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__NOTOC__
{{COVID-19}}
'''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''
'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''
{{CMG}}; {{AE}} {{HAR}}
{{SK}} '''Multisystem Inflammatory Syndrome in Children (MIS-C)'''
==Overview==
Multisystem Inflammatory Syndrome in Children (MIS-C) 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 MIS-C had antibodies against [[COVID-19]] suggesting children had [[COVID-19]] infection in the past. This syndrome appears to be similar in presentation to [[Kawasaki disease]], hence also called Kawasaki -like a disease. It also shares features with s[[Streptococcal toxic shock syndrome|taphylococcal and streptococcal toxic shock syndromes]], [[Sepsis|bacterial sepsis]], and macrophage activation syndromes.<ref name="CC"">{{Cite web|url=https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf|title=Guidance: Paediatric multisystem inflammatory
syndrome temporally associated with COVID-19|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
== Classification of Disease Severity of MIS-C ==
*'''Mild Disease'''
*Children with MIS-C fall under this category who-<ref name="AL">{{Cite web|url=https://www.chkd.org/uploadedFiles/Documents/COVID-19/CHKD%20MIS-C%20Guideline%20D2.pdf |title=Evaluation and Management of COVID-19 Multisystem Inflammatory
Syndrome in Children (MIS-C) |first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
**require minimal to no respiratory support.
**minimal to no organ injury
**normotensive
**Do not meet the criteria for ICU admission.
*'''Severe Disease'''
*Children with MIS-C fall under this category who-<ref name="AL" />
**have significant oxygen requirements (HFNC, BiPAP, mechanical ventilation).
**have a mild-severe organ injury and ventricular dysfunction.
**have a vasoactive requirement.
**meet the criteria for ICU admissions
==Pathophysiology==
* The excat pathophysiological mechanism of MIS-C is unclear. Since there is a lag time between MIS-C appearance and COVID-19 infection it is suspected to be causing by antibody dependent enhancement.<ref name="Rowley2020">{{cite journal|last1=Rowley|first1=Anne H.|title=Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children|journal=Nature Reviews Immunology|year=2020|issn=1474-1733|doi=10.1038/s41577-020-0367-5}}</ref>
* Another hypothesis is that since coronavirus block type1 and type III interferons, it results in delayed cytokine response in children with initially high viral load or whose immune response is unable to control infections causing MIS-C. Therefore, IFN responses result in viral clearance when the viral load is low resulting in mild infection. However, when the viral load is high and /or immune system is not able to clear the virus, the cytokine storm result in multisystem inflammatory syndrome in children (MIS-C).<ref name="Rowley2020"/>
* It is also suspected that since MIS-C presents predominantly with gastrointestinal manifestations, it replicates predominantly in the gastrointestinal tract.<ref name="Rowley2020"/>
==Differentiating Any Disease from other disease==
It should be differentiated from following diseases
* Bacterial sepsis
* Staphylococcal and streptococcal toxic shock syndrome
* Kawasaki disease.
* More information about the differential diagnosis could be found [[COVID-19-associated dermatologic manifestations|her]]<nowiki/>e.
== Epidemiology and Demographics ==
*According to a recent study among the 186 children with MIS-C, the rate of hospitalization was 12%  between March 16 and April 15 and 88% between April 16 and May 20.
*80% of the children were admitted to the intensive care unit and 20% of the children required mechanical ventilation.<ref name="FeldsteinRose2020">{{cite journal|last1=Feldstein|first1=Leora R.|last2=Rose|first2=Erica B.|last3=Horwitz|first3=Steven M.|last4=Collins|first4=Jennifer P.|last5=Newhams|first5=Margaret M.|last6=Son|first6=Mary Beth F.|last7=Newburger|first7=Jane W.|last8=Kleinman|first8=Lawrence C.|last9=Heidemann|first9=Sabrina M.|last10=Martin|first10=Amarilis A.|last11=Singh|first11=Aalok R.|last12=Li|first12=Simon|last13=Tarquinio|first13=Keiko M.|last14=Jaggi|first14=Preeti|last15=Oster|first15=Matthew E.|last16=Zackai|first16=Sheemon P.|last17=Gillen|first17=Jennifer|last18=Ratner|first18=Adam J.|last19=Walsh|first19=Rowan F.|last20=Fitzgerald|first20=Julie C.|last21=Keenaghan|first21=Michael A.|last22=Alharash|first22=Hussam|last23=Doymaz|first23=Sule|last24=Clouser|first24=Katharine N.|last25=Giuliano|first25=John S.|last26=Gupta|first26=Anjali|last27=Parker|first27=Robert M.