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CME

COVID-19 and Pediatric Patients

Overview

  • about 2% of confirmed COVID-19 cases reported in cohort studies from China and United States were in children and adolescents
  • most commonly reported symptoms in children are similar to those of other viral respiratory infections
    • fever
    • cough
    • nasal congestion
    • rhinorrhea
    • sore throat
  • other reported symptoms include diarrhea, vomiting, fatigue, headache, poor appetite, and shortness of breath
  • mild respiratory disease reported in about half of children with confirmed or suspected COVID-19, and another reported 30% have moderate respiratory disease
  • multisystem inflammatory syndrome in children (MIS-C) is a new syndrome being reported in small number of children during the COVID-19 pandemic
    • syndrome has features similar to other pediatric inflammatory conditions including Kawasaki disease
    • children often require intensive care
  • testing and screening for COVID-19
  • management of pediatric patients with COVID-19
    • decision to admit pediatric patient with mild-to-moderate COVID-19 should be made on case-by-case basis
    • currently there are no approved antiviral drugs for COVID-19; FDA has issued Emergency Use Authorization for use of remdesivir for treatment of suspected or confirmed COVID-19 in children and adults hospitalized with severe disease
    • supportive care may help to relieve symptoms and should include support of vital organ functions in severe cases; see COVID-19 (Novel Coronavirus) for guidance on supportive management and additional investigational therapies
    • professional organizations provide initial guidance for management of neonates born to mothers with COVID-19
  • 42 deaths among children with confirmed COVID-19 reported by state health departments in United States as of May 27, 2020
  • infection control
    • pediatric population likely contributes to transmission of COVID-19 in the community due to the higher prevalence of mild and asymptomatic disease; children, with help from parents, can adopt measures to slow spread of COVID-19 including frequent handwashing and social distancing
    • because of concerns about viral transmission from asymptomatic children, Royal College of Paediatrics and Child Health/British Paediatric Allergy Immunity and Infection Group (RCPCH/BPAIIG) recommends only performing oropharynx exam in children if essential and, if considered essential, using personal protective equipment even if child does not have symptoms consistent with COVID-19
  • health maintenance for all children during pandemic
    • American Academy of Pediatrics (AAP) strongly supports continued provision of health care for children during the COVID-19 pandemic
      • pediatricians should work with families to ensure that all children (of any age) are current on immunizations and regular well-visits
        • identify children who have missed well-child visits or recommended immunizations
        • contact families of these children to schedule in person appointments
        • get children back on schedule as quickly as possible
      • telehealth may be used for acute or chronic care and also for well visits, provided components of the exam are completed in person in the clinic when circumstances allow
    • existing mental health problems in children may worsen during pandemic, and children who rely on receiving mental health services in the school setting may be particularly vulnerable due to school closures

General Information

Description

  • global pandemic of acute respiratory disease caused by novel coronavirus (SARS-CoV-2) (CDC 2020)
  • PubMed32123347Nature microbiologyNat Microbiol2020040154536-544536SARS-CoV-2 is a member of beta genus coronaviruses closely related to SARS-COV (Nat Microbiol 2020 Apr;5(4):536)

Disease Burden in Children

  • organizations monitoring COVID-19 in children and adolescents
    • Coronavirus in Kids (COVKID) Tracking and Education Project compiles epidemiologic surveillance data on COVID-19 in children and adolescents from state health departments in United States including COVID-19 identified cases and intensive care unit (ICU) admissions (Women's Institute for Independent Social Enquiry 2020)
    • Virtual Pediatric Systems compiles hospital-reported data on children and adults with positive COVID-19 test admitted to pediatric ICUs in North America (Virtual Pediatric Systems 2020)
  • fewer cases of COVID-19 reported in children compared to adults
    • PubMed32091533JAMAJAMA202002242.2% of 44,672 confirmed cases reported to Chinese Center for Disease Control and Prevention through February 11, 2020 were in children and adolescents < 19 years old (JAMA 2020 Feb 24 early online)
    • 1.7% of 149,082 confirmed cases of SARS-CoV-2 infection in United States between February 12 and April 2, 2020 were in children and adolescents < 18 years old (median age 11 years) (MMWR Morb Mortal Wkly Rep 2020 Apr 10;69(14):422full-text)
    • reported 1.2% of cases in Italy were in children and adolescents ≤ 18 years old1
    • reported 0.8% of confirmed cases in Spain were in children and adolescents < 18 years old1
  • age distribution of pediatric cases
    • among 44,672 confirmed cases of COVID-19 in China
    • among 149,082 confirmed cases of SARS-CoV-2 infection in United States, 2,572 cases were children and adolescents < 18 years old (median age 11 years, 57% males)
  • for additional information on epidemiology, see COVID-19 (Novel Coronavirus)

Possible Risk Factors

  • exposure to household members with confirmed COVID-19 reported in most pediatric cases of COVID-19 in China1
  • although data are limited, increased risk of infection and/or disease severity might occur in children and adults with underlying health issues including1
    • immunocompromising conditions such as ongoing treatment for cancer
    • serious heart conditions including congenital heart defects
    • chronic lung disease
    • moderate-to-severe asthma
    • severe obesity (body mass index ≥ 40 kg/m2)
    • diabetes
    • chronic kidney disease on dialysis
    • liver disease
  • infants < 1 year old may be at increased risk of severe or critical disease compared to older children1

Etiology and Pathogenesis

Pathogen

  • novel coronavirus clusters with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)
    • genus Betacoronavirus
    • no consensus on exact taxonomic position within subgenus Sarbecovirus
    • species severe acute respiratory syndrome-related coronavirus
    • designated name SARS-CoV-2
    • PubMed32123347Nature microbiologyNat Microbiol20200302Reference - Nat Microbiol 2020 Apr;5(4):536

Transmission

  • SARS-CoV-2 is transmitted person-to-person (CDC 2020 May 22)
    • between close contacts (within 6 feet) via respiratory droplets produced when an infected person coughs or sneezes
    • contact with fomites may be possible, but it is not thought to be the primary route of transmission
    • PubMed32182409The New England journal of medicineN Engl J Med20200317viability of SARS-CoV-2 suggests aerosol and fomite transmission possible
      • median estimated half-life of SARS-CoV-2
        • 6.8 hours on plastic
        • 5.6 hours on stainless steel
        • 3.5 hours on cardboard
        • 1.1 hours in aerosol
        • 0.8 hours on copper
      • stability of SARS-CoV-2 similar to that of SARS-CoV-1
      • PubMed32182409The New England journal of medicineN Engl J Med20200416382161564-15671564Reference - N Engl J Med 2020 Apr 16;382(16):1564
  • SARS-CoV-2 may be spread by people who are not showing symptoms (CDC 2020 May 22)

Pathogenesis

  • pathogenesis of COVID-19 largely unknown, but early studies suggest
    • angiotensin-converting enzyme–related carboxypeptidase (ACE2) receptor used to gain entry to cells
      • ACE2 expressed in cardiopulmonary tissues
      • also expressed in hematopoietic cells such as monocytes and macrophages
    • lymphopenia associated with severe disease
    • T cell apoptosis and exhaustion may contribute to immunopathology
    • cytokine storm may play a role in severe COVID-19
      • cytokine release syndrome contributes to pathology of MERS-CoV and SARS-CoV-1 infections
      • elevated interleukin-6 (IL-6) is associated with ARDS and respiratory failure in patients with COVID-19
      • cytokine storm may activate coagulation cascade leading to thrombotic events
    • PubMed32303591Science (New York, N.Y.)Science20200417Reference - Science 2020 May 1;368(6490):473, J Thromb Haemost 2020 Apr 15 early online
  • significantly reduced gene expression of ACE2 (receptor used by SARS-CoV-2 for host entry) in nasal epithelium of children aged < 10 years compared to older children and adults in cohort study originally designed to study biomarkers of asthma in 305 children and adults (aged 4-60 years; 50% had asthma) (JAMA 2020 May 20 early online)

