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Dec.23.2022

COVID-19 in Children

Synopsis

Key Points

  • COVID-19 is a systemic infection primarily affecting the respiratory system, caused by a recently recognized coronavirus, SARS-CoV-2
  • Children tend to experience less severe illness and fewer complications than adults. Fewer children than adults with infection require hospitalization; however, a similar proportion of children and adults who do need hospital admission require ICU level of care
  • Asymptomatic infection may occur in up to half of children
  • Fever, cough, and upper respiratory symptoms are very common in children who develop symptoms but wide variation in presentation is possible, including asthma exacerbation, influenzalike illness, or gastroenteritis
  • The following groups may be at increased risk for severe disease: infants younger than 1 year, adolescents, Black/Hispanic/Native American children, unvaccinated children, and children with medical comorbidity (eg, moderate or severe immunosuppression; obesity; significant cardiac, neurologic, respiratory, or lung disease) r1
  • Suspect diagnosis of COVID-19 based on clinical presentation with manifestations consistent with possible COVID-19 or contact with SARS-CoV-2; maintain awareness that many patients do not have known exposure due to high transmissibility of Omicron subvariants
  • Confirm diagnosis by detecting viral nucleic acid (nucleic acid amplification test) or protein (antigen test) on respiratory specimen
  • Maintain a broad differential to evaluate for additional conditions in children infected with SARS-CoV-2
    • Other conditions (eg, diabetic ketoacidosis, intussusception, community-acquired pneumonia, streptococcal pharyngitis, influenza) may present concomitantly in children who test positive for SARS-CoV-2; coinfection with more than a single pathogen may occur
  • Supportive care is the mainstay of management for the overwhelming majority of pediatric patients, and most children can be managed safely at home
  • Use of COVID-19–specific therapies is indicated in certain patients
    • Remdesivir and dexamethasone are the primary pharmacotherapeutics in certain hospitalized children
    • Nirmatrelvir-ritonavir or remdesivir are used for certain nonhospitalized patients with COVID-19 at high risk of progression to severe disease
    • Tixagevimab-cilgavimab may be used for preexposure prophylaxis in certain high-risk patients
  • Most children experience mild illness with full recovery; a small percentage have complications (eg, MIS-C) or symptoms beyond 4 weeks
  • Vaccination is safe and highly effective at preventing serious COVID-19 illness among pediatric patients
  • Measures to protect pediatric population and the community from SARS-CoV-2 infection include vaccination, isolation of those with COVID-19 even without symptoms, staying home when sick, mask wearing, testing including repeat or serial tests when indicated, improving ventilation, and general hygiene measures

Urgent Action

  • Promptly institute appropriate isolation measures when any patient presents to health care facility after possible exposure to SARS-CoV-2 or with manifestations concerning for possible COVID-19
  • Patients with respiratory distress and/or hypoxia require urgent management with appropriate respiratory support and oxygen administration r2
  • Patients with shock require resuscitation and urgent diagnosis and management of underlying cause of shock. Rapidly administer fluids to patients with hypovolemic shock, administer empiric antibiotics to patients with concern for septic shock, and provide vasopressor support for patients with cardiogenic shock r2

Pitfalls

  • Be aware that some children have sudden worsening of manifestations (eg, dyspnea, cyanosis) after about 1 week of mild to moderate symptoms; these worsening manifestations require heightened respiratory support (eg, oxygen, noninvasive or invasive ventilatory support) r3r4
  • Patient findings consistent with coinfection (eg, exudative pharyngitis, otitis media, vesicular pharyngitis) and other pathogens (eg, concomitant influenza, Mycoplasma pneumoniae, streptococcal pharyngitis, respiratory syncytial virus) do not exclude COVID-19 diagnosis or reduce risk for positive SARS-CoV-2 test result r5
    • Proceed with SARS-CoV-2 testing in patients when clinical suspicion exists for COVID-19 regardless of clinical evidence of focal infection or positive testing for other infectious pathogens
  • Vaccine coverage is less than optimal among children and adolescents in the United States r6
    • Encourage and support community vaccination measures because vaccination is a critical measure to diminish risk of severe disease and decrease pandemic-related adverse indirect effects (eg, higher rates of psychiatric morbidities, loss of education, loss of caregivers, increased child neglect) in pediatric age groups
  • Knowledge of COVID-19 illness behavior in children is incomplete and evolving, and coronaviruses are known to mutate and recombine often. These unknowns present ongoing challenges to understanding clinical disease progression and treatment strategies
    • Be aware that CDC, NIH, and professional society guideline recommendations are evolving and subject to frequent modifications

Terminology

Clinical Clarification

  • COVID-19 (coronavirus disease 2019) is a systemic infection primarily affecting the respiratory system, caused by a recently recognized coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) d1
  • Children tend to experience less severe illness and fewer complications than adults. Fewer children than adults with infection require hospitalization; however, of those who are admitted, a similar proportion of both groups require ICU-level care r1
    • Most children who develop severe and critical illness have significant underlying comorbidity; however, approximately 30% of hospitalized children aged 5 to 11 years and 63% of hospitalized children aged 0 to 4 years had no underlying medical conditions in studies from the United States r7r8
  • Infants younger than 6 months are at higher risk of hospitalization than infants and children aged 6 months to 11 years; infants may present with isolated gastrointestinal symptoms or feeding difficulties r7r9
    • Infection in neonates is uncommon; most neonatal infections are asymptomatic r7
  • Knowledge of disease processes in both children and adults is incomplete and evolving; moreover, coronaviruses are known to mutate and recombine often, presenting an ongoing challenge to understanding and to clinical management
    • CDC website maintains information about geographic distribution of variants in the United States; current dominant variant is Omicron (several Omicron subvariants), which has increased transmissibility and immune evasion r10

Classification

  • Illness severity criteria based on NIH COVID-19 treatment guidelines r1r11
    • Asymptomatic or presymptomatic
      • Absence of signs or symptoms (and normal chest radiograph results, if obtained)
    • Mild illness
      • Symptomatic without shortness of breath, dyspnea, or abnormal chest imaging
    • Moderate illness
      • Evidence of lower airway disease by clinical assessment or imaging, and SpO₂ of 94% or greater on room air at sea level
    • Severe illness is defined by presence of any of the following:
      • SpO₂ of less than 94% on room air at sea level
      • PaO₂/FiO₂ of less than 300 mm Hg
      • Greater than 50% lung infiltrates
      • Significant tachypnea
    • Critical illness
      • Respiratory failure (eg, new or increased noninvasive or invasive mechanical ventilation requirement), septic shock, or multiple organ failure
  • WHO guidelines similarly classify disease severity into nonsevere (mild or moderate), severe, and critical illness, with slight variations (threshold for severe: SpO₂ 90% versus 94% for NIH) and additional pediatric-specific criteria r11r12
    • Nonsevere (mild or moderate) disease: no criteria of severe or critical disease
    • Severe disease: child with any of the following:
      • Clinical signs of pneumonia (eg, cough, difficulty breathing, tachypnea, retractions)
      • SpO₂ of less than 90% on room air at sea level
      • Pediatric danger signs
        • Very severe chest indrawing (retractions)
        • Central cyanosis
        • Grunting
        • Inability to breastfeed or drink
        • Lethargy or reduced level of consciousness
        • Convulsions
    • Critical disease: child with acute respiratory distress syndrome, sepsis, septic shock, or other conditions that normally require intensive care (eg, mechanical ventilation, vasopressor therapy)

Diagnosis

Clinical Presentation

History

  • Exposure to someone with laboratory-confirmed or probable SARS-CoV-2 infection may be elicited c1c2c3
    • Exposure occurs through respiratory aerosols or droplets of various sizes, particularly with close contact r13
    • Incubation period is approximately the same as in adult patients; historic data indicate about half of pediatric patients develop first symptom by 4 to 5 days after exposure r14
      • Omicron variants appear to have shorter incubation period (mean of 3.42 days, compared to Alpha variant mean of 5.0 of days), but considerable range exists (2 to 18 days) for individuals to develop detectable disease, particularly children r15
  • Presenting patterns among infected children vary
    • Asymptomatic infection may occur in up to half of children r16r17c4
    • Fever, cough, vomiting, diarrhea, and sore throat are among most common presenting symptoms in children r18c5c6c7
    • Common presenting clinical syndromes include acute respiratory infection, asthma exacerbation, influenzalike illness, isolated fever, and gastroenteritis r19
    • Several nonspecific symptoms may occur at once or over the course of illness. Manifestations also may be limited to predominantly 1 system (eg, only upper respiratory symptoms, only gastrointestinal symptoms)
    • Patients with underlying medical conditions may present with concomitant worsening of underlying disease (eg, diabetic ketoacidosis, acute chest syndrome)
  • Course of illness
    • Most children experience mild illness with full recovery within 1 to 2 weeks after onset of symptoms r20c8
    • Rarely, rapid progression to severe illness with hypoxia, respiratory distress, or shock is observed within first few days of illness r4c9c10c11
    • In some children, a sudden worsening of manifestations (eg, dyspnea, cyanosis) may occur after about 1 week of minor symptoms r3r4c12c13
  • Common symptoms include: r18r21
    • Respiratory
      • Cough c14
      • Shortness of breath, difficulty breathing c15c16
    • Ears, nose, and throat
      • Sore throat c17
      • Nasal congestion, rhinorrhea, sneezing c18c19
      • New loss of taste or smell (difficult to elicit in young children) c20c21
    • General
      • Fever c22
        • May be low, moderate, or high grade
        • Typical duration of fever is 1 to 2 days, but fever may last up to 1 week during acute infection in a minority of children r4
      • Fatigue, malaise, myalgia c23c24c25c26
      • Poor appetite, poor feeding
    • Gastrointestinal
      • Abdominal pain, vomiting, diarrhea c27c28c29
      • Gastrointestinal symptoms appear to be more common in children than adults r18
    • Neurologic
      • Headache is particularly common c30
      • Mental status changes and seizures suggest significant underlying neurologic complications c31c32
    • Dermatologic
      • Polymorphous rashes c33
    • Ocular
      • Symptoms consistent with conjunctivitis, usually with watery discharge c34
    • Over time, a shift in the most common symptoms has been reported, attributable to vaccination, prior infection, and different variants: r22
      • Sore throat, rhinorrhea, nasal congestion, sneezing, and persistent cough are currently most common, whereas fever and shortness of breath are less common than previously (eg, in unvaccinated individuals)

