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:
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.
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 2
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 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 3
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.
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PHAC EMERGING SCIENCE SUMMARIES 4
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.
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- 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)
Retrospective cohort
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.
- 148 (80%) admitted to ICU, 37 (20%) required mechanical
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)
Retrospective cohort
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
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Belot (2020) (14)
Retrospective cohort
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
- Median age = 8 years (IQR = 5-11 years)
- 53/108 (49%) male
- 72 (67%) admitted to ICU, 46 (43%) required mechanical
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)
Retrospective cohort
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
- 79 (80%) admitted to ICU, 10 (10%) required mechanical
ventilation, 1 (1%) required ECMO
- 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
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- 20 (21%) admitted to ICU, 9 (9%) required mechanical
ventilation
- 2 (2%) died
- All tested positive for COVID-19 by either or both PCR or
serological testing
Davies (2020) (17)
Retrospective cohort
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.
- Median age = 11 years (IQR = 8-14 years)
- 52/78 (67%) male
- 37 (47%) were Black, 22 (28%) Asian, 17 (22%) White, 2
(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
ventilation, 3 (4%) required ECMO
- 2 (3%) died
- 33/35 (94%) tested serology positive while 17/78 (22%)
tested PCR positive
Jonat (2020) (18)
Retrospective cohort
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
- 41/54 (97%) tested serology positive while 20/54 (34%)
tested PCR positive
Cattalini (2020) (19)
(preprint)
Retrospective cohort
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
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PHAC EMERGING SCIENCE SUMMARIES 8
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
- 40/46 (87%) tested serology positive while 15/58 (26%)
tested PCR positive
Duarte-Salles (2020)
(6)
(preprint)
Retrospective cohort
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.
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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)
Retrospective cohort
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)
Retrospective cohort
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)
Retrospective cohort
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
- 35 (100%) admitted to ICU, 22 (63%) required mechanical
ventilation, 10 (29%) required ECMO
- None died
- 14 tested PCR positive, while 30 patients tested serology
positive (28 IgG positive and 2 IgM positive)
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Hameed (2020) (24)
Retrospective cohort
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
- 24 (69%) admitted to ICU, 7 (20%) required mechanical
ventilation, 2 (6%) required ECMO
- 1 (3%) died
- 25 tested IgG positive and 23 IgM positive.
Sethuraman (2020)
(25)
Retrospective cohort
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
ventilation, 2 (6%) required ECMO
- 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)
Retrospective cohort
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)
Retrospective cohort
USA
Apr-May 2020
33 cases of MIS-C
that were
admitted to ICU
are described
- Median age = 10 years (IQR = 6-13 years)
- 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
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Note: 4 patients
were reported in
other studies
- 33 (100%) admitted to ICU, 5 (15%) required mechanical
ventilation, 1 (3%) required ECMO
- 1 (3%) died
- 11 tested PCR positive while 27 tested serology positive
Capone (2020) (28)
Retrospective cohort
USA
Apr-May 2020
33 cases of MIS-C
are described
- Median age = 8.6 years (IQR = 5.5-12.6 years)
- 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.
