COVID-19 associated pediatric complications: Difference between revisions

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{{SI}}
''Main article:'' [[COVID-19]]


To go to the COVID-19 project topics list, click '''[[COVID-19 Project Topics|here]]'''.
'''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''
{{COVID-19}}
 
{{CMG}} {{AE}} {{HAR}}; {{AIA}}; {{Asra}} {{Neepa Shah}}
'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''
 
{{CMG}} {{AE}} {{HAR}}; {{Asra}} {{Neepa Shah}}; {{AIA}}
 
'''''Synonyms and Keywords:''''' [[Novel human coronavirus infection|Novel coronavirus]], [[COVID-19]], [[COVID-19|Wuhan coronavirus]], coronavirus disease-19, [[COVID-19|coronavirus disease 2019]], [[SARS-CoV-2]], [[COVID-19]], COVID-19, 2019-nCoV, Neonatal COVID-19, Pediatric COVID-19, Multisystem Inflammatory Syndrome in Children.


==Overview==
==Overview==


*Cases of [[COVID-19]] have been reported in children. It ranges from [[asymptomatic]], [[mild]] [[cases]] to [[Multisystem]] [[Inflammatory]] [[Syndrome]] in [[Children]] [[MIS-C]]. There are less cases of [[SARS-CoV 2]] in children compared to adults.
Cases of [[COVID-19]] have been reported in children, yet the prevalence is lower than adults. The presentation of COVID-19 in children ranges from [[asymptomatic]] and [[mild]] cases to the multisystem inflammatory syndrome. Given that [[asymptomatic]] patients may not get tested for [[COVID-19]] and are potential [[carriers]] for viral transmission, high clinical suspicion is required to prevent such transmissions to a population at risk of developing severe disease. A pediatrician should be cautious to exclude other causes of respiratory illnesses like [[seasonal influenza]] before any diagnostic tests. As no effective treatment has been approved by the [[FDA]] yet, the goal of managing patients with [[COVID-19]] is to treat the [[symptoms]], prevent and treat [[complications]], and provide [[supportive care]].
 
==Historical Perspective==
*The [[novel coronavirus]], [[SARS-CoV-2]], is identified as the cause of an outbreak of [[respiratory illness]] first detected in Wuhan, China in late December 2019.
*On January 30, 2020,the [[World Health Organization]]([[WHO]]) declared the outbreak as a Public Health Emergency of International Concern.
*On March 12, 2020, the [[World Health Organization]] declared the [[COVID-19]] outbreak a [[pandemic]].
*Shortly after its discovery, reports of [[COVID-19]] infection in children started surfacing.
 
==Classification==
*'''Asymptomatic presentation'''
**Children present with no clinical signs or [[Symptom|symptoms]] with normal chest imaging.
** Among 2,143 children with [[COVID-19|COVID]]-19 infection 4% of children were [[asymptomatic]].
** According to one study, 14.2% of children were asymptomatic. Another study found 18% of asymptomatic children tested positive for [[COVID-19|COVID]]-19.
*'''Mild Disease'''
** Children present with mild symptoms including [[fever]], [[fatigue]], [[myalgia]], [[cough]].
** Among 2,143 children with [[COVID-19|COVID]]-19 infection 51% of children had a mild disease of [[COVID-19|COVID]]-19.
**According to one study, 36.3% of children present with a mild form of the disease.
*'''Moderate'''
** Children present with [[pneumonia]] and symptoms or subclinical disease with abnormal chest imaging.
**Among 2,143 children with [[COVID-19|COVID]]-19 infection 39% of children had a moderate presentation.<ref name="EastinEastin2020">{{cite journal|last1=Eastin|first1=Carly|last2=Eastin|first2=Travis|title=Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China|journal=The Journal of Emergency Medicine|volume=58|issue=4|year=2020|pages=712–713|issn=07364679|doi=10.1016/j.jemermed.2020.04.006}}</ref>
*'''Severe'''
**Children present with [[dyspnea]], [[central cyanosis]], [[hypoxia]].<ref name="EastinEastin2020">{{cite journal|last1=Eastin|first1=Carly|last2=Eastin|first2=Travis|title=Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China|journal=The Journal of Emergency Medicine|volume=58|issue=4|year=2020|pages=712–713|issn=07364679|doi=10.1016/j.jemermed.2020.04.006}}</ref>
**Among 2,143 children with [[COVID-19|COVID]]-19 infection 5% of children had a severe presentation.<ref name="EastinEastin2020">{{cite journal|last1=Eastin|first1=Carly|last2=Eastin|first2=Travis|title=Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China|journal=The Journal of Emergency Medicine|volume=58|issue=4|year=2020|pages=712–713|issn=07364679|doi=10.1016/j.jemermed.2020.04.006}}</ref>
** 2.1% of children present with a severe form of [[COVID-19|COVID]]-19 disease.
** Children with underlying comorbidities are more susceptible to developing severe [[COVID-19|COVID]]-19 symptoms.
*'''Critical'''
**Children present with [[acute respiratory distress syndrome]](ARDS), [[respiratory failure]], [[shock]], or [[multi-organ dysfunction]].<ref name="EastinEastin2020">{{cite journal|last1=Eastin|first1=Carly|last2=Eastin|first2=Travis|title=Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China|journal=The Journal of Emergency Medicine|volume=58|issue=4|year=2020|pages=712–713|issn=07364679|doi=10.1016/j.jemermed.2020.04.006}}</ref>
**Among 2,143 children with [[COVID-19|COVID]]-19 infection, 0.6%% of children had a critical presentation.<ref name="EastinEastin2020">{{cite journal|last1=Eastin|first1=Carly|last2=Eastin|first2=Travis|title=Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China|journal=The Journal of Emergency Medicine|volume=58|issue=4|year=2020|pages=712–713|issn=07364679|doi=10.1016/j.jemermed.2020.04.006}}</ref>
 
==Pathophysiology==
 
===Pathogenesis===
* Coronavirus disease 2019 (COVID-19) is caused by, [[SARS-CoV-2]], a novel coronavirus named for the similarity of its [[Symptom|symptoms]] to those caused by the [[severe acute respiratory syndrome]].
*Unlike SARS-CoV, transmission of COVID-19 takes place during the [[Prodrome|prodromal period]] when those infected are mildly ill and are carrying on with their usual activities. This contributes to the spread of [[infection]].
*The [[virus]] [[Infection|infects]] [[epithelial cells]] of the [[Pulmonary alveoli|lung alveoli]] by receptor‐mediated [[endocytosis]] via the [[Angiotensin-converting enzyme|angiotensin‐converting enzyme]] II (ACE-II) as an entry [[Receptor (biochemistry)|receptor]].
 