Physical examination

  • Vital signs are typically within reference range except patient may have fever (common)
  • Assess oxygenation promptly by peripheral saturation (eg, pulse oximetry) or other methods as needed r1r11
    • Pulse oximetry has been demonstrated to be less effective in patients of all ages with darker skin tones, with risk of occult hypoxemia (ie, arterial oxygen saturation less than 88% with concurrent pulse oximetry value of 92% or more) highest in Black patients r1r23r24r25r26
  • Tachycardia, tachypnea, and diminished oxygen saturation may be present with increasingly severe disease c35c36c37
  • Respiratory distress (grunting, flaring, accessory muscle use) and lower airway findings (crackles) may be evident with significant pulmonary involvement c38c39c40c41
  • Signs of dehydration (eg, dry mucous membranes, delayed capillary refill) may be present with volume depletion c42c43
  • Conjunctivitis with conjunctival hyperemia and chemosis may be present in a minority of patients r27c44c45c46
  • Dermatologic lesions may be present in a minority of patients. Most common findings include maculopapular, urticarial, and vesicular lesions as well as chilblainlike acral lesions and transient livedo reticularis r28c47c48c49c50c51

Causes and Risk Factors

Causes

  • Infection with SARS-CoV-2 causes COVID-19 disease c52
  • Incidence
    • True incidence in children is not definitively known because many children are asymptomatic; however, approximately 75% of children and adolescents in the United States had serologic evidence of previous infection with SARS-CoV-2 as of February 2022 r29
  • Transmissibility
    • Primary modes of transmission include large respiratory droplet, small respiratory droplet via airborne spread, and contact r13
      • Airborne transmission may occur, particularly with prolonged exposure in closed spaces with poor ventilation and high concentration of aerosolized particles (eg, forced expiration during exercise or singing) r14c53
      • Transmission through contact with contaminated surfaces is considered to be infrequent r14c54
      • Vertical transmission is uncommon r30
        • Only about 2% of neonates born to infected mothers developed infection; in utero, intrapartum, and early postnatal transmission has been documented
        • Stillbirth, while still rare, has increased (2.7% of COVID-affected deliveries during Delta variant wave, compared to 0.63% of non-COVID deliveries during Delta variant wave and prepandemic baseline 0.59% of deliveries) and has been associated with placental destruction and resulting fetal asphyxiation r31r32
      • Virus is detectable in stool specimens; however, replication-competent virus has not been isolated from stool samples r14
    • Period of infectivity
      • Infected patients are contagious about 1 to 2 days before onset of symptoms. Patients are most contagious at or before symptom onset (especially with Omicron variant), then contagiousness declines gradually over the course of several days r33r34r35c55
      • Most transmission generally occurs from about 1 to 2 days before to 2 to 3 days after symptom onset r33r34
      • Children appear to be as susceptible to infection as adults and to transmit infection to others r36r37r38
      • Patients with mild to moderate COVID-19 typically remain infectious up to 10 days after symptom onset r39
      • Patients who are immunocompromised and have severe COVID-19 may remain infectious 20 days or longer after symptom onset r40

Risk factors and/or associations

Age
  • Preterm neonates (less than 37 weeks of gestation) and neonates with significant underlying comorbidity may be at higher risk for severe infection than full-term and otherwise healthy neonates r7r41c56c57
  • Children younger than 2 yearsr1 and adolescents older than 12 yearsr42 experience highest rates of hospitalization
Ethnicity/race
  • Hispanic/Latinx and Black children in the United States experience highest hospitalization rates and higher risk for severe disease (ICU admission, invasive ventilation, death) r43c58c59c60c61c62
    • Effects are attributable to increased exposure, inequities in housing and health care access, and other social determinants of health (not genetic or other biologic factors, which race does not reflect) r44r45
Other risk factors/associations
  • Risk factors for severe disease
    • Age c63c64
      • Infants and adolescents have higher risk of ICU admission and death compared to other children r1
      • Children younger than 5 years and adolescents have higher risk of hospitalization compared to other children r1
    • Certain medical conditions have been associated with strong or consistent high risk for severe COVID-19: r46r47r48r49r50
      • Immunosuppressive disease or receipt of immunosuppressive therapy, which may include: c65c66
        • Active solid tumor treatment and hematologic malignancies
        • Solid organ transplant and immunosuppressive therapy
        • Chimeric antigen receptor T-cell or hematopoietic stem cell transplant (patient who is within 2 years of transplant or currently taking immunosuppression therapy)
        • Moderate or severe primary immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome, combined primary immunodeficiency disorders)
        • Untreated or advanced HIV (eg, CD4 T lymphocyte count less than 200 cells/mm³, history of AIDS-defining illness without immune reconstitution, clinical manifestations of symptomatic HIV)
        • Active treatment with any of the following:
          • High-dose corticosteroids (eg, 20 mg or more prednisone or equivalent per day when administered for 14 days or longer)
          • Alkylating agents
          • Antimetabolites
          • Transplant-related immunosuppressive drugs
          • Cancer chemotherapeutic agents classified as severely immunosuppressive
          • Tumor necrosis factor blockers
          • Other biologic agents that are immunosuppressive or immunomodulatory
      • BMI of 95th percentile or greater for age and gender on CDC growth charts
      • Neurodevelopmental disorders (eg, cerebral palsy, trisomy 21 syndrome) that result in impaired airway clearance
      • Medical-related technologic dependence unrelated to COVID-19 (eg, tracheostomy, positive pressure ventilation, gastrostomy)
      • Severe congenital or acquired heart disease
      • Severe chronic lung disease (eg, interstitial lung disease); asthma or chronic respiratory disease that requires daily medication for control
      • Multiple moderate to severe chronic diseases
      • Pregnancy
    • Additional conditions have moderate or inconsistent association with progression to severe COVID-19 disease: r46
      • Sickle cell disease
      • Diabetes, particularly poorly controlled
      • Chronic kidney disease
      • Chronic liver disease (eg, cirrhosis, autoimmune hepatitis)
      • Nonsevere cardiac, neurologic, or metabolic disease
      • Overweight
  • Limited data from retrospective chart review in a small series suggest factors associated with pediatric ICU admission requirement and risk for organ dysfunction, as follows: r51
    • Significant associations with admission to pediatric ICU include:
      • Age older than 12 years
      • Higher initial C-reactive protein level (median of 54 mg/L in pediatric ICU group versus 9 mg/L in adult ICU group)
    • Significant risk factors for organ dysfunction include:
      • Higher C-reactive protein level (median of 110 mg/L in organ dysfunction group versus 14 mg/L in non–organ dysfunction group) c67
      • Leukocytosis (median WBC count of 15,700 cells/μL in organ dysfunction group versus 7800 cells/μL in non–organ dysfunction group) c68
      • Thrombocytopenia (median of 149,000 cells/μL in organ dysfunction group versus 268,000 cells/μL in non–organ dysfunction group) c69

Diagnostic Procedures

Primary diagnostic tools

  • Suspect COVID-19 diagnosis based on clinical presentation with manifestations consistent with possible COVID-19 or SARS-CoV-2 c70
    • While workup is in progress, implement early and maintain strict transmission-based precautions for any patient with concern for SARS-CoV-2 infection: r40
      • Minimum health care facility transmission–based precautions include using contact and droplet precautions as well as airborne precautions when available, particularly during aerosol-generating procedures
      • Standard precautions include use of gown, gloves, and N95 respirator with eye protection (goggles or face shield) or air purifying respirator that provides eye protection
  • Confirm diagnosis of infection by detecting viral nucleic acid (nucleic acid amplification test) or protein (antigen test) on respiratory specimen r52c71c72
    • Positive polymerase chain reaction or antigen test is considered diagnostic in patient with symptoms or known exposure
    • Negative test result, particularly for antigen test, may need to be confirmed in patient with symptoms or known exposure
  • Additional laboratory evaluation and imaging may be necessary as indicated by clinical presentation
    • Additional laboratory tests
      • For clinically unwell patients and those with more than moderate COVID-19 illness, obtain basic set of ancillary laboratory tests: r5
        • CBC with differential c73
        • Inflammatory markers (eg, erythrocyte sedimentation rate and levels of C-reactive protein, procalcitonin, lactate dehydrogenase, and ferritin) c74c75c76c77c78c79
        • Liver function tests c80
        • Renal panel (BUN, creatinine) with glucose level c81
        • Electrolyte levels (including calcium, magnesium, and phosphate) c82c83c84c85
      • For patients in whom there is clinical concern for alternative diagnosis (eg, sepsis) and those who have complications and severe COVID-19:
        • If clinically unwell and sepsis or bacterial infection is of concern: appropriate blood cultures and other specimens r5c86
        • If myocardial involvement is of clinical concern: levels of troponin and N-terminal pro–B-type natriuretic peptide r5c87c88
        • If clinically indicated: coagulation screening (prothrombin time, partial thromboplastin time, INR, D-dimer, fibrinogen), blood gas levels, and lactate level r5
      • For patients in whom there is concern for MIS-C (multisystem inflammatory syndrome in children) because of clinical presentation and abnormal results of ancillary laboratory testing: r53
        • B‐type natriuretic peptide, troponin T, procalcitonin, ferritin, prothrombin time, partial thromboplastin time, D-dimer, fibrinogen, lactate dehydrogenase, urinalysis, cytokine panel, triglycerides, blood smear, and serologic testing including SARS-CoV‐2 IgG, IgM, and IgA if available
    • Chest imaging
      • Indications for chest radiography are based on medical necessity and are similar to general clinical indications for chest radiography in children (eg, concern for community-acquired pneumonia or worsening of respiratory status)
        • Not usually necessary in most children who have lower respiratory tract infection from COVID-19 r54
        • Chest radiograph findings often do not change clinical management or outcomes, and imaging may pose infection control risk r54
      • Point of care chest ultrasonography is an acceptable alternative to chest radiograph for investigating pneumonia, when indicated and available r5
    • ECG and echocardiogram
      • Obtain if cardiac concerns are present clinically, including when complete (tier 2) evaluation is indicated for MIS-C r53
  • In children infected with SARS-CoV-2, maintain broad differential to evaluate for additional conditions, which may present concomitantly
    • These additional conditions include diabetic ketoacidosis, intussusception, community-acquired pneumonia, streptococcal pharyngitis, and influenza
    • Proceed with standard evaluation for potential co-occurring conditions while maintaining appropriate infection control measures
    • Typical seasonal timing of respiratory pathogens is altered by public health measures to control COVID-19; be aware of currently circulating pathogens and test accordingly r55

