Difference between revisions of "COVID-19 associated pediatric complications"

Jump to: navigation, search
(Multisystem Inflammatory Syndrome in Children (MIS-C))
(Multisystem Inflammatory Syndrome in Children (MIS-C))
(4 intermediate revisions by 2 users not shown)
Line 28: Line 28:
  
 
*The 3 most common [[comorbidities]] in children <9 years among a total of 20,458 children<ref name="pmid32555134">{{cite journal| author=Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S | display-authors=etal| title=Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020. | journal=MMWR Morb Mortal Wkly Rep | year= 2020 | volume= 69 | issue= 24 | pages= 759-765 | pmid=32555134 | doi=10.15585/mmwr.mm6924e2 | pmc=7302472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32555134  }} </ref>.  
 
*The 3 most common [[comorbidities]] in children <9 years among a total of 20,458 children<ref name="pmid32555134">{{cite journal| author=Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S | display-authors=etal| title=Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020. | journal=MMWR Morb Mortal Wkly Rep | year= 2020 | volume= 69 | issue= 24 | pages= 759-765 | pmid=32555134 | doi=10.15585/mmwr.mm6924e2 | pmc=7302472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32555134  }} </ref>.  
***Chronic Lung disease [[CLD]] 12.5%
+
**Chronic Lung disease [[CLD]] 12.5%
***Cardiovascular disorder [[CVD]] 2.7%  
+
**Cardiovascular disorder [[CVD]] 2.7%  
***Immunocompromised [[IC]] children 2.1%  
+
**Immunocompromised [[IC]] children 2.1%  
 
*The 3 most common [[comorbidities]] in children 10-19 years among a total of 49,245 children<ref name="pmid32555134">{{cite journal| author=Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S | display-authors=etal| title=Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020. | journal=MMWR Morb Mortal Wkly Rep | year= 2020 | volume= 69 | issue= 24 | pages= 759-765 | pmid=32555134 | doi=10.15585/mmwr.mm6924e2 | pmc=7302472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32555134  }} </ref>.
 
*The 3 most common [[comorbidities]] in children 10-19 years among a total of 49,245 children<ref name="pmid32555134">{{cite journal| author=Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S | display-authors=etal| title=Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020. | journal=MMWR Morb Mortal Wkly Rep | year= 2020 | volume= 69 | issue= 24 | pages= 759-765 | pmid=32555134 | doi=10.15585/mmwr.mm6924e2 | pmc=7302472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32555134  }} </ref>.
***Chronic Lung disease [[CLD]] 18%
+
**Chronic Lung disease [[CLD]] 18%
***Cardiovascular disorder [[CVD]] 2.3%  
+
**Cardiovascular disorder [[CVD]] 2.3%  
***Immunocompromised [IC] children 2.0%  
+
**Immunocompromised [IC] children 2.0%  
  
 
'''ICU and total hospitalization in children'''
 
'''ICU and total hospitalization in children'''
Line 171: Line 171:
 
=== Breastfeeding ===
 
=== Breastfeeding ===
  
*According to the [[CDC]]<ref><https://www.cdc.gov/coronavirus/2019-ncov/hcp/care-for-breastfeeding-women.html></ref>, there is no transmission of the [[SARS CoV-2]] virus from an infected mother to the newborn while breastfeeding. However limited studies are available to yet decide if there is a true transmission risk while breastfeeding.  
+
*According to the [[CDC]]<ref><https://www.cdc.gov/coronavirus/2019-ncov/hcp/care-for-breastfeeding-women.html></ref>, there is no [[transmission]] of the [[SARS CoV-2]] virus from an infected mother to the [[newborn]] while [[breastfeeding]]. However limited studies are available to yet decide if there is a true transmission risk while breastfeeding.  
*[[CDC]] advises all mothers who are positive or suspected to be [[COVID-19]] positive to practice precaution like covering the mouth with a [[face mask]], washing hands with soap and water before and after washing hands.  
+
*[[CDC]] advises all mothers who are [[positive]] or suspected to be [[COVID-19]] positive to practice precaution like covering the mouth with a [[face mask]], washing hands with [[soap]] and [[water]] before and after washing hands.  
*Bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas [[TCGA]] and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression [[FANTOM5 CAGE]] dataset were collected. Ace- 2 receptors are used by the [[coronavirus]] to gain entry into the cells. The [[RNA]] Sequence database found ACE-2 expression in the breast tissue similar to the expression in the lung tissue.<ref name="pmid32094336">{{cite journal| author=Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X | display-authors=etal| title=High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. | journal=Int J Oral Sci | year= 2020 | volume= 12 | issue= 1 | pages= 8 | pmid=32094336 | doi=10.1038/s41368-020-0074-x | pmc=7039956 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32094336  }} </ref>
+
*Bulk [[RNA]]-[[seq]] profiles from two public databases including [[The]] [[Cancer]] [[Genome]] [[Atlas]] [[TCGA]] and [[Functional]] [[Annotation]] of [[The]] [[Mammalian]] [[Genome]] [[Cap]] [[Analysis]] of [[Gene]] [[Expression]] [[FANTOM5]] [[CAGE]] dataset were collected. [[Ace]]-[[2]] receptors are used by the [[coronavirus]] to gain entry into the cells. The [[RNA]] [[Sequence]] database found ACE-2 expression in the [[breast]] [[tissue]] similar to the [[expression]] in the [[lung]] tissue.<ref name="pmid32094336">{{cite journal| author=Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X | display-authors=etal| title=High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. | journal=Int J Oral Sci | year= 2020 | volume= 12 | issue= 1 | pages= 8 | pmid=32094336 | doi=10.1038/s41368-020-0074-x | pmc=7039956 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32094336  }} </ref>
*However, the current data suggest there is one isolated case reported where the breast milk sample was found to be positive for [[COVID-19]] sample on Day 1 and subsequently negative in the day 3 sample. More research needs to be done to conclude if there is any [[transmission]] vis breastfeeding<ref name="pmid32529643">{{cite journal| author=Mahyuddin AP, Kanneganti A, Wong J, Dimri PS, Su LL, Biswas A | display-authors=etal| title=Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2. | journal=Prenat Diagn | year= 2020 | volume=  | issue=  | pages=  | pmid=32529643 | doi=10.1002/pd.5765 | pmc=7307070 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32529643  }} </ref>.
+
*However, the current data suggest there is one isolated case reported where the [[breast]] [[milk]] sample was found to be positive for [[COVID-19]] sample on Day 1 and subsequently [[negative]] in the day 3 sample. More research needs to be done to conclude if there is any [[transmission]] via [[breastfeeding]]<ref name="pmid32529643">{{cite journal| author=Mahyuddin AP, Kanneganti A, Wong J, Dimri PS, Su LL, Biswas A | display-authors=etal| title=Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2. | journal=Prenat Diagn | year= 2020 | volume=  | issue=  | pages=  | pmid=32529643 | doi=10.1002/pd.5765 | pmc=7307070 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32529643  }} </ref>.
  