==== Tropism ====
 
*The virus also relies on the ACE-II receptor not only for [[Host (biology)|host]] cell entry but also for subsequent [[viral replication]].
*High [[Viral load|viral loads]] have been detected in the [[lower respiratory tract]], suggesting that the [[virus]] might have a higher [[Chemical affinity|affinity]] for the [[epithelium]] of the [[lower respiratory tract]] and indicating a need for repeat [[testing]] of the [[Upper respiratory tract|upper]] or [[lower respiratory tract]] samples in the setting of an initial negative result of [[Nasopharynx|nasopharyngeal]] or [[throat]] [[Swabbing|swab]] in a suspected case.
*ACE-II receptors' presence in the extrapulmonary tissues (heart, kidney, endothelium, and intestine) could also explain the multi-organ dysfunction observed in patients.
*ACE-II receptors are also expressed in the oral cavity with a higher level of expression in the tongue than the buccal or gingival tissues. This indicates oral cavity as potentially high risk for [[SARS-CoV-2]] infectious susceptibility.
*ACE-II receptors' high expression on the [[Lumen (anatomy)|luminal]] surface of [[Intestine|intestinal]] [[epithelial cells]] suggests that the [[intestine]] might also be a major entry site for the [[virus]] and that the [[infection]] might have been initiated by consuming food from the Wuhan market (the assumed site of the outbreak).
 
==== Activation of Host Immune Reponses ====
 
* SARS-CoV2 is known to cause a delayed-type I interferon response during the initial phases of infection.
* Infection and viral replication lead to an activation of neutrophils, macrophages, and monocytes. Th1/Th17 induced specific antibodies are produced.
* RNA viruses such as SARS-CoV and MERS are recognized pathogen associated molecular patterns  by endosomal RNA receptors, TLR3 and TLR7 and the cytosolic RNA sensor, RIG-I/MDA5.
*This leads to downstream activation of NF-KB signaling cascade and nuclear translocation of transcription factors, which in turn leads to the production of type 1 interferon pro-inflammatory cytokines.
*Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination.
 
*The main [[pathogenesis]] of COVID-19 is severe [[pneumonia]], RNAemia, combined with the [[incidence]] of ground-glass opacities, and [[Acute (medicine)|acute]] [[Heart|cardiac]] [[injury]].
*As evident from the [[Autopsy|autopsies]] of those [[Infection|infected]] by the [[SARS-CoV]], the extensive [[lung]] damage may be caused by multiple factors, such as:
**High initial virus titers
**Increased [[monocyte]], [[macrophage]], and [[neutrophil]] infiltration in the [[Lung|lungs]]
**Elevated levels of [[serum]] [[proinflammatory]] [[Cytokine|cytokines]] and [[Chemokine|chemokines]]


=== Epidemiology and Demographics ===
===Associated Conditions===


*Less than 2% of the confirmed positive cases of [[COVID-19]] comprise of children less than 19 years of age. <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><ref><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></ref><ref><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></ref>
*The 3 most common [[comorbidities]] in children .  
**[[Chronic Lung disease]]
** [[Cardiovascular disorders]]
** [[Immunocompromised]] children


=== Incidence ===
* [[Co-infection]] with other [[pathogens]] were reported in 27% of cases. Some common [[microorganisms]] associated with [[SARS-CoV-2]] infection in children are:
*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.  <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>
** [[Mycoplasma pneumoniae]]
*Lowest [[cumulative]] [[incidence]] being in the group of children less than 9 years. (51.1) per 100,000 population.
** [[Influenza B virus]]
*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.
** [[Influenza A virus]]
** [[Respiratory syncytial virus]] (RSV)
** [[Cytomegalovirus]] (CMV)
** [[Enterobacter aerogenes]]


==Causes==
* Coronavirus disease 2019 (COVID-19) is caused by [[SARS-CoV-2|severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)]].<ref name="VelavanMeyer2020">{{cite journal|last1=Velavan|first1=Thirumalaisamy P.|last2=Meyer|first2=Christian G.|title=The COVID‐19 epidemic|journal=Tropical Medicine & International Health|volume=25|issue=3|year=2020|pages=278–280|issn=1360-2276|doi=10.1111/tmi.13383}}</ref>
*[[SARS-CoV-2]] belongs to the large family of viruses known as Coronaviruses (CoV).


=== Prevalence ===
==Differentiating COVID-19 in Children from other Diseases==


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


*The following data is from [[CDC]] Surveillance from January 22 to May 30.<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>
* [[Adenovirus]] infection
* [[Chlamydia]] [[pneumoniae]]
* [[Human metapneumovirus]] infection
* [[Influenza]]
* [[Mycoplasma]] [[pneumonia]]
* [[Parainfluenza virus]] infection
* [[Respiratory syncytial virus]] infection
* [[Rhinovirus]] infection
* [[Severe acute respiratory syndrome]] (SARS-Cov-1)


'''Comorbidities'''
==Epidemiology and Demographics==


*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>.
*Less than 2% of the confirmed positive cases of [[COVID-19]] comprise of children less than 19 years of age<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%
**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<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%
**Cardiovascular disorder [[CVD]] 2.3%
**Immunocompromised [IC] children 2.0%


'''ICU and total hospitalization in children'''
=== 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 <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>.
*Lowest [[cumulative]] [[incidence]] being in the group of children less than 9 years. (51.1) per 100,000 population.
*To accurately calculate the [[incidence]] of [[COVID-19]] in children, a study called [[Human]] [[Epidemiology]] and [[Response]] to [[SARS-CoV-2]] [[HEROS]] led by Dr. Hartet is under process and has started enrolling 6000 healthy children as well as children with [[asthma]], [[allergies]] from 2000 U.S families across 11 states.
 
=== Prevalence ===
 
Prevalence of [[coronavirus]] in children is less compared to adults as the number of cases are less and most of the cases are with the [[mild]] presentation.


*<9 years of age among 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>
**Total number of all [[hospitalization]] is 4.1%
**Total number of [[ICU]] admissions is 0.7% 
*10-19 years of age among 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>
**Total number of [[all]] [[hospitalization]] is 2.5%
**Total number of [[ICU]] admissions is 0.4%
{| class="wikitable"
|+
Data of children with different comorbidities as reported by the CDC for a period of January 22 to May 30<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>
!
! colspan="2" |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
|}
{| class="wikitable"
|+Data of children with hospitalized children and ICU admissions as reported by CDC for a period of January 22 to May 30<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>
!Age
! colspan="9" |All admissions in the hospital and ICU divided according to associated comorbidity
|-
! rowspan="3" |<9 years (20458 cases)
! colspan="3" |All patients (20458)
! colspan="3" |Among all patients with reported underlying disease (619)
! colspan="3" |Among all patients with no reported underlying disease (2277)
|-
! colspan="2" |All admissions in the hospital including ICU
!ICU admissions
! colspan="2" |All admissions in the hospital including ICU
!ICU admissions
!All admissions in the hospital including ICU
! colspan="2" |ICU admissions
|-
| colspan="2" |848/20458 (4.1%)
|141/20458 (0.7%)
| colspan="2" |138/619 (22.3%)
|31/619 (5%)
|84/2277(3.7%)
| colspan="2" |116/2277 (0.7%)
|-
! colspan="10" |
|-
! rowspan="3" |10-19 years (49245 cases)
! colspan="2" |All patients (49245)
! colspan="3" |Among all patients with reported
underlying disease (2076)
! colspan="4" |Among all patients with no reported underlying disease (5047)
|-
!All admissions in the hospital including ICU
!ICU admissions
! colspan="2" |All admissions in the hospital including ICU  (2076)
!ICU admissions
! colspan="3" |All admissions in the hospital including ICU (5047)
!ICU admissions
|-
|1234/49245 (2.5%)
|216/49245 (0.4%)
| colspan="2" |309/2076 (14.9%)
|72/2076 (3.5%)
| colspan="2" |115/5047 (2.3%)
| colspan="2" |17/5047 (0.3%)
|}
=== Age ===
=== Age ===


