COVID-19 associated pediatric complications: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
(grammar)
 
(87 intermediate revisions by 6 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
<br />
{{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.<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>
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]]
 
===Associated Conditions===
 
*The 3 most common [[comorbidities]] in children .  
**[[Chronic Lung disease]]
** [[Cardiovascular disorders]]
** [[Immunocompromised]] children
 
* [[Co-infection]] with other [[pathogens]] were reported in 27% of cases. Some common [[microorganisms]] associated with [[SARS-CoV-2]] infection in children are:
** [[Mycoplasma pneumoniae]]
** [[Influenza B virus]]
** [[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).
 
==Differentiating COVID-19 in Children from other Diseases==
 
COVID-19 disease in children should be differentiated from the following conditions:


==Epidemiology and Demographics ==
* [[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)
 
==Epidemiology and Demographics==
 
*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>


*Less than 2% of the confirmed positive cases of [[COVID-19]] comprise of children less than 19 years of age<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>.
=== Incidence ===
=== 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><http://dx.doi.org/10.15585/mmwr.mm6924e2></ref> <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>.
*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.
*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.<ref><https://www.niaid.nih.gov/news-events/study-determine-incidence-novel-coronavirus-infection-us-children-begins></ref>
*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 ===
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.<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 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>
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 <ref name="pmid32555134">{{cite journal| author=Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S | display-authors=etal| title=Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020. | journal=MMWR Morb Mortal Wkly Rep | year= 2020 | volume= 69 | issue= 24 | pages= 759-765 | pmid=32555134 | doi=10.15585/mmwr.mm6924e2 | pmc=7302472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32555134  }} </ref>
**The 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<ref name="pmid32555134">{{cite journal| author=Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S | display-authors=etal| title=Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020. | journal=MMWR Morb Mortal Wkly Rep | year= 2020 | volume= 69 | issue= 24 | pages= 759-765 | pmid=32555134 | doi=10.15585/mmwr.mm6924e2 | pmc=7302472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32555134  }} </ref>
**The [[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 ===
*[[COVID-19]] has become a [[pandemic]] with current cases around 188 countries.
*The following data is up to 29th June 2020
**The total number of [[Coronavirus]] cases worldwide is 10,055,037.
**The total number of [[deaths]] worldwide is 499,990.
**The top 5 [[countries]] worldwide with the highest number of [[COVID-19]] cases are the [[U.S]], [[Brazil]], [[Russia]], [[India]], and the [[U.K.]] 
*The total number of [[COVID-19]] cases in the [[U.S]] is 2,534,981.
 
==Risk Factors==
*[[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.
* 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
 
''' 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.
*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>.
 
''' 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.<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>
*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==
 
* There are no special guidelines [[Medical guideline|guidelines]] in place for the routine [[Screening (medicine)|screening]] for [[coronavirus]] disease 2019 ([[COVID-19]]) in children.
* 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>
**History of international travel (this requirement is actively changing and evolving with time)
**History of exposure to a confirmed COVID-19 [[patient]]
**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]]
 
====A. Multisystem Inflammatory Syndrome in Children (MIS-C)====
* To view detailed information on multisystem inflammatory syndrome in children, [[COVID-19-associated_multisystem_inflammatory_syndrome|click here]].<br />
 
==== 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>


'''Comorbidities'''
==== C. Negative effects of lockdown in children ====


** 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>.
*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]].
***Chronic Lung disease (CLD) 12.5%
*Children whose parents have either suffered [[economically]] or have [[mental]] [[health]] issues are more prone to [[physical]] and [[mental]] [[abuse]].  
***Cardiovascular disorder 2.7%
*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.
***Immunocompromised children 2.1%
*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]].
** The 3 most common comorbidities in children 10-19 yearsamong 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 2.3%
***Immunocompromised children 2.0%


'''ICU and total hospitalization 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<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%


**<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"
{| 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>
|+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>
Line 135: Line 266:
|}
|}