Clinical Presentation

  • symptoms in children are typically milder than in adults1
  • most children have clinical presentation similar to other respiratory viral infections including1
    • fever
    • cough
    • nasal congestion
    • rhinorrhea
    • sore throat
  • additional signs and symptoms may include1
    • diarrhea
    • nausea and vomiting
    • fatigue
    • headache
    • poor appetite or poor feeding
    • shortness of breath
    • myalgia
  • asymptomatic cases have been reported with prevalence as high as 13% in 1 study, but actual prevalence not known due to lack of routine testing of asymptomatic individuals1
  • Study Summary
    wide spectrum of clinical features and disease severity in children with SARS-CoV-2 infection in China
    Details
    Critical_Care Family_Medicine Immunologic_Disorders Internal_Medicine Pediatrics Primary_Care Pulmonary_Disorderswide spectrum of clinical features and disease severity reported in children with SARS-CoV-2 infection in China (N Engl J Med 2020 Apr 23)03/24/2020 07:02:35 PMstudySummary
    • Cohort StudySystematic Review based on retrospective cohort study and systematic review of observational studies
    • 171 children (median age 6 years, 61% male) with SARS-CoV-2 infection at Wuhan Children's Hospital between January 28, 2020 and February 26, 2020 were evaluated
      • spectrum of illness
        • pneumonia in 111 children (64.9%), of whom 12 had radiologic features of pneumonia without symptoms
        • upper respiratory tract infection in 33 children (19.3%)
        • asymptomatic infection without radiologic features of pneumonia in 27 children (15.8%)
      • clinical features included
        • cough in 48.5%
        • pharyngeal erythema in 46.2%
        • fever in 41.5%
        • tachycardia on admission in 42.1%
        • tachypnea on admission in 28.7%
        • diarrhea in 8.8%
        • fatigue in 7.6%
        • rhinorrhea in 7.6%
        • vomiting in 6.4%
        • nasal congestion in 5.3%
        • oxygen saturation < 92% during hospitalization in 2.3%
      • chest computed tomography findings included
        • ground-glass opacity in 32.7%
        • local patchy shadowing in 18.7%
        • bilateral patchy shadowing in 12.3%
        • interstitial abnormalities in 1.2%
      • blood testing identified lymphopenia < 1.2 × 109 cells/L in 3.5%
      • 3 children required intensive care support and invasive mechanical ventilation (all had co-existing conditions)
      • 1 child died (10-month-old child with intussusception died of multiorgan failure)
      • PubMed32187458The New England journal of medicineN Engl J Med20200318Reference - N Engl J Med 2020 Apr 23;382(17):1663
    • Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Pediatrics Primary_Carewide spectrum of clinical features and disease severity in children with SARS-CoV-2 infection in China (J Formos Med Assoc 2020 Apr 16 early online)04/27/2020 03:24:32 PMsystematic review of 9 observational studies evaluating pediatric patients with COVID-19 or born to mothers with COVID-19 in China between January 2020 and March 15, 2020
      • 7 studies evaluated 93 pediatric patients aged 1 day to 17 years with COVID-19 and 2 studies evaluated 19 neonates born to mothers with COVID-19
      • clinical characteristics in pooled analysis of 7 studies with 93 pediatric patients (52% male) with COVID-19
        • 98% had mild-to-moderate disease (severe or critical disease in 1% each)
        • common symptoms included
          • fever in 59%
          • cough in 46%
          • gastrointestinal symptoms in 12%
        • asymptomatic at presentation in 26%
        • 2 children required intensive care including 1 with complications
      • chest computed tomography findings in pooled analysis of 3 studies with 52 pediatric patients
        • ground glass opacities in 48%
        • patchy consolidations in 31%
        • no lesions in 27%
      • lymphopenia in pooled analysis of 22 children with available laboratory data
        • lymphocyte count < 1,500 cells/mcL in 32%
        • lymphocyte count < 1,000 cells/mcL in 9%
      • pooled analysis of neonates born to mothers with COVID-19 in 2 studies with 19 neonates
        • age 31-39 weeks gestation
        • maternal fever in 83%
        • cesarean section in 89%
        • preterm birth in 53%
        • birth weight < 2,500 g in 47%
        • mean 1 minute Apgar score 9
        • mean 5 minute Apgar score 10
        • no neonates tested positive for SARS-CoV-2
        • no neonatal death reported
      • PubMed32307322Journal of the Formosan Medical Association = Taiwan yi zhiJ Formos Med Assoc20200416Reference - J Formos Med Assoc 2020 Apr 16 early onlinefull-text
      • PubMed32202343Acta paediatrica (Oslo, Norway : 1992)Acta Paediatr20200323similar findings in 2 systematic reviews of symptoms and prognosis in children with COVID-19 in
  • Study Summary
    wide spectrum of clinical features reported in children and adolescents with confirmed SARS-CoV-2 infection in United States
    Details
    Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Pediatrics Primary_Carewide spectrum of clinical features reported in children and adolescents with confirmed SARS-CoV-2 infection in United States (MMWR Morb Mortal Wkly Rep 2020 Apr 10)04/13/2020 09:20:09 AMstudySummary
    • Cohort Study based on cohort study
    • 149,082 confirmed cases of SARS-CoV-2 infection in United States between February 12 and April 2, 2020 were assessed
    • 2,572 cases were in children and adolescents < 18 years old (median age 11 years, 57% males)
      • 32% were aged 15-17 years
      • 27% were aged 10-14 years
      • 15% were aged 5-9 years
      • 11% were aged 1-4 years
      • 15% were < 1 year old
    • prevalence of underlying condition among 345 children and adolescents with available data
      • overall 23%
      • chronic lung disease in 11.6%
      • cardiovascular disease in 7.2%
      • immunosuppression in 2.9%
    • clinical features among 291 children and adolescents with available data
      • ≥ 1 of fever, cough, or shortness of breath in 73%
      • fever in 56%
      • cough in 54%
      • headache in 28%
      • sore throat in 24%
      • myalgia in 23%
      • shortness of breath in 13%
      • diarrhea in 13%
      • nausea or vomiting in 11%
      • runny nose in 7.2%
      • abdominal pain in 5.8%
    • level of care among 745 children and adolescents with available data
      • hospitalization in 19.7% (estimated range 5.7%-20%)
      • admission to intensive care unit in 2% (estimated range 0.5%-2%)
    • level of care among 95 infants < 1 year old with available data
      • hospitalization in 62%
      • admission to intensive care unit in 5.3%
    • prevalence of underlying condition by level of care among 295 children and adolescents with available data
      • 77% for hospitalized children
      • 12% for children not hospitalized
    • 3 deaths reported (cause of death is pending)
    • PubMed32271728MMWR. Morbidity and mortality weekly reportMMWR Morb Mortal Wkly Rep202004106914422-426422Reference - MMWR Morb Mortal Wkly Rep 2020 Apr 10;69(14):422full-text
  • Study Summary
    most children with COVID-19 admitted to pediatric intensive care unit have significant preexisting comorbidities
    Details
    Infectious_Diseases Pediatricsmost children with COVID-19 admitted to pediatric intensive care unit have significant preexisting comorbidities (JAMA Pediatr 2020 May)05/14/2020 08:14:01 AMstudySummary
    • Cohort Study based on cohort study
    • 48 children aged 4.2-16.6 years with COVID-19 admitted to 46 North American pediatric intensive care units between March 14 and April 3, 2020 were identified
    • 83% had preexisting comorbidities including
      • developmental delay and/or genetic anomaly requiring longterm technological support such as tracheostomy in 40%
      • malignancy or immune suppression in 23%
      • obesity in 15%
      • diabetes in 8%
      • seizures in 6%
      • congenital heart disease in 6%
      • sickle cell disease in 4%
      • chronic lung disease in 4%
      • other congenital malformations in 4%
    • 73% presented with respiratory symptoms and 38% required invasive ventilation
    • 1 child required extracorporeal membrane oxygenation
    • 2 children died
    • 15 children remained hospitalized at follow-up on April 10, 2020 including 9 children with severe or critical condition
    • among 33 children discharged at follow-up, median hospital stay was 7 days, and median intensive care unit stay was 5 days
    • PubMed32392288JAMA pediatricsJAMA Pediatr20200511Reference - JAMA Pediatr 2020 May 11 early online
  • see Multisystem Inflammatory Syndrome in children (MIS-C) for case definitions, descriptive reports, and evidence for association with COVID-19
  • skin manifestations
    • Study Summary
      chilblain-like lesions reported in children during COVID-19 pandemic in Spain
      Details
      studySummary
      • Cohort Study based on cohort study
      • 22 children and adolescents with chilblain-like lesions treated at emergency department of children's hospital over 10-day period during peak incidence of COVID-19 in Spain
      • no previous history of rheumatic disease, lupus erythematosus, acrocyanosis, or Raynaud's phenomenon
      • lesions characterized as erythematous to pupuric macules plus swelling on toes and feet (all children) and hands and fingers (3 children)
      • only 1 of 19 children tested had positive SARS-CoV2 test
      • skin symptoms included pruritus (41%) and mild pain (32%)
      • mild respiratory symptoms in 9 children, but none had fever
      • skin biopsy consistent with chilblains in all 6 patients who had biopsy
      • spontaneous resolution or marked improvement in all children at 3-5 weeks follow-up
      • PubMed32386460Pediatric dermatologyPediatr Dermatol20200509Reference - Pediatr Dermatol 2020 May 9 early online
    • chilblain-like lesionsPubMed32374033Pediatric dermatologyPediatr Dermatol20200506 following suspected COVID-19 reported in 4 children in Italy during pandemic (Pediatr Dermatol 2020 May 6 early online)
    • acro-ischemic lesions presenting on toe of 13-year-old boy before development of fever, muscle pain, and headache during pandemic in Italy in case report FIP-IFP 2020 Apr