Laboratory

  • SARS-CoV-2 testing on respiratory specimens
    • Specimen sources
      • For upper respiratory specimens, nasopharyngeal swabs are preferred; other common sources include anterior nares, nasal midturbinate, or oropharyngeal swabs r1c89c90
      • Occasionally, lower respiratory tract specimens may be used (eg, from bronchoalveolar lavage, sputum, endotracheal aspirates) but extreme care must be taken to avoid aerosolization of virus r1c91c92
    • Nucleic acid amplification testing r52c93
      • Reverse transcription polymerase chain reaction for SARS-CoV-2 RNA is most common nucleic acid amplification test used to detect viral RNA
        • Laboratory-based polymerase chain reaction testing has high sensitivity and high specificity and is considered reference standard
        • Point of care nucleic acid amplification testing is also available
        • Test does not differentiate between viable and nonviable virus
          • Patients may shed detectable SARS-CoV-2 RNA in upper respiratory specimens up to 3 months after onset of illness but this does not necessarily represent live virus
        • Nucleic acid amplification testing that generates presumptive results is not appropriate for use as confirmatory testing
    • Antigen testing r52c94
      • Antigen testing has benefit of rapid turnaround with specificity nearly equivalent to polymerase chain reaction testing
      • Antigen testing is useful to diagnose acute SARS-CoV-2 infection in symptomatic patients and for screening purposes (especially when used serially)
      • Risk of false-negative result in infected individual with low viral load early in illness is higher than with nucleic acid amplification testing. Serial testing can help diminish false-negative results in such cases
      • Confirmatory nucleic acid amplification testing may be necessary in the following scenarios:
        • Negative antigen test result when pretest probability is high (eg, symptomatic, close contact with person who tested positive)
        • Positive antigen test result when pretest probability of virus is low (eg, asymptomatic, low prevalence setting)
  • SARS-CoV-2 serology r52c95
    • Serology has the most clinical utility in children during workup for MIS-C to document previous viral exposure
    • Current antibody testing may target different viral antigens, including nucleocapsid protein, spike protein, or subunits (eg, receptor binding domain of spike protein)
      • All current vaccines induce antibodies to spike protein; therefore, serology interpretation needs to take into account antigenic target and previous vaccination
    • Seroconversion takes up to 2 weeks from symptom onset in most patients; therefore, antibody testing is more likely to be useful for detecting previous SARS-CoV-2 infection 15 days or more into course of illness r56r57
    • When indicated, measure anti–SARS-CoV-2 IgG or total antibody. Fractionating to identify IgM component is not helpful because IgM typically develops somewhat simultaneous to IgG production in response to SARS-CoV-2 infection r57
    • Sensitivity of tests that measure IgG is estimated at 97% and specificity at 98% in appropriately timed, collected, and processed specimens; however, degree of cross-reactivity with other coronaviruses is largely unknown r57r58
    • Patients with severe illness may experience a delay in seroconversion but overall antibody response appears to be more robust than in patients with less severe illness course r57
    • Duration that antibodies are detectable is uncertain
  • Routine blood work is not diagnostic, but patterns of typical abnormalities are noted, particularly among patients with severe disease
    • WBC count c96
      • Leukocyte count within reference range is noted in about 70% of pediatric patients with COVID-19 r59
      • Mild abnormalities in WBC count may be noted, including increased or decreased leukocyte and lymphocyte counts
    • Inflammatory markers
      • Mildly elevated markers of inflammation (eg, erythrocyte sedimentation rate, C-reactive protein, ferritin, l-lactate dehydrogenase, D-dimer, interleukin-6) are common, including slight elevation of procalcitonin c97c98c99c100c101
      • Marked elevation of procalcitonin suggests possible concomitant bacterial infection r28
      • Marked elevation in markers of inflammation suggests possibility of severe disease and MIS-C r28
      • Mean C-reactive protein in patients requiring admission is estimated at approximately 9 mg/L r51
    • Liver function tests c102
      • Mild elevation is common

Imaging

  • Chest imaging
    • Findings on chest imaging in patients with COVID-19 are, in general, nonspecific, overlapping with those of other infections r54
    • Chest radiograph c103
      • Unilateral or bilateral patchy findings are common
      • Roughly one-third of chest radiographs are normal, one-third demonstrate focal consolidations, and remainder exhibit ground-glass opacities r60r61
      • Lower and peripheral zones are often affected r57
      • Pleural effusion is an infrequent finding r4
    • Lung ultrasonogram c104
      • May be useful in facilities with experience using this modality for diagnosis, monitoring, and follow-up r57
      • Possible findings include multiple B lines, irregular thickened pleural line with scattered discontinuities, and subpleural and alveolar consolidation with resolution and improvement in aeration during recovery (ie, reappearance of bilateral A lines) r57
    • Chest CT c105
      • Not routine but may be required for subset of hospitalized, symptomatic patients with specific indications for chest CT r54
      • Low-dose CT imaging protocol is preferred for pediatric patients to reduce radiation exposure r62
      • Findings are often milder and more focal as compared with adults
      • Most common abnormal findings include ground-glass opacities and consolidation with unilateral lower lobe predominance. Other reported findings include halo sign, pulmonary nodules, bronchial wall thickening, and crazy paving pattern r62
      • Bilateral lobar consolidation may be noted in children with severe disease r57
      • Peripheral distribution of findings is commonly reported r62
      • Effusion is infrequent
      • In 1 series, normal findings were noted in up to 27% of CT scans in children with COVID-19 r62

Differential Diagnosis

Most common

  • Upper respiratory tract infection in children c106d2
  • Community-acquired pneumonia in children c107d3
  • Bronchiolitis c108d4
  • Pharyngitis c109d5
  • Influenza c110d6
  • Respiratory syncytial virus c111d7
  • Mycoplasma c112d8
  • Legionnaires' disease (Legionella pneumophila) c113d9
  • Mycobacterium tuberculosisc114d10
  • Chlamydia pneumoniaec115d11
  • Blastomycosis c116d12
  • Histoplasmosis c117
  • Gastroenteritis d13
  • Differential Diagnosis: COVID-19 in children.Numerous pathogens responsible for pneumonia-type presentation may be considered in differential diagnosis including viral, bacterial, and fungal pathogens as well as legionella and tuberculosis. Coinfection with more than a single pathogen may occur in up to 6% of patients with acute SARS-CoV-2 infection.Data from Miao H et al: Update on recommendations for the diagnosis and treatment of SARS-CoV-2 infection in children. Eur J Clin Microbiol Infect Dis. 39(12):2211-23, 2020; Perlman et al: Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In: Bennett JE et al, eds: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020:2072-80.e5; Hoang A et al: COVID-19 in 7780 pediatric patients: a systematic review. EClinicalMedicine. 24:100433, 2020; and Iroh Tam PY: Approach to common bacterial infections: community-acquired pneumonia. Pediatr Clin North Am. 60(2):437-53, 2013.
    Disease conditionDescriptionDifferentiated by
    Viral pneumoniaNumerous viral pathogens may result in an identical presentation including influenza, respiratory syncytial virus, adenovirus, parainfluenza, rhinovirus, human metapneumovirus, and human bocavirus

    Chest radiograph findings in patients with these pathogens may be quite similar to findings in those with acute COVID-19
    Positive SARS-CoV-2 test result does not completely exclude the possibility of coinfection with 1 or more additional viral pathogens

    Using clinical suspicion (eg, based on age, epidemiologic factors) to direct use of specific tests for additional viral pathogens can aid identification of additional and alternate viral pathogens. Multiplex nucleic acid amplification test panels (testing for multiple common pathogens in a single specimen) are available. Rapid antigen testing is available for some common pathogens (eg, respiratory syncytial virus, influenza)
    Atypical pneumonia Pneumonia caused by atypical organisms (eg, Mycoplasma pneumonia, Chlamydia pneumoniae) may have a similar presentation with fever, cough, tachypnea, difficulty breathing, and possibly hypoxia

    Chest radiograph findings may be quite similar to those noted in patients with acute COVID-19
    Positive SARS-CoV-2 testing does not completely exclude the possibility of coinfection with atypical organism

    Improvement with empiric treatment for presumed atypical pneumonia may be consistent with diagnosis

    Diagnosis is confirmed by clinical presentation and clinical course in most cases

    Demonstration of pathogen by nucleic acid amplification test is possible with polymerase chain reaction testing of respiratory specimens. Multiplex nucleic acid amplification test panels (testing for multiple common pathogens in a single specimen) are available
    Bacterial pneumonia Similar presentation with fever, cough, tachypnea, difficulty breathing, and possibly hypoxia

    Chest radiographic findings may be quite similar to those noted in patients with acute COVID-19

    Pathogen responsible for disease is highly dependent on child's age, presence of underlying comorbidities (eg, sickle cell, immunosuppression), and potential exposures (eg, travel, community exposures)
    Positive SARS-CoV-2 test result does not completely exclude possibility of bacterial coinfection

    Improvement with empiric treatment for presumed bacterial pneumonia may be consistent with diagnosis

    Diagnosis is confirmed by clinical presentation and clinical course in most cases

Treatment

Goals

  • Provide symptomatic and supportive care
  • Prevent and manage complications where possible

Disposition

Admission criteria

Admission decisions consider a combination of clinical presentation, supportive care requirement, underlying medical comorbidity, and caregiver's ability to provide home care

Admit all children with severe COVID-19 for expedient management, preferably at regional center with critical care and extracorporeal membrane oxygenation capability r5

Febrile neonates (younger than 28 days) require admission for further diagnosis, management, and monitoring r63

Most children with mild to moderate COVID-19 do not need admission, but decisions should be individualized