 
=== Vertical transmission ===
 
=== Vertical transmission ===
Line 269: Line 269:
 
*[[Abdominal pain]]
 
*[[Abdominal pain]]
 
'''Laboratory Findings'''{{cite web |url=https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf |title=www.rcpch.ac.uk |format= |work= |accessdate=}}
 
'''Laboratory Findings'''{{cite web |url=https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf |title=www.rcpch.ac.uk |format= |work= |accessdate=}}
 +
*[[Lymphopenia]]
 +
*[[Neutrophilia]]
 +
*[[Anemia]]
 +
*[[Thrombocytopenia]]
 
*Abnormal fibrinogen
 
*Abnormal fibrinogen
 
*[[High CRP]]
 
*[[High CRP]]
Line 274: Line 278:
 
*[[High Ferritin]]
 
*[[High Ferritin]]
 
*[[Hypoalbuminaemia]]
 
*[[Hypoalbuminaemia]]
*[[Lymphopenia]]
+
*[[Elevated Procalcitonin]]
*[[Neutrophilia]]
 
*Absence of other potential causative organisms.
 
*[[Anemia]]
 
 
*High IL-10
 
*High IL-10
 
*High IL-6
 
*High IL-6
Line 283: Line 284:
 
*Raised LDH
 
*Raised LDH
 
*Raised triglycerides
 
*Raised triglycerides
*Raised troponin
+
*Raised [[troponin]]
*[[Thrombocytopenia]]
+
*Elevated BNP
 +
*Absence of other potential causative organisms.
 
'''Radiological Findings'''{{cite web |url=https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf |title=www.rcpch.ac.uk |format= |work= |accessdate=}}
 
'''Radiological Findings'''{{cite web |url=https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf |title=www.rcpch.ac.uk |format= |work= |accessdate=}}
 
{| border="1" cellpadding="2"
 
{| border="1" cellpadding="2"
Line 325: Line 327:
 
'''Treatment'''
 
'''Treatment'''
 
*All the children with MIS-C are treated as suspected COVID-19.{{cite web |url=https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf |title=www.rcpch.ac.uk |format= |work= |accessdate=}}
 
*All the children with MIS-C are treated as suspected COVID-19.{{cite web |url=https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf |title=www.rcpch.ac.uk |format= |work= |accessdate=}}
 +
*Mild to Moderate cases of MIS-C are managed supportively.
 +
*Fluid resuscitation in 10 ml/kg aliquots with reevaluation after each bolus. Maintain euvolemia. Avoid hypervolemia.
 