Line 143: Line 123:
**The cumulative [[incidence]] of [[COVID-19]] cases in children age 10-19 is 117.3 from 49,245 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 ===
=== Race ===


[[Non-Hispanic American Indian]] or Alaska Native persons have an age-adjusted hospitalization rate approximately 5 times that of non-Hispanic White persons, while non-Hispanic Black persons and Hispanic or Latino persons each have a rate approximately 4.5 times that of non-Hispanic White persons
[[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
Line 164: Line 144:
*The total number of [[COVID-19]] cases in the [[U.S]] is 2,534,981.
*The total number of [[COVID-19]] cases in the [[U.S]] is 2,534,981.


==Mode of transmission==
==Risk Factors==
*[[SARS-CoV 2]] spreads by [[respiratory]] [[droplets]] within 6 feet from the infected person.
*[[SARS-CoV 2]] spreads by [[respiratory]] [[droplets]] within 6 feet from the infected person.
*Pregnant women with [[COVID- 19]] are at more risk of developing adverse [[obstetric]] and [[perinatal]] outcomes.
*Pregnant women with [[COVID- 19]] are at more risk of developing adverse [[obstetric]] and [[perinatal]] outcomes.
* Most children who were [[COVID-19]] positive were found to have acquired infection from parents and other household contacts.
* Most children who were [[COVID-19]] positive were found to have acquired infection from parents and other household contacts.
* For newborn babies testing positive for the [[COVID-19]] could be infected via [[vertical]] [[transmission]], [[breastfeeding]], or contact with virus-contaminated surfaces
* For newborn babies testing positive for the [[COVID-19]] could be infected via [[vertical]] [[transmission]], [[breastfeeding]], or contact with virus-contaminated surfaces
=== Breastfeeding ===
 
''' Breastfeeding '''


*According to the [[CDC]], 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]], 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.
*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]] 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>.
*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 '''


*A study by Marzieh Zamaniyan et all  discusses about a pregnant women who developed severe [[pneumonia]] with 32 weeks of gestation delivered a healthy [[pre-term]] baby without [[COVID-19]] symptoms.
*A study by Marzieh Zamaniyan et all  discusses about a pregnant women who developed severe [[pneumonia]] with 32 weeks of gestation delivered a healthy [[pre-term]] baby without [[COVID-19]] symptoms.
Line 187: Line 168:
*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.
*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==
==Screening==


* Presentation of COVID-19 is less severe in children as compared to adults. Most of the children are asymptomatic.
* There are no special guidelines [[Medical guideline|guidelines]] in place for the routine [[Screening (medicine)|screening]] for [[coronavirus]] disease 2019 ([[COVID-19]]) in children.
*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.
* The same clinical and non-clinical features related to [[COVID-19]] being used to [[Screening (medicine)|screen]] suspected adults can be used in children and include:<ref name="VelavanMeyer2020">{{cite journal|last1=Velavan|first1=Thirumalaisamy P.|last2=Meyer|first2=Christian G.|title=The COVID‐19 epidemic|journal=Tropical Medicine & International Health|volume=25|issue=3|year=2020|pages=278–280|issn=1360-2276|doi=10.1111/tmi.13383}}</ref>
* Illness severity of [[COVID-19]] in children ranges from [[asymptomatic]] to critical.
**History of international travel (this requirement is actively changing and evolving with time)
*The incubation period of SARS-CoV-2 varies from 2 to 14 days with most patients developing symptoms 3 to 7 days after exposure.<ref name="pmid32026148">{{cite journal| author=Chen ZM, Fu JF, Shu Q, Chen YH, Hua CZ, Li FB | display-authors=etal| title=Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus. | journal=World J Pediatr | year= 2020 | volume= 16 | issue= 3 | pages= 240-246 | pmid=32026148 | doi=10.1007/s12519-020-00345-5 | pmc=7091166 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32026148  }} </ref>
**History of exposure to a confirmed COVID-19 [[patient]]
=== Symptoms ===
**Close contacts of a confirmed COVID-19 [[patient]]
**[[Fever]]
**[[Cough]]
**[[Fatigue]]
**[[Dyspnea|Shortness of breath]]
 
==Natural History, Complications, and Prognosis==
 
===Complications===
 
* [[Multisystem Inflammatory Syndrome in Children (MISC-C)]]
* [[Exacerbation of the underlying conditions]]
* [[Acute Respiratory Distress syndrome]]
* [[Sepsis]]
* [[Septic shock]]
* [[Secondary Bacterial infections]].
* [[Acute Heart Failure]]
* [[Myocarditis]]
* [[Acute Kidney Injury]]


*[[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
====A. Multisystem Inflammatory Syndrome in Children (MIS-C)====
*[[Dyspnea]], [[nasal congestion]], [[Erythema|pharyngeal erythema]], and [[sore throat]] are also common presentations in children.
* To view detailed information on multisystem inflammatory syndrome in children, [[COVID-19-associated_multisystem_inflammatory_syndrome|click here]].<br />
*'''[[Gastrointestinal symptoms]]'''-The gastrointestinal manifestation in [[COVID-19]] positive children are [[diarrhea]], [[vomiting]], [[abdominal pain]], [[nausea]], and [[anorexia]]. Children can present with [[Gastrointestinal disorders and of COVID-19|gastrointestinal]] symptoms in the absence of [[COVID-19 Pulmonary Complications|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.
*'''Neurological manifestation'''- The presentation of neurological manifestation in children is rare. However, a case report described a rare case of a 6-week old infant with COVID-19 who had 10-15 seconds episodes of upward gaze and bilateral leg stiffening.