  • Consider admission for children with moderate COVID-19 symptoms (eg, clinical or radiographic evidence of lower airway disease) for supportive care and observation r5
  • Consider admitting children with mild to moderate disease and significant underlying comorbidity for management and close monitoring for clinical deterioration r28
Criteria for ICU admission
  • General ICU admission criteria apply: septic shock, cardiogenic shock, acute respiratory distress syndrome, need for advanced airway or ventilatory support, or multiple organ failure r5
  • Admit children with progressing severe disease and critical COVID-19 illness to pediatric ICU for expedient management, preferably at regional center with extracorporeal membrane oxygenation capability r5

Recommendations for specialist referral

  • COVID-19 is a notifiable disease; all patients should be managed according to public health policies in their jurisdiction
  • Consult infectious disease specialist to coordinate diagnosis and management with public health authorities
  • Manage complications and severe or critical disease in consultation with appropriate specialty service (eg, pediatric pulmonologist, pediatric intensive care specialist)

Treatment Options

Standard treatment includes infection control and supportive care for all patients and medications for certain children

  • Evidence for treatment in children is sparse; recommendations are primarily based on data in adults, expert opinion, and evidence from non-COVID illnesses
    • The older the child and the more severe the illness, the more applicable adult COVID-19 treatment guidelines become r1d1
    • Children most likely to benefit from medications are nonhospitalized patients with mild to moderate COVID-19 who are at highest risk for severe COVID-19
    • Enroll children in clinical trialsr64 and multicenter pragmatic trials whenever possible r1
  • Resources available with treatment recommendations include:
    • NIH COVID-19 treatment guidelines and WHO clinical management guidelines include pediatric-specific information r1r11
    • Infectious Diseases Society of America and WHO guidelines for treatment and management of patients with COVID-19 primarily address management of adults but contain information relevant to pediatric populations r12r65
    • American Academy of Pediatrics guidance r66

Infection controlmeasures include isolation, source control, and transmission precautions

  • For children managed at home: r67
    • Keep child at home, except to seek medical care
    • Isolation is required for everyone with positive COVID-19 test result, even in absence of symptoms
    • Try to keep child isolated to single area of house, including use of separate bathroom if available
    • Patient with COVID-19 aged 2 years or older should wear face mask when in contact with others
    • Caregivers should wear face mask, preferably high-quality (eg, N95 or equivalent), when in contact with child with COVID-19
    • Restrict contact to minimum number of caregivers and, in particular, ensure that persons with underlying medical conditions are not exposed to patient where possible
    • Caregivers should:
      • Wash hands for at least 20 seconds after all contact; alcohol-based hand sanitizer is acceptable if soap and water are not available
      • Clean and disinfect regularly
      • Improve ventilation where possible
      • Not share personal items (eg, towels, dishes, utensils) before proper cleaning
  • For hospitalized children: r40
    • Place patients in single room, preferably with dedicated bathroom, or cohort patients with same respiratory pathogens (with consideration of other communicable diseases)
    • Children aged 2 years and older should wear face mask for source control when in contact with others
    • Health care workers should use gown, gloves, eye protection (eg, goggles, face shield), and N95 respirator or equivalent when caring for patients with suspected or diagnosed COVID-19 infection
    • Instruct visitors on infection control and provide them with appropriate personal protective equipment
    • Follow transmission-based precautions until meeting criteria for discontinuation
  • Criteria for discontinuing isolation r40r68
    • Asymptomatic, no immunocompromise
      • Isolate for 5 days and wear mask for 5 additional days, with day 0 as day test was performed
        • If unable to wear mask (eg, younger than age 2 years), isolate for 10 days
      • If symptoms develop during these 10 days, start isolation over with day 0 as first day of symptoms
    • Mild symptoms, no immunocompromise
      • Isolate for 5 days and wear mask for 5 additional days, with day 0 as first day of symptoms
      • Isolation may end when at least 24 hours have passed since last fever without use of antipyretics and symptoms have improved
    • Moderate symptoms (eg, shortness of breath), no immunocompromise
      • Isolate for 10 days, with day 0 as first day of symptoms
      • Isolation may end when at least 24 hours have passed since last fever without use of antipyretics and symptoms have improved
    • Severe to critical illness, no immunocompromise
      • Isolate for at least 10 days and up to 20 days, with day 0 as first day of symptoms, and
        • At least 24 hours have passed since last fever without use of antipyretics, and
        • Symptoms have improved
        • Test-based strategy may be used to inform duration of isolation: negative results from at least 2 consecutive respiratory specimens collected 48 hours apart (total of 3 negative specimens) tested using antigen or nucleic acid amplification test
          • Nucleic acid amplification test may be used but is frequently positive for days to weeks and does not necessarily correlate with being infectious r52
    • Immunocompromised patients
      • Moderately to severely immunocompromised individuals may shed replication-competent virus for an extended period; therefore, test-based strategy is recommended
      • Consult with infectious diseases specialist when available
      • Isolate for at least 20 days, with day 0 as first day of symptoms or as day testing was performed, if entirely asymptomatic, plus:
        • At least 24 hours have passed since last fever without use of antipyretics, and
        • Symptoms have improved, and
        • Results are negative from at least 2 consecutive respiratory specimens collected 48 hours apart (total of 2 negative specimens) tested using antigen or nucleic acid amplification test
          • Nucleic acid amplification test may be used but is frequently positive for days to weeks and does not necessarily correlate with being infectious r52

Supportive care is the mainstay of management for overwhelming majority of pediatric patients; most children can be managed safely in the home environment r69

  • For children managed at home: r11r67
    • Encourage fluids and nutrition as tolerated by mouth
    • Antipyretics and OTC pain relievers (eg, ibuprofen, acetaminophen) may be given as needed for fever, aches, and other symptoms
    • Caregiver education
      • Educate about emergency signs for worsening COVID-19 manifestations: r11
        • Difficulty breathing, fast or shallow breathing, or grunting in infants
        • Blue lips or face
        • Chest pain or pressure
        • New confusion
        • Inability to awaken or not interacting when awake
        • Inability to drink, keep down any liquids, or breastfeed
      • Provide recommended isolation measures to minimize secondary spread of COVID-19 r67
      • Advise on when clearance by health care provider is needed to resume sports and physical activity (eg, moderate to severe COVID-19, symptoms of myocarditis following recovery) r70
    • Consider providing pulse oximeter for home monitoring of those at high risk for severe disease r11
    • Resources for parents are available from various organizations (eg, American Academy of Pediatrics,r71CDCr67) to help guide home care for children with COVID-19
  • For hospitalized children:
    • Treat dehydration and provide hydration support in standard fashion
      • Use parenteral hydration via IV or enteral hydration via nasogastric tube if patient is unable to tolerate fluids by mouth r5
        • Advantage of enteral route is ability to provide added nutritional support when needed
        • Parenteral hydration is preferred for patients with poor or declining clinical status
      • Goal is euvolemic state; aggressive fluid management may impair alveolar oxygen exchange
    • Provide advanced nutritional support if needed r28
    • Monitor oxygenation by pulse oximetry or other methods as needed, with awareness that pulse oximetry may be artificially low in darker skin tones r1
    • Start oxygen when indicated for persistent SpO₂ less than 90% to 92% r72
      • Optimal oxygen saturation is unknown; NIH guidelines recommend target of 92% to 97% for children, and WHO recommends greater than 90% r1r11
    • Provide airway and respiratory support when clinically indicated
      • Conventional oxygenation may use a variety of delivery methods (eg, nasal cannula at 5 L/minute, face mask with reservoir bag at 10-15 L/minute)
      • Perform time-limited (eg, 30- to 90-minute) trial of noninvasive ventilatory support such as high-flow nasal canula (eg, 2 L/kg/min), CPAP, or BPAP before advancing to invasive mechanical ventilation, when clinical status allows r1r57
        • There is insufficient evidence in children to recommend high-flow oxygen over noninvasive ventilation or vice versa
        • For increased work of breathing, BPAP is preferred over CPAP to unload respiratory muscles, except for children who cannot achieve adequate seal with noninvasive ventilation interface or who have significant patient-ventilator asynchrony
        • If indications for endotracheal intubation are already present, high-flow nasal cannula or noninvasive positive pressure ventilation should not be used to delay needed mechanical ventilation
      • There is insufficient evidence regarding awake prone positioning for children with persistent hypoxemia who require high-flow oxygen or noninvasive ventilation and do not require endotracheal intubation; however, do not attempt prone positioning as a rescue to avoid needed intubation
  • For critical illness: d14
    • In general, evidence to guide critical treatment in pediatric populations is limited but uses information from adult trials and expert opinion r1
    • General management of critically ill children is also based on guidance for non-COVID critical illness, such as:
      • Surviving Sepsis Campaign septic shock guideliner73
      • Society of Critical Care Medicine guideline on prevention and management of pain, agitation, neuromuscular blockade, and delirium in childrenr74
      • Pediatric Acute Lung Injury Consensus Conferencer75 recommendations

Medications to treat COVID-19 and coinfections and to prevent complications are indicated in certain children