*Anti-inflammatory treatments with Intravenous immunoglobulin(IVIG) with or without corticosteroids have shown a good response rate.<ref name="RajapakseDixit2020">{{cite journal|last1=Rajapakse|first1=Nipunie|last2=Dixit|first2=Devika|title=Human and novel coronavirus infections in children: a review|journal=Paediatrics and International Child Health|year=2020|pages=1–20|issn=2046-9047|doi=10.1080/20469047.2020.1781356}}</ref>
 
*Anti-inflammatory treatments with Intravenous immunoglobulin(IVIG) with or without corticosteroids have shown a good response rate.<ref name="RajapakseDixit2020">{{cite journal|last1=Rajapakse|first1=Nipunie|last2=Dixit|first2=Devika|title=Human and novel coronavirus infections in children: a review|journal=Paediatrics and International Child Health|year=2020|pages=1–20|issn=2046-9047|doi=10.1080/20469047.2020.1781356}}</ref>
 
*Aspirin has been used primarily for its antiplatelet effect. It is recommended in all patients with MIS-C.<ref name="RajapakseDixit2020">{{cite journal|last1=Rajapakse|first1=Nipunie|last2=Dixit|first2=Devika|title=Human and novel coronavirus infections in children: a review|journal=Paediatrics and International Child Health|year=2020|pages=1–20|issn=2046-9047|doi=10.1080/20469047.2020.1781356}}</ref>
 
*Aspirin has been used primarily for its antiplatelet effect. It is recommended in all patients with MIS-C.<ref name="RajapakseDixit2020">{{cite journal|last1=Rajapakse|first1=Nipunie|last2=Dixit|first2=Devika|title=Human and novel coronavirus infections in children: a review|journal=Paediatrics and International Child Health|year=2020|pages=1–20|issn=2046-9047|doi=10.1080/20469047.2020.1781356}}</ref>
 +
*Anakinra is considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.
 +
*Tocilizumab is also considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.
 
*Empiric antibiotics like vancomycin, ceftriaxone, and clindamycin are given for community-acquired shock presentation until cultures are negative for 48 hours.
 
*Empiric antibiotics like vancomycin, ceftriaxone, and clindamycin are given for community-acquired shock presentation until cultures are negative for 48 hours.
*Fluid resuscitation in 10 ml/kg aliquots with reevaluation after each bolus. Maintain euvolemia. Avoid hypervolemia.
+
 
*Mild to Moderate cases of MIS-C are managed supportively.
+
{| border="1" cellpadding="2"
 +
!width="225"|Prsentation
 +
!width="225"|Treatment
 +
|-
 +
|Mild Disease || 
 +
*Symptomatic Treatment
 +
|-
 +
|Severe Disease ||
 +
*Symptomatic Treatment
 +
*IVIG(IV)
 +
*Corticosteroids(IV/PO)
 +
*Consider adding Anakinra or Tocilizumamb if fever persist for more than 24 hours post steroids and IVIG use.
 +
|}
  
 
'''Prevention of MIS-C'''
 
'''Prevention of MIS-C'''
Line 348: Line 366:
 
*Toxic shock syndrome
 
*Toxic shock syndrome
 
*Staph Scalded Skin Syndrome
 
*Staph Scalded Skin Syndrome
Kawasaki disease
+
*Kawasaki disease
Rickettsial Illness
+
*Rickettsial Illness
Viral Infections
+
*Viral Infections
Myocarditis
+
*Myocarditis
Serum Sickness.
+
*Serum Sickness.
  
 
=== '''Acute Heart Failure''' ===
 
=== '''Acute Heart Failure''' ===

Revision as of 12:29, 1 July 2020


To go to the COVID-19 project topics list, click here.

COVID-19 Microchapters

Home

Frequently Asked Outpatient Questions

Frequently Asked Inpatient Questions

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating COVID-19 from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Interventions

Surgery

Primary Prevention

Secondary Prevention

Future or Investigational Therapies

Ongoing Clinical Trials

Case Studies

Case #1

COVID-19 associated pediatric complications On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of COVID-19 associated pediatric complications

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on COVID-19 associated pediatric complications

CDC on COVID-19 associated pediatric complications

COVID-19 associated pediatric complications in the news

Blogs on COVID-19 associated pediatric complications

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for COVID-19 associated pediatric complications

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

Overview

Epidemiology and Demographics

  • Less than 2% of the confirmed positive cases of COVID-19 comprise of children less than 19 years of age[4][5].

Incidence

  • Among the 1,761,503 aggregate cases reported to CDC from January 22–May 30, the incidence of confirmed cases was 403.6 cases per 100,000 population[6] [1].
  • Lowest cumulative incidence being in the group of children less than 9 years. (51.1) per 100,000 population.
  • To accurately calculate the incidence of COVID-19 in children a study called Human Epidemiology and Response to SARS-CoV-2 HEROS led by Dr. Hartet is under process and has started enrolling 6000 healthy children as well as children with asthma, allergies from 2000 U.S families across 11 states.[7]


Prevalence

Prevalence of coronavirus in children is less compared to adults as the number of cases are less and most of the cases are with the mild presentation.[8][9]

  • The following data is from CDC Surveillance from January 22 to May 30.[1]

Comorbidities

  • The 3 most common comorbidities in children <9 years among a total of 20,458 children[1].
    • Chronic Lung disease CLD 12.5%
    • Cardiovascular disorder CVD 2.7%
    • Immunocompromised IC children 2.1%
  • The 3 most common comorbidities in children 10-19 years among a total of 49,245 children[1].
    • Chronic Lung disease CLD 18%
    • Cardiovascular disorder CVD 2.3%
    • Immunocompromised [IC] children 2.0%