*[[Neonates]] and [[Infants]] with COVID-19 are often asymptomatic or present with fever with or without mild cough and congestion.  
==== B. Acute Heart Failure ====
*[[Acute Cardiac decompensation]] have been reported in children due to severe inflammatory state following COVID-19 infection. A case series describe 35 children in 14 centers admitted to PICU for [[cardiogenic shock]], [[left ventricular dysfunction]], and severe inflammatory state.
* Treatent with [[immunoglobulin]] is associated with recovery of [[left ventricular systolic function]].<ref name="BelhadjerMéot2020">{{cite journal|last1=Belhadjer|first1=Zahra|last2=Méot|first2=Mathilde|last3=Bajolle|first3=Fanny|last4=Khraiche|first4=Diala|last5=Legendre|first5=Antoine|last6=Abakka|first6=Samya|last7=Auriau|first7=Johanne|last8=Grimaud|first8=Marion|last9=Oualha|first9=Mehdi|last10=Beghetti|first10=Maurice|last11=Wacker|first11=Julie|last12=Ovaert|first12=Caroline|last13=Hascoet|first13=Sebastien|last14=Selegny|first14=Maëlle|last15=Malekzadeh-Milani|first15=Sophie|last16=Maltret|first16=Alice|last17=Bosser|first17=Gilles|last18=Giroux|first18=Nathan|last19=Bonnemains|first19=Laurent|last20=Bordet|first20=Jeanne|last21=Di Filippo|first21=Sylvie|last22=Mauran|first22=Pierre|last23=Falcon-Eicher|first23=Sylvie|last24=Thambo|first24=Jean-Benoît|last25=Lefort|first25=Bruno|last26=Moceri|first26=Pamela|last27=Houyel|first27=Lucile|last28=Renolleau|first28=Sylvain|last29=Bonnet|first29=Damien|title=Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic|journal=Circulation|year=2020|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.120.048360}}</ref>


=== '''Clinical Course of COVID-19 in children.''' ===
==== C. Negative effects of lockdown in children ====


*'''Asymptomatic presentation'''-
*Children less than 10 years in the school develop very important [[language]], [[social]] and [[developmental]] traits with the [[mitigation]] in place these kids are at risk to develop [[anxiety]], [[anger]], and [[post-traumatic stress disorder]].
**Children present with no clinical signs or [[Symptom|symptoms]] with normal chest imaging.
*Children whose parents have either suffered [[economically]] or have [[mental]] [[health]] issues are more prone to [[physical]] and [[mental]] [[abuse]].  
** Among 2143 children with [[COVID-19|COVID]]-19 infection 4% of children were [[asymptomatic]].
*With the schools using digital media to continue classes during [[mitigation]], those kids who are not able to get these devices are [[suffering]] from little to no education in this period of lockdown.
** According to one study 14.2% of children were asymptomatic. Another study showed 18% of asymptomatic children with [[COVID-19|COVID]]-19.
*Children of [[healthcare]] workers are facing a great deal with change in the [[environment]] with a new baby sitter and not being able to interact and hug the parents working in the [[frontline]].
*'''Mild Disease'''
** Children present with mild symptoms including [[fever]], [[fatigue]], [[myalgia]], [[cough]].
** Among 2143 children with [[COVID-19|COVID]]-19 infection 51% of children had a mild disease of [[COVID-19|COVID]]-19.
**A study showed 36.3% of children present with a mild form of the disease.
*'''Moderate'''
** Children present with [[pneumonia]] with symptoms or subclinical disease with abnormal chest imaging.
**Among 2143 children with [[COVID-19|COVID]]-19 infection 39% of children had a moderate presentation.<ref name="EastinEastin2020">{{cite journal|last1=Eastin|first1=Carly|last2=Eastin|first2=Travis|title=Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China|journal=The Journal of Emergency Medicine|volume=58|issue=4|year=2020|pages=712–713|issn=07364679|doi=10.1016/j.jemermed.2020.04.006}}</ref>
*'''Severe'''
**Children present with [[dyspnea]], [[central cyanosis]], [[hypoxia]].<ref name="EastinEastin2020">{{cite journal|last1=Eastin|first1=Carly|last2=Eastin|first2=Travis|title=Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China|journal=The Journal of Emergency Medicine|volume=58|issue=4|year=2020|pages=712–713|issn=07364679|doi=10.1016/j.jemermed.2020.04.006}}</ref>
**Among 2143 children with [[COVID-19|COVID]]-19 infection 5% of children had a severe presentation.<ref name="EastinEastin2020">{{cite journal|last1=Eastin|first1=Carly|last2=Eastin|first2=Travis|title=Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China|journal=The Journal of Emergency Medicine|volume=58|issue=4|year=2020|pages=712–713|issn=07364679|doi=10.1016/j.jemermed.2020.04.006}}</ref>
** 2.1% of children present with a severe form of [[COVID-19|COVID]]-19 disease.
** Children with underlying comorbidities are more susceptible to getting severe [[COVID-19|COVID]]-19 disease.
*'''Critical'''
**Children present with [[acute respiratory distress syndrome]](ARDS), [[respiratory failure]], [[shock]], or [[multi-organ dysfunction]].<ref name="EastinEastin2020">{{cite journal|last1=Eastin|first1=Carly|last2=Eastin|first2=Travis|title=Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China|journal=The Journal of Emergency Medicine|volume=58|issue=4|year=2020|pages=712–713|issn=07364679|doi=10.1016/j.jemermed.2020.04.006}}</ref>
**Among 2143 children with [[COVID-19|COVID]]-19 infection, 0.6%% of children had a critical presentation.<ref name="EastinEastin2020">{{cite journal|last1=Eastin|first1=Carly|last2=Eastin|first2=Travis|title=Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China|journal=The Journal of Emergency Medicine|volume=58|issue=4|year=2020|pages=712–713|issn=07364679|doi=10.1016/j.jemermed.2020.04.006}}</ref>


==Complications==
===Prognosis===
Some of the complications associated with [[COVID-19|COVID]]-19 pediatric population are


*[[Multisystem Inflammatory Syndrome in Children (MISC-C)]]
Most children recover fully from the infection. Few children, however, require hospitalization and ICU admission.
*[[Exacerbation of the underlying conditions]]
*[[Acute Respiratory Distress syndrome]]
*[[Sepsis]]
*[[Septic shock]]
*[[Secondary Bacterial infections]].
*[[Acute Heart Failure]]
*[[Negative effects of lockdown in children]]
*[[Myocarditis]]
*[[Acute Kidney Injury]]
=== '''Multisystem Inflammatory Syndrome in Children (MIS-C)''' ===


*It is a condition that causes [[inflammation]] of some parts of the body like [[heart]], [[blood vessels]], [[Kidney|kidneys]], digestive system, [[brain]], [[skin]], or [[Eye|eyes]].
*<9 years of age among 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>
*According to recent evidence, it is suggested that children with MISC had antibodies against COVID-19 suggesting children had [[COVID-19|COVID]]-19 infection in the past.
**Total number of all [[hospitalization]] is 4.1%
*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.  
**Total number of [[ICU]] admissions is 0.7% 
*10-19 years of age among 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>
**Total number of [[all]] [[hospitalization]] is 2.5%
**Total number of [[ICU]] admissions is 0.4%