=== Age ===
==Diagnosis==
 
*According to the data published by [[CDC]] for a period of January 22 to May 30<ref><http://dx.doi.org/10.15585/mmwr.mm6924e2></ref> <ref name="pmid32555134">{{cite journal| author=Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S | display-authors=etal| title=Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020. | journal=MMWR Morb Mortal Wkly Rep | year= 2020 | volume= 69 | issue= 24 | pages= 759-765 | pmid=32555134 | doi=10.15585/mmwr.mm6924e2 | pmc=7302472 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32555134  }} </ref>
**The cumulative [[incidence]] of [[COVID-19]] cases in children age 0-9 is 51.1 from 20,458 cases.
**The cumulative [[incidence]] of [[COVID-19]] cases in children age 10-19 is 117.3 from 49,245 cases.
 
=== Racial predilection to COVID-19 ===
 
[[Non-Hispanic American Indian]] or Alaska Native persons have an age-adjusted hospitalization rate approximately 5 times that of non-Hispanic White persons, while non-Hispanic Black persons and Hispanic or Latino persons each have a rate approximately 4.5 times that of non-Hispanic White persons<ref><https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html></ref>
 
=== Gender ===
 
*According to the data published 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>
**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 ===
*[[COVID-19]] has become a [[pandemic]] with current cases around 188 countries.<ref><https://coronavirus.jhu.edu/map.html</ref>
*The following data is up to 29th June 2020<ref><https://coronavirus.jhu.edu/map.html</ref>
**The total number of [[Coronavirus]] cases worldwide is 10,055,037.
**The total number of [[deaths]] worldwide is 499,990.
**The top 5 [[countries]] worldwide with the highest number of [[COVID-19]] cases are the [[U.S]], [[Brazil]], [[Russia]], [[India]], and the [[U.K.]] 
*The total number of [[COVID-19]] cases in the [[U.S]] is 2,534,981.
 
==Mode of transmission==
*[[SARS-CoV 2]] spreads by [[respiratory]] [[droplets]] within 6 feet from the infected person.<ref><Hui DS, Zumla A. Severe Acute Respiratory Syndrome: Historical, Epidemiologic, and
Clinical Features. Infectious Disease Clinics. 2019 Dec 1;33(4):869-89></ref>
*Pregnant women with [[COVID- 19]] are at more risk of developing adverse [[obstetric]] and [[perinatal]] outcomes.<ref name="pmid32105680">{{cite journal| author=Rasmussen SA, Smulian JC, Lednicky JA, Wen TS, Jamieson DJ| title=Coronavirus Disease 2019 (COVID-19) and pregnancy: what obstetricians need to know. | journal=Am J Obstet Gynecol | year= 2020 | volume= 222 | issue= 5 | pages= 415-426 | pmid=32105680 | doi=10.1016/j.ajog.2020.02.017 | pmc=7093856 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32105680  }} </ref>
* 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<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>
=== Breastfeeding ===
 
*According to the [[CDC]]<ref><https://www.cdc.gov/coronavirus/2019-ncov/hcp/care-for-breastfeeding-women.html></ref>, there is no transmission of the [[SARS CoV-2]] virus from an infected mother to the newborn while breastfeeding. However limited studies are available to yet decide if there is a true transmission risk while breastfeeding.
*[[CDC]] advises all mothers who are positive or suspected to be [[COVID-19]] positive to practice precaution like covering the mouth with a [[face mask]], washing hands with soap and water before and after washing hands.
*Bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas [[TCGA]] and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression [[FANTOM5 CAGE]] dataset were collected. Ace- 2 receptors are used by the [[coronavirus]] to gain entry into the cells. The [[RNA]] Sequence database found ACE-2 expression in the breast tissue similar to the expression in the lung tissue.<ref name="pmid32094336">{{cite journal| author=Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X | display-authors=etal| title=High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. | journal=Int J Oral Sci | year= 2020 | volume= 12 | issue= 1 | pages= 8 | pmid=32094336 | doi=10.1038/s41368-020-0074-x | pmc=7039956 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32094336  }} </ref>
*However, the current data suggest there is one isolated case reported where the breast milk sample was found to be positive for [[COVID-19]] sample on Day 1 and subsequently negative in the day 3 sample. More research needs to be done to conclude if there is any [[transmission]] vis breastfeeding<ref name="pmid32529643">{{cite journal| author=Mahyuddin AP, Kanneganti A, Wong J, Dimri PS, Su LL, Biswas A | display-authors=etal| title=Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2. | journal=Prenat Diagn | year= 2020 | volume=  | issue=  | pages=  | pmid=32529643 | doi=10.1002/pd.5765 | pmc=7307070 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32529643  }} </ref>.
 