Multisystem Inflammatory Syndrome in Children (MIS-C)

Overview

  • MIS-C is a new syndrome appearing in children during the COVID-19 pandemic; information about prevalence, risk factors, and clinical course is limited and rapidly evolving1
  • presentation includes, but is not limited to, persistent fever plus elevated inflammatory markers and multiorgan involvement1
  • symptoms of MIS-C may appear weeks after SARS-CoV-2 infection, which may have been asymptomatic, and child and parents may not know that child had been infected1
  • see Management for guidance from Royal College of Paediatrics and Child Health (RCPCH) on monitoring and treating MIS-C

Case Definitions from Professional Organizations

  • Centers for Disease Control and Prevention (CDC) Health Advisory on MIS-C associated with COVID-19
    • report all suspected cases to local, state, or territorial health department
    • case definition for MIS-C aged < 21 years
      • child or adolescent aged < 21 years with presentation consisting of
        • fever ≥ 38 degrees C (≥ 100.4 degrees F) for ≥24 hours
        • laboratory evidence of inflammation
        • clinically severe illness requiring hospitalization
        • ≥ 2 organs involved (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, and neurological)
      • no alternative plausible diagnosis
      • either
        • positive for current or recent SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR), serology, or antigen test
        • COVID-19 exposure during 4 weeks prior to symptom onset
    • some children may also meet partial or full criteria for Kawasaki disease; only report those meeting case definition
    • consider MIS-C in any pediatric death with evidence for SARS-CoV-2 infection
    • laboratory evidence of inflammation includes, but is not limited to
      • elevated
        • C-reactive protein
        • erythrocyte sedimentation rate (ESR)
        • fibrinogen
        • procalcitonin
        • d-dimer
        • ferritin
        • lactic acid dehydrogenase
        • interleukin-6
        • neutrophils
      • reduced lymphocytes
      • low albumin
    • Reference - CDC Health Advisory 2020 May 14
  • World Health Organization (WHO) preliminary case definition for MIS-C
    • children and adolescents aged < 19 years with fever for ≥ 3 days
    • plus any 2 of
      • rash or bilateral conjunctivitis (non-purulent) or signs of mucocutaneous inflammation of mouth, feet, or hands
      • hypotension or shock
      • features of myocardial dysfunction including
        • pericarditis
        • valvulitis
        • coronary abnormalities including abnormal findings on echocardiogram and elevated troponin/N-terminal pro-hormone b-type natriuretic peptide (NT-proBNP)
      • evidence of coagulopathy (abnormal prothrombin time [PT], partial thromboplastin time [PTT], or elevated D-dimers)
      • acute gastrointestinal problems including abdominal pain, diarrhea, and vomiting
    • plus all of
      • elevated markers of inflammation (ESR, C-reactive protein, or procalcitonin)
      • no other obvious cause of inflammation (bacterial sepsis, staphylococcal or streptococcal shock syndromes)
      • evidence of COVID-19 by RT-PCR, antigen test, or serology positive or likely exposure to patients with COVID-19
    • Reference - WHO Scientific Brief 2020 May 15
  • Royal College of Paediatrics and Child Health (RCPCH) guidance for pediatric multisystem inflammatory syndrome temporally associated with COVID-19
    • multisystem inflammatory syndrome is rare, but early recognition by pediatricians is essential
    • refer all stable children to appropriate specialists to ensure prompt treatment; use low threshold for referral to pediatric intensive care unit
    • syndrome shares features of other pediatric inflammatory conditions including
      • Kawasaki disease
      • staphylococcal and streptococcal toxic shock syndromes
      • macrophage activation syndromes
      • bacterial sepsis
    • case definition
      • presents with
        • fever
        • inflammation evidenced by neutrophilia, lymphopenia, and elevated C-reactive protein levels
        • evidence of dysfunction in ≥1 organ (shock, cardiac, respiratory, renal, gastrointestinal, or neurological disorder)
        • additional features may include full or partial criteria for Kawasaki disease
      • other possible microbial cause ruled out (do not delay expert consult while awaiting test results) including
        • bacterial sepsis
        • staphylococcal and streptococcal toxic shock syndromes
        • myocarditis-associated infections such as enterovirus
      • SARS-CoV-2 test may be positive or negative
      • for guidance from RCPCH for managing multisystem inflammatory syndrome, see Management
    • Reference - RCPCH 2020 May 1PDF