'''Pathophysiology'''
{| class="wikitable"
*Exact cause of MIS-C is unclear. It is suspected that it is caused by a delayed immune response to the SARS-CoV-2, causing inflammation of organs.
|+Data of children with hospitalized children and ICU admissions as reported by CDC for a period of January 22 to May 30<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>
*It is also suspected that it is occurring due to [[antibody-mediated reaction]].
!Age
'''Symptoms'''
! colspan="9" |All admissions in the hospital and ICU divided according to associated comorbidity
*[[Fever]] lasting 24 hours or longer.
|-
*[[Vomiting]]
! rowspan="3" |<9 years (20458 cases)
*[[Diarrhea]]
! colspan="3" |All patients (20458)
*[[Abdominal pain]]
! colspan="3" |Among all patients with reported underlying disease (619)
*[[Skin rash]]
! colspan="3" |Among all patients with no reported underlying disease (2277)
*[[Conjuctivitis]]
|-
*[[High ESR]]
! colspan="2" |All admissions in the hospital including ICU
*Redness or swelling of the lips and tongue
!ICU admissions
*[[Lethargy]]
! colspan="2" |All admissions in the hospital including ICU
*[[Redness]] or swelling of the hands or feet
!ICU admissions
*[[Confusion]]
!All admissions in the hospital including ICU
*[[Headache]]
! colspan="2" |ICU admissions
*[[Sore throat]]
*[[Syncope]]
*[[Lymphadenopath]]
'''Emergency Warning Signs'''
*[[Difficulty Breathing]]
*[[Chest pain]]
*[[Confusion|New onset confusion]]
*[[Lethargy]]
*[[Cyanosis]]
*[[Abdominal pain]]
'''Laboratory Findings'''
*[[Lymphopenia]]
*[[Neutrophilia]]
*[[Anemia]]
*[[Thrombocytopenia]]
*Abnormal fibrinogen
*[[High CRP]]
*[[High D Dimer]]
*[[High Ferritin]]
*[[Hypoalbuminaemia]]
*[[Elevated Procalcitonin]]
*High IL-10
*High IL-6
*Raised CK
*Raised LDH
*Raised triglycerides
*Raised [[troponin]]
*Elevated BNP
*Absence of other potential causative organisms.
'''Radiological Findings''
{| border="1" cellpadding="2"
!width="225"|Test
!width="225"|Findings
|-
|-
|Chest Xray || patchy symmetrical infiltrates, pleural effusion
| colspan="2" |848/20458 (4.1%)
|141/20458 (0.7%)
| colspan="2" |138/619 (22.3%)
|31/619 (5%)
|84/2277(3.7%)
| colspan="2" |116/2277 (0.7%)
|-
|-
|Echocardiogram and EKG ||  myocarditis, valvulitis, pericardial effusion, coronary artery dilatation
! colspan="10" |
|-
|-
|Abdominal USG|| colitis, ileitis, lymphadenopathy, ascites, hepatosplenomegaly
! rowspan="3" |10-19 years (49245 cases)
|}
! colspan="2" |All patients (49245)
 
! colspan="3" |Among all patients with reported
==== Diagnosis ====
underlying disease (2076)
=====Preliminary [[World Health Organization|WHO]] case definition: Children and adolescents=====
! colspan="4" |Among all patients with no reported underlying disease (5047)
 
* 0–19 years of age with [[fever]] >3 days
 
AND
 
* Two of the following:
 
# [[Rash]] or bilateral non-purulent [[conjunctivitis]] or muco-cutaneous inflammation signs (oral, hands or feet)
# Hypotension or shock
# Features of myocardial dysfunction, [[pericarditis]], [[valvulitis]], or coronary abnormalities (including ECHO findings or elevated [[Troponin]]/[[NT-proBNP]])
# Evidence of [[coagulopathy]] (by PT, [[Partial thromboplastin time|PTT]], elevated [[D-dimer|D-Dimers]])
# Acute gastrointestinal problems ([[diarrhea]], [[vomiting]], or [[abdominal pain]])
 
AND
 
* Elevated markers of [[inflammation]] such as [[Erythrocyte sedimentation rate|ESR]], [[C-reactive protein]], or [[procalcitonin]]
 
AND
 
* No other obvious microbial cause of [[inflammation]], including bacterial [[sepsis]], [[staphylococcal]] or [[streptococcal]] shock syndromes
 
AND
 
* Evidence of [[COVID-19|COVID]]-19 ([[Reverse transcription-polymerase chain reaction|RT-PCR]], antigen test or serology-positive), or likely contact with patients with [[COVID-19|COVID]]-19
 
=====CDC Case Definition for MIS-C=====
 
*An individual aged <21 years presenting with fever*, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological);
 
AND
 
No alternative plausible diagnoses;
 
AND
 
 
Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.
 
'''Classification of Disease Severity of MIS-C'''
*'''Mild Disease'''
*Children with MIS-C fall under this category who-
**require minimal to no respiratory support.
**minimal to no organ injury
**normotensive
**Do not meet the criteria for ICU admission.
*'''Severe Disease'''
*Children with MIS-C fall under this category who-
**have significant oxygen requirements (HFNC, BiPAP, mechanical ventilation).
**have a mild-severe organ injury and ventricular dysfunction.
**have a vasoactive requirement.
**meet the criteria for ICU admissions.
'''Treatment'''
*All the children with MIS-C are treated as suspected COVID-19.
*Mild to Moderate cases of MIS-C are managed supportively.
*Supplemental oxygen is required in children with low oxygen saturation. 
*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.
*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.
 
{| border="1" cellpadding="2"
!width="225"|Prsentation
!width="225"|Treatment
|-
|-
|Mild Disease || 
!All admissions in the hospital including ICU
*Symptomatic Treatment
!ICU admissions
! colspan="2" |All admissions in the hospital including ICU  (2076)
!ICU admissions
! colspan="3" |All admissions in the hospital including ICU (5047)
!ICU admissions
|-
|-
|Severe Disease ||  
|1234/49245 (2.5%)
*Symptomatic Treatment
|216/49245 (0.4%)
*IVIG(IV)
| colspan="2" |309/2076 (14.9%)
*Corticosteroids(IV/PO)
|72/2076 (3.5%)
*Consider adding Anakinra or Tocilizumamb if fever persist for more than 24 hours post steroids and IVIG use.
| colspan="2" |115/5047 (2.3%)
| colspan="2" |17/5047 (0.3%)
|}
|}


'''Prevention of MIS-C'''
==Diagnosis==
*MIS-C can be prevented by reducing the risk of child exposure to [[COVID-19|COVID]]-19 infection.
'''Complications of MIS-C'''
*[[Severe myocardial infarction]]
*[[Cardiac failure/arrest]]
*[[ARDS]]
*[[Fluid Overload]]
*[[Acute Kidney Injury]]
*[[Peritonitis]]
*[[Thrombotic complications.]]
 