=== Vertical transmission ===
 
*A study by Marzieh Zamaniyan et all <ref name="pmid32304114">{{cite journal| author=Zamaniyan M, Ebadi A, Aghajanpoor S, Rahmani Z, Haghshenas M, Azizi S| title=Preterm delivery, maternal death, and vertical transmission in a pregnant woman with COVID-19 infection. | journal=Prenat Diagn | year= 2020 | volume=  | issue=  | pages=  | pmid=32304114 | doi=10.1002/pd.5713 | pmc=7264605 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32304114  }} </ref> 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.<ref name="pmid32215589">{{cite journal| author=Zeng H, Xu C, Fan J, Tang Y, Deng Q, Zhang W | display-authors=etal| title=Antibodies in Infants Born to Mothers With COVID-19 Pneumonia. | journal=JAMA | year= 2020 | volume=  | issue=  | pages=  | pmid=32215589 | doi=10.1001/jama.2020.4861 | pmc=7099444 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32215589  }} </ref>
**[[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<ref name="pmid32215581">{{cite journal| author=Dong L, Tian J, He S, Zhu C, Wang J, Liu C | display-authors=etal| title=Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn. | journal=JAMA | year= 2020 | volume=  | issue=  | pages=  | pmid=32215581 | doi=10.1001/jama.2020.4621 | pmc=7099527 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32215581  }} </ref> 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.<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>
*Detection of [[IgM]] and [[IL-6]] in neonates serum is used as one of the markers for possible [[transplacental]] transmission.
*Some studies which detected the virus hours to days after birth in the [[nasopharyngeal]] samples and hence those newborns could have been exposed to the virus after birth via the nosocomial infection.
 
==Presentations==
 
* Presentation of [[COVID-19]] is less severe in children as compared to adults.
*According to [[Centers for Disease Control and Prevention|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.
 
=== Symptoms ===
 
*[[Fever]] and [[Cough]] are one of the most common symptoms reported in children. One study showed [[fever]] is prevalent in 47.5% of children and [[cough]] in 41.5% among the 1124 children with [[COVID-19]].According to the CDC, [[fever]], and [[cough]] was reported in 56% and 54% of children with COVID 19
*[[Dyspnea]], [[nasal congestion]], [[Erythema|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 disorders and of COVID-19|gastrointestinal]] symptoms in the absence of [[COVID-19 Pulmonary Complications|respiratory]] symptoms.
*'''[[Cutaneous Findings]]'''
 
=== '''Clinical Course of COVID-19 in children.''' ===
 
*'''Asymptomatic presentation'''-
**Children present with no clinical signs or [[Symptom|symptoms]] with normal chest imaging.
** Among 2143 children with [[COVID-19|COVID]]-19 infection 4% of children were [[asymptomatic]].
** According to one study 14.2% of children were asymptomatic. Another study showed 18% of asymptomatic children with [[COVID-19|COVID]]-19.
*'''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.
*'''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==
Some of the complications associated with [[COVID-19|COVID]]-19 pediatric population are
 
*[[Multisystem Inflammatory Syndrome in Children (MISC-C)]]
*[[Exacerbation of the underlying conditions]]
*[[Sepsis]]
*[[Septic shock]]
*[[Secondary Bacterial infections]].
*[[Acute Heart Failure]]
*[[Negative effects of lockdown in children]]
 
=== '''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]].
*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.
 