ICU and total hospitalization in children

  • <9 years of age among 20,458 children[1]
  • 10-19 years of age among 49,245 children[1]
Data of children with different comorbidities as reported by the CDC for a period of January 22 to May 30[1]
Age
Different comorbidities <9 10-19
Underlying medical condition 2896(14.2%) 7123(14.5%)
Cardiovascular disorders 78(2.7%) 164(2.3%)
Chronic lung disease 363(12.5%) 1285(18%)
Renal disease 21(0.7%) 34(0.5%)
Diabetes 12(0.4%) 34(0.5%)
Liver disease 5(0.2%) 19(0.3%)
Immunicompromised 61(2.1%) 146(2.0%)
Neurological disease 41(1.4%) 113(1.6%)
Total cases in the population 1,320,488 20458 49245
Data of children with hospitalized children and ICU admissions as reported by CDC for a period of January 22 to May 30[1]
Age All admissions in the hospital and ICU divided according to associated comorbidity
<9 years (20458 cases) All patients (20458) Among all patients with reported underlying disease (619) Among all patients with no reported underlying disease (2277)
All admissions in the hospital including ICU ICU admissions All admissions in the hospital including ICU ICU admissions All admissions in the hospital including ICU ICU admissions
848/20458 (4.1%) 141/20458 (0.7%) 138/619 (22.3%) 31/619 (5%) 84/2277(3.7%) 116/2277 (0.7%)
10-19 years (49245 cases) All patients (49245) Among all patients with reported

underlying disease (2076)

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

Age

  • According to the data published by CDC for a period of January 22 to May 30[10] [1]
    • The cumulative incidence of COVID-19 cases in children age 0-9 is 51.1 from 20,458 cases.
    • The cumulative incidence of COVID-19 cases in children age 10-19 is 117.3 from 49,245 cases.

Racial predilection to COVID-19

Non-Hispanic American Indian or Alaska Native persons have an age-adjusted hospitalization rate approximately 5 times that of non-Hispanic White persons, while non-Hispanic Black persons and Hispanic or Latino persons each have a rate approximately 4.5 times that of non-Hispanic White persons[11]

Gender

  • According to the data published by CDC for a period of January 22 to May 30[1]
    • The cumulative incidence of COVID-19 cases:
      • Boys age 0-9 years is 52.5 (1.7%) out of 10,743
      • Boys age 10-19 years is 113.4 (3.8%) out of 24,302
      • Girls age 0-9 years is 49.7 (1.4%) out of 9,715
      • Girls age 10-19 years is 121 (3.7%)out of 24,943

Region

Mode of transmission

Breastfeeding

Vertical transmission

  • A study by Marzieh Zamaniyan et all [19] discusses about a pregnant women who developed severe pneumonia with 32 weeks of gestation delivered a healthy pre-term baby without COVID-19 symptoms.
    • The first neonatal nasal swab, vaginal secretion and umbilical cord RT-PCR was negative.
    • However, the second neonate and amniotic sample for RT-PCR tested positive for COVID-19. This study shows more research needs to be done to identify more cases with possible intrauterine infection.
  • Another study documented a possible vertical transmission as increased levels of neonatal Ig M antibodies were found in 3 cases.[20]
    • Seropositivity with IgM antibodies found in neonates needs reflex testing for example - virus neutralization, IgG avidity index, molecular and immunoblotting. A study by Dong E et all[21] discussed decreasing levels of neonatal IgM antibodies in the serum 2 weeks later. So far RT-PCR is the preferred test to docuement for possible vertical transmission.
  • Pregnant women with severe COVID-19 pneumonia were found to have placental inflammation which increases the risk for transplacental infection and pre-term births.[16]
  • Detection of IgM and IL-6 in neonates serum is used as one of the markers for possible transplacental transmission.
  • Some studies which detected the virus hours to days after birth in the nasopharyngeal samples and hence those newborns could have been exposed to the virus after birth via the nosocomial infection.

Presentations

  • Presentation of COVID-19 is less severe in children as compared to adults. Most of the children are asymptomatic.[22]
  • According to CDC, as of April 2, 2020, 1.7% confirmed cases of COVID-19 were reported in children aged <18 years age among the total number of confirmed cases of COVID-19.
  • Illness severity of COVID-19 in children ranges from asymptomatic to critical.
  • The incubation period of SARS-CoV-2 varies from 2 to 14 days with most patients developing symptoms 3 to 7 days after exposure.[22]