|last28=Maddux|first28=Aline B.|last29=Havalad|first29=Vinod|last30=Ramsingh|first30=Stacy|last31=Bukulmez|first31=Hulya|last32=Bradford|first32=Tamara T.|last33=Smith|first33=Lincoln S.|last34=Tenforde|first34=Mark W.|last35=Carroll|first35=Christopher L.|last36=Riggs|first36=Becky J.|last37=Gertz|first37=Shira J.|last38=Daube|first38=Ariel|last39=Lansell|first39=Amanda|last40=Coronado Munoz|first40=Alvaro|last41=Hobbs|first41=Charlotte V.|last42=Marohn|first42=Kimberly L.|last43=Halasa|first43=Natasha B.|last44=Patel|first44=Manish M.|last45=Randolph|first45=Adrienne G.|title=Multisystem Inflammatory Syndrome in U.S. Children and Adolescents|journal=New England Journal of Medicine|year=2020|issn=0028-4793|doi=10.1056/NEJMoa2021680}}</ref>
*4% of the children required extracorporeal membrane oxygenation.<ref name="FeldsteinRose2020" />
*The mortality rate among 186 children with MIS-C was 2%.<ref name="FeldsteinRose2020" />
'''Age'''
*Among the 186 children with MIS-C distribution of age group was<ref name="FeldsteinRose2020" />
**<1yr-7%
**1-4yr-28%
**5-9yr-25%
**10-14yr-24%
**15-20yr-16%.
'''Gender'''
*Among the 186 children with MIS-C
'''Comorbidities'''
*Children with MIS-C had following underlying comorbidities.<ref name="FeldsteinRose2020" />
**Clinically diagnosed Obesity-8%
**BMI-Based Obesity-29%
**Cardiovascular diasease-3%
**Respiratory disease-18%
**Autoimmune disease or immunocompromising condition-5%
'''Organ System Involved'''
*71% of children had involvement of at least four organ systems.<ref name="FeldsteinRose2020" />
The most common organ system involved in MIS-C children among a total of 186 children were.<ref name="FeldsteinRose2020" />
*Gastrointestinal(92%)
*Cardiovascular(80%)
*Hematologic(76%)
*Mucocutaneous(74%)
*Pulmonary(70%)
*Historical perspective
== Complications and Prognosis==
===Complications===
*[[Myocardial infarction|Severe myocardial infarction]]<ref name="FeldsteinRose2020" />
*[[Cardiac arrest in covid-19|Cardiac failure/arrest]]<ref name="FeldsteinRose2020" />
*[[ARDS]]<ref name="FeldsteinRose2020" />
*[[Hypervolemia]]<ref name="FeldsteinRose2020" />
*[[Acute kidney injury|Acute Kidney Injury]]
*[[Peritonitis]]<ref name="FeldsteinRose2020" />
*[[Thrombotic complications.]]<ref name="FeldsteinRose2020" />
== Diagnosis ==
===Diagnostic Criteria===
=====Preliminary [[World Health Organization|WHO]] case definition: Children and adolescents=====
*0–19 years of age with [[fever]] >3 days<ref >{{Cite web|url=https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19|title=Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19|first=|date=|website=|archive-url=|archive-date=15 May 2020|dead-url=|access-date=}}</ref>
AND
*Two of the following:
#[[Rash]] or bilateral non-purulent [[conjunctivitis]] or mucocutaneous inflammation signs (oral, hands or feet)
#Hypotension or shock
#Features of myocardial dysfunction, [[pericarditis]], [[valvulitis]], or coronary abnormalities (including ECHO findings or elevated [[Troponin]]/[[NT-proBNP]])
#Evidence of [[coagulopathy]] (by PT, [[Partial thromboplastin time|PTT]], elevated [[D-dimer|D-Dimers]])
#Acute gastrointestinal problems ([[diarrhea]], [[vomiting]], or [[abdominal pain]])
AND
*Elevated markers of [[inflammation]] such as [[Erythrocyte sedimentation rate|ESR]], [[C-reactive protein]], or [[procalcitonin]]
AND
*No other obvious microbial cause of [[inflammation]], including bacterial [[sepsis]], [[staphylococcal]] or [[streptococcal]] shock syndromes
AND
*Evidence of [[COVID-19|COVID]]-19 ([[Reverse transcription-polymerase chain reaction|RT-PCR]], antigen test or serology-positive), or likely contact with patients with [[COVID-19|COVID]]-19
=====CDC Case Definition for MIS-C=====
*An individual aged <21 years presenting with fever, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological);<ref >{{Cite web|url=https://www.cdc.gov/mis-c/hcp/|title=CDC case definationlast=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
AND
No alternative plausible diagnoses;
AND
Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.
=== Signs and Symptoms ===
*[[Fever]] lasting 24 hours or longer.<ref name="CC""/>
*[[Vomiting]]<ref name="CC""/>
*[[Diarrhea]]<ref name="CC""/>
*[[Abdominal pain]]<ref name="CC""/>
*[[Skin rash]]<ref name="CC""/>
*[[Conjuctivitis]]<ref name="CC""/>
*[[Erythrocyte sedimentation rate|High ESR]]<ref name="CC""/>
*Redness or swelling of the lips and tongue<ref name="CC""/>
*[[Lethargy]]<ref name="CC""/>
*[[Redness]] or swelling of the hands or feet<ref name="CC""/>
*[[Confusion]]<ref name="CC""/>