'''Pathophysiology'''
*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.{{cite web |url=http://www.childrenshospital.org/conditions-and-treatments/conditions/m/mis-c |title=Multisystem Inflammatory Syndrome in Children (MIS-C) &#124; Boston Children's Hospital |format= |work= |accessdate=}}
*It is also suspected that it is occurring due to [[antibody-mediated reaction]].{{cite web |url=http://www.childrenshospital.org/conditions-and-treatments/conditions/m/mis-c |title=Multisystem Inflammatory Syndrome in Children (MIS-C) &#124; Boston Children's Hospital |format= |work= |accessdate=}}
 
'''Symptoms'''
*[[Fever]] lasting 24 hours or longer.
*[[Vomiting]]
*[[Diarrhea]]
*[[Abdominal pain]]
*[[Skin rash]]
*[[Red eyes]]
*Redness or swelling of the lips and tongue
*[[Lethargy]]
*[[Redness]] or swelling of the hands or feet
'''Emergency Warning Signs'''
*[[Difficulty Breathing]]
*[[Chest pain]]
*[[Confusion|New onset confusion]]
*[[Lethargy]]
*[[Cyanosis]]
*[[Abdominal pain]]
 
==== Diagnosis ====
Preliminary [[World Health Organization|WHO]] case definition: Children and adolescents
 
* 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
 
'''Prevention of MIS-C'''
*MIS-C can be prevented by reducing the risk of child exposure to [[COVID-19|COVID]]-19 infection.
 
=== '''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.<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>
* 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]].<ref><[[Posttraumatic]] stress disorder [[(PTSD)]] in parents and youth after health-related disasters.
Sprang G, Silman M
Disaster Med Public Health Prep. 2013 Feb; 7(1):105-10.></ref>
*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
Line 318: Line 285:
*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.
 
===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.<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>
 
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]], [[Erythema|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 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 [[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, [[COVID-19_physical_examination|click here]].<br />
 
===Laboratory Findings===


===Lab abnormalities===
Studies reportedly showed following lab abnormalities in pediatric patients with [[COVID-19|COVID]]-19  
Studies reportedly showed following lab abnormalities in pediatric patients with [[COVID-19|COVID]]-19
*[[Leucocytosis]] or [[Leucopenia]]
*[[Leucocytosis]](7.5%) or [[Leucopenia]](16.6%)
*Increased or decreased [[neutrophils]]
*Increased (27.4%) or decreased (24%) [[neutrophils]]
*[[Lymphopenia]] or [[Lymphocytosis]]
*[[Lymphopenia]] (12.9%) or [[Lymphocytosis]] (11.7%)
*Increased or decreased [[platelets]]
*Increased (9.5%) or decreased (3.2%) [[platelets]]
*Increased [[CRP]] levels  
*Increased [[CRP]] levels (19.3%)
*Increased [[procalcitonin]] levels  
*Increased [[procalcitonin]] levels (49.8%)
*Increased [[liver enzymes]]  
*Increased [[liver enzymes]] (19.2%)
*Increased [[Serum Creatinine]]  
*Increased [[Serum Creatinine]] (4%)
*Increased [[blood urea nitrogen]]  
*Increased [[blood urea nitrogen]] (5%)
*Increased [[lactate dehydrogenase]] (LDH) levels  
*Increased [[lactate dehydrogenase]] (LDH) levels (29%)
*Increased [[Creatine kinase]] levels  
*Increased [[Creatine kinase]] levels (21%)
*Increased [[D-dimer]] levels
*Increased [[D-dimer]] levels (12%)
 
===Co-infections===
===Electrocardiogram===
[[Co-infection]] with other [[pathogens]] were reported in 27% of cases. Some common [[microorganisms]] associated with [[SARS-CoV-2]] infection in children are:
 
*[[Mycoplasma pneumoniae]]
There are no current, evidence-based information on electrocardiographic changes in children with [[COVID-19]].
*[[Influenza B virus]]
 