Symptoms

  • Fever and Cough are one of the most common symptoms reported in children. One study showed fever is prevalent in 47.5% of children and cough in 41.5% among the 1124 children with COVID-19.According to the CDC, fever, and cough was reported in 56% and 54% of children with COVID 19
  • Dyspnea, nasal congestion, pharyngeal erythema, and sore throat are also common presentations in children.
  • Gastrointestinal symptoms-The gastrointestinal manifestation in COVID-19 positive children are diarrhea, vomiting, abdominal pain, nausea, and anorexia. Children can present with gastrointestinal symptoms in the absence of respiratory symptoms.
  • Cutaneous Findings-The cutaneous findings in COVID-19 positive children range from petechiae to papulovesicular rashes to diffuse urticaria. These appear early in the course of COVID-19 and result secondary to viral replication or circulating cytokines. Many patients with COVID-19 are presenting with chilblains like lesions unrelated to cold. Chilblains are painful or itchy swellings of the toes and fingers, caused by small-vessel inflammation from repeated exposure to cold. A retrospective case series presented 22 children and adolescents with COVID-19 who presented with chillblains lesions. [23][24]
  • Neurological manifestation- The presentation of neurological manifestation in children is rare. However, a case report described a rare case of a 6-week old infant with COVID-19 who had 10-15 seconds episodes of upward gaze and bilateral leg stiffening.[25]
  • Neonates and Infants with COVID-19 are often asymptomatic or present with fever with or without mild cough and congestion.

Clinical Course of COVID-19 in children.

  • Asymptomatic presentation-
    • Children present with no clinical signs or symptoms with normal chest imaging.
    • Among 2143 children with COVID-19 infection 4% of children were asymptomatic.
    • According to one study 14.2% of children were asymptomatic. Another study showed 18% of asymptomatic children with COVID-19.
  • Mild Disease
    • Children present with mild symptoms including fever, fatigue, myalgia, cough.
    • Among 2143 children with COVID-19 infection 51% of children had a mild disease of COVID-19.
    • A study showed 36.3% of children present with a mild form of the disease.

Moderate

Complications

Some of the complications associated with COVID-19 pediatric population are

Multisystem Inflammatory Syndrome in Children (MIS-C)

  • It is a condition that causes inflammation of some parts of the body like heart, blood vessels, kidneys, digestive system, brain, skin, or eyes.
  • According to recent evidence, it is suggested that children with MISC had antibodies against COVID-19 suggesting children had COVID-19 infection in the past.
  • This syndrome appears to be similar in presentation to Kawasaki disease, hence also called Kawasaki -like a disease. It also shares features with staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, and macrophage activation syndromes. "www.rcpch.ac.uk" (PDF).

Pathophysiology

Symptoms"www.rcpch.ac.uk" (PDF).

Emergency Warning Signs

Laboratory Findings"www.rcpch.ac.uk" (PDF).

Radiological Findings"www.rcpch.ac.uk" (PDF).

Test Findings
Chest Xray patchy symmetrical infiltrates, pleural effusion
Echocardiogram and EKG myocarditis, valvulitis, pericardial effusion, coronary artery dilatation
Abdominal USG colitis, ileitis, lymphadenopathy, ascites, hepatosplenomegaly

Diagnosis

Preliminary WHO case definition: Children and adolescents

  • 0–19 years of age with fever >3 days

AND

  • Two of the following:
  1. Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet)
  2. Hypotension or shock
  3. Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP)
  4. Evidence of coagulopathy (by PT, PTT, elevated D-Dimers)
  5. Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain)

AND

AND

AND

  • Evidence of COVID-19 (RT-PCR, antigen test or serology-positive), or likely contact with patients with COVID-19

Treatment

  • All the children with MIS-C are treated as suspected COVID-19."www.rcpch.ac.uk" (PDF).
  • Mild to Moderate cases of MIS-C are managed supportively.
  • Fluid resuscitation in 10 ml/kg aliquots with reevaluation after each bolus. Maintain euvolemia. Avoid hypervolemia.
  • Anti-inflammatory treatments with Intravenous immunoglobulin(IVIG) with or without corticosteroids have shown a good response rate.[27]
  • Aspirin has been used primarily for its antiplatelet effect. It is recommended in all patients with MIS-C.[27]
  • Anakinra is considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.
  • Tocilizumab is also considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.
  • Empiric antibiotics like vancomycin, ceftriaxone, and clindamycin are given for community-acquired shock presentation until cultures are negative for 48 hours.
Prsentation Treatment
Mild Disease
  • Symptomatic Treatment
Severe Disease
  • Symptomatic Treatment
  • IVIG(IV)
  • Corticosteroids(IV/PO)
  • Consider adding Anakinra or Tocilizumamb if fever persist for more than 24 hours post steroids and IVIG use.

Prevention of MIS-C

  • MIS-C can be prevented by reducing the risk of child exposure to COVID-19 infection.

Complications of MIS-C

Prevention of MIS-C

  • MIS-C can be prevented by reducing the risk of child exposure to COVID-19 infection.

Differential Diagnosis of MIS-C MIS-C should be differentiated from other disorders.

  • Bacterial infection/sepsis
  • Toxic shock syndrome
  • Staph Scalded Skin Syndrome
  • Kawasaki disease
  • Rickettsial Illness
  • Viral Infections
  • Myocarditis
  • Serum Sickness.