- 26 (79%) admitted to ICU, 6 (18%) required mechanical
ventilation
- None died
- 30 tested IgG positive
- MIS-C cases peaked 5 weeks after local COVID-19
hospitalization peaked
Moraleda (2020) (29)
Retrospective cohort
Spain
Mar-Jun 2020
31 cases of MIS-C
are described
- Median age = 7.6 years (IQR = 4.5-11.5 years)
- 18/31 (58%) male
- 3 (10%) were obese, 4 (13%) had asthma, and 1 each
(3%) had chronic cardiac disease, hematological disease
and cancer
- 20 (65%) admitted to ICU, 6 (19%) required mechanical
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)
Retrospective cohort
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
- 14 (45%) were Black, 9 (29%) Asian, 4 (13%) White, 3
(10%) mixed, 1 (3%) unknown ethnicity
- 5 (16%) were overweight and 7 (23%) were obese
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- 14 (45%) required mechanical ventilation, 1 (3%) required
ECMO
- None died
- 20 tested PCR positive while 28 tested serology positive
Felsenstein (2020)
(31)
Retrospective cohort
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
- 14 tested serology positive, 3 tested PCR positive
- MIS-C cases peaked 4 weeks after local COVID-19 cases
peaked
Lee (2020) (32)
Retrospective cohort
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
- 17 tested PCR positive while 18 tested serology positive
Matsubara (2020)
(33)
Retrospective cohort
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)
Retrospective cohort
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
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- 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
- Median age = 12.5 years (range = 7.7-14.4 years)
- 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
- 21 (84%) admitted to ICU, 2 (8%) required mechanical
ventilation
- None died
- 18 tested serology positive and 1 tested PCR positive
Dionne (2020) (36)
Retrospective cohort
USA
Mar-May 2020
25 cases of MIS-C
are described
- Median age = 9.7 years (IQR = 2.7-15.0 years)
- 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
- 14 (56%) admitted to ICU, 1 (4%) required mechanical
ventilation
- None died
- 15 tested PCR positive, while 13 tested serology positive
Jain (2020) (37)
Retrospective cohort
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%)
- 7 tested serology positive, 9 tested PCR positive
- MIS-C cases peaked 2-4 weeks after local COVID-19
cases peaked
Webb (2020) (38)
Retrospective cohort
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
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 14
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
- 12 (52%) admitted to ICU, 6 (26%) required mechanical
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
- Median age = 7.9 years (range = 3.7-16.6 years)
- 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
- 17 (81%) admitted to ICU, 11 (53%) required mechanical
ventilation
- None died
- 19 tested IgG positive, 8 tested PCR positive
Grimaud (2020) (40)
Retrospective cohort
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
- 20 (100%) admitted to ICU, 8 (40%) required mechanical
ventilation, none required ECMO
- None died
- 15 tested serology positive, 10 tested PCR positive
Dhanalakshmi (2020)
(41)
Retrospective cohort
India
May-Jul 2020
19 cases of MIS-C
are described
- Median age = 6 years (range = 13 months – 16 years)
- 8/19 (42%) male
- 1 (5%) had developmental delays
- 12 (63%) admitted to ICU, none required mechanical
ventilation or ECMO
- None died
- 8 tested serology positive, 4 tested PCR positive
Blumfield & Levin
(42)
19 cases of MIS-C
are described
- Median age = 8 years (range = 2 months – 18 years)
- 10/19 (53%) male
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 15
Retrospective cohort
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
- 14 (74%) admitted to ICU, 8 (42%) required mechanical
ventilation
- 2 died (11%) – both had comorbidities
- 18 tested PCR positive
Yonker (2020) (8)
Retrospective cohort
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)
Retrospective cohort
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
- 1 (6%) admitted to ICU, none required mechanical
ventilation or ECMO
- None died
- 9 tested serology positive, while 8 tested PCR positive
Pouletty (2020) (44)
Retrospective cohort
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
- 7 (44%) admitted to ICU, 2 (13%) required mechanical
ventilation, none required ECMO
- None died
- 7/8 tested IgG positive, while 11/16 tested PCR positive
Ramcharan (2020)
(45)
Retrospective cohort
UK
15 cases of MIS-C
are described
- Median age = 8.8 years (IQR = 6.4-11.2 years)
- 11/15 (73%) male
- 6 (40%) were Black, 6 (40%) South Asian, 3 (20%) other
ethnicity
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 16
Apr-May 2020 - 4 (27%) required mechanical ventilation, none required
ECMO
- None died
- 12 tested serology positive, 2 tested PCR positive
Riollano-Cruz (2020)
(46)
Retrospective cohort
USA
Apr-Jun 2020
15 cases of MIS-C
are described
- Median age = 12 years (range = 3-20 years)
- 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
- 15 (100%) admitted to ICU, 3 (20%) required mechanical
ventilation, 1 (7%) required ECMO
- 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)
Retrospective cohort
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.
