-19 infection. In most studies, there was a lag of several weeks between the peak of COVID-19 cases within communities and the rise of MIS-C cases.
  • Most MIS-C cases have occurred in older children (≥5 yr of age) and adolescents who were previously healthy. Black and Hispanic children appear to be disproportionally affected.
  • Signs/symptoms include fever, abdominal pain, vomiting, diarrhea, skin rash, mucocutaneous lesions, hypotension, and shock.
  • Laboratory evidence: Elevated inflammatory markers (CRP, ESR, procalcitonin), elevated markers of cardiac damage (troponin, brain natriuretic peptide [BNP]).
  • Cardiac dysfunction on echocardiogram.
  • Over 50% of children with MIS-C require ICU admission.
Etiology

The WHO has classified SARS-CoV-2 as a new betacoronavirus that infects humans. Bats are the suspected natural reservoir of SARS-CoV-2.

Diagnosis ⬆ ⬇

Differential Diagnosis
Acute COVID-19 Infection

  • Influenza virus, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, non-COVID-19cc coronavirus, and other known viral respiratory infections
  • Atypical organisms: Mycoplasma pneumoniae, chlamydia pneumonia, and legionellosis
  • Bacterial pneumonia
  • Streptococcal pharyngitis
  • Viral and bacterial gastrointestinal infections
MIS-C

  • Kawasaki disease or Kawasaki disease shock syndrome
  • Toxic shock syndrome
  • Myocarditis or heart failure
  • Macrophage activation syndrome
  • Hemophagocytic lymphohistiocytosis
Workup
Acute COVID-19 Infection

  • Laboratory studies:
    1. SARS-CoV-2 polymerase chain reaction (PCR) on upper and/or lower respiratory secretions. Rapid antigen test using nasal swab can detect viral proteins but with less sensitivity than PCR.
    2. CBC, complete metabolic panel (CMP), inflammatory markers (CRP, ESR, procalcitonin).
  • Chest x-ray, chest CT (used sparingly and only for hospitalized children with specific clinical indications).
MIS-C

  • Laboratory studies:
    1. SARS-CoV-2 PCR or antigen testing; serologic testing if available.
    2. Inflammatory markers: CRP, ESR, fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase (LDH), interleukin-6 (IL-6), neutrophil and lymphocyte count, and albumin.
    3. Markers of cardiac injury: Troponin and BNP.
  • Due to frequent association with cardiac involvement, echocardiogram and electrocardiogram are recommended to evaluate myocardial function, coronary arteries, and cardiac rhythm.

Treatment ⬆ ⬇

Acute COVID-19 Infection

  • Children with mild disease usually recover at home with supportive care and appropriate isolation guidelines.
  • Mainstay of hospital-based treatment is supportive care: Fluid resuscitation, inotropic support, respiratory support (including prone positioning for severe hypoxemia), and (rarely) extracorporeal membrane oxygenation (ECMO).
  • Remdesivir is the only FDA-approved treatment of COVID-19 in children. It is available for use in high-risk, nonhospitalized patients within 7 days of symptom onset; high-risk hospitalized patients; or children with severe and/or critical disease.
  • The National Institutes of Health Panel on COVID-19 has provided recommendations on specific therapies:
    1. Dexamethasone has been shown to be beneficial in children with COVID-19 who require high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, or ECMO.
    2. For patients who do not have improvement in oxygenation within 24 hr after initiation of dexamethasone, baricitinib or tocilizumab may be considered.
    3. Paxlovid (ritonavir-boosted nirmatrelvir) may be used in high-risk, nonhospitalized children within 5 days of symptom onset.
    4. There is insufficient evidence to recommend for or against usage of anti-SARS-CoV-2 monoclonal antibody products in children (such as bebtelovimab, bamlanivimab plus etesevimab, or casirivimab plus imdevimab), but may be considered on a case-by-case basis for nonhospitalized children who are at high risk for severe disease.
    5. The use of convalescent plasma is not recommended for the pediatric population, unless considered on a case-by-case basis in consultation with an infectious disease specialist.
  • Antibacterial therapy is reasonable if there is a concern for a superimposed bacterial pneumonia.
  • Vaccination to prevent severe COVID-19 disease is now available for adults and for children 6 mo and older.
MIS-C

  • Mainstay is supportive care: Fluid resuscitation, inotropic support, respiratory support, and (rarely) ECMO.
  • Antiinflammatory treatments, including intravenous immunoglobulin (IVIG) and steroids, have been used with success as a first-line therapy. IL-1 antagonists have also been used in refractory cases.
  • Aspirin therapy is recommended if coronary arteries are involved.
  • Thrombosis prophylaxis is often used, given the hypercoagulability associated with MIS-C.
Disposition

  • Most children infected with COVID-19 experience mild, self-limiting illness.
  • The duration of hospitalization is usually less than 7 days. Of the patients requiring intensive care, the majority recover well.
  • Except for rare situations, a test-based strategy is no longer recommended to determine when an individual with a COVID-19 infection is no longer infectious.
  • Patients recovering from MIS-C who had significant myocardial involvement require pediatric cardiology follow-up.

Pearls & Considerations ⬆ ⬇

Suggested Readings ⬆ ⬇

  1. American Academy of Pediatrics: Critical updates on COVID-19. Published 2021. https://www.cdc.gov/coronavirus/2019-nCoV/index.html.
  2. American Academy of Pediatrics: Critical Updates on COVID-19. Published 2022. https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/.
  3. Brewster R et al: COVID-19-associated croup in children, Pediatrics 149(6):e2022056492. 2022.
  4. Centers for Disease Control and Prevention COVID Data Tracker: Pediatric data. Published 2022. https://covid.cdc.gov/covid-data-tracker/#pediatric-data.
  5. Chiotos K. : Multisystem inflammatory syndrome in children during the coronavirus 2019 pandemic: a case seriesJ Pediatric Infect Dis Soc. ;9(3):393-398, 2020.
  6. Feldstein L.R. : Multisystem inflammatory syndrome in U.S. children and adolescentsN Engl J Med. ;383(4):334-346, 2020.
  7. Graff K. : Risk factors for severe COVID-19 in childrenPediatr Infect Dis J. ;40(4):E137-E145, 2021.
  8. Infectious Diseases Society of America (IDSA) guidelines on the treatment and management of patients with COVID-19: pediatric considerations of treatment of SARS-CoV-2 infection and multisystem inflammatory syndrome in children. Published 2022. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/.
  9. Kotlyar A. : Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysisAm J Obstet Gynecol. ;224(1):35-53.e3, 2021.
  10. McArdle A.J. : Treatment of multisystem inflammatory syndrome in childrenN Engl J Med. ;385(1):11-22, 2021.
  11. McCormick D et al: Deaths in children and adolescents associated with COVID-19 and MIS-C in the United States, Pediatrics 148(5):e2021052273. 2021.
  12. National Institute of Health COVID-19 treatment guidelines: clinical management of children. Published 2022. https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-of-children/.
  13. Rafferty M. : Multisystem inflammatory syndrome in children (MIS-C) and the coronavirus pandemic: current knowledge and implications for public healthJ Infect Public Health. ;14(4):484-494, 2021.

Related Content ⬆

    1. Halasa N.B. : Maternal vaccination and risk of hospitalization for Covid-19 among infantsN Engl J Med. ;387(2):109-119, 2022.