Acute Heart Failure

Negative effects of lockdown in children

Diagnosis


Most of the children with SARS-CoV-2 infection are either asymptomatic or produce mild symptoms. As asymptomatic patients do not get tested for COVID-19 and are potential carriers for viral transmission, high clinical suspicion is required to prevent such transmissions to a population at risk of developing severe disease. A pediatrician should be cautious to eliminate other causes of respiratory illnesses like seasonal influenza before any diagnostic tests. No diagnostic test is required for a kid with mild illness and no history of exposure to SARS-CoV-2.

Reverse-Transcriptase Polymerase Chain Reaction

U.S. Food and Drug Administration (FDA) has approved real-time Reverse-Transcription Polymerase Chain Reaction (RT-PCR) as the preferred test for diagnosing COVID-19 in children

Lab abnormalities

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

Co-infections

Co-infection with other pathogens were reported in 27% of cases. Some common microorganisms associated with SARS-CoV-2 infection in children are:

Radiological findings

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

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

Management

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

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

As no effective treatment has been approved by the FDA yet, the main goal of managing patients with COVID-19 is to treat the symptoms, provide supportive care, prevent and treat complications, treat underlying diseases and secondary infections, and provide organ function support. Following measures are reported to be crucial in the management of COVID-19[30]

Symptomatic treatment and Supportive Care

Fever should be treated with physical cooling and antipyretics. If the body temperature exceeds 38.5C, antipyretic drugs should be started. Drugs that can be used in children are acetaminophen 10-15 mg/kg and ibuprofen 5-10 mg/kg orally.[30]

Respiratory support

Mechanical Ventilation

Low tidal volume mechanical ventilation is preferred to prevent ventilation related lung injury. Criteria for starting mechanical ventilation[30]

OR

OR

Antibiotics

Antibiotics and antifungals help in reducing symptoms and preventing complications of secondary infections[32]

Corticosteroids

Steroids are used in severe cases and to prevent complications[32]. Any of the following criteria must be met before starting corticosteroid therapy in patients with COVID-19[30]. Intravenous methylprednisolone 1-2mg/kg/day used for 3-5 days. Long-term usage is highly discouraged.

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

OR

OR

OR

Anticoagulation therapy

Convalescent plasma therapy

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

Immunoglobulin therapy

  • Intravenous immunoglobulins (IVIG) can be used in severe cases[32]
  • Dose of 1g/kg/day for 2days or 400mg/kg/day for 8 days is recommended for children
  • More studies are required to support its efficacy and safety in children with COVID-19

Antiviral therapy

Following are the experimental drugs that are being considered to treat children with COVID-19[33]. Various clinical trials are being conducted on the efficacy and safety of these drugs in children with COVID-19.

Interferon-alpha

Inhaled interferon-alpha was the most commonly used antiviral in patients with COVID-19. Reports suggest that it helps in decreasing the viral load, alleviating symptoms and shortening the disease course.[34][35]

Remdesivir

Favipiravir


Prevention

Re-opening of schools

  • The pandemic which started in China in January 2020 and now is all over the world has had a tremendous effect on the everyday life of many however children are the most affected.
  • With the peak of the coronavirus cases being over in many countries like the USA and Europe, there is a dilemma for the school officials about when to reopen schools for children.
  • According to the data collected by the CDC[1] and other articles[41][42] children are affected less compared to adults with asymptomatic to mild COVID-19 symptoms.
  • The challenge faced by the school committees around the world is to decide between the pros and cons of whether to reopen the school with children facing the emotional toll of the lockdown and quarantine. [43]

The CDC guidelines for re-opening schools are as follows [44]