- 9 tested serology positive, 2 tested PCR positive
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 17
- 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
- 6 (60%) admitted to ICU, none required mechanical
ventilation or ECMO
- None died
- 5/10 tested IgG positive, 5/9 tested PCR positive
- MIS-C cases peaked 2 weeks after local COVID-19 cases
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
- 10 (100%) admitted to ICU
- All tested IgG and IgM positive, 2 tested PCR positive
Gruber (2020) (53)
Retrospective cohort
USA
9 cases of MIS-C
are described
- Median age = 11.5 years
- 4/9 (44%) male
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 18
Apr-Jun 2020 - 6 (67%) were Hispanic, 2 (22%) Black, 1 (11%) unknown
ethnicity
- 2 (22%) had asthma, 1 (11%) PTSD
- None died
- 9 tested serology positive, 3 tested PCR positive
Kim (2020) (9)
Retrospective cohort
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)
Retrospective cohort
UK
Apr 2020
8 cases of MIS-C
are described
- Median age = 8 years (range = 4-14 years)
- 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
- 8 (100%) admitted to ICU, 5 (63%) required mechanical
ventilation, 1 (13%) required ECMO
- 1 died (13%)
Perez-Toledo (2020)
(56)
(preprint)
Retrospective cohort
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)
Retrospective cohort
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
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 19
Apr-May 2020
Pereira (2020) (58)
Retrospective cohort
Brazil
Apr-Jun 2020
6 cases of MIS-C
are described,
from a group of
66 hospitalized
pediatric COVID-
19 patients
- Of 66 hospitalized COVID-19 pediatric patients, 6 were
diagnosed with MIS-C (9% of hospitalized children with
COVID-19)
- Median age = 7.8 years (range = 0.01-17.6 years)
- 5/6 (83%) male
- 5 (83%) had a pre-existing condition, 4 were
immunocompromised, 3 had cancer, 1 had chronic
kidney disease
- 6 (100%) admitted to ICU, 5 (83%) required mechanical
ventilation
- 4 (67%) died
Chiara-Chilet (2020)
(7)
(preprint)
Retrospective cohort
Peru
Mar-Jul 2020
6 cases of MIS-C
are described,
from a total of 91
hospitalized
pediatric COVID-
19 cases
- Of 91 hospitalized COVID-19 pediatric patients, 6 were
diagnosed with MIS-C (7% of hospitalized children with
COVID-19)
- 2 (33%) admitted to ICU
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
- 6 (100%) admitted to ICU, 3 (50%) required mechanical
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
- Median age = 6 years (IQR = 5-7 years)
- 2/6 (33%) male
- 4 (66%) were White, 1 (17%) Black, 1 (17%) other
ethnicity
- 5 (83%) admitted to ICU, 2 (33%) required mechanical
ventilation, and none required ECMO
- None died
* Article publication date because case date(s) unavailable
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 20
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
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 21
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
- Admitted to ICU and intubated, no ECMO
- 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
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 22
Klocperk (2020) (75)
Case report
Czechia
Jul 2020*
Descriptive case
report of 1 MIS-C
patient
- 8 year-old girl with no comorbidities
- No ICU admission, intubation or ECMO
- 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
- No ICU admission, intubation or ECMO
- Patient survived
- Patient tested PCR positive, no serology results
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
- Patient tested PCR positive, no serology results
Gupta (2020) (78)
(preprint)
Case report
India
Sep 2020*
Descriptive case
report of 1 MIS-C
patient
- 2 year-old boy
- No ICU admission, intubation or ECMO
- 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
- 5 year-old boy with no comorbidities
- Admitted to ICU; not intubated and no ECMO
- 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
- No ICU admission, intubation or ECMO
- Patient survived
- Patient tested PCR negative, serology positive
Tiwari (2020) (81)
Case report
India
Oct 2020*
Descriptive case
report of 1 MIS-C
patient
- 9 year-old girl
- Admitted to ICU and intubated, no ECMO
- Patient survived
- Patient tested PCR and serology positive
Bahrami (2020) (82)
Case report
Iran
Jul 2020*
Descriptive case
report of 1 MIS-C
patient
- 5 year-old girl with no comorbidities
- No ICU admission, intubation or ECMO
- 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
- Patient tested PCR positive, no serology results
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 23
Iran
May 2020
Regev (2020) (84)
Case report
Israel
Aug 2020*
Descriptive case
report of 1 MIS-C
patient