Evidence for Association with COVID-19 and Descriptive Reports

  • Study Summary
    SARS-CoV-2 infection associated with outbreak of severe Kawasaki-like disease in children in Italy, characterized by greater cardiac involvement and later age of onset than Kawasaki-like disease prior to epidemic
    Details
    Infectious_Diseases PediatricsSARS-CoV-2 infection associated with outbreak of severe Kawasaki-like disease in children in Italy, characterized by greater cardiac involvement and later age of onset than Kawasaki-like disease prior to epidemic (Lancet 2020 May 13 early online)05/18/2020 01:00:56 PMstudySummary
    • Cohort Study based on cohort study
    • 10 children diagnosed with Kawasaki-like disease at single hospital in Bergamo, Italy between February 17, 2020 and April 20, 2020 (during SARS-CoV-2 epidemic) were compared to 19 children diagnosed with Kawasaki-like disease at same hospital between January 1, 2015 and February 17, 2020 (up to 5 years prior to epidemic)
    • in children diagnosed during epidemic
      • 2 children had SARS-CoV-2 detected by polymerase chain reaction (PCR) testing
      • 8 children had detection of SARS-CoV-2 antibodies (IgM and IgG) using lateral flow chromatographic immunoassay
      • mean date of admission 6 days after fever onset
      • 50% had classic Kawasaki presentation including nonexudative conjunctivitis, hand and feet anomalies (erythema or firm induration), and polymorphic rash; 4 children also had changes to lips or oral cavity (50% presented with incomplete Kawasaki disease [≤ 3 criteria])
      • 50% had infiltrates on chest x-ray
    • comparing children presenting during SARS-CoV-2 epidemic vs. prior to epidemic
      • mean age 7.5 years vs. 3 years (p < 0.001)
      • abnormal echocardiography in 60% vs. 10.5% (p < 0.008)
      • Kawasaki disease shock syndrome (KDSS) in 50% vs. 0% (p = 0.02)
      • macrophage activation syndrome in 50% vs. 0% (p = 0.02)
      • Kobayashi score ≥ 5 in 70% vs. 10% (p = 0.002)
      • need for adjunctive steroid therapy in 80% vs. 16% (p = 0.005)
      • incomplete Kawasaki presentation in 50% vs. 31% (not significant)
    • children presenting during SARS-CoV-2 epidemic had significantly reduced white cell count, lymphocyte count, and platelet count compared to earlier group
    • all children in both groups had favorable response to treatment and complete recovery
    • PubMed32410760Lancet (London, England)Lancet20200513Reference - Lancet 2020 May 13 early online
  • Study Summary
    acute heart failure reported in multisystem inflammatory syndrome in children with confirmed or suspected COVID-19
    Details
    Infectious_Diseases Pediatricsacute heart failure reported in multisystem inflammatory syndrome in children with confirmed or suspected COVID-19 (Circulation 2020 May 17)05/21/2020 03:35:26 PMstudySummary
    • Cohort Study based on cohort study
    • 35 children aged 2-16 years with severe inflammatory state plus either cardiogenic shock or left ventricular dysfunction treated in hospitals in France and Switzerland between March 22, 2020 and April 30, 2020 were included
    • none had underlying cardiac disease; 17% and body mass index > 25
    • SARS-CoV-2 infection confirmed in 88.6%
      • 40% had positive RT-PCR test (nasopharyngeal swab in 12 cases and fecal sample in 2 cases)
      • 86% had positive antibody test
    • 80% presented to intensive care unit with cardiogenic shock requiring IV inotropic drugs; 10 children required veno-arterial extracorporeal membrane oxygenation (V-A ECMO)
    • all children had reduced ejection fraction on echocardiography (< 30% in 10 children and 30%-50% in 25 children)
    • additional signs and symptoms included
      • fever > 38.5 degrees C (101.3 degrees F) and weakness in 100%
      • elevated C-reactive protein, D-dimer, and B-type natriuretic peptide (BNP) or NT-proBNP in 100%
      • vomiting, diarrhea, or abdominal pain in 83%
      • respiratory distress in 65%
      • adenopathy in 60%
      • skin rash in 57%
      • rhinorrhea in 43%
      • meningism in 31%
    • 25 children received IV immunoglobulins
    • at last follow-up, 34 children had been discharged after median hospital stay of 8 days, and 1 child still on ECMO remained hospitalized
    • 71% had complete recovery of left ventricular function at median day 2 after admission
    • 5 children had residual mild to moderate ventricular systolic dysfunction with left ventricular ejection fraction > 45% at median 12 days follow-up
    • PubMed32418446CirculationCirculation20200517Reference - Circulation 2020 May 17 early online
  • Study Summary
    hyperinflammatory syndrome with multiorgan involvement reported in 8 children seropositive for COVID-19
    Details
    Infectious_Diseases Pediatricshyperinflammatory syndrome with multiorgan involvement reported in 8 children seropositive for COVID-19 (Lancet 2020 May)05/14/2020 08:14:44 AMstudySummary
    • Cohort Study based on cohort study
    • 8 children aged 4-14 years with hyperinflammatory shock treated at pediatric intensive care unit in London, United Kingdom over 10-day period
    • all children were previously healthy
    • 4 children had family exposure to COVID-19
    • 7 children were > 75th percentile for weight, and 6 children were of Afro-Caribbean descent
    • features of common clinical presentation
      • persistent fever (38-40 degrees C [100.4-104 degrees F])
      • variable rash
      • peripheral edema
      • conjunctivitis
      • generalized pain in extremities
      • significant diarrhea and vomiting with abdominal pain
      • small pericardial, pleural, and ascitic effusions
      • bright coronary vessels on echocardiography
    • respiratory involvement was minimal, but 7 children required mechanical ventilation for cardiovascular stabilization
    • none tested positive for SARS-CoV-2 on bronchoalveolar lavage or nasopharyngeal aspirates, and no pathological organisms were identified, except for 1 child with adenovirus and enterovirus identified
    • all children were given intravenous immunoglobulin 2 g/kg plus antibiotics including ceftriaxone and clindamycin
    • 1 child died who had developed an arrhythmia with refractory shock that required extracorporeal life support and developed a large cerebrovascular infarct
    • post discharge from pediatric intensive care unit (stay ranged 4-7 days)
      • 2 children (including 1 postmortem) tested positive for SARS-CoV-2, and all 8 children were seropositive for COVID-19
      • 1 child developed giant coronary aneurysm within 1 week of discharge
    • PubMed32386565Lancet (London, England)Lancet20200507Reference - Lancet 2020 May 7 early online
  • New York City (NYC) Health Department reports 145 cases of multi-system inflammatory syndrome meeting NYC reporting criteria in NYC hospitals as of May 17, 2020 (NYC Health 2020 May 18 PDF)
  • Kawasaki disease with concurrent COVID-19 reported in 6-month-old infant presenting with fever and erythematous, blotchy rash in case report (Hosp Pediatr 2020 Apr 7 early online)

Diagnosis

DiagnosisDiagnosis

Who to Test

  • testing and screening for COVID-19 in children is similar to that in the general population, see COVID-19 (Novel Coronavirus) for additional information
  • Centers for Disease Control and Prevention (CDC) recommendations for evaluation of neonates at risk for COVID-19
    • testing is recommended for all neonates born to mothers with confirmed or suspected COVID-19 even if neonate has no signs of infection
      • diagnosis confirmed with detection of SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR) in nasopharynx, oropharynx, or nasal swab samples
      • serologic testing is not recommended to diagnose acute infection in neonates
    • timing of testing
      • for both symptomatic and asymptomatic neonates born to mothers with confirmed or suspected COVID-19, test at approximately 24 hours of age regardless of mother's symptoms
        • if initial test result is negative or not available, repeat test at 48 hours of age
        • for asymptomatic neonates expected to be discharged before 48 hours of age, 1 test can be performed between 24 and 48 hours of age
      • optimal timing of testing is not known
        • false positives may occur due to SARS-CoV-2 RNA contamination from maternal fluids of neonate's nares, nasopharynx, and/or oropharynx
        • false negatives may also occur due to undetectable levels of SARS-CoV-2 RNA such as may occur immediately in cases of exposure immediately after delivery
    • if testing capacity is limited, prioritize testing for
      • neonates with signs suggesting COVID-19
      • neonates with COVID-19 exposure who require higher levels of care with expected prolonged hospitalization (> 48-73 hours depending on delivery type)
    • Reference - Clinical care guidance for evaluation and management of neonates at risk of COVID-19 CDC 2020 May 19

Blood Tests

  • in contrast to adult cases, no consistent leukocyte abnormalities reported in pediatric cases1

Imaging Studies

  • imaging studies alone (chest x-ray or computed tomography [CT]) not recommended for diagnosis of COVID-191
  • imaging findings in children with COVID-191
    • patchy infiltrates on chest x-ray as seen in viral pneumonia
    • nodular ground glass opacities on chest CT
  • imaging studies may be normal in some children with COVID-191
  • Study Summary
    ground-glass opacities evident on chest CT in about one-third of children with SARS-CoV-2 infection
    Details
    studySummary
    • Cohort Study based on retrospective cohort study
    • 171 children (median age 6 years, 61% male) with SARS-CoV-2 infection at Wuhan Children's Hospital between January 28 and February 26, 2020 were evaluated
    • spectrum of illness
      • pneumonia in 64.9% (111 children, of whom 12 had radiologic features of pneumonia without symptoms)
      • upper respiratory tract infection in 19.3% (33 children)
      • asymptomatic infection without radiologic features of pneumonia in 15.8% (27 children)
    • chest CT findings included
      • ground-glass opacity in 32.7%
      • local patchy shadowing in 18.7%
      • bilateral patchy shadowing in 12.3%
      • interstitial abnormalities in 1.2%
    • Reference - N Engl J Med 2020 Mar 18 early online
  • abdominal ultrasound findings consistent with lymphadenopathy and presence of inflammatory fat throughout mesentery with thickening of terminal ileum reported in 8 children with suspected COVID-19 who were initially referred for surgical review due to suspected appendicitis; none had inflamed appendix (Lancet Child Adolesc Health 2020 May 19 early online full-text)