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

Domestic violence in children

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S; et al. (2020). "Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020". MMWR Morb Mortal Wkly Rep. 69 (24): 759–765. doi:10.15585/mmwr.mm6924e2. PMC 7302472 Check |pmc= value (help). PMID 32555134 Check |pmid= value (help).
  2. <Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection in children and adolescents - a systematic review. JAMA Pediatr Rev. 2020. 10.1001/jamapediatrics.2020.1467>
  3. <Dong Y, Mo X, Hu Y, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020. 10.1542/peds.2020-0702>
  4. <Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection in children and adolescents - a systematic review. JAMA Pediatr Rev. 2020. 10.1001/jamapediatrics.2020.1467>
  5. <Dong Y, Mo X, Hu Y, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020. 10.1542/peds.2020-0702>
  6. <http://dx.doi.org/10.15585/mmwr.mm6924e2>
  7. <https://www.niaid.nih.gov/news-events/study-determine-incidence-novel-coronavirus-infection-us-children-begins>
  8. <Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection in children and adolescents - a systematic review. JAMA Pediatr Rev. 2020. 10.1001/jamapediatrics.2020.1467>
  9. <Dong Y, Mo X, Hu Y, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020. 10.1542/peds.2020-0702>
  10. <http://dx.doi.org/10.15585/mmwr.mm6924e2>
  11. <https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html>
  12. <https://coronavirus.jhu.edu/map.html
  13. <https://coronavirus.jhu.edu/map.html
  14. <Hui DS, Zumla A. Severe Acute Respiratory Syndrome: Historical, Epidemiologic, and Clinical Features. Infectious Disease Clinics. 2019 Dec 1;33(4):869-89>
  15. Rasmussen SA, Smulian JC, Lednicky JA, Wen TS, Jamieson DJ (2020). "Coronavirus Disease 2019 (COVID-19) and pregnancy: what obstetricians need to know". Am J Obstet Gynecol. 222 (5): 415–426. doi:10.1016/j.ajog.2020.02.017. PMC 7093856 Check |pmc= value (help). PMID 32105680 Check |pmid= value (help).
  16. 16.0 16.1 16.2 Mahyuddin AP, Kanneganti A, Wong J, Dimri PS, Su LL, Biswas A; et al. (2020). "Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2". Prenat Diagn. doi:10.1002/pd.5765. PMC 7307070 Check |pmc= value (help). PMID 32529643 Check |pmid= value (help).
  17. <https://www.cdc.gov/coronavirus/2019-ncov/hcp/care-for-breastfeeding-women.html>
  18. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X; et al. (2020). "High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa". Int J Oral Sci. 12 (1): 8. doi:10.1038/s41368-020-0074-x. PMC 7039956 Check |pmc= value (help). PMID 32094336 Check |pmid= value (help).
  19. Zamaniyan M, Ebadi A, Aghajanpoor S, Rahmani Z, Haghshenas M, Azizi S (2020). "Preterm delivery, maternal death, and vertical transmission in a pregnant woman with COVID-19 infection". Prenat Diagn. doi:10.1002/pd.5713. PMC 7264605 Check |pmc= value (help). PMID 32304114 Check |pmid= value (help).
  20. Zeng H, Xu C, Fan J, Tang Y, Deng Q, Zhang W; et al. (2020). "Antibodies in Infants Born to Mothers With COVID-19 Pneumonia". JAMA. doi:10.1001/jama.2020.4861. PMC 7099444 Check |pmc= value (help). PMID 32215589 Check |pmid= value (help).
  21. Dong L, Tian J, He S, Zhu C, Wang J, Liu C; et al. (2020). "Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn". JAMA. doi:10.1001/jama.2020.4621. PMC 7099527 Check |pmc= value (help). PMID 32215581 Check |pmid= value (help).
  22. 22.0 22.1 Chen ZM, Fu JF, Shu Q, Chen YH, Hua CZ, Li FB; et al. (2020). "Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus". World J Pediatr. 16 (3): 240–246. doi:10.1007/s12519-020-00345-5. PMC 7091166 Check |pmc= value (help). PMID 32026148 Check |pmid= value (help).
  23. Diotallevi, Federico; Campanati, Anna; Bianchelli, Tommaso; Bobyr, Ivan; Luchetti, Michele Maria; Marconi, Barbara; Martina, Emanuela; Radi, Giulia; Offidani, Annamaria (2020). "Skin involvement in SARS‐CoV‐2 infection: Case series". Journal of Medical Virology. doi:10.1002/jmv.26012. ISSN 0146-6615.
  24. Andina, David; Noguera‐Morel, Lucero; Bascuas‐Arribas, Marta; Gaitero‐Tristán, Jara; Alonso‐Cadenas, José Antonio; Escalada‐Pellitero, Silvia; Hernández‐Martín, Ángela; Torre‐Espi, Mercedes; Colmenero, Isabel; Torrelo, Antonio (2020). "Chilblains in children in the setting of COVID‐19 pandemic". Pediatric Dermatology. 37 (3): 406–411. doi:10.1111/pde.14215. ISSN 0736-8046.
  25. Dugue, Rachelle; Cay-Martínez, Karla C.; Thakur, Kiran T.; Garcia, Joel A.; Chauhan, Lokendra V.; Williams, Simon H.; Briese, Thomas; Jain, Komal; Foca, Marc; McBrian, Danielle K.; Bain, Jennifer M.; Lipkin, W. Ian; Mishra, Nischay (2020). "Neurologic manifestations in an infant with COVID-19". Neurology. 94 (24): 1100–1102. doi:10.1212/WNL.0000000000009653. ISSN 0028-3878.
