Emerging Evidence on COVID-19 Rapid Review of Multisystem ...

January 28, 2021

PHAC EMERGING SCIENCE SUMMARIES 1

Emerging Evidence on COVID-19

Rapid Review of Multisystem Inflammatory Syndrome in

Children (MIS-C)

INTRODUCTION

What are the epidemiological characteristics of multisystem inflammatory syndrome in children (MIS-C)?

The goal of this review is to summarize the epidemiological characteristics of multisystem inflammatory

syndrome in children (MIS-C), which is also referred to as Paediatric Inflammatory Multisystem Syndrome

(PIMS). MIS-C is an emerging condition that has been identified during the COVID-19 pandemic. Children

presenting with Kawasaki-like illness following positive COVID-19 tests were first reported in the UK on April

27, 2020 (1). Case definitions have since been released by World Health Organization (2), the Centers for

Disease Control in the United States (USA) (3), and the Royal College of Paediatrics and Child Health in the

United Kingdom (4). As illustrated in the appendix, the three case definitions are similar, but not the same.

In this review, the term MIS-C is used for consistency, but broadly refers to the syndrome known as PIMS or

MIS-C. There is no definitive diagnostic test for MIS-C. MIS-C is considered a separate, but related, syndrome

to incomplete, complete or atypical Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), toxic

shock syndrome (TSS), and macrophage activated syndrome (MAS), with many overlapping features (5).This

review includes evidence from articles where one of the three definitions were applied, or Kawasaki Disease or

an inflammatory syndrome following COVID-19 was diagnosed.

The vast majority of the MIS-C articles were case reports and cohort studies. To give a rough indication of the

strength of the evidence, the articles were then organized as large, medium, and small based on the number

of MIS-C patients presented in the article ≥50, 6-49, and ≤5, respectively. Outcomes related to the

epidemiology of MIS-C were summarized, including: demographics of MIS-C patients (age, sex, ethnicity/race

and comorbidities), common severity outcomes (intensive care unit (ICU) admission, mechanical ventilation

and extracorporeal membrane oxygenation (ECMO) utilization), mortality and the timing of MIS-C compared

to acute COVID-19 infection. Note that similar cases of multisystem inflammatory syndrome have been

reported in adults (known as MIS-A), which is the topic of a separate review available upon request:

[email protected]

KEY POINTS

There were 102 articles identified. Eleven articles were large cohort studies, describing more than 50 cases of

MIS-C each. Forty-three articles were medium-sized, describing 6-49 cases of MIS-C each. Forty-eight articles

were case reports where the number of cases of MIS-C described ranged from one to five.

mailto:[email protected]

COVID-19 Summary of MIS-C January 28, 2021


Prevalence among Paediatric COVID-19 Cases

A large, international, multi-site study estimated that MIS-C affected between 0.5%-3.1% of all diagnosed

pediatric COVID-19 patients and between 0.9%-7.6% of hospitalized pediatric COVID-19 patients aged less

than 18 years (6). Three other articles looked at the frequency of MIS-C amongst hospitalized pediatric

COVID-19 cases, with estimates varied from 6% in Peru (7) to 9% and 11% in the USA (8,9).

Age

MIS-C can affect children of any age as indicated by the ranges across articles. However, the median age of

cases was in the range of 7-11 years. This was consistent in the large, medium and small articles.

Sex

In the large, medium and small articles, 57-58% of cases were male.

Comorbidities

In the articles that reported on comorbidities, the definition of comorbidity was inconsistent. The most

commonly reported comorbidity was obesity. Obesity rates were consistent, but lower in small articles (8%)

compared with medium (22%) and large (24-29%) articles. Another common comorbidity was asthma (6-

18%). Patients with at least one comorbidity ranged from 19% when excluding obesity to 29% with obesity

included. Few articles made comparisons of the rates of a given comorbidity to the prevalence of that

comorbidity in the general pediatric population. One article found that the proportion of MIS-C patients with

obesity is slightly higher than reported in the underlying population (10).

No articles attempted to disentangle the relationship between any given condition, COVID-19 infection and

the development of MIS-C. For example, children with obesity or asthma could be more likely to contract

COVID-19, and would therefore be overrepresented in MIS-C cases, without being specifically predisposed to

MIS-C. This relationship is largely unexplored and needs to be studied further.

Ethnicity

Although some articles reported on ethnicity or race, few articles provided comparisons to the composition of

the underlying population. However, in 14 medium-sized articles from the USA, Black and Hispanic children

were the largest portion of patients at 36% and 29% respectively. A large article from the USA reported

similar demographics (33% Hispanic and 27% Black) (10). The USA CDC states that, compared with White

people, Black people are 2.6 times more likely and Hispanic people 2.8 times more likely to be infected with

COVID-19 (11). This may partially or wholly explain any disproportionately high rates of MIS-C among these

populations. This complex relationship needs to be studied further.

Onset of MIS-C relative to SARS-CoV-2 infection

Clinical case data suggests that there is a delay in the onset of MIS-C after acute infection with SARS-CoV-2.

In three articles that documented the timing of acute COVID-19 infection for each MIS-C patient, the onset of

MIS-C occurred 15-24 days after the onset of acute COVID-19 symptoms. A handful of articles (n=6)

determined the time between the peak of MIS-C cases was approximately two to five weeks after the peak of



COVID-19 cases at the state or country level. The delay in onset is further supported by low positivity rates

(<50%) using RT-PCR compared to IgG serology (>75%). This suggests that MIS-C is often a post-infection

syndrome, having a delayed onset after the acute COVID-19 infection.

Severity Outcomes

The evidence suggests MIS-C patients often need intensive care, but that the overall survival rate is high.

Eight large articles reported ICU admission rates of 21-80%; this was consistent with the medium-sized

articles reporting 65% and the small articles reporting 74%. In addition, between 25-40% of MIS-C cases were

intubated and 5-11% required ECMO. In the large articles, fatality rates ranged from 0 to 2.2% of hospitalized

patients and 2.6% of MIS-C patients admitted to the ICU. This was consistent with the medium-sized articles

that reported a 2% mortality rate but was lower than the 7% mortality reported in the small articles. There

may be duplicate cases and deaths included in these totals, but the number of deaths could also be an

underestimation as not all cases were resolved at the time of publication of the papers.

OVERVIEW OF THE EVIDENCE

In a literature search up to November 10, 2020, 102 articles were found that contain information on the

epidemiological characteristics of MIS-C. Nearly all of these articles were case reports or retrospective

cohorts.

There were 11 large articles that were mostly retrospective cohorts. These included two multi-national studies,

four articles from the USA, three from the UK, and two from mainland Europe (Table 1).