Management

ManagementManagement

Management Overview

  • decision to admit pediatric patient with mild-to-moderate COVID-19 should be made on case-by-case basis1
  • currently no recommended antiviral drugs for COVID-19, but supportive care may help to relieve symptoms and should include support of vital organ functions in severe cases; see COVID-19 (Novel Coronavirus) for guidance on supportive management and investigational therapies
  • experience with investigational therapies in pediatric patients with COVID-19 is very limited
    • Infectious_Diseases PediatricsFDA issues Emergency Use Authorization (EUA) permitting emergency use of remdesivir for treatment of suspected or confirmed COVID-19 in children and adults hospitalized with severe disease (FDA Emergency Use Authorization 2020 May 1)05/06/2020 10:20:56 AMNational Institutes of Health (NIH) guideline on treatment of COVID-19
      • insufficient data to recommend for or against use of specific antivirals or immunomodulatory agents for treatment of children and adolescents with COVID-19 (NIH Grade AIII)
      • if clinical trials are available, enrollment of children should be a priority
      • Reference - NIH 2020 Apr 21
    • characteristics of antivirals under investigation including pediatric dosing can be found in (NIH 2020 May 12)
    • FDA issues Emergency Use Authorization (EUA) permitting emergency use of remdesivir for treatment of suspected or confirmed COVID-19 in children and adults hospitalized with severe disease
      • remdesivir is an investigational direct-acting ribonucleic acid (RNA) polymerase inhibitor
      • severe disease defined as patients with peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air and requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)
      • efficacy based on randomized trial (NIAID ACTT-1 trial) comparing remdesivir vs. placebo in 1,063 adults; in interim analysis (following 606 recoveries)
        • median time to recovery 11 days vs. 15 days (p < 0.001)
        • mortality 8% vs. 11.6% (p = 0.059)
      • dosing and administration
        • administer remdesivir as IV infusion over 30-120 minutes
          • for children and adults weighing ≥ 40 kg: single loading dose of 200 mg on day 1, followed by maintenance dose of 100 mg once daily
          • for children weighing 3.5 kg to < 40 kg: single loading dose of 5 mg/kg on day 1, followed by maintenance dose of 2.5 mg/kg once daily
        • treatment duration based on disease severity and clinical response; treatment recommended for
          • 10 days in patients who require invasive mechanical ventilation or ECMO
          • 5 days in patients who do not require invasive mechanical ventilation or ECMO; up to 10 days of total treatment may be warranted in those who do not demonstrate clinical improvement
      • perform hepatic function testing in all patients prior to starting remdesivir and monitor daily during treatment
        • remdesivir should not be started in patients with alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (ULN) at baseline
        • discontinue treatment if either
          • ALT increases to ≥ 5 times ULN during treatment; may restart when ALT returns to < 5 times ULN
          • ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalized ratio (INR)
      • measure serum creatinine and estimated glomerular filtration rate (eGFR) in all patients before starting therapy; remdesivir not recommended in patients > 28 days old with eGFR < 30 mL/minute or in full-term neonates (≥ 7 days to ≤ 28 days old) with serum creatinine ≥ 1 mg/dL unless potential benefit outweighs potential risk
      • adverse effects may include elevated liver enzymes and infusion-related reactions (such as hypotension, nausea, vomiting, diaphoresis, and/or shivering); provide patients and caregivers with fact sheet
      • Reference - FDA Emergency Use Authorization 2020 May 1, FDA Press Release 2020 May 1, FDA Fact Sheet for Healthcare Providers 2020 May 1
  • complications of COVID-19 appear to be less common in children, but there are reports of severe and critical pediatric cases that may include1
  • Royal College of Paediatrics and Child Health provides guidance on management of pediatric multisystem inflammatory syndrome temporally associated with COVID-19
  • professional organizations provide guidance for management of neonates born to mothers with COVID-19
  • successful treatment of PubMed32320556The New England journal of medicineN Engl J Med20200422late-onset neonatal sepsis in three-week-old boy with COVID-19 reported in case report (N Engl J Med 2020 Apr 22 early online)

Management of Multisystem Inflammatory Syndrome (MIS-C)

  • Royal College of Paediatrics and Child Health guidance on management of pediatric multisystem inflammatory syndrome temporally associated with COVID-19
    • use appropriate personal protective equipment
    • early management and evaluation consists of
      • advanced pediatric life support and supportive management as needed
      • starting empiric antibiotics per local sepsis protocols with blood cultures taken
      • cardiorespiratory monitoring (including blood pressure) with pulse oximetry and (electrocardiogram) ECG monitoring
      • patients may deteriorate quickly, transfer critically unwell patients and those requiring ongoing specialist care to pediatric intensive care unit (PICU)
      • consider early monitoring with 12-lead ECG depending on clinical presentation
      • take additional blood samples for initial testing and save serum in a lavender-top tube for inclusion in research trials
        • full blood count and peripheral smear
        • urea and electrolytes
        • liver function tests
        • blood glucose
        • blood gas with lactate
        • coagulation testing plus fibrinogen
        • D-dimer
        • lactate dehydrogenase (LDH)
        • triglycerides
        • ferritin
        • troponin
        • pro-hormone brain natriuretic peptide (proBNP)
        • creatine kinase
        • vitamin D
        • amylase
        • urinalysis
        • lavender-top tube for serological studies and polymerase chain reaction (PCR) testing
        • blood culture
        • urine and stool culture
        • throat swab culture
        • nasopharyngeal or throat swab for respiratory panel plus SARS-CoV-2 testing
        • antistreptolysin O titer (ASOT)
        • SARS-CoV-2 serology if available
        • stool and blood for SARS-CoV-2 PCR
        • pneumococcal, meningococcal, Group A strep, Staph aureus blood PCR
        • Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus, enterovirus blood PCR
        • stool for virology
    • monitoring
      • assess Pediatric Early Warning System (PEWS) hourly and monitor closely with frequent vital signs until stable > 12 hours
      • monitor for signs of cardiovascular or respiratory deterioration
      • monitor for signs of worsening inflammation
        • worsening fever
        • cardiorespiratory deterioration
        • gastrointestinal symptoms that are worsening
        • hepatosplenomegaly or lymphadenopathy that is increasing
        • expanding rash
        • worsening neurological symptoms
        • laboratory signs of increasing inflammation
          • decreasing blood cell counts
          • increasing ferritin
          • unexpectedly low or decreasing erythrocyte sedimentation rate (ESR)
          • increasing fibrinogen or new-onset low fibrinogen
        • increasing LDH and liver enzymes including aspartate aminotransferase (AST) and alanine transaminase (ALT)
        • increasing triglycerides
        • increasing D-dimers
        • low serum sodium with worsening renal function
    • general principles for treatment
      • consult early with pediatric intensive care unit and pediatric specialists including infectious disease, immunology, and rheumatology
      • treat all children as suspected COVID-19
      • if disease is mild or moderate, only supportive care is recommended
      • if condition is deteriorating or disease is severe, transfer to PICU
      • management of COVID-19
        • follow local policy for management of COVID-19 or suspected COVID-19 plus empiric or targeted antimicrobial guidelines
        • only offer investigational antiviral therapies in the context of a clinical trial if available
      • consider immunomodulatory therapy on a case-by-case basis and in the context of a trial if available after consult with pediatric infectious disease specialist and/or appropriate specialist (rheumatologist, immunologist, or hematologist)
    • RCPCH 2020 May 13PDF