*[[Headache]]<ref name="CC""/>
*[[Sore throat]]<ref name="CC""/>
*[[Syncope]]<ref name="CC""/>
*[[Lymphadenopathy]]<ref name="CC""/>
'''Emergency Warning Signs'''
*[[Shortness of breath|Difficulty Breathing]]<ref name="CC""/>
*[[Chest pain]]
*[[Confusion|New onset confusion]]
*[[Lethargy]]
*[[Cyanosis]]
*[[Abdominal pain]]
=== Physical Examination ===
'''Blood Investigations'''
*[[Lymphopenia]], [[Neutrophilia]], [[Anemia]], [[Thrombocytopenia]] have been seen in MIS-C pateints. [[Fibrinogen|Abnormal fibrinogen]], [[Hypoalbuminaemia]], elevated [[Creatine kinase|creatiine kinase]] (CK), [[Lactate dehydrogenase|LDH]], [[Triglyceride|triglycerides]] have been observed in MIS-C patients.<ref name="CC""/>
==== Inflammatory biomarkers ====
Elevation of inflammatory markers including ESR, C reactive protein and procalcitonin are  usually seen in MIS-C. Increased level of  [[Interleukin-6]] (IL-6), Interleukin-10(IL-10) [[d-dimer]], serum [[ferritin]], [[prothrombin time]] have also been seen in MIS-C.<ref name="CC""/>
==== Cardiac biomarkers ====
Elevation of cardic enzymes including  [[Cardiac troponin|cardiac troponins]] ([[Cardiac troponin I (cTnI) and T (cTnT)|cardiac troponin I(cTnI) and cardiac troponin T (cTnT)]]) and [[Brain natriuretic peptide]] ([[BNP]])) has been observed in MIS-C patients.<ref name="CC""/>
=== Radiological Findings ===
* Following Radiological Findings are observed in MIS-C patients.<ref name="CC""/>
{| border="1" cellpadding="2"
! width="225" |Test
! width="225" |Findings
|-
|Chest Xray||patchy symmetrical infiltrates, [[pleural effusion]]
|-
|Echocardiogram and EKG||[[myocarditis]], valvulitis, [[pericardial effusion]], coronary artery dilatation
|-
|Abdominal USG||[[colitis]], [[ileitis]], [[lymphadenopathy]], [[ascites]], [[hepatosplenomegaly]]
|}
'''Blood Culture, Viral PCR'''
* Absence of other potential causative organisms. IgG levels and IgM levels of [[SARS-CoV-2]] are detected.
== Treatment ==
=== Medical Therapy ===
*All the children with MIS-C are treated as suspected [[COVID-19|COVID-19.]]
*Mild to Moderate cases of MIS-C are managed supportively.<ref name="A1"">{{Cite web|url=https://www.chop.edu/clinical-pathway/multisystem-inflammatory-syndrome-mis-c-clinical-pathway|title=Emergency Department, ICU and Inpatient Clinical Pathway for
Evaluation of Possible Multisystem Inflammatory Syndrome (MIS-C)|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name="A2">{{Cite web|url=https://www.chkd.org/uploadedFiles/Documents/COVID-19/CHKD%20MIS-C%20Guideline%20D2.pdf|title= Evaluation and Management of COVID-19 Multisystem Inflammatory
Syndrome in Children (MIS-C)|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
*Supplemental [[oxygen]] is required in children with low oxygen saturation.<ref name="A2"/>
*[[Fluid replacement|Fluid resuscitation]] in 10 ml/kg aliquots with reevaluation after each bolus. Maintain euvolemia. Avoid hypervolemia.<ref name="A2"/>
*Anti-inflammatory treatments with [[Intravenous immunoglobulin|Intravenous immunoglobulin(IVIG]]) with or without [[Corticosteroid|corticosteroids]] have shown a good response rate.<ref name="A1""/><ref name="A2"/>
*[[Aspirin]] has been used primarily for its antiplatelet effect. It is recommended in all patients with [[MIS-C]].<ref name="A1""/><ref name="A2"/>
*[[Anakinra]] is considered if fevers last more than 24 hours post [[Steroid|steroids]]/[[Intravenous immunoglobulin|IVIG]] or in the moderate or severe presentation.<ref name="A1""/><ref name="A2"/>
*[[Tocilizumab]] is also considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.<ref name="A1""/><ref name="A2"/>
*Empiric antibiotics like [[vancomycin]], [[ceftriaxone]], and [[clindamycin]] are given for community-acquired shock presentation until cultures are negative for 48 hours.<ref name="A1""/><ref name="A2"/>
{| border="1" cellpadding="2"
! width="225" |Presentation
! width="225" |Treatment
|-
|Mild Disease||
*Symptomatic Treatment
|-
|Severe Disease||
*Symptomatic Treatment
*[[Intravenous immunoglobulin|IVIG(IV)]]
*[[Corticosteroid|Corticosteroids]](IV/PO)
*Consider adding [[Anakinra]] or [[Tocilizumab]] if [[fever]] persist for more than 24 hours post [[Steroid|steroids]] and I[[Intravenous immunoglobulin|VIG]] use.
|}
== Prevention of MIS-C ==
*MIS-C can be prevented by reducing the risk of child exposure to [[COVID-19|COVID]]-19 infection.
== References ==
<references />
== References ==
<references />
==Presentations==
==Presentations==
<br />
<br />
Line 6: Line 237:
*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 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>