=== '''Acute Heart Failure''' ===
*[[Acute Cardiac decompensation]] have been reported in children due to severe inflammatory state following COVID-19 infection. A case series describe 35 children in 14 centers admitted to PICU for [[cardiogenic shock]], [[left ventricular dysfunction]], and severe inflammatory state.
* Treatent with [[immunoglobulin]] is associated with recovery of [[left ventricular systolic function]].<ref name="BelhadjerMéot2020">{{cite journal|last1=Belhadjer|first1=Zahra|last2=Méot|first2=Mathilde|last3=Bajolle|first3=Fanny|last4=Khraiche|first4=Diala|last5=Legendre|first5=Antoine|last6=Abakka|first6=Samya|last7=Auriau|first7=Johanne|last8=Grimaud|first8=Marion|last9=Oualha|first9=Mehdi|last10=Beghetti|first10=Maurice|last11=Wacker|first11=Julie|last12=Ovaert|first12=Caroline|last13=Hascoet|first13=Sebastien|last14=Selegny|first14=Maëlle|last15=Malekzadeh-Milani|first15=Sophie|last16=Maltret|first16=Alice|last17=Bosser|first17=Gilles|last18=Giroux|first18=Nathan|last19=Bonnemains|first19=Laurent|last20=Bordet|first20=Jeanne|last21=Di Filippo|first21=Sylvie|last22=Mauran|first22=Pierre|last23=Falcon-Eicher|first23=Sylvie|last24=Thambo|first24=Jean-Benoît|last25=Lefort|first25=Bruno|last26=Moceri|first26=Pamela|last27=Houyel|first27=Lucile|last28=Renolleau|first28=Sylvain|last29=Bonnet|first29=Damien|title=Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic|journal=Circulation|year=2020|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.120.048360}}</ref>
 
=== '''Negative effects of lockdown in children''' ===
 
*Children less than 10 years in the school develop very important [[language]], [[social]] and [[developmental]] traits with the [[mitigation]] in place these kids are at risk to develop [[anxiety]], [[anger]], and [[post-traumatic stress disorder]].
*Children whose parents have either suffered [[economically]] or have [[mental]] [[health]] issues are more prone to [[physical]] and [[mental]] [[abuse]].
*With the schools using digital media to continue classes during [[mitigation]], those kids who are not able to get these devices are [[suffering]] from little to no education in this period of lockdown.
*Children of [[healthcare]] workers are facing a great deal with change in the [[environment]] with a new baby sitter and not being able to interact and hug the parents working in the [[frontline]].


==Diagnosis==
===Diagnostic Study of Choice===
<br />
In case of clinical suspicion, the best diagnostic test to diagnose COVID-19 infection in children is [[Reverse-Transcriptase Polymerase Chain Reaction]]
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]].
* [[U.S. Food and Drug Administration]] [[(FDA)]] has approved [[Polymerase Chain Reaction|real-time Reverse-Transcription Polymerase Chain Reaction]] [[(RT-PCR)]] as the preferred test for diagnosing [[COVID-19]] in children
===Reverse-Transcriptase Polymerase Chain Reaction===
[[U.S. Food and Drug Administration]] [[(FDA)]] has approved [[Polymerase Chain Reaction|real-time Reverse-Transcription Polymerase Chain Reaction]] [[(RT-PCR)]] as the preferred test for diagnosing [[COVID-19]] in children
*[[RT-PCR]] has high [[specificity]] and [[sensitivity]] of 66-80% in diagnosing [[SARS-CoV-2]] infection
*[[RT-PCR]] has high [[specificity]] and [[sensitivity]] of 66-80% in diagnosing [[SARS-CoV-2]] infection
*The test is negative during the first 7-10 days of the infection and remains positive for several weeks after the infection subsides
*The test is negative during the first 7-10 days of the infection and remains positive for several weeks after the infection subsides
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*The [[virus]] [[RNA]] was also detected in blood and stools specimen
*The [[virus]] [[RNA]] was also detected in blood and stools specimen
*[[Real-time Fluorescent RT-PCR]] is used in children with [[atypical symptoms]]
*[[Real-time Fluorescent RT-PCR]] is used in children with [[atypical symptoms]]
*Alternatively, some researchers suggest using [[metagenomic next-generation sequencing]] [[(mNGS)]] of viral [[RNA]] for the diagnosis
*Alternatively, some researchers suggest using [[metagenomic next-generation sequencing]] [[(mNGS)]] of viral [[RNA]] for the diagnosis.


===Lab abnormalities===
===History and Symptoms===
Studies reportedly showed following lab abnormalities in pediatric patients with [[COVID-19|COVID]]-19
* Presentation of COVID-19 is less severe in children as compared to adults. Most of the children are asymptomatic.
*[[Leucocytosis]](7.5%) or [[Leucopenia]](16.6%)
*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.
*Increased (27.4%) or decreased (24%) [[neutrophils]]
* Illness severity of [[COVID-19]] in children ranges from [[asymptomatic]] to critical.
*[[Lymphopenia]] (12.9%) or [[Lymphocytosis]] (11.7%)
*The incubation period of SARS-CoV-2 varies from 2 to 14 days with most patients developing symptoms 3 to 7 days after exposure.<ref name="pmid32026148">{{cite journal| author=Chen ZM, Fu JF, Shu Q, Chen YH, Hua CZ, Li FB | display-authors=etal| title=Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus. | journal=World J Pediatr | year= 2020 | volume= 16 | issue= 3 | pages= 240-246 | pmid=32026148 | doi=10.1007/s12519-020-00345-5 | pmc=7091166 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32026148  }} </ref>
*Increased (9.5%) or decreased (3.2%) [[platelets]]
 
*Increased [[CRP]] levels (19.3%)
The common symptoms of COVID-19 infection in children are:
*Increased [[procalcitonin]] levels (49.8%)
*[[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
*Increased [[liver enzymes]] (19.2%)
*[[Dyspnea]], [[nasal congestion]], [[Erythema|pharyngeal erythema]], and [[sore throat]] are also common presentations in children.
*Increased [[Serum Creatinine]] (4%)
*[[Gastrointestinal symptoms]]: The gastrointestinal manifestation in [[COVID-19]] positive children are [[diarrhea]], [[vomiting]], [[abdominal pain]], [[nausea]], and [[anorexia]]. Children can present with [[Gastrointestinal disorders and of COVID-19|gastrointestinal]] symptoms in the absence of [[COVID-19 Pulmonary Complications|respiratory]] symptoms.
*Increased [[blood urea nitrogen]] (5%)
*[[Cutaneous Findings]]: The cutaneous findings in [[COVID-19]] positive children range from [[petechiae]] to papulovesicular [[rash]] and diffuse [[urticaria]]. These appear early in the course of [[COVID-19]] due to to viral replication or circulating [[cytokines]]. Many patients with COVID-19 present with chilblain-like lesions unrelated to cold (COVID toes). Chilblains are painful or itchy swellings of the toes and fingers, caused by small-vessel inflammation from repeated exposure to cold. A retrospective case series presented 22 children and adolescents with COVID-19 who presented with chillblains.
*Increased [[lactate dehydrogenase]] (LDH) levels (29%)
*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.
*Increased [[Creatine kinase]] levels (21%)
 
*Increased [[D-dimer]] levels (12%)
*[[Neonates]] and [[Infants]] with COVID-19 are often asymptomatic or present with fever with or without mild cough and congestion.
===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:
===Physical Examination===
*[[Mycoplasma pneumoniae]]
The physical examination findings of COVID-19 in children are similar to those in adults. To view physical examination findings in COVID-19, [[COVID-19_physical_examination|click here]].<br />
*[[Influenza B virus]]
 
*[[Influenza A virus]]
===Laboratory Findings===
*[[Respiratory syncytial virus]] (RSV)
 
*[[Cytomegalovirus]] (CMV)
Studies reportedly showed following lab abnormalities in pediatric patients with [[COVID-19|COVID]]-19  
*[[Enterobacter aerogenes]]
*[[Leucocytosis]] or [[Leucopenia]]
===Radiological findings===
*Increased or decreased [[neutrophils]]
[[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
*[[Lymphopenia]] or [[Lymphocytosis]]
*Increased or decreased [[platelets]]
*Increased [[CRP]] levels  
*Increased [[procalcitonin]] levels  
*Increased [[liver enzymes]]  
*Increased [[Serum Creatinine]]  
*Increased [[blood urea nitrogen]]  
*Increased [[lactate dehydrogenase]] (LDH) levels  
*Increased [[Creatine kinase]] levels  
*Increased [[D-dimer]] levels
 
===Electrocardiogram===
 
There are no current, evidence-based information on electrocardiographic changes in children with [[COVID-19]].
 