There were 43 medium-sized articles (with a total of 861 cases of MIS-C) included in this review. These

included both case series and retrospective cohort studies. In total, 18 were from the USA (379 cases), 13 from

Europe (314 cases), four were from South America (50 cases), two from the Middle East (53 cases), two from

India (42 cases) and one from South Africa (23 cases) (Table 2).

Case reports tend to be published when a new condition has been identified. They are good for generating

hypotheses but are generally considered weak evidence. These 48 case reports are keeping with this trend as

they capture some of the earlier case reports of MIS-C, prior to official recognition of the syndrome and to

highlight the range of countries that have reported cases of MIS-C: 20 were from the USA, 13 from Europe,

and the rest were from India (6 articles), the Middle East (5 articles), South America (2 articles), Africa (1

article) and Canada (1 article) (Table 3).

Limitations

The majority of articles in this review are from the USA and Europe. In contrast, only two articles are

from Africa, and only a portion of one review drew data from Asia. There is only one case report from

Canada.



There is an issue with double counting patients, as some articles were drawing from the same

hospitals, regions or data sources. This could bias the results. When reported by the author, this is

identified in the tables below. To avoid the extensive double counting, systematic and other reviews

were not included.

Many articles had incomplete data, especially co-morbidity and ethnicity data, which were often

collected from only a portion of the cases.

Because this is an emerging syndrome, case definitions and inclusion criteria have evolved over time.

Each case may or may not meet one of the three standard case definitions, or the requirements for

Kawasaki disease.

None of the articles provide any follow-up to patients after they recover from acute MIS-C. Therefore,

sequelae or further complications are still unknown.

CONTENTS

LARGE ARTICLES ..................................................................................................................... 4

MEDIUM-SIZED ARTICLES ....................................................................................................... 9

SMALL ARTICLES................................................................................................................... 20

For each study contained in the evidence tables below, the following information on MIS-C is provided when

available: Age, sex, ethnicity/race, comorbidities, severity outcomes (ICU admission, intubation, ECMO and

death), PCR and serology testing results for SARS-CoV-2, and interval between acute COVID-19 infection and

MIS-C onset. These variables are not included when they were not reported.

LARGE ARTICLES

Table 1: Articles describing 50 or more cases of MIS-C, by descending order of size

Study Method Key Findings

Godfred-Cato (2020)

(10)

Retrospective cohort

USA

Mar-Jul, 2020

Data on 570 MIS-

C cases was

collected from 40

state health

departments in

the District of

Columbia and

New York City

- Median age = 8 years (range = 2 weeks – 20 years)

- 316/570 (55%) male

- 187 (33%) were Hispanic, 153 (27%) Black, 61 (11%)

White, 13 (2%) Asian, 48 (8%) other ethnicity and 108

(19%) unknown ethnicity. This study finds that the

proportion of Hispanic, Black and White MIS-C patients

with obesity is slightly higher than reported in the

population.

https://www.cdc.gov/mmwr/volumes/69/wr/mm6932e2.htm



- 146 (26%) were obese, 48 (8%) had a chronic lung

disease

- 364 (64%) admitted to ICU, 69 (12%) required mechanical

ventilation

- 10 (2%) died

- All but 5 tested positive for COVID-19 by either or both

PCR or serological testing and the other 5 had an

epidemiological link to a known COVID-19 case

Feldstein (2020) (12)


USA

Mar-May, 2020

Prospective and

retrospective

surveillance of

186 patients with

MIS-C admitted

to participating

health centers in

26 states in the

USA

- Median age = 8.3 years (IQR = 3.3-12.5 years)

- 115/186 (62%) male

- 57 (31%) were Hispanic, 46 (25%) Black, 35 (19%) Asian, 9

(5%) other ethnicity, 41 (22%) unknown ethnicity

- 45 (24%) were obese. In addition, 51 (27%) had a

comorbidity, including 33 (18%) with respiratory

conditions, 5 (3%) with cardiac conditions, 10 (5%) with

immune-related conditions and 20 (11%) with other

conditions.


ventilation, 8 (4%) required ECMO

- 4 (2%) died

- 131 tested positive for COVID-19 by either or both PCR

or serological testing and the other 55 had an

epidemiological link to a known COVID-19 case

- MIS-C cases occurred a median of 25 days (range = 6-51

days) after acute COVID-19 infection

Deep (2020) (13)


UK

Mar-May, 2020

Note: 78 of the

children in this study

had been previously

reported.

116 children

admitted to 24

PICUs in the UK

were assessed for

acute kidney

injury

Patients with

existing kidney

problems were

excluded

- Median age = 11 years (IQR = 7-14 years)

- 76/116 (66%) male

- 51 (45%) were Black, 29 (26%) Asian, 24 (21%) White, 9

(8%) other ethnicity

- 20 (17%) had a comorbidity, including 5 (4%) with

asthma, 3 (3%) with cystic fibrosis, 1 (1%) with chronic

lung disease, 1 (1%) with autism, 10 (9%) others

- 116 (100%) admitted to ICU (as required by the study

design), 41 (35%) required mechanical ventilation, 3 (3%)

required ECMO

- 2 (2%) died

https://www.nejm.org/doi/full/10.1056/NEJMoa2021680

https://pubmed.ncbi.nlm.nih.gov/33044282/



Belot (2020) (14)


France

Mar-May, 2020

All paediatric

departments in

France reported

108 cases of MIS-

C diagnosed after

March 1, 2020, to

estimate the

burden of this

condition in

France


- 53/108 (49%) male


ventilation

- 1 (1%) died

- 79 tested positive for COVID-19 by either or both PCR or

serological testing. 16 had proven contact with COVID-

19 cases and 13 were suspected to have had COVID-19

based upon symptoms and history.

- MIS-C cases peaked 4-5 weeks after local COVID-19

cases peaked

Dufort (2020) (15)


USA

Mar-May, 2020

Hospitals in New

York State that

provide pediatric

care reported 99

potential cases of

MIS-C

- Age categories were given: 31 (31%) were aged 0 to 5

years, 42 (42%) were aged 6 to 12 years, and 26 (26%)

were aged 3 to 20 years

- 53/99 (54%) male

- 31 (31%) were Black, 29 (29%) White, 4 (4%) Asian, 14

(14%) other ethnicity, 21 (21%) unknown ethnicity

- 36 (36%) had a comorbidity, including 29 (29%) with

obesity and 14 (14%) with chronic lung disease



- 2 (2%) died

- 76/77 (99%) tested serology positive while 50/99 (56%)

tested PCR positive

- MIS-C cases peaked 31 days after local COVID-19 cases

peaked

Antunez-Montes

(2020) (16)

Ambidirectional

cohort

Mexico, Colombia,

Peru, Costa Rica and

Brazil

Jul-Aug, 2020

A physician group

in Central and

South America

collected 95 MIS-

C cases from 409

confirmed

pediatric

SARS-CoV-2

infections

- 95 cases of MIS-C were identified from 409 pediatric

patients admitted to hospital with a positive COVID-19

test (23%)

- Median age = 7 years (range = 1 month - 17 years). The

MIS-C patients were significantly older than non-MIS-C

pediatric patients admitted to hospital with COVID-19.