*[[Influenza A virus]]
===X-ray===
*[[Respiratory syncytial virus]] (RSV)
 
*[[Cytomegalovirus]] (CMV)
===CT scan===
*[[Enterobacter aerogenes]]
[[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>
===Radiological findings===
[[CT chest]] is an important diagnostic modality in pediatric patients with COVID-19. [[Chest CT scans]] has reportedly shown higher positive rates in suspected patients than [[RT-PCR]]. It has better sensitivity. [[CT chest]] and a series of [[chest X-rays]] can be used to monitor the progression of the disease. Imaging findings reported in the studies are
*Local [[patchy shadows]] (18.7%)
*Local [[patchy shadows]] (18.7%)
*Bilateral [[patchy shadows]] (12.3%)
*Bilateral [[patchy shadows]] (12.3%)
Line 352: Line 337:
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 358: Line 352:
*After confirming the diagnosis, they should be hospitalized and isolated in the wards maintained for [[pediatric]] patients with [[COVID-19]]
*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
*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]]<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>
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]]
*Bed rest
*Bed rest
*Adequate calorie and water intake
*Adequate calorie and water intake
Line 371: Line 365:
[[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.<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>
[[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.<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>
===Respiratory support===
===Respiratory support===
*When the [[ oxygen saturations]] are low, [[oxygen therapy]] should be started using a [[nasal catheter]] or mask oxygen<ref name="pmid32338347">{{cite journal| author=Sankar J, Dhochak N, Kabra SK, Lodha R| title=COVID-19 in Children: Clinical Approach and Management. | journal=Indian J Pediatr | year= 2020 | volume= 87 | issue= 6 | pages= 433-442 | pmid=32338347 | doi=10.1007/s12098-020-03292-1 | pmc=7183927 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32338347  }} </ref>
*When the [[ oxygen saturations]] are low, [[oxygen therapy]] should be started using a [[nasal catheter]] or mask oxygen
*Alternatively, [[heated humidified high flow nasal cannula]] (HHHFNC) can be used to improve [[oxygenation]]
*Alternatively, [[heated humidified high flow nasal cannula]] (HHHFNC) can be used to improve [[oxygenation]]
*If symptoms of [[respiratory difficulty]] persist, [[continuous positive airway pressure]] (CPAP) or [[non-invasive high-frequency ventilation]] should be considered
*If symptoms of [[respiratory difficulty]] persist, [[continuous positive airway pressure]] (CPAP) or [[non-invasive high-frequency ventilation]] should be considered
Line 404: Line 398:
*More studies are required to support its efficacy and safety in children with [[COVID-19]]
*More studies are required to support its efficacy and safety in children with [[COVID-19]]
===Antiviral therapy===
===Antiviral therapy===
Following are the [[experimental drugs]] that are being considered to treat children with [[COVID-19]]<ref name="pmid32506621">{{cite journal| author=Deniz M, Tapısız A, Tezer H| title=Drugs being investigated for children with COVID-19. | journal=Acta Paediatr | year= 2020 | volume=  | issue=  | pages=  | pmid=32506621 | doi=10.1111/apa.15399 | pmc=7300686 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32506621  }} </ref>. Various [[clinical trials]] are being conducted on the efficacy and safety of these drugs in children with [[COVID-19]].
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====
====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.<ref name="pmid31771760">{{cite journal| author=Wang BX, Fish EN| title=Global virus outbreaks: Interferons as 1st responders. | journal=Semin Immunol | year= 2019 | volume= 43 | issue=  | pages= 101300 | pmid=31771760 | doi=10.1016/j.smim.2019.101300 | pmc=7128104 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31771760  }} </ref><ref name="pmid32275690">{{cite journal| author=Chen L, Shi M, Deng Q, Liu W, Li Q, Ye P | display-authors=etal| title=Correction: A multi-center randomized prospective study on the treatment of infant bronchiolitis with interferon α1b nebulization. | journal=PLoS One | year= 2020 | volume= 15 | issue= 4 | pages= e0231911 | pmid=32275690 | doi=10.1371/journal.pone.0231911 | pmc=7147733 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32275690  }} </ref>
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====
====Remdesivir====
*It is a [[nucleotide]] analogue that inhibits [[viral]] [[RNA polymerase]]
*It is a [[nucleotide]] analogue that inhibits [[viral]] [[RNA polymerase]]
*It was effectively used during [[Ebola]], [[SARS]], and [[MERS]] outbreaks
*It was effectively used during [[Ebola]], [[SARS]], and [[MERS]] outbreaks
*It was effective in-vitro against [[SARS-CoV-2]]<ref name="pmid32275812">{{cite journal| author=Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A | display-authors=etal| title=Compassionate Use of Remdesivir for Patients with Severe Covid-19. | journal=N Engl J Med | year= 2020 | volume= 382 | issue= 24 | pages= 2327-2336 | pmid=32275812 | doi=10.1056/NEJMoa2007016 | pmc=7169476 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32275812  }} </ref>