{{familytree/start |summary=Sample 1}}
{{familytree | | | | | | | | | A01 | | | | | | | | |A01=*Evaluation of Child for MIS-C.}}
{{familytree | | | | |,|-|-|-|-|^|-|-|-|-|.| | | | }}
{{familytree | | | B01 | | | | | | | |  B02  | |B01='''Stable Child'''
*Fever(≥ 38.0°C) for ≥ 3 days.
Presence of clinical features|B02=Unstable Child(Sepsis)
Fever(≥ 38.0°C) for ≥ 1 day
Presence of signs/symptom
*Evidence of myocardial dysfunction or hypotension }}
{{familytree | | | |!| | | | | | | | | |!| }}
{{familytree | | | C01 | | | | | | | | |!| |}}
{{familytree | |,|-|^|.| | | | | | | | |!| }}
{{familytree | D01 | | D02 | | | | | | D03 |D01=D01|D02=D02|D03=D03}}
{{familytree | |!| | | | | | | | | |,|-|^|.| }}
{{familytree | E01 | | | | | | | E02 | | | E03 |E01=E01|E02=E02|E03=E03}}
{{familytree | | | | | | | | | | |!| | | | |!| }}
{{familytree | | | | | | | | | | F01 | | | F02 |F01=F01|F02=F02}}
; Symptoms
; 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  
*'''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  