- 52/95 (55%) male

- 11 (12%) had comorbidities, and had significantly lower

socioeconomic status than pediatric patients admitted

with acute COVID-19

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30271-6/fulltext

https://www.nejm.org/doi/full/10.1056/NEJMoa2021756

https://www.medrxiv.org/content/10.1101/2020.08.29.20184242v1





ventilation

- 2 (2%) died

- All tested positive for COVID-19 by either or both PCR or

serological testing

Davies (2020) (17)


UK

Apr-May, 2020

Note: Eight of the

children included in

this study had been

reported previously

A description of

78 PIMS cases,

aged 17 and

under, admitted

to PICUs in the

UK

- Prior to COVID-19, historical data for similar

inflammatory disease averaged 1 ICU admission per

week (95% CI 0.85–1.22). In comparison, there was an

average of 14 cases per week for PIMS, and a peak of 32

admissions per week during the study period.


- 52/78 (67%) male


(3%) other ethnicity

- 17 (22%) had comorbidities, including 2 (3%) with major

pre-existing conditions

- 78 (100%) admitted to ICU (as it was required for

inclusion in the study), 36 (46%) required mechanical


- 2 (3%) died


tested PCR positive

Jonat (2020) (18)


USA

Mar-Jun, 2020

A description of

all 54 cases of

MIS-C identified

in a single

hospital in the

given date range

- Median age = 7 years (range = 10 months - 20 years)

- 25/54 (46%) male

- 19 (35%) were White, 10 (19%) Black, 8 (15%) other

ethnicity, 17 (31%) unknown ethnicity

- 7 had pre-existing conditions (excluding obesity)

- 31 (57%) admitted to the ICU. No patients required

mechanical ventilation or ECMO

- None died


tested PCR positive

Cattalini (2020) (19)

(preprint)


A survey sent to

the Italian

Pediatric Society

and 53 patients

- Median age of KawaCOVID cases = 7 years (IQR: 4.5-11

years), while the median age of Kawasaki cases = 2 years

https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30215-7/fulltext

https://journals.lww.com/pccmjournal/Abstract/9000/Multisystem_Inflammatory_Syndrome_in_Children.97935.aspx

https://www.researchgate.net/publication/343972203_Are_Kawasaki_Disease_and_Pediatric_Multi-Inflammatory_Syndrome_Two_Distinct_Entities_Results_from_a_Multicenter_Survey_During_SARS-CoV-2_Epidemic_in_Italy



Italy

Feb-May, 2020

met the diagnosis

of “KawaCOVID”

(equivalent to

MIS-C)

(IQR: 1-4 years). Median age is significantly different

(p<0.0001).

- There was no significant difference in the sex ratio of

KawaCOVID compared to Kawasaki disease

- ICU admission was more common in KawaCOVID

compared to Kawasaki cases (23.1% vs 1.1%; p<0.0001)

- KawaCOVID cases had more serious cardiac involvement

than Kawasaki cases - myocarditis (60.4% vs 3.1%;

p<0.0001), pericarditis (26.4% vs 7.3%; p=0·0013), heart

failure (35.8% vs 1%; p<0.00001) and others

- All KawaCOVID patients tested positive for COVID-19 by

either or both PCR or serological testing (31 tested

serology positive while 14 tested PCR positive)

- None died

Whittaker (2020) (20)

Retrospective survey

UK

Mar-May, 2020

Note: Eight of the

children included in

this study have

previously been

reported

An online survey

with data on 58

children who had

been admitted to

8 hospitals in

England with

PIMS (MIS-C)

- Median age = 9 years (IQR = 5.7-14 years, range = 3

months – 17 years)

- 38/58 (66%) male

- 7 (12%) had comorbidities, including 3 (5%) with asthma,

and 1 each (2%) with neurodisability, epilepsy, sickle cell

trait, and alopecia

- 29 (50%) of patients were admitted to ICU, 25 (43%)

required mechanical ventilation, 2 (3%) required ECMO

- 1 (2%) died


tested PCR positive

Duarte-Salles (2020)

(6)

(preprint)


US, Spain, France,

Germany and South

Korea

Jan-Jun, 2020

Based on medical

records, hospital

billing data and

insurance claims

data from the US,

Europe, and Asia,

children

diagnosed or

hospitalized with

COVID-19 were

compared with a

- This study includes 55,270 children and adolescents

diagnosed with COVID-19, including 3,693 hospitalized

with COVID-19 and were compared with a historical

cohort of 1,952,693 children diagnosed with influenza.

- MIS-C was relatively uncommon, affecting between 0.5%

and 3.1% of patients diagnosed with COVID-19, and

between 0.9% and 7.6% of patients hospitalized with

COVID-19.

- MIS-C was thought to be linked with COVID-19, as

similar syndromes are much less common in the

historical influenza cohort.

https://jamanetwork.com/journals/jama/fullarticle/2767209




previous seasonal

influenza cohort

MEDIUM-SIZED ARTICLES

Table 2: Articles describing 6 to 49 cases of MIS-C, by descending order of size

STUDY METHOD KEY OUTCOMES

Mamishi (2020) (21)


Iran

Mar-Jun 2020

45 cases of MIS-C

are described

- Median age = 7 years (range = 10 months – 17 years)

- 24/45 (46%) male

- 6 (13%) had pre-existing conditions

- 5 (11%) died - 4 of them had underlying diseases (acute

lymphocytic leukaemia, chronic kidney disease, cerebral

palsy and Budd–Chiari syndrome)

- 35 tested serology positive, 10 tested PCR positive

Miller (2020) (22)


USA

Apr-May 2020

44 cases of MIS-C

are described

- Median age = 7.3 years (SD = 4.98 years, range = 7

months – 20 years)

- 20/44 (45%) male

- 15 (34%) were Hispanic, 9 (20%) Black, 9 (20%) White, 11

(25%) unknown ethnicity

- 16 (36%) were overweight

- 1 (2%) required mechanical ventilation

- None died

- 31/32 tested serology positive while 15/44 tested PCR

positive

Belhadjer (2020) (23)


France

Mar-Apr 2020

35 cases of MIS-C

that had cardiac

involvement and

required ICU

admission are

described

- Median age = 10 years (range = 2-16 years)

- 18/35 (51%) male

- 6 (17%) were overweight, 3 (9%) had asthma, 1 (3%) had

lupus



- None died

- 14 tested PCR positive, while 30 patients tested serology

positive (28 IgG positive and 2 IgM positive)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484297/


https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.048360



Hameed (2020) (24)


UK

Apr-May 2020

Note: 8 patients

were reported in

other studies

35 cases of MIS-C

under the age of

17 are described

- Median age = 11 (IQR = 8 years)

- 27/35 (77%) male



- 1 (3%) died

- 25 tested IgG positive and 23 IgM positive.