*It was effective in-vitro against [[SARS-CoV-2]]
*No adverse effects were reported in a newborn treated for [[Ebola]]<ref name="pmid28073857">{{cite journal| author=Dörnemann J, Burzio C, Ronsse A, Sprecher A, De Clerck H, Van Herp M | display-authors=etal| title=First Newborn Baby to Receive Experimental Therapies Survives Ebola Virus Disease. | journal=J Infect Dis | year= 2017 | volume= 215 | issue= 2 | pages= 171-174 | pmid=28073857 | doi=10.1093/infdis/jiw493 | pmc=5583641 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28073857  }} </ref>
*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<ref name="pmid04292899">{{cite journal| author=Campbell CH| title=Effect of incubation temperature and serum content in agar overlay on plaque production by foot-and-mouth disease virus. | journal=Can J Comp Med Vet Sci | year= 1967 | volume= 31 | issue= 10 | pages= 251-5 | pmid=04292899 | doi= | pmc=1494743 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4292899  }} </ref>
*[[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{{cite web |url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment |title=Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment &#124; FDA |format= |work= |accessdate=}}
*[[FDA]] has approved the emergency use of [[Remdesivir]] in treating hospitalized children with severe disease{{cite web |url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment |title=Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment &#124; FDA |format= |work= |accessdate=}}
====Favipiravir====
====Favipiravir====
*[[Favipiravir]] is an [[RNA dependent RNA polymerase inhibitor]]
*[[Favipiravir]] is an [[RNA dependent RNA polymerase inhibitor]]
*In patients above 16 years, reports showed faster [[viral clearance]] and higher [[recovery rate]] with [[Favipiravir]]<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>
*In patients above 16 years, reports showed faster [[viral clearance]] and higher [[recovery rate]] with [[Favipiravir]]
*It was effective during [[Ebola]] and [[Influenza]] outbreak<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 was effective during [[Ebola]] and [[Influenza]] outbreak
*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 427: Line 420:
*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.  
*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]].  
*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]]<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> and other articles<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> children are affected less compared to adults with [[asymptomatic]] to [[mild]] [[COVID-19]] symptoms.
*According to the data collected by the [[CDC]]<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> 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]]. <ref name="pmid32517815">{{cite journal| author=Fantini MP, Reno C, Biserni GB, Savoia E, Lanari M| title=COVID-19 and the re-opening of schools: a policy maker's dilemma. | journal=Ital J Pediatr | year= 2020 | volume= 46 | issue= 1 | pages= 79 | pmid=32517815 | doi=10.1186/s13052-020-00844-1 | pmc=7280677 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32517815  }} </ref>
*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 <ref><https://www.cdc.gov/coronavirus/2019-ncov/community/schools-childcare/schools.html></ref> ===
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.  
Line 452: Line 445:
=== Domestic violence in children ===
=== Domestic violence in children ===
*In this [[lockdown]] even though children are affected less compared to adults with [[COVID -19]] that however is not the case when it comes to [[mental]] [[health]] and [[safety]].
*In this [[lockdown]] even though children are affected less compared to adults with [[COVID -19]] that however is not the case when it comes to [[mental]] [[health]] and [[safety]].
*A study by Silvia Bressan et all <ref name="pmid32487724">{{cite journal| author=Bressan S, Gallo E, Tirelli F, Gregori D, Da Dalt L| title=Lockdown: more domestic accidents than COVID-19 in children. | journal=Arch Dis Child | year= 2020 | volume= | issue=  | pages=  | pmid=32487724 | doi=10.1136/archdischild-2020-319547 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32487724  }} </ref> reported a [[sharp]] increase in [[pediatric]] [[emergency]] visit due to [[domestic]] [[violence]] with majority of [[limb]] [[fractures]], [[facial]] [[fracture]], [[subdural]] [[hematoma]] and ingestion of [[caustic]] cleaning product.  
*A study by Silvia Bressan et all  reported a [[sharp]] increase in [[pediatric]] [[emergency]] visit due to [[domestic]] [[violence]] with majority of [[limb]] [[fractures]], [[facial]] [[fracture]], [[subdural]] [[hematoma]] and ingestion of [[caustic]] cleaning product.
*Increased measures for children's safety and frequent [[disinfection]] should be encouraged.
*Increased measures for children's safety and frequent [[disinfection]] should be encouraged.