  26. 26.0 26.1 26.2 26.3 26.4 26.5 Eastin, Carly; Eastin, Travis (2020). "Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China". The Journal of Emergency Medicine. 58 (4): 712–713. doi:10.1016/j.jemermed.2020.04.006. ISSN 0736-4679.
  27. 27.0 27.1 Rajapakse, Nipunie; Dixit, Devika (2020). "Human and novel coronavirus infections in children: a review". Paediatrics and International Child Health: 1–20. doi:10.1080/20469047.2020.1781356. ISSN 2046-9047.
  28. 28.0 28.1 Belhadjer, Zahra; Méot, Mathilde; Bajolle, Fanny; Khraiche, Diala; Legendre, Antoine; Abakka, Samya; Auriau, Johanne; Grimaud, Marion; Oualha, Mehdi; Beghetti, Maurice; Wacker, Julie; Ovaert, Caroline; Hascoet, Sebastien; Selegny, Maëlle; Malekzadeh-Milani, Sophie; Maltret, Alice; Bosser, Gilles; Giroux, Nathan; Bonnemains, Laurent; Bordet, Jeanne; Di Filippo, Sylvie; Mauran, Pierre; Falcon-Eicher, Sylvie; Thambo, Jean-Benoît; Lefort, Bruno; Moceri, Pamela; Houyel, Lucile; Renolleau, Sylvain; Bonnet, Damien (2020). "Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic". Circulation. doi:10.1161/CIRCULATIONAHA.120.048360. ISSN 0009-7322.
  29. <Posttraumatic stress disorder (PTSD) in parents and youth after health-related disasters. Sprang G, Silman M Disaster Med Public Health Prep. 2013 Feb; 7(1):105-10.>
  30. 30.0 30.1 30.2 30.3 Shen K, Yang Y, Wang T, Zhao D, Jiang Y, Jin R; et al. (2020). "Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement". World J Pediatr. doi:10.1007/s12519-020-00343-7. PMC 7090771 Check |pmc= value (help). PMID 32034659 Check |pmid= value (help).
  31. Sankar J, Dhochak N, Kabra SK, Lodha R (2020). "COVID-19 in Children: Clinical Approach and Management". Indian J Pediatr. 87 (6): 433–442. doi:10.1007/s12098-020-03292-1. PMC 7183927 Check |pmc= value (help). PMID 32338347 Check |pmid= value (help).
  32. 32.0 32.1 32.2 Zhang L, Peres TG, Silva MVF, Camargos P (2020). "What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases". Pediatr Pulmonol. doi:10.1002/ppul.24869. PMC 7300763 Check |pmc= value (help). PMID 32519809 Check |pmid= value (help).
  33. Deniz M, Tapısız A, Tezer H (2020). "Drugs being investigated for children with COVID-19". Acta Paediatr. doi:10.1111/apa.15399. PMC 7300686 Check |pmc= value (help). PMID 32506621 Check |pmid= value (help).
  34. Wang BX, Fish EN (2019). "Global virus outbreaks: Interferons as 1st responders". Semin Immunol. 43: 101300. doi:10.1016/j.smim.2019.101300. PMC 7128104 Check |pmc= value (help). PMID 31771760.
  35. Chen L, Shi M, Deng Q, Liu W, Li Q, Ye P; et al. (2020). "Correction: A multi-center randomized prospective study on the treatment of infant bronchiolitis with interferon α1b nebulization". PLoS One. 15 (4): e0231911. doi:10.1371/journal.pone.0231911. PMC 7147733 Check |pmc= value (help). PMID 32275690 Check |pmid= value (help).
  36. Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A; et al. (2020). "Compassionate Use of Remdesivir for Patients with Severe Covid-19". N Engl J Med. 382 (24): 2327–2336. doi:10.1056/NEJMoa2007016. PMC 7169476 Check |pmc= value (help). PMID 32275812 Check |pmid= value (help).
  37. Dörnemann J, Burzio C, Ronsse A, Sprecher A, De Clerck H, Van Herp M; et al. (2017). "First Newborn Baby to Receive Experimental Therapies Survives Ebola Virus Disease". J Infect Dis. 215 (2): 171–174. doi:10.1093/infdis/jiw493. PMC 5583641. PMID 28073857.
  38. Campbell CH (1967). "Effect of incubation temperature and serum content in agar overlay on plaque production by foot-and-mouth disease virus". Can J Comp Med Vet Sci. 31 (10): 251–5. PMC 1494743. PMID 04292899.
  39. 39.0 39.1 Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J; et al. (2020). "Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study". Engineering (Beijing). doi:10.1016/j.eng.2020.03.007. PMC 7185795 Check |pmc= value (help). PMID 32346491 Check |pmid= value (help).
  40. 40.0 40.1 Bouazza N, Treluyer JM, Foissac F, Mentré F, Taburet AM, Guedj J; et al. (2015). "Favipiravir for children with Ebola". Lancet. 385 (9968): 603–604. doi:10.1016/S0140-6736(15)60232-X. PMID 25706078.
  41. <Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection in children and adolescents - a systematic review. JAMA Pediatr Rev. 2020. 10.1001/jamapediatrics.2020.1467>
  42. <Dong Y, Mo X, Hu Y, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020. 10.1542/peds.2020-0702>
  43. Fantini MP, Reno C, Biserni GB, Savoia E, Lanari M (2020). "COVID-19 and the re-opening of schools: a policy maker's dilemma". Ital J Pediatr. 46 (1): 79. doi:10.1186/s13052-020-00844-1. PMC 7280677 Check |pmc= value (help). PMID 32517815 Check |pmid= value (help).
  44. <https://www.cdc.gov/coronavirus/2019-ncov/community/schools-childcare/schools.html>
  45. Bressan S, Gallo E, Tirelli F, Gregori D, Da Dalt L (2020). "Lockdown: more domestic accidents than COVID-19 in children". Arch Dis Child. doi:10.1136/archdischild-2020-319547. PMID 32487724 Check |pmid= value (help).

Linked-in.jpg