Sethuraman (2020)

(25)


USA

Apr-Jul 2020

34 cases of MIS-C

are described

- Median age = 6 years (IQR = 8 years)

- 16/34 (47%) male

- 23 (68%) were Black, other ethnicity/race not reported

- 2 (6%) were obese and 9 (26%) had asthma

24 (71%) admitted to ICU, 8 (24%) required mechanical


- None died

- 18/25 tested IgG positive, 8/34 tested PCR positive

- MIS-C cases peaked 3 weeks after local COVID-19 cases

peaked

Minocha (2020) (26)


USA

Mar-Jun 2020

33 cases of MIS-C

are described

- Median age = 2.8 years (IQR = 1.4-9 years)

- 19/33 (56%) male

- 12 (36%) Hispanic, 10 (30%) White, 7 (21%) Black, 4 (12%)

Asian

- 7 (21%) were obese, 5 (15%) had asthma, 1 (3%) was

born prematurely

- 11 (33%) admitted to ICU

- None died

- 14/23 tested IgG positive, while 11/33 tested PCR

positive

Kaushik, Aydin,

(2020) (27)


USA

Apr-May 2020

33 cases of MIS-C

that were

admitted to ICU

are described


- 20/33 (61%) male

- 15 (45%) were Hispanic, 13 (39%) Black, 3 (9%) White, 1

(3%) Asian, 1 (3%) other ethnicity

- 16 (48%) of patients had comorbidities - 4 (12%) were

obese, 2 (6%) were overweight, 5 (15%) had asthma, 3

(9%) had allergies/eczema, 2 (6%) had cardiac issues, 2

(6%) had hematological issues

https://pubs.rsna.org/doi/10.1148/radiol.2020202543


https://journals.sagepub.com/doi/full/10.1177/0009922820961771





Note: 4 patients

were reported in

other studies



- 1 (3%) died

- 11 tested PCR positive while 27 tested serology positive

Capone (2020) (28)


USA

Apr-May 2020

33 cases of MIS-C

are described


- 20/33 (61%) male

- 8 (24%) were Black, 3 (9%) White, 3 (9%) Asian, 19 (58%)

other/mixed/unknown. The ethnic rates of MIS-C were

similar to the ethnic rates of the in-hospital population.

- 12 (36%) were obese, 2 (6%) were overweight. The

childhood obesity rate in the region is 18%, so obese

patients are overrepresented in MIS-C cases in this study.


ventilation

- None died

- 30 tested IgG positive

- MIS-C cases peaked 5 weeks after local COVID-19

hospitalization peaked

Moraleda (2020) (29)


Spain

Mar-Jun 2020

31 cases of MIS-C

are described


- 18/31 (58%) male

- 3 (10%) were obese, 4 (13%) had asthma, and 1 each

(3%) had chronic cardiac disease, hematological disease

and cancer


ventilation

- 1 (3%) died

- 17 tested PCR positive, 10 IgM positive and 19 IgG

positive

- MIS-C cases peaked 1 month after local COVID-19

hospitalizations peaked

Alders (2020) (30)


UK

Mar-May 2020

31 cases of MIS-C

are described

- Median age = 10.1 years (range = 8.7-13.9 years)

- 21/31 (68%) male


(10%) mixed, 1 (3%) unknown ethnicity

- 5 (16%) were overweight and 7 (23%) were obese


https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1042/5876334




- 14 (45%) required mechanical ventilation, 1 (3%) required

ECMO

- None died


Felsenstein (2020)

(31)


UK

Mar-Jun 2020

29 cases of MIS-C

are described

- Median age = 6 years (IQR = 3.8-9.9 years)

- 20/29 (69%) male

- 12 (41%) were Caucasian, 6 (21%) South East Asian, 4

(14%) Black, 2 (7%) East Asian, 5 (17%) unknown ethnicity

- None died



peaked

Lee (2020) (32)


USA

Mar-Jun 2020

28 cases of MIS-C

are described

- Median age = 9 years (range = 1 month - 17 years)

- 16/28 (57%) male

- 12 (43%) Hispanic, 10 (36%) were White, 5 (18%) Black

- 14 (50%) of had comorbidities; 4 (14%) were obese, 3

(11%) had asthma, and 1 (4%) each had congenital heart

disease, sickle cell anemia, and mitochondrial disorder

- 17 (61%) admitted to ICU, none required mechanical

ventilation or ECMO

- None died


Matsubara (2020)

(33)


USA

Apr-Jun 2020

28 cases of MIS-C

are described

- Median age = 11.4 years (IQR = 8-13.7 years)

- 14/28 (50%) male

- 13 (46%) were Black, 7 (25%) White, 4 (14%) Hispanic, 1

(4%) Asian, 3 (11%) unknown ethnicity

- 8 tested IgG positive

Torres (2020) (34)


Chile

May-Jun 2020

27 cases of MIS-C

in children up to

age 14 are

described

- Median age = 6 (range = 0-14 years)

- 14/27 (52%) male

- 23 (85%) parents were Chilean, 2 (7%) Venezuelan, 1 (4%)

Haitian, 1 (4%) Peruvian

- 4 (15%) were overweight or obese, 1 (4%) had asthma, 1

(4%) was immunocompromised


https://www.jci.org/articles/view/141113

https://www.sciencedirect.com/science/article/pii/S0735109720364883




- 16 (59%) of were admitted to ICU, 12 (44%) required

mechanical ventilation

- None died

- 14 tested PCR positive, 10 tested serology positive

Carter (2020) (35)

Prospective cohort

UK

Apr-May 2020

25 cases of MIS-C

are described


- 15/25 (60%) male

- 10 (40%) were White, 9 (36%) Black, 5 (20%) Asian, 1 (4%)

other ethnicity

- 5 (20%) had comorbidities, including 2 (8%) with asthma

(1 also with autism and 1 with eczema), 1 (4%) food

allergy, 1 (4%) with hemoglobin C trait, and 1 (4%) with

aplastic anemia and immunosuppression


ventilation

- None died

- 18 tested serology positive and 1 tested PCR positive

Dionne (2020) (36)