  • Because most children have mild to moderate disease, the risk-benefit ratio for medications in children is different from adults
    • NIH guidelines divide children into low, medium, and high risk for progression to severe disease on basis of age, vaccination status, and medical conditions r1
      • Ages younger than 1 year and 10 to 14 years are associated with increased risk for severe disease
      • Being unvaccinated is associated with increased risk for severe disease
      • Medical conditions in children with the most evidence associated with increased risk include:
        • Moderate to severe immunosuppression
        • Dependence on respiratory support (eg, tracheostomy, noninvasive ventilation)
        • Obesity, particularly in adolescents
        • Severe disability with impaired airway clearance or limitations in self care/activities of daily living
        • Severe asthma/chronic lung disease requiring 2 or more daily inhaled medications or any daily systemic medications
        • Severe cardiac disease
        • Multiple moderate or severe chronic illnesses
      • Many other medical conditions may be associated with risk for severe COVID-19, but evidence in children is more limited or inconsistent r48
    • Clinicians should individualize treatment decisions taking into account all factors (eg, ethnicity, number of risk factors)
  • For nonhospitalized children: r1
    • NIH guidelines recommend use of ritonavir-boosted nirmatrelvir (first choice) or remdesivir (alternate) for children aged 12 years and older at high risk for progression to severe disease
      • There is insufficient evidence to recommend for or against use of remdesivir in children younger than age 12 years, and ritonavir-boosted nirmatrelvir is not authorized for use in children younger than 12 years
    • There is insufficient evidence to recommend for or against use of any antiviral treatment in children at intermediate risk for progression
    • These recommendations also apply to children who are hospitalized for reasons other than COVID-19
      • It is unknown whether children receiving respiratory support for asthma, croup, or bronchiolitis who have concurrent COVID-19 infection would benefit from remdesivir
    • Children at low risk for progression to severe disease are recommended to receive supportive care and infection control measures only
  • For children hospitalized for COVID-19: r1
    • For children who do not require oxygen:
      • Remdesivir is recommended for those aged 12 to 17 years at high risk for progression to severe disease
      • Remdesivir may be considered on individual basis for those younger than 12 years at high risk for severe disease but there is insufficient evidence to recommend for or against use of remdesivir in this population
    • For children who require conventional oxygen:
      • Remdesivir is recommended, with the addition of dexamethasone for those with increasing oxygen needs, particularly adolescents
    • For children who require high-flow oxygen or noninvasive ventilation:
      • Dexamethasone alone or dexamethasone with remdesivir is recommended
      • If these children do not improve rapidly (eg, within 24 hours) after dexamethasone is started, baricitinib or tocilizumab may be considered (aged 2 years and older)
        • Tofacitinib may be considered if baricitinib is unavailable
    • For children who require mechanical ventilation or extracorporeal membrane oxygenation:
      • Dexamethasone is recommended
      • If these children do not improve rapidly (eg, within 24 hours) after dexamethasone is started, baricitinib or tocilizumab may be considered (aged 2 years and older)
        • Tofacitinib may be considered if baricitinib is unavailable
    • All children aged 12 years and older who are hospitalized for COVID-19 should receive prophylactic anticoagulation unless contraindicated
    • Administer specific antivirals (eg, oseltamivir for influenza) and appropriate antibiotics (eg, empiric antibiotics for sepsis before confirmation of infectious agent) in accordance with disease severity, acquisition site (community or hospital), epidemiologic risk factors, and local antimicrobial susceptibility patterns r1r11
      • Note the co-occurrence of bacterial infection at presentation appears to be low; guidelines recommend against routine empiric antibiotics and recommend daily reassessment for discontinuation in those on antibiotics for suspected bacterial infections
  • Details on pharmacotherapeutic options r76r77
    • Antiviral agents
      • Nirmatrelvir-ritonavir r77
        • Protease inhibitor combination that prevents viral replication with antiviral activity against coronaviruses
        • Authorized by FDA for emergency use in adults and children aged 12 years and older and weighing 40 kg or more who are at high risk for progression to severe disease
        • First choice pharmacotherapeutic indicated for treatment of patients aged 12 years and older with mild to moderate COVID-19 who do not require hospitalization for COVID-19 but are at high risk of progression to severe disease
        • Initiate oral dosing as soon as possible and within 5 days of symptom onset
        • Ritonavir-boosted nirmatrelvir has significant and complex drug interactions; carefully review medication profile (including OTC and herbal supplements) before initiation
          • Liverpool COVID-19 drug interaction website,r78ritonavir-boosted nirmatrelvir fact sheetr77, and NIH guidelinesr1 can help identify potential drug interactions
        • Viral rebound and/or recurrence of symptoms and antigen test positivity has been reported following a 5-day course of ritonavir-boosted nirmatrelvir; there is no evidence that additional treatment is needed, but patients should continue to isolate until they meet criteria for discontinuation r1
      • Remdesivir r76
        • Nucleotide analogue prodrug that inhibits viral RNA polymerases
        • Most beneficial when started early in course of illness (fewer than 7 days after first symptom) in patients meeting criteria for treatment r1
        • FDA-approved to treat COVID-19 in adult and pediatric patients aged 28 days and older and weighing 3 kg or more r76
        • NIH-recommended for the following pediatric patients: r1
          • For nonhospitalized children aged 12 years and older at high risk of severe disease, remdesivir is second choice treatment after nirmatrelvir-ritonavir
          • For hospitalized children aged 12 years and older at high risk of severe disease who have no oxygen requirement
          • For hospitalized children who are on conventional oxygen
          • For hospitalized children who require high-flow oxygen or noninvasive ventilation, recommended with dexamethasone
        • Also consider for the following pediatric patients, although insufficient evidence exists to recommend for or against treatment in these circumstances: r1
          • For nonhospitalized children younger than 12 years at high risk of severe disease
          • For hospitalized children younger than 12 years at high risk of severe disease who have no oxygen requirement
    • Immunomodulatory agents
      • Dexamethasone
        • Efficacy and safety data in children are limited; treatment in context of enrollment in a clinical trial is ideal r79
        • Recommended for hospitalized pediatric patients under the following circumstances: r1
          • For children (particularly adolescents) who require conventional oxygen and have increasing oxygen requirements, as an option along with remdesivir
          • For children requiring high-flow oxygen or noninvasive ventilation (with or without concurrent remdesivir)
          • For children requiring mechanical ventilation or extracorporeal membrane oxygenation
        • Routine use for pediatric patients requiring conventional oxygen is not recommended r1
        • Alternative glucocorticoids (eg, prednisone, methylprednisolone, hydrocortisone) may be substituted if dexamethasone is not available r1
      • Baricitinib
        • Janus kinase inhibitor that has FDA approval for treating COVID-19 in adults and emergency use authorization for children aged 2 years and older requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation r1r76r77
        • Given paucity of data in pediatric population, NIH suggests considering baricitinib (or tocilizumab) in the following circumstances: r1
          • For children aged 12 to 17 years requiring high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation who do not have rapid improvement (eg, within 24 hours) after dexamethasone is started (moderate recommendation)
          • For children aged 2 to 11 years requiring high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation who do not have rapid improvement (eg, within 24 hours) after dexamethasone is started (weak recommendation)
        • Infectious Diseases Society of America guidelines endorsed by Pediatric Infectious Diseases Society note that there is very limited data in pediatric populations, including use for other conditions (eg, rheumatoid arthritis) as baricitinib is not approved in children r65
      • Tocilizumab r77
        • Interleukin-6 receptor antagonist with limited use in pediatric population for COVID-19 r80
          • Because tocilizumab is FDA-approved for use in children with other indications (eg, juvenile idiopathic arthritis, cytokine release syndrome), pediatric subspecialists such as rheumatologists or infectious disease specialists may have experience with the drug
        • Authorized by FDA for emergency use in combination with systemic glucocorticoids in children aged 2 years and older who require supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation r77
        • NIH recommendations for tocilizumab, based primarily on extrapolation from adults, are the same as for baricitinib: r1
          • For children aged 12 to 17 years requiring high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation who do not have rapid improvement (eg, within 24 hours) after dexamethasone is started (moderate recommendation)
          • For children aged 2 to 11 years requiring high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation who do not have rapid improvement (eg, within 24 hours) after dexamethasone is started (weak recommendation)
      • Tofacitinib
        • Janus kinase inhibitor that has been used off-label in treatment of COVID-19; pediatric use is extrapolated from use in adults
        • Due to FDA approval for use in children aged 2 years and older for juvenile idiopathic arthritis, tofacitinib has an established safety profile in pediatric patients; therefore, NIH guidelines recommend use of tofacitinib as alternative if baricitinib is not available for same indications: r1
          • For children aged 12 to 17 years requiring high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation who do not have rapid improvement (eg, within 24 hours) after dexamethasone is started (moderate recommendation)
          • For children aged 2 to 11 years requiring high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation who do not have rapid improvement (eg, within 24 hours) after dexamethasone is started (weak recommendation)
    • Thrombosis prevention and treatment
      • For children aged 12 years and older hospitalized with COVID-19, thromboprophylaxis is recommended unless contraindicated; there is insufficient evidence to recommend for or against prophylactic anticoagulation for children younger than 12 years r1
        • Otherwise, children with COVID-19 with indications for prophylactic or therapeutic anticoagulation (eg, institutional protocol, diagnosed thrombosis, receipt of extracorporeal membrane oxygenation or continuous renal replacement therapy) should be managed the same as children without COVID-19 with these indications
        • Low molecular weight heparin (preferred) and unfractionated heparin (alternative) are recommended over oral agents for hospitalized patients
        • Early ambulation and lower-extremity compression garments and devices are low risk and easily implemented precautionary measures
      • Children on anticoagulation or antiplatelet treatment for another indication should continue therapy if diagnosed with COVID-19 (unless significant bleeding or other contraindications develop) r1
      • Data regarding risk of thrombotic events in children with acute COVID-19 and effectiveness of thromboprophylaxis are limited r1
        • Higher risk patients for venous thromboembolism may include, but are not limited to, pediatric patients with:
          • Elevated D-dimer results
          • Risk factors for severe COVID-19 illness
          • General risk factors for thromboembolic events (eg, obesity, family history, chronic inflammatory conditions)
      • Certain antiplatelet and anticoagulation therapy is recommended for patients with MIS-C; details are available in NIHr1 and American College of Rheumatologyr53 guidelines d15
    • Antibody products
      • Anti–SARS-CoV-2 monoclonal antibody products
        • Neutralizing IgG monoclonal antibodies that bind spike protein of SARS-CoV-2 and prevent attachment of virus to human ACE2 receptors
        • Many products had been used for treatment or prevention under emergency use authorization in adults and in some children, but effectiveness depends heavily on circulating variants
          • Circulating Omicron subvariants have rendered bamlanivimab-etesevimab, bebtelovimab, casirivimab-imdevimab, and sotrovimab ineffective, and emergency use authorizations have been revised or revoked for these products r77
          • Some newer Omicron subvariants that are increasing in prevalence (eg, BQ.1, BQ.1.1) are expected to be resistant to tixagevimab-cilgavimab r1
          • Check FDA emergency use authorizations websiter77, NIH guidelinesr1, and CDC variant proportionsr10 in region to decide whether use of tixagevimab-cilgavimab is beneficial
      • Convalescent plasma
        • Plasma from donors with high titers of anti–SARS-CoV-2 antibodies has been granted emergency use authorization for treatment of persons with significant immunosuppression r77
        • Evidence in adult population is mixed; evidence in pediatric population is very limited and other options are available (eg, ritonavir-boosted nirmatrelvir, remdesivir)
        • NIH guidelines suggest considering use on case-by-case basis for hospitalized immunocompromised children who meet emergency use authorization criteria for high-titer convalescent plasma use r1
          • Given currently circulating Omicron subvariants, NIH guidelines recommend against use of any convalescent plasma collected before emergence of Omicron variants