Management of Neonates with Suspected COVID-19

  • see Who to test for guidance from professional organizations for testing of neonates born to mothers with suspected COVID-19
  • Centers for Disease Control and Prevention (CDC) management considerations for neonates at risk for COVID-19
    • transmission routes of SARS-CoV-2 to neonates
      • transmission to neonates is thought to occur via respiratory droplets during postnatal period when neonates are exposed to individuals with COVID-19 including mothers, caregivers, and hospital personnel
      • cases of possible intrapartum or peripartum transmission have been reported, but clinical significance of these limited reports is unclear
    • infection control
      • consider all neonates born to mothers with confirmed or suspected COVID-19 as having suspected COVID-19 when testing results are not available
      • isolate neonates with suspected COVID-19 from other healthy neonates and provide care per CDC guidance for infection prevention and control for patients with suspected or confirmed COVID-19 in healthcare settings
    • contact between mother and neonate
      • to reduce risk of transmission to neonate, strongly consider temporary separation of neonate from mother with confirmed or suspected COVID-19
      • ways to maintain adequate separation in hospital setting
        • use of a separate room
        • use of temperature-controlled isolette in mother's room
        • maintaining ≥ 6 feet between mother and neonate
      • if test results for mother become known and are negative, separation precautions can be stopped
      • risk and benefits of temporary separation should be discussed with mother, and decisions about temporary separation should be made in accordance with her wishes
      • considerations when making decision include
        • clinical condition of mother and neonate; separation may be necessary for neonates at higher risk for severe disease such as those with preterm birth or other medical conditions
        • availability of staffing, space, testing, personal protective equipment
        • results of testing; separation is not necessary if neonate tests positive for SARS-CoV-2
      • measures to minimize risk of transmission if decision is made not to separate neonate from mother
        • use of cloth face covering by mother and strict hand hygiene during all contact with neonate (children aged < 2 years should not use cloth face coverings)
        • implementation of physical barriers such as placing the neonate in temperature-controlled isolette and maintaining ≥ 6 feet distance as much as possible
    • discharge
      • results from SARS-CoV-2 testing are not required if neonate meets clinical criteria for discharge
      • communicate test results to family and outpatient provider
      • neonates with suspected or confirmed COVID-19 should have close follow-up in outpatient setting
    • Reference - Clinical care guidance for evaluation and management of neonates at risk of COVID-19 CDC 2020 May 19
    • additional CDC guidance
      • interim guidance for discontinuing home isolation for persons with COVID-19 (CDC 2020 May 3)
      • interim guidance for breastfeeding and breast milk feeds in the setting of COVID-19 (CDC 2020 May 5)
  • American Academy of Pediatrics initial guidance for management of neonates born to mothers with suspected or confirmed COVID-19
    • if attending delivery from a mother with COVID-19, use personal protective equipment (PPE) including gown, gloves, and either an N95 respiratory mask plus eye protection goggles or an air-purifying respirator with eye protection
    • delayed cord clamping and bathing after delivery
      • continue delayed cord clamping procedures according to usual practice
      • if infection control measures are taken, including maternal use of mask, mother can briefly hold baby during delayed cord clamping if she is able
      • bathe neonates after birth to remove any potential virus on skin surfaces
    • separation of mother and infant
      • although controversial and risk to infant is unknown at this time, the safest option from the perspective of minimizing infection of infant is to temporarily separate mother and infant
      • if mother chooses to not separate from her infant or if rooming-in is necessary because of limited space, following precautions should be taken to minimize risk of postnatal infection
        • maintaining ≥ 6 feet between mother and infant whenever possible
        • use of mask and hand hygiene whenever mother provides hands-on care
        • use of isolette may provide infant with additional protection
    • breastfeeding
      • breastmilk is considered an unlikely source of transmission of SARS-CoV-2
      • breastmilk expressed after appropriate breast and hand hygiene may be fed to infant by unaffected caregiver
      • if mother chooses to nurse infant, she should follow all preventative precautions including use of mask and breast and hand hygiene
    • management of neonate requiring intensive care
      • if possible, admit neonate requiring intensive care to single patient room with potential for negative room pressure
      • if separate room not possible, maintain ≥ 6 feet between neonates and/or use air temperature controlled isolettes (isolettes do not provide same environmental protection as use of negative pressure or air filtration)
      • if infant requires supplemental oxygen at flow > 2 liters per minute (LPM), continuous positive airway pressure or mechanical ventilation, use PPE including gown, gloves, and either an N95 respiratory mask plus eye protection goggles or an air-purifying respirator with eye protection
    • discharge
      • discharge all well neonates based on normal criteria; neonates born to mothers with COVID-19 do not require earlier discharge
      • if SARS-CoV-2 testing is positive but infant is without symptoms of COVID-19
        • frequent outpatient follow-up by phone or in-office should continue through 14 days after birth
        • precautions to prevent spread from infants to caregivers should be implemented including use of masks, glove, hand hygiene
      • if SARS-CoV-2 testing is negative
        • ideally, mother and infant have additional support of healthy caregiver who is not infected
        • take every effort to provide infection-prevention education to all caregivers including written and verbal education with use of interpreter services where appropriate
        • once home, mother should maintain ≥ 6 foot distance for as often as possible and should use a mask and hand hygiene for newborn care until either
          • resolution of fever for 72 hours without use of antipyretics plus > 10 days since appearance of symptoms (or ≥ 10 days since positive screening test in asymptomatic women)
          • 2 consecutive negative SARS-CoV-2 tests from nasopharyngeal swab specimens collected ≥ 24 hours apart
        • other caregivers in the home who have uncertain status should also use same precautions (masks, maintaining ≥ 6 feet, and hand hygiene) for hands-on care of neonate until their status is known
      • if neonate cannot be tested
        • treat as though SARS-CoV-2 positive for 14-day period of observation
        • mother should use same precautions as above
    • visiting neonate admitted to neonatal intensive care unit (NICU)
      • visitation to NICU is limited during COVID-19 pandemic
      • if mother or partner are COVID-19 persons under investigation (unknown status), they should not enter NICU until status is known
      • 2 approaches for determining when a person with COVID-19 is no longer infectious
        • with symptom/time-based strategy, mother can visit if she has both
          • resolution of fever without use of antipyretics for > 72 hours with improving respiratory symptoms
          • ≥ 10 days since symptoms first appeared or since positive screening test in asymptomatic women
        • with test-based strategy, mother can visit if she has negative SARS-CoV-2 test from at least 2 consecutive specimens collected ≥ 24 hours apart
    • Reference - AAP 2020 May 21
  • neonatal outcomes in case series of 18 pregnant women (median gestational age 37 0/7 weeks) in New York City, New York, United States between March 13, 2020 to March 27, 2020
    • 4 women presented with symptomatic infection, 14 women initially asymptomatic and identified as COVID-19 positive after development of symptoms upon admission or early in postpartum or via universal testing for SARS-CoV-2 for all obstetric admissions
    • all infants had Apgar scores ≥ 7 at 1 minute and ≥ 9 at 5 minutes
    • all infants were tested for SARS-CoV-2 via nasopharyngeal swab
      • test result on day of life 0 and follow-up
        • negative in 15 infants on day of life 0
        • unclear in 2 infants on day of life 0 (negative retest on day of life 1-2)
        • indeterminant in 1 infant on day of life 0 (no signs of COVID-19 infection on day of life 6)
    • neonatal intensive care unit admission in 3 infants
      • respiratory distress with concern for sepsis at 37 weeks gestation in 1 infant but negative COVID-19 result
      • prematurity at 34 6/7 weeks in 1 infant
      • evaluation of congenitally diagnosed multicystic dysplastic kidney after delivery at 39 5/7 weeks gestation in 1 infant
    • none of the infants had positive IgG or IgM SARS-CoV-2
    • PubMed32292903American journal of obstetrics & gynecology MFMAm J Obstet Gynecol MFM20200409100118100118Reference - Am J Obstet Gynecol MFM 2020 Apr 9 early onlinefull-text