Latest revision as of 19:51, 13 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Harmeet Kharoud M.D.[2]

Synonyms and keywords: Multisystem Inflammatory Syndrome in Children (MIS-C)

Overview

Multisystem Inflammatory Syndrome in Children (MIS-C) is a condition that causes inflammation of some parts of the body like heart, blood vessels, kidneys, digestive system, brain, skin, or eyes. According to recent evidence, it is suggested that children with MIS-C had antibodies against COVID-19 suggesting children had COVID-19 infection in the past. This syndrome appears to be similar in presentation to Kawasaki disease, hence also called Kawasaki -like a disease. It also shares features with staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, and macrophage activation syndromes.[1]

Classification of Disease Severity of MIS-C

  • Mild Disease
  • Children with MIS-C fall under this category who-[2]
    • require minimal to no respiratory support.
    • minimal to no organ injury
    • normotensive
    • Do not meet the criteria for ICU admission.
  • Severe Disease
  • Children with MIS-C fall under this category who-[2]
    • have significant oxygen requirements (HFNC, BiPAP, mechanical ventilation).
    • have a mild-severe organ injury and ventricular dysfunction.
    • have a vasoactive requirement.
    • meet the criteria for ICU admissions

Pathophysiology

  • The excat pathophysiological mechanism of MIS-C is unclear. Since there is a lag time between MIS-C appearance and COVID-19 infection it is suspected to be causing by antibody dependent enhancement.[3]
  • Another hypothesis is that since coronavirus block type1 and type III interferons, it results in delayed cytokine response in children with initially high viral load or whose immune response is unable to control infections causing MIS-C. Therefore, IFN responses result in viral clearance when the viral load is low resulting in mild infection. However, when the viral load is high and /or immune system is not able to clear the virus, the cytokine storm result in multisystem inflammatory syndrome in children (MIS-C).[3]
  • It is also suspected that since MIS-C presents predominantly with gastrointestinal manifestations, it replicates predominantly in the gastrointestinal tract.[3]

Differentiating Any Disease from other disease

It should be differentiated from following diseases

  • Bacterial sepsis
  • Staphylococcal and streptococcal toxic shock syndrome
  • Kawasaki disease.
  • More information about the differential diagnosis could be found here.

Epidemiology and Demographics

  • According to a recent study among the 186 children with MIS-C, the rate of hospitalization was 12% between March 16 and April 15 and 88% between April 16 and May 20.
  • 80% of the children were admitted to the intensive care unit and 20% of the children required mechanical ventilation.[4]
  • 4% of the children required extracorporeal membrane oxygenation.[4]
  • The mortality rate among 186 children with MIS-C was 2%.[4]

Age

  • Among the 186 children with MIS-C distribution of age group was[4]
    • <1yr-7%
    • 1-4yr-28%
    • 5-9yr-25%
    • 10-14yr-24%
    • 15-20yr-16%.

Gender

  • Among the 186 children with MIS-C

Comorbidities

  • Children with MIS-C had following underlying comorbidities.[4]
    • Clinically diagnosed Obesity-8%
    • BMI-Based Obesity-29%
    • Cardiovascular diasease-3%
    • Respiratory disease-18%
    • Autoimmune disease or immunocompromising condition-5%

Organ System Involved

  • 71% of children had involvement of at least four organ systems.[4]

The most common organ system involved in MIS-C children among a total of 186 children were.[4]

  • Gastrointestinal(92%)
  • Cardiovascular(80%)
  • Hematologic(76%)
  • Mucocutaneous(74%)
  • Pulmonary(70%)
  • Historical perspective

Complications and Prognosis

Complications

Diagnosis

Diagnostic Criteria

Preliminary WHO case definition: Children and adolescents
  • 0–19 years of age with fever >3 days[5]

AND

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

AND

AND

AND

  • Evidence of COVID-19 (RT-PCR, antigen test or serology-positive), or likely contact with patients with COVID-19
CDC Case Definition for MIS-C
  • An individual aged <21 years presenting with fever, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological);[6]

AND

No alternative plausible diagnoses;

AND

Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.