Many therapies are under investigation for treatment of COVID-19 in pediatric population; consider use of the following only within a clinical trial: r1

  • Sarilumab
  • Anakinra
  • Fluvoxamine
  • GM-CSF inhibitors (granulocyte-macrophage colony-stimulating factor)
  • Inhaled corticosteroids
  • Canakinumab
  • Bruton tyrosine kinase inhibitors (eg, acalabrutinib, ibrutinib, zanubrutinib)
  • Janus kinase inhibitors other than baricitinib and tofacitinib (eg, ruxolitinib)
  • Siltuximab

Avoid potential harmful therapies not supported by evidence for treatment of acute COVID-19 in pediatric patients, such as the following: r1r5

  • Molnupiravir
  • Colchicine
  • ACE inhibitors and angiotensin receptor blockers (used specifically for COVID-19; continue use if patient is taking for another indication)
  • HIV antivirals (eg, lopinavir, ritonavir)
  • Chloroquine and hydroxychloroquine
  • Azithromycin, without suspicion of bacterial infection
  • Ivermectin
  • Interferons

Drug therapy

  • Corticosteroids r1
    • Dexamethasone c118
      • Oral
        • Dexamethasone Oral solution; Children and Adolescents: 0.15 mg/kg/dose (Max: 6 mg/dose) PO once daily for up to 10 days for hospitalized pediatric patients requiring high-flow oxygen, noninvasive or invasive mechanical ventilation, or ECMO.
      • Intravenous
        • Dexamethasone Sodium Phosphate Solution for injection; Children and Adolescents: 0.15 mg/kg/dose (Max: 6 mg/dose) IV once daily for up to 10 days for hospitalized pediatric patients requiring high-flow oxygen, noninvasive or invasive mechanical ventilation, or ECMO.
  • Antiviral RNA-polymerase inhibitors
    • Remdesivir c119
      • Avoid in patients with ALT level more than 5 times the upper reference limit and when estimated GFR is less than 30 mL/minute/1.73 m² r28
      • For patients weighing less than 40 kg, use only lyophilized powder formulation to prepare doses
      • For nonhospitalized patients with mild to moderate COVID-19 who are at high risk for disease progression
        • Remdesivir Solution for injection; Infants, Children, and Adolescents weighing 3 to 39 kg: 5 mg/kg/dose IV once on day 1, followed by 2.5 mg/kg/dose IV once daily for 2 days.
        • Remdesivir Solution for injection; Children and Adolescents weighing 40 kg or more: 200 mg IV once on day 1, followed by 100 mg IV once daily for 2 days.
      • For admitted patients with COVID-19
        • Remdesivir Solution for injection; Neonates†: 5 mg/kg/dose IV once on day 1, followed by 2.5 mg/kg/dose IV once daily for up to 10 days is being used in an ongoing investigational study (NCT04431453) in neonates 14 to 27 days of age, gestational age more than 37 weeks, and weight 2.5 kg or more. 2.5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 4 days was successfully used in a case report of 2 ex-premature neonates.
        • Remdesivir Solution for injection; Infants, Children, and Adolescents weighing 3 to 39 kg requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO): 5 mg/kg/dose IV once on day 1, followed by 2.5 mg/kg/dose IV once daily for 9 days. The NIH recommends against starting remdesivir, but treatment may be continued (in combination with dexamethasone) in patients who progress to mechanical ventilation or ECMO.
        • Remdesivir Solution for injection; Infants, Children, and Adolescents weighing 3 to 39 kg NOT requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO): 5 mg/kg/dose IV once on day 1, followed by 2.5 mg/kg/dose IV once daily for 4 days; may extend treatment for up to 5 additional days if no clinical improvement.
        • Remdesivir Solution for injection; Children and Adolescents weighing 40 kg or more requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO): 200 mg IV once on day 1, followed by 100 mg IV once daily for 9 days. The NIH recommends against starting remdesivir, but treatment may be continued (in combination with dexamethasone) in patients who progress to mechanical ventilation or ECMO.
        • Remdesivir Solution for injection; Children and Adolescents weighing 40 kg or more NOT requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO): 200 mg IV once on day 1, followed by 100 mg IV once daily for 4 days; may extend treatment for up to 5 additional days if no clinical improvement.
  • SARS-CoV-2 protease inhibitor antivirals
    • Nirmatrelvir-ritonavir r77c120
      • Do not use in severe hepatic impairment (Child-Pugh class C)
      • Use with caution in preexisting liver disease
      • Nirmatrelvir Oral tablet, Ritonavir Oral tablet; Children and Adolescents 12 to 17 years weighing 40 kg or more: 300 mg nirmatrelvir (two 150 mg tabs) and 100 mg ritonavir (one 100 mg tab) taken together by mouth twice daily for 5 days. Start as soon as possible after the positive test for SARS-CoV-2 and within 5 days of symptom onset.
      • Dosage reduction is necessary when estimated GFR is at least 30 but less than 60 mL/minute; do not use when estimated GFR is less than 30 mL/minute
  • Antiviral monoclonal antibodies
    • For use only against a susceptible variant
    • For preexposure prophylaxis in patients with moderate to severe immunocompromise
      • Tixagevimab-cilgavimab c121
        • Cilgavimab Solution for injection, Tixagevimab Solution for injection; Children and Adolescents 12 years and older weighing 40 kg or more: 300 mg tixagevimab and 300 mg cilgavimab given as 2 separate consecutive IM injections. For persons who have only received the previously authorized lower dose (i.e., 150 mg tixagevimab and 150 mg cilgavimab), give 300 mg tixagevimab and 300 mg cilgavimab as soon as possible. If ongoing protection is required, repeat dosing of 300 mg tixagevimab and 300 mg cilgavimab may be administered every 6 months. Time repeat dosing from the date of the most recent dose.
  • Janus kinase inhibitor
    • Baricitinib r77c122
      • Baricitinib Oral tablet; Children 2 to 8 years†: 2 mg PO once daily for 14 days or until hospital discharge, whichever comes first. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Baricitinib Oral tablet; Children and Adolescents 9 to 17 years†: 4 mg PO once daily for 14 days or until hospital discharge, whichever comes first. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Dosage reduction is necessary when estimated GFR is less than 60 mL/minute; do not use in children aged 2 to less than 9 years when estimated GFR is less than 30 mL/minute or children aged 9 years and older when estimated GFR is less than 15 mL/minute
      • Interrupt therapy if absolute lymphocyte count or absolute neutrophil count decreases to less than 200 cells/µL or 500 cells/µL respectively
      • Interrupt therapy if AST or ALT increases and drug-induced liver injury is suspected
  • Interleukin-6 receptor-inhibiting monoclonal antibody
    • Tocilizumab r77c123
      • Tocilizumab Solution for injection; Children and Adolescents 2 to 17 years weighing less than 30 kg†: 12 mg/kg IV infusion once with a systemic corticosteroid. If symptoms worsen or do not improve, 1 additional dose may be administered at least 8 hours after the first.
      • Tocilizumab Solution for injection; Children and Adolescents 2 to 17 years weighing 30 kg or more†: 8 mg/kg (Max: 800 mg/dose) IV infusion once with a systemic corticosteroid. If symptoms worsen or do not improve, 1 additional dose may be administered at least 8 hours after the first.
      • Do not use with elevated ALT or AST above 10 times the upper limit of reference range

Nondrug and supportive care

  • Supportive care and infection control, as detailed above, remain a critical aspect of treatment of COVID-19 in children
  • Additional measures intended to avoid secondary spread of virus from infected individuals
    • Use health care facility–based infection prevention and control measures r40
      • Maintain a process to identify individuals (patients, visitors, health care workers) with suspected or confirmed COVID-19 infection
      • Utilize universal source control in patient care areas, particularly when community transmission is high
        • CDC-defined community transmission (based on new cases and percentage positivity in testing, to capture potential spread in an area) is different from community levels (based on hospital admissions and proportion of hospitalizations due to COVID-19, to capture effect of transmission on health care system) r81
      • Ensure optimal facility ventilation and indoor air quality

Comorbidities

  • Children with immunodeficiency or immunocompromise c124
    • Consider managing in consultation with infectious disease specialist. COVID-19 treatment-specific therapies and pharmacotherapeutics may be indicated
    • Temporarily stopping or reducing the dose of chronic immunosuppressive treatment should be considered in consultation with appropriate prescribing specialist r1r28
      • Some experts recommend reducing T-cell immunosuppression, when applicable, in infected children r69
    • Isolation measures should be modified to 20 days or more after symptom onset and after resolution of fever and improvement of other symptoms r40
      • Test-based strategy is recommended: 2 consecutive negative tests collected at least 48 hours apart; consider consultation with infectious disease specialists
        • Nucleic acid amplification or antigen testing is acceptable; however, nucleic acid amplification testing may remain positive for days to weeks and does not necessarily correlate with being infectious r52
    • Children with immunocompromise aged 6 months and older are recommended to have COVID-19 vaccination d1
      • Primary vaccine series for those with moderate to severe immunocompromise includes: r82
        • For children aged 6 months through 11 years: 3 doses of Pfizer or Moderna
        • For children aged 12 years and older: 3 doses of Pfizer or Moderna or 2 doses of Novavax
      • Booster dose recommendations are the same as for children who are nonimmunocompromised
  • Children with asthma c125c126
    • Evidence for risk of COVID-19 transmission during nebulizer treatment is inconclusive r5r83
      • Consider administering respiratory medications via metered dose inhaler with spacer and/or dry powder inhaler (eg, turbuhaler or diskus) when appropriate
      • Utilize personal protective equipment adequate for aerosol-generating procedure when nebulizer is used
  • Children with croup c127
    • Consider early use of steroids in effort to prevent return visits to health care facility and reduce risk for admission r5
    • Evidence for risk of COVID-19 transmission during nebulizer treatment is inconclusive r5r83
      • Consider using epinephrine via metered dose inhaler with spacer or subcutaneous/intramuscular dosing when appropriate
      • Utilize personal protective equipment adequate for aerosol-generating procedure when nebulized epinephrine is used