USA

Mar-May 2020

25 cases of MIS-C

are described


- 15/25 (60%) male

- 4 (16%) were obese, 4 (16%) had asthma, and 1 (4%)

each had sickle cell anemia, mitochondrial disease,

prematurity/respiratory failure


ventilation

- None died

- 15 tested PCR positive, while 13 tested serology positive

Jain (2020) (37)


India

May-Jul 2020

23 cases of MIS-C

are described

- Median age = 7.2 years (range = 0.8-14 years)

- 11/23 (48%) male

- 9 (39%) required mechanical ventilation

- 1 died (4%)


- MIS-C cases peaked 2-4 weeks after local COVID-19

cases peaked

Webb (2020) (38)


23 suspected

cases of MIS-C

are described in

- Mean age = 6.6 years (95% CI = 4.8-8.4 years)

- 17/23 (74%) male

https://www.nature.com/articles/s41591-020-1054-6

https://pediatrics.aappublications.org/content/146/5/e2020009704





South Africa

Jun-Jul 2020

an area where

COVID-19 testing

is limited

- 18 (78%) were Black, 5 (22%) were South African

coloured

- 2 (9%) were obese, 4 (17%) prenatal exposure to HIV, but

HIV-, 1 (4%) had asthma, 1 (4%) had leukemia


ventilation

- None died

- 4 tested PCR positive

- MIS-C cases occurred on average 24 days after acute

COVID-19 infection (95% CI = 9-39 days)

Toubiana (2020) (39)

Ambidirectional

cohort

France

Apr-May 2020

21 cases of MIS-C

are described

- 21 cases of MIS-C are described


- 24 (57%) parents of the patients were Black, 12 (29%)

White, 4 (10%) Asian, 2 (5%) Middle Eastern

- 24% of patients weighed above the 75th percentile


ventilation

- None died

- 19 tested IgG positive, 8 tested PCR positive

Grimaud (2020) (40)


France

Apr 2020

20 cases of MIS-C

admitted to ICU

are described

- Median age = 10 years (range = 2.9-15 years)

- 10/20 (50%) male


ventilation, none required ECMO

- None died


Dhanalakshmi (2020)

(41)


India

May-Jul 2020

19 cases of MIS-C

are described


- 8/19 (42%) male

- 1 (5%) had developmental delays


ventilation or ECMO

- None died


Blumfield & Levin

(42)

19 cases of MIS-C

are described


- 10/19 (53%) male

https://www.bmj.com/content/369/bmj.m2094

https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00690-8


https://link.springer.com/article/10.1007/s00247-020-04782-2




USA

Feb-Mar 2020

- 3 (16%) were obese, 5 (26%) had existing neurological

impairment, and 1 (5%) each had congenital heart

disease, cardiomyopathy, cancer, asthma, hypertension,

sickle cell disease, prior thromboembolic events and

Fragile X syndrome


ventilation

- 2 died (11%) – both had comorbidities

- 18 tested PCR positive

Yonker (2020) (8)


USA

Aug 2020*

18 cases of MIS-C

are described

from a total of

192 hospitalized

pediatric COVID-

19 cases

- 18/192 (9%) children presenting to urgent care or

hospitalized related to COVID-19 had MIS-C

- Mean age = 7.7 years (SD = 7 years)

- 14/18 (78%) male

- 9 (50%) were White, 6 (33%) Hispanic, 2 (11%) White, and

1 (6%) Asian

- 2 (11%) were obese, 1 each (6%) had inflammatory bowel

disease, ADHD and autism

Cheung (2020) (43)


USA

Apr-May 2020

17 cases of MIS-C

are described

- Median age = 8 years (range = 1.8-16 years)

- 8/17 (47%) male

- 3 (18%) had asthma


ventilation or ECMO

- None died

- 9 tested serology positive, while 8 tested PCR positive

Pouletty (2020) (44)


France

Apr 2020

16 cases of MIS-C

are described

- Median age = 12 years (range = 4.7-12.5 years)

- 8/16 (50%) male

- 4 (25%) were overweight, 2 (13%) had asthma


ventilation, none required ECMO

- None died

- 7/8 tested IgG positive, while 11/16 tested PCR positive

Ramcharan (2020)

(45)


UK

15 cases of MIS-C

are described


- 11/15 (73%) male

- 6 (40%) were Black, 6 (40%) South Asian, 3 (20%) other

ethnicity

https://www.jpeds.com/article/S0022-3476(20)31023-4/fulltext

https://jamanetwork.com/journals/jama/fullarticle/2767207

https://ard.bmj.com/content/79/8/999




Apr-May 2020 - 4 (27%) required mechanical ventilation, none required

ECMO

- None died


Riollano-Cruz (2020)

(46)


USA

Apr-Jun 2020

15 cases of MIS-C

are described


- 11/15 (73%) male

- 10 (67%) were Hispanic, 2 (13%) Black, 2 (13%) White,

and 1 (7%) unknown ethnicity

- 2 (13%) were obese, 2 (13%) were overweight, 4 (27%)

had asthma, and 1 (7%) had hypothyroidism



- 1 (7%) died

- 15 tested serology positive while 9 tested PCR positive

- MIS-C onset began 21 days after acute COVID-19

infection (IQR= 21-24 days)

Rosat Consiglio

(2020) (47)


Italy, Sweden

Mar-May, 2020

13 cases of MIS-C

are described

- Median age = 106 months (IQR = 71-165 months)

- 8/11 (73%) male (2 missing)

- 3/4 (75%) tested IgG positive

Gaitonde (2020) (48)

Case-control

USA

Mar-Jun 2020

12 cases of MIS-C

are described

- Median age = 8 years (IQR = 5.5-11.5 years)

- 9/12 (75%) male

- 8 (80%) were Black, 3 (30%) White, 1 (10%) other

ethnicity

- None died

de Farias (2020) (49)

Prospective cohort

Brazil

Apr-Jun 2020

11 cases of MIS-C

are described

- Median age = 4 years (range = 7 months - 11 years)

- 9/11 (82%) male

- 2 (18%) were malnourished, 3 (27%) were obese, 3 (27%)

were overweight

- 11 admitted to ICU – required for inclusion (100%), 3

(27%) required mechanical ventilation

- 2 (18%) died– both were malnourished.


https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.26224



https://www.onlinejase.com/article/S0894-7317(20)30479-X/abstract




- MIS-C onset began 15 days after acute COVID-19

infection (range = 7-60 days)

Ouldali (2020) (50)

Natural experiment

France

Dec 2005-May 2021

10 cases of MIS-C

are described

after the onset of

the COVID-19

pandemic, and

compared to

Kawasaki cases

prior to April

2020

- Prior to April 2020, Kawasaki Disease hospitalization rate

was 1.2 cases per month. In April 2020, this spiked to 6

cases per month (497% increase). Another peak in

December 2009 reached 6 cases per month (365%

increase) around the time of the influenza A H1N1

pandemic.