- 16 year-old boy with no comorbidities
- Admitted to ICU and intubated, no ECMO
- Patient survived
- Patient tested PCR and IgG positive
Schnapp (2020) (85)
Case report
Israel
Jun 2020*
Descriptive case
report of 1 MIS-C
patient
- 16 year-old boy with no comorbidities
- Admitted to ICU and intubated, no ECMO
- 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
- Patient tested PCR positive, no serology results
Giannattasio (2020) (87)
Case report
Italy
Jun 2020*
Descriptive case
report of 1 MIS-C
patient
- 9 year-old boy
- No ICU admission, intubation or ECMO
- 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
- No ICU admission, intubation or ECMO
- 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
- Admitted to ICU and intubated, no ECMO
- Patient survived
- Patient tested PCR negative, IgG positive
Bapst (2020) (91)
Case report
Switzerland
Apr 2020
Descriptive case
report of 1 MIS-C
patient
- 13 year-old boy with no comorbidities
- No ICU admission, intubation or ECMO
- Patient survived
- Patient tested PCR negative, serology positive
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
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 24
Jul 2020*
Domico (2020) (93)
Case report
UK
Apr 2020
Descriptive case
report of 1 MIS-C
patient
- 11 year-old boy with no comorbidities
- Admitted to ICU and intubated, no ECMO
- 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
- 10 year-old boy with no comorbidities
- Admitted to ICU
- Patient tested PCR positive, no serology results
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
- Admitted to ICU and intubated, no ECMO
- Patient survived
- Patient tested PCR positive, no serology results
Clouser (2020) (96)
Case report
USA
May 2020
Descriptive case
report of 1 MIS-C
patient
- 11 year-old Black girl with obesity
- Admitted to ICU and intubated, no ECMO
- Patient survived
- Patient tested PCR positive, no serology results
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
- 6 year-old girl with no comorbidities
- Admitted to ICU, intubated and was placed on ECMO
- Patient survived
- Patient tested PCR positive, no serology results
Dolhnikoff (2020) (99)
Case report
USA
Aug 2020*
Descriptive case
report of 1 MIS-C
patient
- 11 year-old Black girl with no comorbidities
- Admitted to ICU and intubated, no ECMO
- Patient died
- Patient tested PCR positive, no serology results
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
- Patient tested PCR positive, no serology results
Greene (2020) (101)
Case report
USA
Jun 2020*
Descriptive case
report of 1 MIS-C
patient
- 11 year-old girl with no comorbidities
- Admitted to ICU; not intubated and no ECMO
- Patient survived
- Patient tested PCR positive, no serology results
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 25
Jones (2020) (102)
Case report
USA
Jun 2020*
Descriptive case
report of 1 MIS-C
patient
- 6 month-old girl with no comorbidities
- No ICU admission, intubation or ECMO
- Patient survived
- Patient tested PCR positive, no serology results
Kaushik, Ahluwalia,
(2020) (103)
Case report
USA
Sep 2020*
Descriptive case
report of 1 MIS-C
patient
- 5 year-old boy with no comorbidities
- Admitted to ICU, intubated and placed on ECMO
- Patient died
- Patient tested PCR negative, serology positive
Nelson (2020) (104)
Case report
USA
Oct 2020*
Descriptive case
report of 1 MIS-C
patient
- 15 year-old girl with no comorbidities
- No ICU admission, intubation or ECMO
- 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
- Admitted to ICU; not intubated and no ECMO
- Patient survived
- Patient tested PCR positive, no serology results
Stevens (2020) (106)
Case report
USA
Apr 2020
Descriptive case
report of 1 MIS-C
patient
- 10 year-old Black girl with asthma
- Admitted to ICU; not intubated and no ECMO
- Patient survived
- Patient tested PCR negative, IgG positive
Vari (2020) (107)
Case report
USA
Apr 2020
Descriptive case
report of 1 MIS-C
patient
- 14 year-old boy
- Admitted to ICU and intubated, no ECMO
- Patient survived
- Patient tested PCR negative, IgG positive
Verkuil (2020) (108)
Case report
USA
Aug 2020*
Descriptive case
report of 1 MIS-C
patient
- 14 year-old girl with no comorbidities
- Admitted to ICU and intubated, no ECMO
- Patient survived
- Patient tested PCR negative, IgG positive
* 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
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 26
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-
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).
COVID-19 Summary of MIS-C January 28, 2021
PHAC EMERGING SCIENCE SUMMARIES 27
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.
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