Signs and Symptoms

Emergency Warning Signs

Physical Examination

Blood Investigations

Inflammatory biomarkers

Elevation of inflammatory markers including ESR, C reactive protein and procalcitonin are usually seen in MIS-C. Increased level of Interleukin-6 (IL-6), Interleukin-10(IL-10) d-dimer, serum ferritin, prothrombin time have also been seen in MIS-C.[1]

Cardiac biomarkers

Elevation of cardic enzymes including cardiac troponins (cardiac troponin I(cTnI) and cardiac troponin T (cTnT)) and Brain natriuretic peptide (BNP)) has been observed in MIS-C patients.[1]

Radiological Findings

  • Following Radiological Findings are observed in MIS-C patients.[1]
Test Findings
Chest Xray patchy symmetrical infiltrates, pleural effusion
Echocardiogram and EKG myocarditis, valvulitis, pericardial effusion, coronary artery dilatation
Abdominal USG colitis, ileitis, lymphadenopathy, ascites, hepatosplenomegaly

Blood Culture, Viral PCR

  • Absence of other potential causative organisms. IgG levels and IgM levels of SARS-CoV-2 are detected.

Treatment

Medical Therapy

  • All the children with MIS-C are treated as suspected COVID-19.
  • Mild to Moderate cases of MIS-C are managed supportively.[7][8]
  • Supplemental oxygen is required in children with low oxygen saturation.[8]
  • Fluid resuscitation in 10 ml/kg aliquots with reevaluation after each bolus. Maintain euvolemia. Avoid hypervolemia.[8]
  • Anti-inflammatory treatments with Intravenous immunoglobulin(IVIG) with or without corticosteroids have shown a good response rate.[7][8]
  • Aspirin has been used primarily for its antiplatelet effect. It is recommended in all patients with MIS-C.[7][8]
  • Anakinra is considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.[7][8]
  • Tocilizumab is also considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.[7][8]
  • Empiric antibiotics like vancomycin, ceftriaxone, and clindamycin are given for community-acquired shock presentation until cultures are negative for 48 hours.[7][8]
Presentation Treatment
Mild Disease
  • Symptomatic Treatment
Severe Disease

Prevention of MIS-C

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

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 "Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19" (PDF). line feed character in |title= at position 46 (help)
  2. 2.0 2.1 "Evaluation and Management of COVID-19 Multisystem Inflammatory Syndrome in Children (MIS-C)" (PDF). line feed character in |title= at position 63 (help)
  3. 3.0 3.1 3.2 Rowley, Anne H. (2020). "Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children". Nature Reviews Immunology. doi:10.1038/s41577-020-0367-5. ISSN 1474-1733.
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 Feldstein, Leora R.; Rose, Erica B.; Horwitz, Steven M.; Collins, Jennifer P.; Newhams, Margaret M.; Son, Mary Beth F.; Newburger, Jane W.; Kleinman, Lawrence C.; Heidemann, Sabrina M.; Martin, Amarilis A.; Singh, Aalok R.; Li, Simon; Tarquinio, Keiko M.; Jaggi, Preeti; Oster, Matthew E.; Zackai, Sheemon P.; Gillen, Jennifer; Ratner, Adam J.; Walsh, Rowan F.; Fitzgerald, Julie C.; Keenaghan, Michael A.; Alharash, Hussam; Doymaz, Sule; Clouser, Katharine N.; Giuliano, John S.; Gupta, Anjali; Parker, Robert M.; Maddux, Aline B.; Havalad, Vinod; Ramsingh, Stacy; Bukulmez, Hulya; Bradford, Tamara T.; Smith, Lincoln S.; Tenforde, Mark W.; Carroll, Christopher L.; Riggs, Becky J.; Gertz, Shira J.; Daube, Ariel; Lansell, Amanda; Coronado Munoz, Alvaro; Hobbs, Charlotte V.; Marohn, Kimberly L.; Halasa, Natasha B.; Patel, Manish M.; Randolph, Adrienne G. (2020). "Multisystem Inflammatory Syndrome in U.S. Children and Adolescents". New England Journal of Medicine. doi:10.1056/NEJMoa2021680. ISSN 0028-4793.
  5. "Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19".
  6. "CDC case definationlast=".
  7. 7.0 7.1 7.2 7.3 7.4 7.5 "Emergency Department, ICU and Inpatient Clinical Pathway for Evaluation of Possible Multisystem Inflammatory Syndrome (MIS-C)". line feed character in |title= at position 61 (help)
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 "Evaluation and Management of COVID-19 Multisystem Inflammatory Syndrome in Children (MIS-C)" (PDF). line feed character in |title= at position 63 (help)