- Median age = 11.5 years (range = 1-15 years)

- 4/10 (40%) male


ventilation or ECMO

- None died

- 5/10 tested IgG positive, 5/9 tested PCR positive


peaked

Verdoni (2020) (51)

Natural experiment

Italy

Feb-Apr 2020

10 cases of MIS-C

are described

after the onset of

the COVID-19

pandemic,

compared to

Kawasaki cases

prior to Feb 2020

- This is an early study that compared Kawasaki disease

rates between Jan 1, 2015, and Feb 17, 2020 (19 patients)

with Feb 18, 2020 and April 20, 2020 (10 patients). The

study found a 30 fold increase in Kawasaki like disease in

early 2020 in Italy

- Median age = 7.5 years (SD = 3.5 years)

- 7/10 (70%) male

- 8 tested IgG positive, 2 tested IgM positive, 2 tested PCR

positive

Rostad (2020) (52)

Ambidirectional

cohort

USA

Mar-May 2020

10 cases of MIS-C

are described

- Median age = 106 months (range = 71-165 months)

- 6/10 (60%) male

- 6 (60%) were Black, 3 (30%) White, 1 (10%) other

ethnicity

- 3 (30%) had underlying respiratory conditions


- All tested IgG and IgM positive, 2 tested PCR positive

Gruber (2020) (53)


USA

9 cases of MIS-C

are described

- Median age = 11.5 years

- 4/9 (44%) male


https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31103-X/fulltext





Apr-Jun 2020 - 6 (67%) were Hispanic, 2 (22%) Black, 1 (11%) unknown

ethnicity

- 2 (22%) had asthma, 1 (11%) PTSD

- None died


Kim (2020) (9)


USA

Mar-Jul 2020

9 cases of MIS-C

are described

from a total of 83

hospitalized

pediatric COVID-

19 cases

- Of 83 hospitalized COVID-19 pediatric patients, 9 were

diagnosed with MIS-C (11% of hospitalized children with

COVID-19)

- Age: 0-2 years (1), 2-4 years (5), 5-17 years (3)

Khan & Ullah (2020)

(54)

Case series

Pakistan

Aug 2020*

8 cases of MIS-C

are described

with data derived

from news

reports

- Age range = 5-15 years

- All tested serology positive

Riphagen (2020) (55)


UK

Apr 2020

8 cases of MIS-C

are described


- 5/8 (63%) male

- 6 (75%) were Black, 1 (13%) Asian, 1 (13%) Middle

Eastern

- 2 (25%) were obese, 1 (13%) overweight, 1 (13%) had

autism, 1 (13%) hayfever



- 1 died (13%)

Perez-Toledo (2020)

(56)

(preprint)


UK

Apr-May 2020

8 cases of MIS-C

are described,

where patients

tested PCR

negative but

serology positive

- Median age = 9 years (range 7-14 years)

- 5/8 (63%) male

- 6 (75%) admitted to the ICU

- None died

Syrimi (2020) (57)

(preprint)


UK

7 cases of MIS-C

are described

- Ages: <5 years (1), 5-10 years (3), 10-15 years (3)

- 4/7 (57%) male

- 4 (57%) were Black, 2 (29%) Asian, 1 (14%) White

- 6 (86%) admitted to the ICU

https://www.cdc.gov/mmwr/volumes/69/wr/mm6932e3.htm


https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31094-1/fulltext





Apr-May 2020

Pereira (2020) (58)


Brazil

Apr-Jun 2020

6 cases of MIS-C

are described,

from a group of

66 hospitalized

pediatric COVID-

19 patients



COVID-19)


- 5/6 (83%) male

- 5 (83%) had a pre-existing condition, 4 were

immunocompromised, 3 had cancer, 1 had chronic

kidney disease


ventilation

- 4 (67%) died

Chiara-Chilet (2020)

(7)

(preprint)


Peru

Mar-Jul 2020

6 cases of MIS-C

are described,

from a total of 91

hospitalized

pediatric COVID-

19 cases



COVID-19)


Chiotos (2020) (59)

Case series

USA

May 2020*

6 cases of MIS-C

that were

admitted to the

ICU are described

- Median age = 7.5 years (range = 5-14 years)

- 1/6 (17%) male

- 2 (33%) were Black, 2 (33%) White, 2 (33%) unknown

ethnicity


ventilation, and none required ECMO

- None died

- 5 tested IgG positive, while 2 tested PCR positive

Diorio (2020) (60)

Prospective cohort

USA

Apr-May 2020

6 cases of MIS-C

are described


- 2/6 (33%) male

- 4 (66%) were White, 1 (17%) Black, 1 (17%) other

ethnicity


ventilation, and none required ECMO

- None died

* Article publication date because case date(s) unavailable



https://academic.oup.com/jpids/article/9/3/393/5848127

https://www.jci.org/articles/view/140970



SMALL ARTICLES

Table 3: Articles describing of one to five cases of MIS-C, by country and study size

STUDY METHOD KEY OUTCOMES

CASE SERIES

Blondiaux (2020) (61)

Case series

France

Apr 2020

Descriptive case

series of 4 MIS-C

patients

- 3 girls aged 6, 8 and 11; 1 boy aged 12

- All 4 admitted to ICU, 1 was intubated, none were

placed on ECMO

- None died

- All tested PCR negative and IgG positive, 1 tested IgM

positive

Labé (2020) (62)

Case series

France

May 2020*

Descriptive case

series of 2 MIS-C

patients

- 2 boys aged 3 and 6

- No ICU admission, intubation or ECMO

- None died

- 1 tested PCR positive, no serology results

Licciardi (2020) (63)

Case series

Italy

Arp 2020

Descriptive case

series of 2 MIS-C

patients

- 2 boys, aged 7 and 12, neither with comorbidities

- Both admitted to ICU; neither intubated and no ECMO

- None died

- Both tested PCR negative, but IgG and IgM positive

Pang (2020) (64)

Case series

UK

Mar-May 2020

Descriptive case

series of 5 MIS-C

patients

- 3 boys aged 8, 12 and 14; 2 girls aged 5 and 15

- 2 were Asian, 1 was Black, 1 was White and 1 was

mixed-race

- 2 had seizure disorders

- 4 were admitted to ICU and intubated

- None died

- All tested PCR positive, no serology results

Ng (2020) (65)

Case series

UK

Apr-May 2020

Descriptive case

series of 3 MIS-C

patients

- 2 boys aged 13 and 17; 1 girl aged 16

- 2 were Black, 1 was Asian

- 1 was obese

- All 3 admitted to ICU; 1 was intubated; no ECMO

- None died

- All 3 tested IgG positive, 1 tested PCR positive

Del Greco (2020) (66)