Prognosis

  • tracking infection, hospitalization, and deaths in children and adolescents
    • Coronavirus in Kids (COVKID) Tracking and Education Project compiles epidemiologic surveillance data from state health departments on COVID-19 in children and adolescents in United States including intensive care unit (ICU) admissions and number of confirmed deaths (Women's Institute for Independent Social Enquiry 2020)
    • Virtual Pediatric Systems compiles hospital-reported data on children and adults with positive COVID-19 test admitted to pediatric ICUs in North America (Virtual Pediatric Systems 2020)
  • data on incubation period for COVID-19 are limited1
    • may extend to 14 days in adults
    • reports of incubation period in children range from 2 to 10 days
  • Study Summary
    mild or moderate respiratory disease reported in almost 90% of children with confirmed or suspected COVID-19
    Details
    Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Pediatrics Primary_Care Pulmonary_Disordersmild or moderate respiratory disease reported in almost 90% of children with confirmed or suspected COVID-19 (Pediatrics 2020 Mar 16 early online)03/30/2020 09:08:49 AMstudySummary
    • Cohort Study based on retrospective cohort study
    • 2,143 children (median age 7 years) with COVID-19 reported to Chinese Center for Disease Control and Prevention (CDC) between January 16 and February 8, 2020 were evaluated
    • 34.1% had laboratory-confirmed COVID-19 and 65.9% had suspected disease
    • severity of disease
      • asymptomatic in 4.4%
      • mild (nonpneumonia upper respiratory infection) in 50.9%
      • moderate (pneumonia without obvious hypoxia) in 38.8%
      • severe (pneumonia with hypoxia) in 5.2%
      • critical (acute respiratory distress syndrome, respiratory failure, shock, encephalopathy, myocardial injury or heart failure, coagulation dysfunction, or acute kidney injury) in 0.6%
    • among 13 critical patients, 7 (53.8%) were < 1 year old
    • PubMed32179660PediatricsPediatrics20200316Reference - Pediatrics 2020 Mar 16 early online
  • Study Summary
    estimated 6% -20% of children with COVID-19 are hospitalized with estimated 0.6% -2% admitted to intensive care unit
    Details
    studySummary
    • Cohort Study based on cohort study
    • 149,082 confirmed cases of SARS-CoV-2 infection in United States between February 12 and April 2, 2020 were assessed
    • 2,572 cases were children and adolescents < 18 years old (median age 11 years, 57% males)
    • level of care in 745 children and adolescents with available data
      • hospitalization in 19.7% (estimated range 5.7%-20%)
      • admission to intensive care unit in 2% (estimated range 0.6%-2%)
    • level of care in 95 infants < 1 year old with available data
      • hospitalization in 62%
      • admission to intensive care unit in 5.3%
    • prevalence of underlying condition by level of care in 295 children and adolescents with available data
      • 77% for hospitalized patients
      • 12% for patients not hospitalized
    • 3 deaths reported (cause of death is pending)
    • PubMed32271728MMWR. Morbidity and mortality weekly reportMMWR Morb Mortal Wkly Rep202004106914422-426422Reference - MMWR Morb Mortal Wkly Rep 2020 Apr 10;69(14):422full-text
  • Study Summary
    multi-organ failure reported in about one fifth of children with COVID-19 admitted to pediatric intensive care unit with invasive ventilation required in about 38%
    Details
    studySummary
    • Cohort Study based on cohort study
    • 48 children aged 4.2-16.6 years with COVID-19 admitted to 46 North American pediatric intensive care units between March 14 and April 3, 2020 were identified
    • 83% had preexisting comorbidities including 40% with developmental delay and/or genetic anomaly requiring longterm technological support such as tracheostomy
    • 61% had targeted therapies including hydroxychloroquine, azithromycin, and remdesivir
    • 11 (23%) children had failure of ≥ 2 organs
    • 18 (38%) children required intubation or tracheostomy ventilation
    • 1 child required extracorporeal membrane oxygenation
    • 2 children died
    • 15 children remained hospitalized at follow-up on April 10, 2020 including 9 children with severe or critical condition
    • among 33 children discharged at follow-up, median hospital stay was 7 days, and median intensive care unit stay was 5 days
    • PubMed32392288JAMA pediatricsJAMA Pediatr20200511Reference - JAMA Pediatr 2020 May 11 early online
  • Study Summary
    elevated inflammatory markers associated with increased risk of admission to intensive care unit in children with COVID-19
    Details
    Infectious_Diseases Pediatricselevated inflammatory markers associated with increased risk of admission to intensive care unit in children with COVID-19 (J Pediatr 2020 May 11)05/29/2020 12:11:10 PMstudySummary
    • Cohort Study based on cohort study
    • 67 children (aged 1 month to 21 years) with COVID-19 treated at children's hospital between March 15 and April 13, 2020 were included
    • 21 children were managed as outpatients, and 46 were hospitalized (72% admitted to general pediatric unit and 28% to pediatric intensive care unit [PICU])
    • compared to children admitted to general pediatric unit, children admitted to PICU had significantly elevated levels of C-reactive protein, procalcitonin, and pro-B type natriuretic peptide
    • asthma and obesity each occurred in 24% of hospitalized children, but neither were significantly associated with increased risk of PICU admission
    • presentation of children admitted to PICU included
      • severe sepsis and septic shock syndromes in 54%
      • acute respiratory distress in 77% including 6 children who required invasive mechanical ventilation for median 9 days
    • among 13 children treated in PICU, 8 children were discharged home after median stay of 7 days, 4 children remained hospitalized on ventilatory support on day 14, and 1 patient with metastatic cancer died
    • PubMed32407719The Journal of pediatricsJ Pediatr20200511Reference - J Pediatr 2020 May 11 early online full-text
  • Study Summary
    ≥ 3 affected lung segments associated with increased likelihood of severe disease in hospitalized children in Wuhan, China
    Details
    studySummary
    • Case-Control Study based on case-control study
    • 8 hospitalized children with severe COVID-19 pneumonia were matched to 35 hospitalized children with non-severe COVID-19 in Wuhan, China
    • most common symptoms in children with severe pneumonia
      • dyspnea in 87.5%
      • fever in 62.5%
      • cough in 62.5%
    • compared to < 3 affected lung segments, ≥ 3 affected lung segments associated with increased likelihood of severe disease (adjusted odds ratio 25, 95% CI 2.5-248.57)
    • PubMed32384397The Pediatric infectious disease journalPediatr Infect Dis J20200506Reference - Pediatr Infect Dis J 2020 May 6 early online

Infection Control

  • see COVID-19 (Novel Coronavirus) for measures to prevent spread of virus in cases of confirmed or suspected COVID-19
  • Royal College of Paediatrics and Child Health/British Paediatric Allergy Immunity and Infection Group (RCPCH/BPAIIG) recommendations for tonsillar exam in children
    • because of concerns about viral transmission from asymptomatic children, oropharynx should not be routinely examined in children
    • if throat exam is essential, use personal protective equipment even if child does not have symptoms consistent with COVID-19
    • Reference - RCPCH 2020 May 13PDF
  • infection control in the community
    • pediatric population likely contributes to transmission of COVID-19 in the community due to the higher prevalence of mild and asymptomatic disease (MMWR Morb Mortal Wkly Rep 2020 Apr 10;69(14):422full-text)
    • children, with help from parents, can adopt measures to slow spread of COVID-19 including frequent handwashing, social distancing, and limiting time with older adults and those with underlying medical conditions (CDC 2020 May 20)
    • additional considerations for young children
      • Centers for Disease Control and Prevention recommends that face masks and cloth face coverings should not be used in children < 2 years old or in anyone who has trouble breathing, or anyone who is unconscious (CDC 2020 May 18)
      • use of alcohol-based hand sanitizers in children
        • children < 6 years old should be supervised when using hand sanitizer
        • although dangerous when ingested by children, it is safe for children to eat with their hands after using hand sanitizer (safe even if they lick their fingers)
        • important to store hand sanitizer out of reach of children
        • calls to Poison Control related to unintentional exposure to hand sanitizer in children have increased since the start of COVID-19 pandemic
        • Reference - FDA 2020 Apr 13

Health Maintenance During Pandemic

  • American Academy of Pediatrics (AAP) strongly supports continued provision of health care for children during the COVID-19 pandemic
    • well-child care should occur in person when possible and within child's medical home in order to establish and maintain continuity of care
    • if telehealth has been successfully implemented to address elements of the well exam, these virtual visits may continue followed by timely in person visit
    • work with families to ensure that all children (of any age) are current on immunizations and regular well-visits
      • identify children who have missed well-child visits or recommended immunizations
      • contact families of these children to schedule in person appointments
      • get children back on schedule as quickly as possible
    • inform families about strategies implemented to assure safety of patients including
      • scheduling well and sick visits at different times in the day
      • use of designated areas for sick patients that are spatially separate from areas used for well visits
      • collaborating with other providers in the community to identify separate locations for providing well visits
    • Reference - AAP 2020 May 8
  • AAP strongly supports use of telehealth to provide appropriate elements of health supervision visits, or acute and chronic care visits by pediatricians, pediatric medical and surgical specialists
    • care should not be unnecessarily delayed, and referrals for subspecialty and surgical care should continue to be made
    • well visits may be conducted via telehealth for children; however, aspects of the exam should be completed in person in the clinic when circumstances allow, including
      • comprehensive physical exam
      • office testing including laboratory testing
      • immunizations
      • hearing, vision, and oral health screening
    • visits with pediatric medical subspecialists and pediatric surgical specialists may occur via telehealth with recognition that some elements of acute or chronic care visit may need to be completed in person
    • Reference - AAP 2020 May 8
  • AAP recommendations for newborn screening during COVID-19
    • follow federal and state guidelines for newborn screening
    • whenever possible, provide care following recommended schedule for preventative pediatric health care (see AAP 2019 Oct PDF for schedule)
    • follow specific state guidance for follow-up of results (for state-specific guidance, see national resource for newborn screening Baby's First Test)
    • Reference - AAP 2020 Apr 15
  • AAP offers suggested considerations for pediatric practices adjusting usual clinical operations during pandemic (AAP 2020 May 4)
  • mental health for children and adolescents during COVID-19 pandemic
    • existing mental health problems may worsen, and new cases may increase due to the public health crisis, social isolation, and economic recession
    • school closures will result in reduced delivery of mental healthcare in school setting
    • school closure will be more disruptive for mental healthcare in certain individuals; adolescents receiving mental health services exclusively in the school setting are more likely to be from lower family income, be part of ethnic or racial minority group, and have public health insurance
    • telemental health services reported to be as effective as in-person services
    • providing mental health services using technology-enabled modalities may help in the short term, but not all clinicians and families have the required technology
    • United States Department of Health and Human Services has allowed a loosening in Health Insurance Portability and Accountability (HIPAA) rules during COVID-19 pandemic to allow clinicians to use previously considered non-HIPPA compliant tools such as Facetime for evaluation and treatment
    • PubMed32286618JAMA pediatricsJAMA Pediatr20200414Reference - JAMA Pediatr 2020 Apr 14 early online