===X-ray===
 
===CT scan===
[[CT chest]] is an important diagnostic modality in pediatric patients with COVID-19. [[Chest CT scans]] has reportedly shown higher positive rates in suspected patients than [[RT-PCR]]. It has better sensitivity. [[CT chest]] and a series of [[chest X-rays]] can be used to monitor the progression of the disease. Imaging findings reported in the studies are<ref name="pmid32524611">{{cite journal| author=Du H, Dong X, Zhang JJ, Cao YY, Akdis M, Huang PQ | display-authors=etal| title=Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status. | journal=Allergy | year= 2020 | volume=  | issue=  | pages=  | pmid=32524611 | doi=10.1111/all.14452 | pmc=7307120 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32524611  }} </ref><ref name="pmid32492251">{{cite journal| author=de Souza TH, Nadal JA, Nogueira RJN, Pereira RM, Brandão MB| title=Clinical manifestations of children with COVID-19: A systematic review. | journal=Pediatr Pulmonol | year= 2020 | volume=  | issue=  | pages=  | pmid=32492251 | doi=10.1002/ppul.24885 | pmc=7300659 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32492251  }} </ref><ref name="pmid32519809">{{cite journal| author=Zhang L, Peres TG, Silva MVF, Camargos P| title=What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases. | journal=Pediatr Pulmonol | year= 2020 | volume=  | issue=  | pages=  | pmid=32519809 | doi=10.1002/ppul.24869 | pmc=7300763 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32519809  }} </ref>
*Local [[patchy shadows]] (18.7%)
*Local [[patchy shadows]] (18.7%)
*Bilateral [[patchy shadows]] (12.3%)
*Bilateral [[patchy shadows]] (12.3%)
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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]].
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==
===MRI===
* To view the MRI findings on COVID-19, [[COVID-19 MRI|click here]].<br />
 
===Other Imaging Findings===
* To view other imaging findings on COVID-19, [[COVID-19 other imaging findings|click here]].<br />
 
===Other Diagnostic Studies===
* To view other diagnostic studies for COVID-19, [[COVID-19 other diagnostic studies|click here]].<br />
 
==Treatment==
Management of [[COVID-19]] in [[pediatric]] patients depends on the severity of symptoms.
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
*Hospital admission and level of care depend on the clinical presentation, supportive care requirement, underlying comorbidities, and availability of health care facilities at home
Line 485: Line 377:
*Increased [[airway secretions]], severe [[cough]], and [[hemodynamic instability]]
*Increased [[airway secretions]], severe [[cough]], and [[hemodynamic instability]]
===Antibiotics===
===Antibiotics===
[[Antibiotics]] and [[antifungals]] help in reducing symptoms and preventing complications of [[secondary infections]]
[[Antibiotics]] and [[antifungals]] help in reducing symptoms and preventing complications of [[secondary infections]]<ref name="pmid32519809">{{cite journal| author=Zhang L, Peres TG, Silva MVF, Camargos P| title=What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases. | journal=Pediatr Pulmonol | year= 2020 | volume=  | issue=  | pages=  | pmid=32519809 | doi=10.1002/ppul.24869 | pmc=7300763 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32519809  }} </ref>
===Corticosteroids===
===Corticosteroids===
[[Steroids]] are used in severe cases and to prevent complications<ref name="pmid32519809">{{cite journal| author=Zhang L, Peres TG, Silva MVF, Camargos P| title=What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases. | journal=Pediatr Pulmonol | year= 2020 | volume=  | issue=  | pages=  | pmid=32519809 | doi=10.1002/ppul.24869 | pmc=7300763 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32519809  }} </ref>. Any of the following criteria must be met before starting [[corticosteroid]] therapy in patients with [[COVID-19]]<ref name="pmid32034659">{{cite journal| author=Shen K, Yang Y, Wang T, Zhao D, Jiang Y, Jin R | display-authors=etal| title=Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement. | journal=World J Pediatr | year= 2020 | volume=  | issue=  | pages=  | pmid=32034659 | doi=10.1007/s12519-020-00343-7 | pmc=7090771 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32034659  }} </ref>. Intravenous [[methylprednisolone]] 1-2mg/kg/day used for 3-5 days. Long-term usage is highly discouraged.
[[Steroids]] are used in severe cases and to prevent complications<ref name="pmid32519809">{{cite journal| author=Zhang L, Peres TG, Silva MVF, Camargos P| title=What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases. | journal=Pediatr Pulmonol | year= 2020 | volume=  | issue=  | pages=  | pmid=32519809 | doi=10.1002/ppul.24869 | pmc=7300763 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32519809  }} </ref>. Any of the following criteria must be met before starting [[corticosteroid]] therapy in patients with [[COVID-19]]<ref name="pmid32034659">{{cite journal| author=Shen K, Yang Y, Wang T, Zhao D, Jiang Y, Jin R | display-authors=etal| title=Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement. | journal=World J Pediatr | year= 2020 | volume=  | issue=  | pages=  | pmid=32034659 | doi=10.1007/s12519-020-00343-7 | pmc=7090771 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32034659  }} </ref>. Intravenous [[methylprednisolone]] 1-2mg/kg/day used for 3-5 days. Long-term usage is highly discouraged.
Line 522: Line 414:
*The safety and efficacy of Favipiravir are still being debated
*The safety and efficacy of Favipiravir are still being debated
*Due to its efficiency in treating [[SARS]], [[MERS]], [[Ebola]], and [[Influenza]],<ref name="pmid25706078">{{cite journal| author=Bouazza N, Treluyer JM, Foissac F, Mentré F, Taburet AM, Guedj J | display-authors=etal| title=Favipiravir for children with Ebola. | journal=Lancet | year= 2015 | volume= 385 | issue= 9968 | pages= 603-604 | pmid=25706078 | doi=10.1016/S0140-6736(15)60232-X | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25706078  }} </ref> it is being considered as a potential treatment for severely ill children who did not respond to other treatment options<ref name="pmid32346491">{{cite journal| author=Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J | display-authors=etal| title=Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. | journal=Engineering (Beijing) | year= 2020 | volume=  | issue=  | pages=  | pmid=32346491 | doi=10.1016/j.eng.2020.03.007 | pmc=7185795 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32346491  }} </ref>
*Due to its efficiency in treating [[SARS]], [[MERS]], [[Ebola]], and [[Influenza]],<ref name="pmid25706078">{{cite journal| author=Bouazza N, Treluyer JM, Foissac F, Mentré F, Taburet AM, Guedj J | display-authors=etal| title=Favipiravir for children with Ebola. | journal=Lancet | year= 2015 | volume= 385 | issue= 9968 | pages= 603-604 | pmid=25706078 | doi=10.1016/S0140-6736(15)60232-X | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25706078  }} </ref> it is being considered as a potential treatment for severely ill children who did not respond to other treatment options<ref name="pmid32346491">{{cite journal| author=Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J | display-authors=etal| title=Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. | journal=Engineering (Beijing) | year= 2020 | volume=  | issue=  | pages=  | pmid=32346491 | doi=10.1016/j.eng.2020.03.007 | pmc=7185795 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32346491  }} </ref>
<br />