Case series

USA

Oct 2020*

Descriptive case

series of 4 MIS-C

patients

- 3 girls aged 4, 10 and 16; 1 boy aged 13

- 1 had asthma, the rest had no comorbidities

- 2 admitted to ICU; none intubated and no ECMO

- None died

- All 4 tested serology positive, 1 tested PCR positive

https://pubs.rsna.org/doi/10.1148/radiol.2020202288








Rogo (2020) (67)

Case series

USA

Apr-May 2020

Descriptive case

series of 4 MIS-C

patients

- 3 boys aged 5, 17 and 20; 1 girl aged 3

- 4 admitted to ICU, 2 intubated, 1 placed on ECMO

- 1 died

- All 4 tested PCR negative and IgG positive

Waltuch (2020) (68)

Case series

USA

May 2020

Descriptive case

series of 4 MIS-C

patients

- 3 boys aged 5, 10, and 13; 1 girl aged 12

- 1 had hypothyroidism, another had asthma

- 4 admitted to ICU; none intubated and no ECMO

- None died

- All 4 tested serology positive, 1 tested PCR positive

Heidemann (2020) (69)

Case series

USA

Aug 2020*

Descriptive case

series of 3 MIS-C

patients

- 2 boys aged 5 and 7; 1 girl aged 6, with no

comorbidities

- 2 admitted to ICU and intubated; 1 was placed on

ECMO

- 1 died

- 1 tested PCR positive, 3 tested serology positive

Schupper (2020) (70)

Case series

USA

Jun 2020*

Descriptive case

series of 2 MIS-C

patients

- 2 boys aged 2 months, 5 years

- 1 had tracheomalacia

- Both admitted to ICU, intubated and placed on ECMO

- 1 died

- 1 tested serology positive, no PCR results

Spencer (2020) (71)

Case series

USA

Sep 2020*

Descriptive case

series of 2 MIS-C

patients

- 1 girl aged 7; 1 boy aged 11

- 1 had seizure disorder

- 1 admitted to ICU, none intubated and no ECMO

- None died

- Both tested PCR positive, no serology results

CASE REPORTS

Khesrani (2020) (72)

Case report

Algeria

Aug 2020*

Descriptive case

report of 1 MIS-C

patient

- 9 year-old girl with idiopathic medullar aplasia

- Admitted to ICU and intubated, no ECMO

- Patient died

- Patient tested PCR positive, no serology results

De Paulis (2020) (73)

Case report

Brazil

May 2020

Descriptive case

report of 1 MIS-C

patient

- 4 year-old girl with no comorbidities


- Patient survived

- Patient tested PCR and IgM negative, but IgG positive

Tam (2020) (74)

Case report

Canada

Sep 2020*

Descriptive case

report of 1 MIS-C

patient

- 10 years old boy with no comorbidities

- Admitted to ICU, not intubated and no ECMO

- Patient survived

- Patient tested PCR negative, serology positive











Klocperk (2020) (75)

Case report

Czechia

Jul 2020*

Descriptive case

report of 1 MIS-C

patient



- Patient survived

- Patient tested PCR positive and IgG positive

Acharyya (2020) (76)

(preprint)

Case report

India

May 2020*

Descriptive case

report of 1 MIS-C

patient

- 4 month-old boy with no comorbidities


- Patient survived


Balasubramanian (2020)

(77)

Case report

India

Jul 2020*

Descriptive case

report of 1 MIS-C

patient

- 8 year-old boy with no comorbidities

- Admitted to ICU; not intubated and no ECMO

- Patient survived


Gupta (2020) (78)

(preprint)

Case report

India

Sep 2020*

Descriptive case

report of 1 MIS-C

patient

- 2 year-old boy


- Patient survived

- Patient tested PCR negative, parents IgG positive

Rauf (2020) (79)

Case report

India

Apr 2020

Descriptive case

report of 1 MIS-C

patient



- Patient survived

- Patient tested PCR and serology negative

Singhi (2020) (80)

Case report

India

Oct 2020*

Descriptive case

report of 1 MIS-C

patient

- 8 year-old girl


- Patient survived


Tiwari (2020) (81)

Case report

India

Oct 2020*

Descriptive case

report of 1 MIS-C

patient

- 9 year-old girl


- Patient survived

- Patient tested PCR and serology positive

Bahrami (2020) (82)

Case report

Iran

Jul 2020*

Descriptive case

report of 1 MIS-C

patient



- Patient survived

- Patient tested PCR negative and serology positive

Parvaneh & Rahmani

(2020) (83)

(preprint)

Case report

Descriptive case

report of 1 MIS-C

patient

- 7 year-old boy

- Patient survived



https://www.researchsquare.com/article/rs-29420/v1


https://www.cps.ca/documents/position/pims



https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30314-X/fulltext

https://onlinelibrary.wiley.com/doi/full/10.1111/jpc.15048





Iran

May 2020

Regev (2020) (84)

Case report

Israel

Aug 2020*

Descriptive case

report of 1 MIS-C

patient



- Patient survived

- Patient tested PCR and IgG positive

Schnapp (2020) (85)

Case report

Israel

Jun 2020*

Descriptive case

report of 1 MIS-C

patient



- Patient survived

- Patient tested PCR negative, IgG positive

Buonsenso (2020) (86)

Case report

Italy

Apr 2020

Descriptive case

report of 1 MIS-C

patient

- 11 year-old girl


Giannattasio (2020) (87)

Case report

Italy

Jun 2020*

Descriptive case

report of 1 MIS-C

patient

- 9 year-old boy


- Patient survived

- Patient tested PCR negative, IgG and IgM positive

Yáñez (2020) (88)

Case report

Peru

Jun 2020

Descriptive case

report of 1 MIS-C

patient

- 3 year-old girl

- No other information provided

Tracewski (2020) (89)

Case report

Poland

May 2020

Descriptive case

report of 1 MIS-C

patient

- 2 year-old boy


- Patient survived

- Patient tested PCR and IgM negative, IgG positive

Rodriguez-Gonzalez

(2020) (90)

Case report

Spain

Jun 2020*

Descriptive case

report of 1 MIS-C

patient

- 6 month-old boy with short bowel syndrome


- Patient survived


Bapst (2020) (91)

Case report

Switzerland

Apr 2020

Descriptive case

report of 1 MIS-C

patient



- Patient survived


Yozgat (2020) (92)

(preprint)

Case report

Turkey

Descriptive case

report of 1 MIS-C

patient

- 3 year-old girl

- Patient survived

- Patient tested PCR negative, no serology results


https://onlinelibrary.wiley.com/doi/full/10.1111/jdv.16749



https://www.bmj.com/content/369/bmj.m2418








Jul 2020*

Domico (2020) (93)