References


Presentations


  • Presentation of COVID-19 is less severe in children as compared to adults. Most of the children are asymptomatic.[1]
  • 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.
  • COVID-19 in children could range from asymptomatic presentation to mild to severe disease.
  • The incubation period of SARS-CoV-2 varies from 2 to 14 days with most patients developing symptoms 3 to 7 days after exposure.[1]
Symptoms
  • Fever and Cough are one of the most common symptoms reported in children. One study showed fever is prevalent in 47.5% of children and cough in 41.5% among the 1124 children with COVID-19. According to the CDC, fever, and cough was reported in 56% and 54% of children with COVID 19
  • Dyspnea, nasal congestion, pharyngeal erythema, and sore throat are also common presentations in children.
  • Gastrointestinal symptoms-The gastrointestinal manifestation in COVID-19 positive children are diarrhea, vomiting, abdominal pain, nausea, and anorexia. Children can present with gastrointestinal symptoms in the absence of respiratory symptoms.
  • Cutaneous Findings- The cutaneous findings in COVID-19 positive children range from petechiae to papulovesicular rashes to diffuse urticaria. These appear early in the course of COVID-19 and result secondary to viral replication or circulating cytokines. Many patients with COVID-19 are presenting with chilblains like lesions unrelated to cold. Chilblains are painful or itchy swellings of the toes and fingers, caused by small-vessel inflammation from repeated exposure to cold. A retrospective case series presented 22 children and adolescents with COVID-19 who presented with chillblains lesions. [2][3]
  • 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.[4]
  • Neonates and Infants with COVID-19 are often asymptomatic or present with fever with or without mild cough and congestion.
Severity of Disease in Children with COVID-19
  • Asymptomatic presentation-
    • A large number of children with COVID-19 are asymptomatic.
    • According to one study 14.2% of children were asymptomatic. Another study showed 18% of asymptomatic children with COVID-19.
  • Mild Disease
    • Few numbers of children also present with mild manifestations of COVID-19.
    • A study showed 36.3% of children present with a mild form of the disease.

Moderate

  • Severe
    • 2.1% of children present with a severe form of COVID-19 disease.
    • Children with underlying comorbidities are more susceptible to getting severe COVID-19 disease.

===Complication 1===[5]


Multisystem Inflammatory Syndrome in Children (MIS-C)

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

Epidemiology and Demographics

  • According to a recent study among the 186 children with MIS-C, the rate of hospitalization was 12% between March 16 and April 15 and 88% between April 16 and May 20.
    • 80% of the children were admitted to the intensive care unit and 20% of the children required mechanical ventilation.
    • 4% of the children required extracorporeal membrane oxygenation.
  • The mortality rate among 186 children with MIS-C was 2%.

Age

  • Among the 186 children with MIS-C distribution of age group was
    • <1yr-7%
    • 1-4yr-28%
    • 5-9yr-25%
    • 10-14yr-24%
    • 15-20yr-16%.