==References==
==References==
<references />
<references />

Latest revision as of 17:20, 22 July 2020

WikiDoc Resources for COVID-19 associated pediatric complications

Articles

Most recent articles on COVID-19 associated pediatric complications

Most cited articles on COVID-19 associated pediatric complications

Review articles on COVID-19 associated pediatric complications

Articles on COVID-19 associated pediatric complications in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on COVID-19 associated pediatric complications

Images of COVID-19 associated pediatric complications

Photos of COVID-19 associated pediatric complications

Podcasts & MP3s on COVID-19 associated pediatric complications

Videos on COVID-19 associated pediatric complications

Evidence Based Medicine

Cochrane Collaboration on COVID-19 associated pediatric complications

Bandolier on COVID-19 associated pediatric complications

TRIP on COVID-19 associated pediatric complications

Clinical Trials

Ongoing Trials on COVID-19 associated pediatric complications at Clinical Trials.gov

Trial results on COVID-19 associated pediatric complications

Clinical Trials on COVID-19 associated pediatric complications at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on COVID-19 associated pediatric complications

NICE Guidance on COVID-19 associated pediatric complications

NHS PRODIGY Guidance

FDA on COVID-19 associated pediatric complications

CDC on COVID-19 associated pediatric complications

Books

Books on COVID-19 associated pediatric complications

News

COVID-19 associated pediatric complications in the news

Be alerted to news on COVID-19 associated pediatric complications

News trends on COVID-19 associated pediatric complications

Commentary

Blogs on COVID-19 associated pediatric complications

Definitions

Definitions of COVID-19 associated pediatric complications

Patient Resources / Community

Patient resources on COVID-19 associated pediatric complications

Discussion groups on COVID-19 associated pediatric complications

Patient Handouts on COVID-19 associated pediatric complications

Directions to Hospitals Treating COVID-19 associated pediatric complications

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

Healthcare Provider Resources

Symptoms of COVID-19 associated pediatric complications

Causes & Risk Factors for COVID-19 associated pediatric complications

Diagnostic studies for COVID-19 associated pediatric complications

Treatment of COVID-19 associated pediatric complications

Continuing Medical Education (CME)

CME Programs on COVID-19 associated pediatric complications

International

COVID-19 associated pediatric complications en Espanol

COVID-19 associated pediatric complications en Francais

Business

COVID-19 associated pediatric complications in the Marketplace

Patents on COVID-19 associated pediatric complications

Experimental / Informatics

List of terms related to COVID-19 associated pediatric complications

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).
Retrieved from "https://www.wikidoc.org/index.php?title=COVID-19_associated_pediatric_complications&oldid=1631141"