Guidelines and Resources

Guidelines and Resources

Guidelines

International Guidelines

  • World Health Organization (WHO) guideline on clinical management of COVID-19 can be found at WHO 2020 May 27
  • PubMed32032273Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care SocietiesPediatr Crit Care Med20200201212e52-e106e52Surviving Sepsis Campaign international guideline on management of septic shock and sepsis-associated organ dysfunction in children can be found in Pediatr Crit Care Med 2020 Feb;21(2):e52

United States Guidelines

  • Centers for Disease Control and Prevention (CDC)
    • overall interim guidance on coronavirus (COVID-19) can be found at CDC Coronavirus (COVID-19) or in Chinese, Korean, Spanish, Vietnamese
    • evaluation and management
      • interim guidance on evaluating and testing persons for coronavirus disease (COVID-19) can be found at CDC 2020 May 3
      • interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19) can be found at CDC 2020 May 20
      • interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease (COVID-19) can be found at CDC 2020 Feb 12
      • interim considerations for discontinuation of transmission-based precautions and disposition of hospitalized patients with COVID-19 can be found at CDC 2020 Apr 30
      • interim guidance for pediatric healthcare providers can be found at CDC 2020 May 20
      • interim guidance for evaluation and management of neonates at risk of COVID-19 can be found at CDC 2020 May 20
    • infection prevention and control
      • interim infection prevention and control recommendations for patients with suspected or confirmed coronavirus disease 2019 (COVID-19) in healthcare settings can be found at CDC 2020 May 18
      • interim guidance for preventing the spread of coronavirus disease (COVID-19) in homes and residential communities can be found at CDC 2020 May 24 or in Chinese or in Spanish
    • interim guidance for administrators of United States K-12 schools and childcare programs can be found at CDC 2020 Mar 12 or in Chinese, Korean, Spanish, Vietnamese
  • American Academy of Pediatrics (AAP) Committee on Fetus and Newborn, Section on Neonatal Perinatal Medicine, and Committee on Infectious Diseases
    • AAP initial guidance on management of infants born to mothers with confirmed or suspected COVID-19 can be found at AAP 2020 May 21
    • AAP guidance on providing pediatric well-care during COVID-19 can be found at AAP 2020 May 8
    • AAP guidance on necessary use of telehealth during COVID-19 pandemic can be found at AAP 2020 May 8
    • AAP guidance on newborn screening during COVID-19 can be found at AAP 2020 Apr 15
    • AAP guidance related to childcare during COVID-19 can be found at AAP 2020 Apr 15
    • AAP guidance on masks and children during COVID-19 can be found at AAP 2020 Apr 9
  • National Institute of Health (NIH) COVID-19 treatment guideline on special considerations in children can be found at NIH 2020 Apr 21
  • PubMed32270695CirculationCirculation20200409American Heart Association/American Academy of Pediatrics/American Association for Respiratory Care/American College of Emergency Physicians/Society of Critical Care Anesthesiologists/American Society of Anesthesiologists (AHA/AAP/AARC/ACEP/SOCCA/ASA) interim guidance on basic and advanced life support in adults, children, and neonates with suspected or confirmed COVID-19 can be found in Circulation 2020 Apr 9 early online
  • American College of Radiology (ACR) recommendation for use of chest radiography and computed tomography (CT) for suspected COVID-19 infection can be found at ACR 2020 Mar 22
  • PubMed32298480Pediatric dermatologyPediatr Dermatol20200416Hemangioma Investigator Group consensus recommendation on management of infantile hemangiomas during the COVID pandemic can be found in Pediatr Dermatol 2020 Apr 16 early online

United Kingdom Guidelines

  • Royal College of Paediatrics and Child Health (RCPCH) COVID-19 guidance on pediatric services can be found at RCPCH 2020 Apr 20PDF
  • Royal College of Paediatrics and Child Health (RCPCH) guidance on pediatric multisystem inflammatory syndrome temporally associated with COVID-19 RCPCH 2020 May 1PDF
  • National Institute for Health and Care Excellence (NICE) COVID-19 rapid guideline on children and young people who are immunocompromised can be found at NICE 2020 May:NG174
  • Paediatric Intensive Care Society (PICS) COVID-19

Canadian Guidelines

  • PubMed32287142Anesthesia and analgesiaAnesth Analg20200413Society for Pediatric Anesthesia's Pediatric Difficult Intubation Collaborative and the Canadian Pediatric Anesthesia Society consensus guideline on pediatric airway management in COVID-19 patients can be found in Anesth Analg 2020 Apr 13 early online
  • Public Health Agency of Canada (PHAC) interim guidance on clinical management of patients with moderate to severe COVID-19 can be found at PHAC 2020 Apr 2
  • Canadian Pediatric Society (CPS)
    • position statement on acute management of paediatric coronavirus disease 2019 (COVID-19) can be found at CPS 2020 Apr 20
    • practice point on use of NSAIDs in children when COVID-19 is suspected can be found at CPS 2020 Mar 24
    • practice point on delivery room considerations for infants born to mothers with suspected or proven COVID-19 can be found at CPS 2020 Apr 6
    • practice point on NICU care for infants born to mothers with suspected or proven COVID-19 can be found at CPS 2020 May 12
    • practice point on breastfeeding when mothers have suspected or proven COVID-19 can be found at CPS 2020 Apr 6

European Guidelines

Asian Guidelines

  • PubMed3220475GenomicsGenomics19880701311-71Society of Pediatrics of Hubei standard management guideline on pediatric wards for hematology and oncology during the epidemic of coronavirus disease 2019 can be found in Zhongguo Dang Dai Er Ke Za Zhi 2020 Mar;22(3):177full-text [Chinese]
  • PubMed32238612Indian pediatricsIndian Pediatr20200415574324-334324expert guideline on preparedness and management in the pediatric intensive care unit in resource-limited settings during novel coronavirus 2019 (2019-nCoV) infection can be found in Indian Pediatr 2020 Apr 15;57(4):324
  • expert guideline on respiratory support in the pediatric intensive care unit in resource-limited settings during novel coronavirus 2019 (2019-nCoV) infection can be found in Indian Pediatr 2020 Apr 15;57(4):335

Australian and New Zealand Guidelines

  • Royal Children's Hospital Melbourne (RCH) guidance on COVID-19 can be found at RCH 2020 Apr
  • New Zealand Resuscitation Council (NZRC) guideline on pediatric advanced life support for COVID-19 patients can be found at NZRC 2020 Apr 8 PDF
  • Queensland Health clinical guidelines on

Review Articles

References

General References Used

  1. Centers for Disease Control and Prevention (CDC). Coronavirus Disease 2019 (COVID-19). Information for Pediatric Healthcare Providers. CDC 2020

Recommendation Grading Systems Used

  • National Institutes of Health (NIH) recommendation rating scheme
    • strength of recommendation
      • A - strong recommendation for the statement
      • B - moderate recommendation for the statement
      • C - optional recommendation for the statement
    • quality of evidence for recommendation
      • I - ≥ 1 randomized trials with clinical outcomes and/or validated laboratory endpoints
      • II - ≥ 1 more well-designed, nonrandomized trials or observational cohort studies
      • III - expert opinion
    • Reference - NIH COVID-19 treatment guideline (NIH 2020 Apr 21)

DynaMed Editorial Process

  • DynaMed topics are created and maintained by the DynaMed Editorial Team and Process.
  • All editorial team members and reviewers have declared that they have no financial or other competing interests related to this topic, unless otherwise indicated.
  • DynaMed content includes Practice-Changing Updates, with support from our partners, McMaster University and F1000.

Special Acknowledgements

  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the DynaMed internal Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
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    Deputy Editors are employees of DynaMed and oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T1587144317856, COVID-19 and Pediatric Patients; [updated 2020 Apr 23, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T1587144317856. Registration and login required.

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