Case report

UK

Apr 2020

Descriptive case

report of 1 MIS-C

patient



- Patient survived

- Patient tested PCR and IgM negative, IgG positive

Chiu (2020) (94)

Case report

USA

Jun 2020*

Descriptive case

report of 1 MIS-C

patient


- Admitted to ICU


Choi (2020) (95)

Case report

USA

Aug 2020*

Descriptive case

report of 1 MIS-C

patient

- 19 years-old Hispanic man with sleep apnea and

obesity


- Patient survived


Clouser (2020) (96)

Case report

USA

May 2020

Descriptive case

report of 1 MIS-C

patient

- 11 year-old Black girl with obesity


- Patient survived


Dasgupta (2020) (97)

Case report

USA

Jun 2020*

Descriptive case

report of 1 MIS-C

patient

- 8 year-old mixed race girl with no comorbidities

- Admitted to ICU

- Patient survived

- Patient tested PCR and IgG negative

Deza Leon (2020) (98)

Case report

USA

May 2020*

Descriptive case

report of 1 MIS-C

patient


- Admitted to ICU, intubated and was placed on ECMO

- Patient survived


Dolhnikoff (2020) (99)

Case report

USA

Aug 2020*

Descriptive case

report of 1 MIS-C

patient

- 11 year-old Black girl with no comorbidities


- Patient died


Dolinger (2020) (100)

Case report

USA

May 2020*

Descriptive case

report of 1 MIS-C

patient

- 14 year-old boy with Crohn’s disease

- Patient survived


Greene (2020) (101)

Case report

USA

Jun 2020*

Descriptive case

report of 1 MIS-C

patient



- Patient survived





https://journals.lww.com/pidj/Fulltext/2020/11000/MIS_C_After_ARDS_Associated_With_SARS_CoV_2.24.aspx


https://academic.oup.com/jpids/article/9/3/407/5842067






Jones (2020) (102)

Case report

USA

Jun 2020*

Descriptive case

report of 1 MIS-C

patient

- 6 month-old girl with no comorbidities


- Patient survived


Kaushik, Ahluwalia,

(2020) (103)

Case report

USA

Sep 2020*

Descriptive case

report of 1 MIS-C

patient


- Admitted to ICU, intubated and placed on ECMO

- Patient died


Nelson (2020) (104)

Case report

USA

Oct 2020*

Descriptive case

report of 1 MIS-C

patient



- Patient survived

- Patient tested PCR negative, no serology results

Rivera-Figueroa (2020)

(105)

Case report

USA

Jul 2020*

Descriptive case

report of 1 MIS-C

patient

- 5 year-old Black boy with no comorbidities


- Patient survived


Stevens (2020) (106)

Case report

USA

Apr 2020

Descriptive case

report of 1 MIS-C

patient

- 10 year-old Black girl with asthma


- Patient survived


Vari (2020) (107)

Case report

USA

Apr 2020

Descriptive case

report of 1 MIS-C

patient

- 14 year-old boy


- Patient survived


Verkuil (2020) (108)

Case report

USA

Aug 2020*

Descriptive case

report of 1 MIS-C

patient



- Patient survived


* Article publication date because case date(s) unavailable

Methods

A daily scan of the literature (published and pre-published) is conducted by the Emerging Science Group at

the Public Health Agency of Canada (PHAC). The scan has compiled COVID-19 literature since the beginning

of the outbreak and is updated daily. Searches to retrieve relevant COVID-19 literature are conducted in

Pubmed, Scopus, BioRxiv, MedRxiv, ArXiv, SSRN, Research Square and cross-referenced with the literature on

the WHO COVID literature list, and COVID-19 information centers run by Lancet, BMJ, Elsevier and Wiley. The






https://journals.lww.com/jpgn/Fulltext/2020/11000/COVID_19_associated_Multisystem_Inflammatory.16.aspx


https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31725-6/fulltext



daily summary and full scan results are maintained in a Refworks database and an Excel list that can be

searched.

Targeted keyword searching is conducted within these databases to identify relevant citations on COVID-19

and SARS-CoV-2. Search terms used included: “MIS-C”, “PIMS”, “Kawasaki”, “multisystem inflam”, “multi-

system inflam”, “inflammatory multisystem”, “inflammatory multi-system”.

382 papers were identified on the topic of MIS-C, after the removal of duplicates. Each potentially relevant

reference was examined to confirm it had relevant data and relevant data is extracted into the review. 102

studies identified as relevant to the study question. This review contains research published up to November

10, 2020.

Prepared by: Megan Striha. Laboratory Incident Notification Canada, PHAC. phac.evidence-

[email protected]

APPENDIX

The case definition of MIS-C published by the USA Centers for Disease Control (CDC) (3) states:

- An individual aged <21 years presenting with fever (>38.0°C for ≥24 hours, or report of subjective

fever lasting ≥24 hours), laboratory evidence of inflammation, and evidence of clinically severe

illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal,

respiratory, hematologic, gastrointestinal, dermatologic or neurological);

AND

- No alternative plausible diagnoses;

AND

- Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or

exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of

symptoms.

The definition of MIS-C published by the World Health Organization (WHO) (2) states:

- Children and adolescents 0–19 years of age with fever > 3 days

AND

- two of the following:

o Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral,

hands or feet).

o Hypotension or shock.

o Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities

(including ECHO findings or elevated Troponin/NT-proBNP),

o Evidence of coagulopathy (by PT, PTT, elevated d-Dimers).

o Acute gastrointestinal problems (diarrhoea, vomiting, or abdominal pain).





AND

- Elevated markers of inflammation such as 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 (RT-PCR, antigen test or serology positive), or likely contact with patients

with COVID-19.

Finally, the definition of PIMS released by the UK Royal College of Paediatrics and Child Health (RCPCH) (4)

states:

- A child presenting with persistent fever, inflammation (neutrophilia, elevated CRP and

lymphopaenia) and evidence of single or multi-organ dysfunction (shock, cardiac, respiratory,

renal, gastrointestinal or neurological disorder) with additional features. This may include children

fulfilling full or partial criteria for Kawasaki disease.

AND

- Exclusion of any other microbial cause, including bacterial sepsis, staphylococcal or streptococcal

shock syndromes, infections associated with myocarditis such as enterovirus (waiting for results of

these investigations should not delay seeking expert advice).

AND

- SARS-CoV-2 PCR testing may be positive or negative.

References

1. European Centre for Disease Prevention and Control. Paediatric inflammatory multisystem syndrome and SARS-

CoV-2 infection in children Paediatric inflammatory multisystem syndrome and SARS-CoV-2 infection in children

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