Special populations

  • Neonates r84
    • Risk of infection in neonates appears highest when COVID-19 infection in pregnancy is diagnosed close to delivery
    • Obtain nucleic acid amplification test result for SARS-CoV-2 in neonates born to mothers with suspected or confirmed COVID-19 at about 24 hours of life; consider repeated testing at 48 hours if initial test result is negative
    • Maintain high suspicion for alternate and/or concomitant diagnosis responsible for symptoms (eg, temperature instability, cough, difficulty breathing) that may be suggestive of COVID-19 in neonates
    • Isolate mothers with suspected or confirmed SARS-CoV-2 infection and their neonates from healthy mothers and neonates
      • Rooming both neonate and mother together is recommended in most instances
      • Avoid isolating neonates in neonatal ICU unless clinical condition warrants neonatal ICU care
    • Encourage measures to minimize risk of transmission, including general infection prevention and control measures (eg, hand hygiene, wearing mask) by all caregivers while caring for neonate
    • Breastfeeding is recommended; mothers should perform hand hygiene and wear mask while breastfeeding
    • Discharge infant (whether test result is positive or negative for COVID-19) based on usual discharge criteria, with close follow-up by phone, telehealth, or in-office visits, particularly for infants who test positive

Monitoring

  • Patients managed at home c128
    • Instruct caregiver to monitor for manifestations associated with worsening illness and clinical deterioration, including difficulty breathing, chest pain, syncope, palpitations, mental status changes, and dehydration r28
  • Hospitalized patients c129
    • Clinically monitor for early warning indicators of worsening disease (eg, increased work of breathing, worsening tachypnea, decreased level of consciousness, decreased perfusion or other signs of impending shock) r85
    • Monitoring of laboratory markers in hospitalized patients is not rigorously standardized
      • Limited data suggest that serial monitoring of C-reactive protein, procalcitonin, and lactate dehydrogenase may be most informative to track illness trajectory r86
  • Patients taking remdesivir
    • Baseline liver function testing, prothrombin time, and estimated GFR, with repeat tests as clinically indicated, are recommended r1c130
  • Return to sports and physical activity recommendations for children who test positive for SARS-CoV-2 r70
    • Exercise is not recommended while in isolation
    • Educate all patients and caregivers to report to physician any chest pain, shortness of breath out of proportion for upper respiratory tract infection, new-onset palpitations, or syncope when returning to exercise
    • American Academy of Pediatrics provides detailed return-to-play algorithm based on severity of symptoms
      • Asymptomatic and mild disease
        • Prior to resuming activity or within 2 to 4 weeks of positive test (whichever is sooner), child may be cleared by phone, telehealth, or electronic communication if symptom-free (no chest pain, new-onset palpitations, syncope, shortness of breath) and isolation is complete
        • For any concerning symptoms, examine child in office; consider ECG for any potential cardiac symptoms (eg, syncope, dyspnea on exertion, chest pain)
        • Refer to cardiologist for abnormal ECG or concerning examination findings
      • Moderate illness (defined as 4 or more days of fever, 1 or more week of myalgia or lethargy, hospitalized but not admitted to ICU, no evidence of MIS-C)
        • Physical examination, screening ECG, and American Heart Association 14-element screening evaluation is recommended r87c131
        • Child may return to return to activity if physical examination, ECG, and American Heart Association screen are all normal and isolation is complete
        • Refer to cardiologist if American Heart Association screening evaluation is positive, examination is abnormal, or ECG is abnormal
      • Severe illness (defined as ICU admission, intubation, or MIS-C)
        • Restrict from exercise for minimum of 3 to 6 months and require cardiology clearance before allowing child to return to training or competition
  • American Academy of Pediatrics recommendations for follow-up after SARS-CoV-2 infection r88
    • At least 1 follow-up is recommended for all patients with infection. Type (eg, telehealth, in-office) and timing of visit depend on severity of illness, presence of underlying comorbidities, presence of complications, and completion of isolation period
    • At visit, monitor residual symptoms, assess for development of new symptoms, guide return to activities (eg, physical activity, school, employment), review routine and COVID-19 immunizations, and provide general anticipatory guidance
    • Telephone or virtual visit is appropriate for children with resolved symptoms after asymptomatic or mild disease (less than 4 days of fever higher than 38 °C and less than 1 week of myalgia, chills, or lethargy)
    • In-person visit is recommend for children with moderate disease (more than 4 days of fever higher than 38 °C; more than 1 week of myalgia, chills, or lethargy; and non-ICU hospital stay) or severe disease (ICU stay and/or intubation)

Complications and Prognosis

Complications

  • Acute complications
    • Coinfection with other viruses and bacteria
      • Coinfection appears to be rare overall but limited data suggest coinfection may occur in some children (6% to 18%) r1r55r61
      • Systematic review data suggest that among children with coinfection, almost 60% have concomitant Mycoplasma pneumoniae, 11% influenza A or B, and about 10% respiratory syncytial virus. Other common viral and bacterial infections occurred in the remainder r61c132c133c134
    • Neurologic complications
      • Up to 20% of hospitalized children may develop neurologic manifestations; these manifestations are transient in most (over 88%) r89
      • Neurologic complications are more frequent in children with underlying neurologic disorders r19
      • Acute disseminated encephalomyelitis, acute transverse myelitis, Guillain-Barré syndrome, cerebral edema, demyelination, and stroke are among the possible life-threatening complications r90c135c136c137c138c139c140
    • Cardiovascular involvement
      • Myocarditis, pericarditis, heart failure, and arrhythmias are described r91c141c142c143c144
      • Underlying mechanisms for cardiotoxicity may be multifactorial caused, at least in part, by direct entry of virus into myocardial cells, hypoxia resulting in hypoxemic myocardial cell damage, and immune-mediated injury secondary to excessive systemic release of cytokines generated by presence of virus r92
      • Myocarditis associated with acute COVID-19 is estimated at 1% to 2% of hospitalized COVID-19 patients (primarily adults); overall risk for myocarditis among children younger than 16 years with COVID-19 diagnosis is estimated at less than 0.13% (adjusted risk ratio greater than 30) r93r94
      • Subclinical myocarditis was documented by cardiac MRI in a minority of patients recovering from mild or asymptomatic infection in a small group of young athletes; additional studies are needed to determine clinical significance of this finding r95
      • Asymptomatic children and children with mild illness may have evidence of cardiac inflammation consistent with myocarditis; therefore, following return to sports and physical activity protocol is necessary r70
    • Thrombotic events
      • Appear to develop at much lower frequency than encountered in adult patients
      • Limited data from retrospective cohort study suggest that serious complications (eg, deep venous thrombosis, stroke, pulmonary embolism) may develop in up to 2% of symptomatic hospitalized children and adolescents with COVID-19 r96
        • Most children hospitalized with COVID-19 who developed thrombotic complications were 12 years and older and many developed these complications despite thromboprophylaxis
        • Risk factors for development of thrombosis include age 12 years and older, comorbid malignancy, presence of central venous catheter, and MIS-C diagnosis
      • Developing a thrombotic event is a marker for increased mortality risk r97
    • Ocular symptoms
      • Anterior uveitis, retinitis, and optic neuritis are among serious but rare ocular complications encountered r27
    • Intussusception
      • Several reports of intussusception among infants with SARS-CoV-2 infection have been reported; however, a clear association pointing to intussusception as part of clinical spectrum of COVID-19 in infants rather than being a mere coincidental finding has yet to be determined r98
    • Additional complications in children with severe and critical disease may include:
      • Respiratory failure
      • Shock
      • Acute renal failure
      • Coagulopathy
      • Multisystem organ failure
  • Postinfectious complication
    • MIS-C c145d15
      • Rare inflammatory condition that may develop about 2 to 6 weeks after acute COVID-19 infection r99
        • Reported to occur in approximately 0.1% of children with COVID-19 diagnosis r61
      • Inflammation may affect any organ but typically involves gastrointestinal system, skin, heart, brain, lungs, kidneys, and eyes
      • Elevated inflammatory markers and abnormal ECG or echocardiogram are common
      • Most MIS-C develops in previously healthy patients r61r99
        • Obesity and asthma are the most commonly associated comorbid conditions
      • Presenting manifestations vary in terms of severity and pattern; some children manifest a more mild illness whereas others present in shock or with a Kawasaki-like illness
      • Establish diagnosis based on CDC or WHO clinical criteria r100r101
      • Treatment involves initial resuscitation, immunomodulatory therapy (eg, IV immunoglobulin and corticosteroids), and antithrombotic therapy (eg, low-dose aspirin with or without anticoagulation) r1r53
  • Persistent symptoms and long-term sequelae after acute COVID-19
    • Research is ongoing in children; types and incidences of postacute symptoms (ie, persistent symptoms lasting more than 1-3 months after onset of COVID-19) and long-term sequelaer102 are still being determined r88
      • Long COVID is variously defined as having symptoms 4 or more weeks, 4 to 8 weeks, and 12 weeks after COVID-19 diagnosis, which complicates research; symptoms may be persistent from time of acute infection or new symptoms may develop after asymptomatic or mild acute illness r103c146
      • Recently published definition for long COVID in children: r104
        • Presence of 1 or more persistent physical symptoms that impair daily function, which may fluctuate and relapse, and that last at least 12 or more weeks after confirmed initial SARS-CoV-2 infection, with no alternative diagnosis
        • Although this definition is intended to standardize research, it corresponds to clinical definitions used for adults
      • Some studies have reported up to 66% of children have symptoms 4 or more weeks from diagnosis; however, studies with a control group suggest 1% to 4% of children may have long COVID-19, depending on age and definition r103r105
      • Limited evidence suggests that symptoms of long COVID-19 have resolved by 5 months in a majority of children r103r105
    • Long COVID symptoms in children may include respiratory, cardiovascular, neurologic, psychologic, and other symptoms r88c147
      • Many symptoms have been reported in children with and without evidence of COVID-19 infection and may be attributable to the pandemic itself (eg, loss of loved ones, changes in schooling, societal disruption, fear of illness and death for self and family, limitations of sports and social activities) r103r105
      • Most commonly reported symptoms that were significantly different from a control group without COVID-19 include: r105
        • Fatigue
        • Loss of smell and/or taste
        • Respiratory difficulties
        • Dizziness
        • Muscle weakness
        • Chest pain
    • Some evidence indicates an increase in incidence of new-onset type 1 diabetes following COVID-19, an increased frequency of diabetic ketoacidosis at time of type 1 diabetes diagnosis, and an increased risk of diabetic ketoacidosis in children with existing diagnosis of type 1 diabetes who have COVID-19 r106r107
  • Indirect complications of coronavirus pandemic are numerous and include, but are not limited to, higher rates of psychiatric morbidities, loss of education, unhealthy lifestyle changes, loss of caregivers, and increased child neglect r108
    • Global estimate of 10.5 million children have lost a parent or caregiver through May 1, 2022 r109r110
      • In the United States, an estimated 228,600 children lost 1 or both parents or primary caregiver grandparent through October 2022, with Black, Hispanic, and Native American children disproportionately affected r110r111
    • American Academy of Pediatrics advocates for policies to keep students safe and physically present in school r112
      • Measures to mitigate risk of COVID-19 spread in schools include:
        • Encouraging vaccination
        • Testing when exposed or symptomatic
        • Isolating when sick
        • Wearing masks
        • Optimizing ventilation and disinfection measures