Gender

  • Among the 186 children with MIS-C

Comorbidities

  • Children with MIS-C had following underlying comorbidities.
    • Clinically diagnosed Obesity-8%
    • BMI-Based Obesity-29%
    • Cardiovascular diasease-3%
    • Respiratory disease-18%
    • Autoimmune disease or immunocompromising condition-5%

Organ System Involved

  • 71% of children had involvement of at least four organ systems.

The most common organ system involved in MIS-C children among a total of 183 children were.

  • Gastrointestinal(92%)
  • Cardiovascular(80%)
  • Hematologic(76%)
  • Mucocutaneous(74%)
  • Pulmonary(70%).

Pathophysiology

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

Emergency Warning Signs

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

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

 
 
 
 
 
 
 
 
*Evaluation of Child for MIS-C.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stable Child
  • Fever(≥ 38.0°C) for ≥ 3 days.
Presence of clinical features
 
 
 
 
 
 
 
Unstable Child(Sepsis)

Fever(≥ 38.0°C) for ≥ 1 day Presence of signs/symptom

  • Evidence of myocardial dysfunction or hypotension
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Test Findings
Chest Xray patchy symmetrical infiltrates, pleural effusion
Echocardiogram and EKG myocarditis, valvulitis, pericardial effusion, coronary artery dilatation
Abdominal USG colitis, ileitis, lymphadenopathy, ascites, hepatosplenomegaly

Diagnosis

Preliminary WHO case definition: Children and adolescents

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

AND

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

AND

AND

AND

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

Treatment

  • All the children with MIS-C are treated as suspected COVID-19.
  • Mild to Moderate cases of MIS-C are managed supportively.
  • Anti-inflammatory treatments with Intravenous immunoglobulin(IVIG) with or without corticosteroids have shown a good response rate.[6]
  • Aspirin has been used primarily for its antiplatelet effect.[6]
  • The antiviral therapy where required are only given in the context of clinical trials(Eg RECOVERY TRIAL).
  • Empiric antibiotics like vancomycin, ceftriaxone, and clindamycin are given for community-acquired shock presentation until cultures are negative for 48 hours."www.childrensmn.org" (PDF).
  • Fluid resuscitation in 10 ml/kg aliquots with reevaluation after each bolus. Maintain euvolemia. Avoid hypervolemia.

Prevention of MIS-C

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

Complications of MIS-C

Acute Heart Failure

Complication 2

COVID-19 and HIV

Overview

  • An observational prospective study found out that the incidence of HIV-infected individuals to be affected by SARS-CoV-2 was similar to the general population.
  • Specific antiretroviral therapy did not affect COVID-19 severity.
  • Immunosuppression(low CD4 cell counts) was associated with COVID-19 severity.
  • Patients with HIV infection often have other comorbidities(lung disease, cardiovascular disease) therefore, increasing the risk for severe-COVID-19 disease.

Risk

  • At present people with HIV who are at greatest risk of Severe COVID-19 infection are people -
    • who have lowCD4 cell count.
    • not on antiretroviral therapy.

Presentation

  • There hasn't been any observable difference in clinical presentation among people with HIV infection as compared to the general population.
  • Common symptoms for COVID-19 are
    • Fever or chills
    • Cough[8]
    • Shortness of Breath or difficulty breathing
    • Fatigue
    • Muscle or Body aches
    • Headache
    • New loss of taste or smell
    • Sore Throat
    • Congestion or runny nose
    • Nausea or vomiting
    • Diarrhea

Recommendations for Patients with HIV

  • Maintain the supply for antiretroviral therapy for a minimum of 30 days.
  • Virtual visit and telemedicine should be considered for non-urgent care and non-adherence counseling
  • People with suppressed HIV viral load and in stable health, should postpone their routine medical care and laboratory visits to the extent possible.
  • If they develop symptoms of COVID-19 like fever, cough, shortness of breath, etc they should seek medical advice.
  • They should make sure their vaccination status is uptodate.

Specific Populations with HIV

Pregnant Patients