==Prevention==
==Prevention==
Line 532: Line 423:
*The challenge faced by the school committees around the world is to decide between the [[pros]] and [[cons]] of whether to reopen the school with children facing the emotional toll of the [[lockdown]] and [[quarantine]].  
*The challenge faced by the school committees around the world is to decide between the [[pros]] and [[cons]] of whether to reopen the school with children facing the emotional toll of the [[lockdown]] and [[quarantine]].  


=== The CDC guidelines for re-opening  schools are as follows ===
The CDC guidelines for re-opening  schools are as follows  
*These guidelines are to be followed by schools by coordinating with the [[local]] [[health]] department to know the level of [[mitigation]] in your community as the [[coronavirus]] cases are increasing.
*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.  
*Educate the teachers and the parents on signs of coronavirus like [[dry cough]], [[cold]], [[high fever]], and other [[flu-like]] symptoms.  

Latest revision as of 17:20, 22 July 2020

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Main article: COVID-19

For COVID-19 frequently asked inpatient questions, click here

For COVID-19 frequently asked outpatient questions, click here

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

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

Overview

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

Historical Perspective

Classification

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

Pathophysiology

Pathogenesis

Tropism

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

Activation of Host Immune Reponses

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

Associated Conditions

Causes

Differentiating COVID-19 in Children from other Diseases

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

Epidemiology and Demographics

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

Incidence

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

Prevalence

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

Age

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

Race

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

Gender

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

Region

Risk Factors

Breastfeeding

Vertical transmission

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

Screening

Natural History, Complications, and Prognosis

Complications

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

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

B. Acute Heart Failure

C. Negative effects of lockdown in children

Prognosis

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

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

underlying disease (2076)

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

Diagnosis

Diagnostic Study of Choice

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

History and Symptoms

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

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

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

Physical Examination

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

Laboratory Findings

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

Electrocardiogram

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

X-ray

CT scan

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

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

MRI

Other Imaging Findings

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

Other Diagnostic Studies

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

Treatment

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

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

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

Symptomatic treatment and Supportive Care

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

Respiratory support

Mechanical Ventilation

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

OR

OR

Antibiotics

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

Corticosteroids

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

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

OR

OR

OR

Anticoagulation therapy

Convalescent plasma therapy

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

Immunoglobulin therapy

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

Antiviral therapy

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

Interferon-alpha

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

Remdesivir

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

Favipiravir

Prevention

Re-opening of schools

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

The CDC guidelines for re-opening schools are as follows

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

Domestic violence in children

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 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.
  2. ↑ 2.0 2.1 Velavan, Thirumalaisamy P.; Meyer, Christian G. (2020). "The COVID‐19 epidemic". Tropical Medicine & International Health. 25 (3): 278–280. doi:10.1111/tmi.13383. ISSN 1360-2276.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S; et al. (2020). "Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020". MMWR Morb Mortal Wkly Rep. 69 (24): 759–765. doi:10.15585/mmwr.mm6924e2. PMC 7302472 Check |pmc= value (help). PMID 32555134 Check |pmid= value (help).
  4. ↑ Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X; et al. (2020). "High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa". Int J Oral Sci. 12 (1): 8. doi:10.1038/s41368-020-0074-x. PMC 7039956 Check |pmc= value (help). PMID 32094336 Check |pmid= value (help).
  5. ↑ 5.0 5.1 Mahyuddin AP, Kanneganti A, Wong J, Dimri PS, Su LL, Biswas A; et al. (2020). "Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2". Prenat Diagn. doi:10.1002/pd.5765. PMC 7307070 Check |pmc= value (help). PMID 32529643 Check |pmid= value (help).
  6. ↑ Belhadjer, Zahra; Méot, Mathilde; Bajolle, Fanny; Khraiche, Diala; Legendre, Antoine; Abakka, Samya; Auriau, Johanne; Grimaud, Marion; Oualha, Mehdi; Beghetti, Maurice; Wacker, Julie; Ovaert, Caroline; Hascoet, Sebastien; Selegny, Maëlle; Malekzadeh-Milani, Sophie; Maltret, Alice; Bosser, Gilles; Giroux, Nathan; Bonnemains, Laurent; Bordet, Jeanne; Di Filippo, Sylvie; Mauran, Pierre; Falcon-Eicher, Sylvie; Thambo, Jean-Benoît; Lefort, Bruno; Moceri, Pamela; Houyel, Lucile; Renolleau, Sylvain; Bonnet, Damien (2020). "Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic". Circulation. doi:10.1161/CIRCULATIONAHA.120.048360. ISSN 0009-7322.
  7. ↑ Chen ZM, Fu JF, Shu Q, Chen YH, Hua CZ, Li FB; et al. (2020). "Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus". World J Pediatr. 16 (3): 240–246. doi:10.1007/s12519-020-00345-5. PMC 7091166 Check |pmc= value (help). PMID 32026148 Check |pmid= value (help).
  8. ↑ Du H, Dong X, Zhang JJ, Cao YY, Akdis M, Huang PQ; et al. (2020). "Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status". Allergy. doi:10.1111/all.14452. PMC 7307120 Check |pmc= value (help). PMID 32524611 Check |pmid= value (help).
  9. ↑ de Souza TH, Nadal JA, Nogueira RJN, Pereira RM, Brandão MB (2020). "Clinical manifestations of children with COVID-19: A systematic review". Pediatr Pulmonol. doi:10.1002/ppul.24885. PMC 7300659 Check |pmc= value (help). PMID 32492251 Check |pmid= value (help).
  10. ↑ 10.0 10.1 10.2 10.3 Zhang L, Peres TG, Silva MVF, Camargos P (2020). "What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases". Pediatr Pulmonol. doi:10.1002/ppul.24869. PMC 7300763 Check |pmc= value (help). PMID 32519809 Check |pmid= value (help).
  11. ↑ 11.0 11.1 11.2 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).
  12. ↑ Bouazza N, Treluyer JM, Foissac F, Mentré F, Taburet AM, Guedj J; et al. (2015). "Favipiravir for children with Ebola". Lancet. 385 (9968): 603–604. doi:10.1016/S0140-6736(15)60232-X. PMID 25706078.
  13. ↑ 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).
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