Prognosis

  • In general, an excellent prognosis is expected for most children diagnosed with COVID-19 r20r61
    • Full recovery in most occurs by 2 weeks after onset of illness, but it may take up to 6 weeks in a minority of children r20r28
  • Overall, children experience less severe illness and fewer acute complications (eg, shock, acute respiratory distress syndrome) than adults, and fewer children require hospital admission r72r113
    • ICU requirements in United States
      • About 20% to 30% of children admitted to hospital require ICU level of care, an ICU admission rate similar to that of adults r113
      • About half of children who require ICU level of care:
        • Have significant underlying comorbidity r108
        • Are aged 12 to 17 years (among children aged 0-17 years) r42
    • Hospitalization requirements in United States
      • Highest rates of hospitalization occur among children younger than 4 years and aged 12 to 17 years r42r114
      • An estimated 2% of pediatric patientsr113 require hospital admission; median length of hospitalization is from 2 to 3 daysr42
  • Severe infection
    • Most children who develop severe infection have underlying comorbid medical conditions (eg, obesity, chronic cardiopulmonary disease, diabetes) r113
    • Most severe cases involve severe respiratory disease (71%) and a minority involve severe cardiac (less than 3%) or cardiopulmonary disease (about 9%) r90
  • Cardiac morbidity
    • Children with severe COVID-19 and reduced left ventricular systolic function
      • Cardiac dysfunction normalizes in approximately 91% of children within 30 days r90
    • Children with MIS-C and coronary artery aneurysm
      • Coronary arteries normalize in approximately 79% of children within 30 days r90
  • Mortality
    • Overall mortality is estimated to be less than 0.04% in children diagnosed with COVID-19 r61r113
    • Mortality is estimated to be approximately 1.6% among children with severe COVID-19 or MIS-C r90
    • Mortality in pediatric patients with COVID-19 appears to be highest among the following groups:
      • Patients aged 10 to 20 years, especially young adults aged 18 to 20 years r115
      • Patients who are Hispanic, Black, and American Indian/Alaska Native r115
      • Patients with significant comorbid underlying medical conditions (eg, chronic lung disease, obesity, neurologic and developmental disorders) r1

Screening and Prevention

Screening

At-risk populations

  • Intent of screening is to identify people infected with COVID-19 who are asymptomatic and do not have known, suspected, or reported exposure to SARS-CoV-2 r52
    • Examples of screening include testing before travel or attending gatherings and serial testing in a facility
    • Rapid antigen tests are ideal for screening due to quick turnaround and correlation with infectious state r52r116

Screening tests

  • Viral nucleic acid amplification test (eg, reverse transcription polymerase chain reaction) performed on upper respiratory specimen
  • Antigen test performed on upper respiratory specimen

Prevention

  • Primary prevention methods
    • Pharmacologic interventions
      • Vaccination r82r117d1
        • Represents a key intervention in prevention of disease in all age groups
        • FDA has approved or granted emergency authorized use of several vaccines in children, and CDC recommends all children aged 6 months and older receive COVID-19 vaccination r82r118
        • Safety and efficacy data among children are reassuring and favorable
          • Although a modest degree of vaccine effectiveness against infection is also reported, data suggest that vaccination is highly effective in preventing serious COVID-19 illness including severe disease, hospitalization, and death r42r82
            • Hospitalization rates were about 10 times higher among unvaccinated adolescents during period of Delta SARS-CoV-2 variant predominance r114
            • Among pediatric patients requiring hospitalization, ICU admission requirement remained stable during period of Delta SARS-CoV-2 variant predominance r114
          • High degree of protection against emergency department visits, hospitalizations, and critical illness remains even against Omicron subvariants r119
          • Data suggest that monovalent booster dose broadens and strengthens protection against Omicron and other SARS-CoV-2 variants r119
            • Data are limited regarding clinical effectiveness of bivalent booster in children, as this was authorized August 31, 2022 for individuals aged 12 years and older, October 12, 2022 for children aged 5 to 11 years, and December 8, 2022 for children aged 6 months through 5 years
            • Duration of immunity following booster doses is not yet known
          • Reported adverse effects are mild and self-limited; most common adverse effect is sore arm r82
          • Myocarditis has been reported following vaccination
            • Risk of myocarditis from COVID-19 (or MIS-C) is dramatically higher than that from vaccine r93
            • Risk of vaccine-associated myocarditis may be decreased by lengthening interval between first and second doses to 8 weeks r82
            • Risk appears highest in males aged 12 to 39 years and seems to be higher after Moderna vaccination than Pfizer r82
        • Vaccine uptake data in United States
          • Data show that uptake of vaccine is significantly lower for younger children than for adolescents
            • Estimated uptake data in United States as of October 19, 2022, by age group r6
              • Children who have had at least 1 primary dose:
                • Younger than 2 years: 5.4%
                • 2 to 4 years: 8.2%
                • 5 to 11 years: 38.7%
                • 12 to 17 years: 71.2%
              • Children who have completed primary series:
                • Younger than 2 years: 1.9%
                • 2 to 4 years: 3.5%
                • 5 to 11 years: 31.6%
                • 12 to 17 years: 60.9%
              • Eligible children who have received a booster dose:
                • 5 to 11 years: 15.8%
                • 12 to 17 years: 29.5%
        • Vaccination after MIS-C r82
          • Experts consider benefits of COVID-19 vaccination outweigh theoretical risk of MIS-like illness or myocarditis for most unvaccinated people, once clinical recovery has been achieved (including return to baseline cardiac function) and at least 90 days have passed since diagnosis of MIS-C
          • Continuing vaccination may also outweigh risks in some patients who developed MIS-C after vaccination was initiated if all of the following criteria are met:
            • MIS-C occurred 90 days or more after most recent dose of vaccine
            • Clinical recovery has been achieved (including return to baseline cardiac function)
            • At least 90 days have passed since diagnosis of MIS-C
          • If MIS-C occurred within 90 days of vaccination, consider:
            • Deferring additional doses
            • Consulting infectious disease specialist, rheumatologist, and/or cardiologist
            • Consulting with Clinical Immunization Safety Assessment COVIDvax project
        • Vaccine-related resources for caregivers and families
          • American Academy of Pediatrics: COVID-19 vaccine campaign toolkitr120 and information on COVID-19 for parentsr71 in English and Spanish
          • CDC: COVID-19 vaccination resources r121
      • Preexposure prophylaxis with monoclonal antibodies r1
        • NIH guidelines recommend use of preexposure anti–SARS-CoV-2 monoclonal antibody tixagevimab-cilgavimab for those aged 12 years and older and weighing 40 kg who are either:
          • Moderately or severely immunocompromised, with potentially inadequate immune response to COVID-19 vaccination, or
          • Unable to be fully vaccinated owing to severe documented adverse reaction to COVID-19 vaccine or vaccine components
        • Available option is tixagevimab-cilgavimab
          • Dose should be repeated every 6 months r1
          • May be given to eligible high-risk patients at least 2 weeks after their last COVID-19 vaccine dose r82
          • Rapidly spreading Omicron subvariants (eg, BQ.1, BQ.1.1, and others) are likely to be resistant to tixagevimab-cilgavimab based on laboratory data
            • Use is still recommended while prevalence is still low; check FDA EUA websiter77, NIH guidelinesr1, and CDC variant proportionsr10 in region to decide whether tixagevimab-cilgavimab is indicated
          • Use is not authorized by FDA in unvaccinated individuals for whom COVID-19 vaccination is recommended
      • Postexposure prophylaxis with monoclonal antibodies
        • Previously, bamlanivimab-etesevimab or casirivimab-imdevimab were used as postexposure prophylaxis for some individuals; however, they have diminished efficacy against the Omicron variant and subvariants, and there are currently no options for postexposure prophylaxis r1
    • Nonpharmacologic interventions for prevention of infection r14r67
      • Proper use of face masks (eg, covering nose and mouth in individuals aged 2 years and older, particularly when physical distancing is not possible or ventilation is poor)
      • Testing (eg, polymerase chain reaction, antigen) is recommended for everyone with symptoms that may be from COVID-19, for those with exposure, and for screening (eg, before gatherings, for certain workplaces, some travel destinations) r52
      • Following a known exposure, individuals should wear mask for 10 days, monitor for symptoms, and get tested
        • Testing should be performed immediately if symptoms develop
        • Testing is recommended on day 6 (where day 0 is day of last exposure to someone with COVID-19) regardless of symptoms; if negative, continue to mask until day 10
          • For household members, day 0 ("last exposure") starts when patient has completed isolation
      • Physical distancing
      • Improve ventilation
      • Diligent hand and cough hygiene
        • Recommend supervised use of hand sanitizers for young children. Keep hand sanitizers containing alcohol out of their reach; ingesting a small amount can cause significant toxicity
        • Avoid touching face and mucous membranes
      • Disinfect frequently touched surfaces
      • Hospital protocols include: r40
        • Personal protective equipment for providers: N95 masks, eye shields, gowns, and gloves
        • Engineering measures: negative pressure and air filtering
        • Masks for patients if transport is required
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