Received: 23 May 2020 | Accepted: 26 July 2020
DOI: 10.1002/ppul.24991
REVIEW
Clinical characteristics of COVID‐19 in children: A systematic
review
Jun Yasuhara MD1 | Toshiki Kuno MD, PhD2 | Hisato Takagi MD, PhD3 |
Naokata Sumitomo MD, PhD4
1
Center for Cardiovascular Research, The
Abigail Wexner Research Institute and The
Heart Center, Nationwide Children's Hospital,
Columbus, Ohio
2
Department of Medicine, Icahn School of
Medicine at Mount Sinai, Mount Sinai Beth
Israel, New York, New York
3
Division of Cardiovascular Surgery, Shizuoka
Medical Center, Shizuoka, Japan
4
Department of Pediatric Cardiology, Saitama
Medical University International Medical
Center, Saitama, Japan
Correspondence
Jun Yasuhara, MD, Center for Cardiovascular
Research, The Abigail Wexner Research
Institute and The Heart Center, Nationwide
Children's Hospital, 700 Children's Drive
Room WB4237, Columbus, OH 43205.
Email: jun.yasuhara@nationwidechildrens.org
1 | INTRODUCTION
Coronavirus disease 2019 (COVID‐19), caused by a novel coronavirus,
called severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2),
emerged from Wuhan, China in December 2019.
Pediatric Pulmonology. 2020;55:2565–2575.
Abstract
Background: Limited pediatric cases with coronavirus disease 2019 (COVID‐19) have
been reported and the clinical profiles regarding COVID‐19 in children remain obscure.
Our aim was to investigate the clinical characteristics of COVID‐19 in children.
Methods: PUBMED and EMBASE were searched through 20 June 2020, for case
reports and case series reporting pediatric COVID‐19 cases. Epidemiological, clinical,
laboratory, and radiological data were collected and analyzed to compare by age.
Results: Our search identified 46 eligible case reports and case series. A total of
114 pediatric cases with COVID‐19 were included. The main clinical features were
mild symptoms including fever (64%), cough (35%), and rhinorrhea (16%), or no
symptoms (15%). Ground‐like opacities were common radiological findings (54%).
The main laboratory findings were lymphopenia (33%) and elevated D‐dimer (52%)
and C‐reactive protein (40%) levels. We identified 17 patients (15%) with multi-
system inflammatory syndrome in children (MIS‐C) manifesting with symptoms
overlapping with, but distinct from, Kawasaki disease, including gastrointestinal
symptoms, left ventricular systolic dysfunction, shock, and marked elevated in-
flammatory biomarkers. Twelve percent of the patients including 65% of the MIS‐C
cases required intensive care because of hypotension. No deaths were reported.
Conclusion: This systematic review found that children with COVID‐19 are gen-
erally less severe or asymptomatic. However, infants might be seriously ill and older
children might develop MIS‐C with severe illness. Early detection of children with
mild symptoms or an asymptomatic state and early diagnosis of MIS‐C are manda-
tory for the management of COVID‐19 and the prevention of transmission and a
severe inflammatory state.
KEYWORDS
clinical features, COVID‐19, Kawasaki disease, multisystem inflammatory syndrome in children
(MIS‐C), SARS‐CoV‐2
SARS‐CoV‐2 infections exploded all over the world, constituting a
major global health concern. As of 24 June 2020, a total of almost 9
million COVID‐19 patients including 477 634 deaths (5.2%) in 216
countries have been confirmed by the World Health Organization. So
1‐4
The outbreak of far, the notifiable cases have mostly been among adults and few cases
wileyonlinelibrary.com/journal/ppul © 2020 Wiley Periodicals LLC | 2565
2566 | YASUHARA
of children have been reported.5 Children with COVID‐19 have been
reported to be asymptomatic or with mild clinical symptoms compared
to adults.6‐8 Recently, there have been increasing reports about cases
of older school‐aged children and adolescents presenting with pro-
longed fever, shock, abdominal pain, and cardiac dysfunction after
SARS‐CoV‐2 infections that overlapped with Kawasaki disease (KD),
manifesting as a hyperinflammatory syndrome and multiorgan in-
volvement.9,10 The Centers for Disease Control and Prevention (CDC)
has termed the condition multisystem inflammatory syndrome in
children (MIS‐C) associated with COVID‐19 and developed a case
definition for MIS‐C.11 However, the clinical profiles regarding
COVID‐19 in children remain obscure, including the pathophysiology
and outcomes of MIS‐C. Herein, we aimed to conduct a systematic
review of the available published literature, and to report the clinical
characteristics in pediatric patients after SARS‐CoV‐2 infections.
2 | METHODS
2.1 | Search strategy
We conducted a comprehensive literature search and a systematic
review of case reports of COVD‐19 in children. The reason why we
chose case reports and case series was that they provided the clinical
information of patients described in detail, allowing for identification
of COVID‐19 patients with similar characteristics. All case reports
and case series that reported the clinical manifestations of COVID‐
19 in pediatric patients were identified using PUBMED and EMBASE
through 20 June 2020. The search terms included COVID‐19, SARS‐
CoV‐2, or coronavirus, children, pediatric case, infants, or neonates,
and case reports or case series. Two independent and blinded au-
thors (JY and TK) reviewed the search results separately to select the
reports based on the inclusion and exclusion criteria. We included
articles that met the following criteria: case reports and case series
that were published in peer‐reviewed journals, reported pediatric
cases (age <18 years old) with laboratory‐confirmed SARS‐CoV‐2
infections using a quantitative real‐time polymerase chain reaction
(PCR) or dual fluorescence PCR. We did not apply any language re-
strictions. Although the published guidelines for systematic reviews
recommend a quality assessment of the included literature, there are
only a limited number of case reports and series available, therefore,
we decided to include as many articles that met the inclusion criteria
as possible. We excluded patients with suspected COVID‐19 that
were not confirmed by a laboratory test and unpublished reports, or
which had suspicion of a duplicate reporting. The study was con-
ducted in accordance with the Preferred Reporting Items for Sys-
tematic Reviews and Meta‐Analyses guidelines.12
Epidemiological, clinical, laboratory, and radiological data were
collected, including the age at onset of the infection, sex, clinical signs
and symptoms, outcomes, laboratory data, chest X‐ray findings, chest
computed tomography (CT), and echocardiography. To compare the
clinical characteristics according to the age, the patients were divided
into age groups of less than 1, 1 to 10, and more than 10 years.
ET AL.
2.2 | Statistical analysis
Continuous variables are expressed as the means ± standard devia-
tions, or medians (interquartile range), as appropriate for the data
distribution. Categorical variables are expressed as frequencies and
percentages.
3 | RE SU LTS
Forty‐six articles met the inclusion and exclusion criteria and were
analyzed for the systemic review (Figure 1).13‐58 The study characteristics
and results of the systematic review are demonstrated in Table 1. All the
included articles were published from 1 February 2020 to 20 June 2020.
Twenty studies were conducted in China,13‐18,22,23,25‐29,35,37,49‐51,56,57
thirteen in the United States,32,33,39‐42,44,46‐48,53‐55 two each in Italy21,58
and Iran,20,24 and one each in Korea,19 Vietnam,30 Malaysia,31 Spain,34
Lebanon,36 Belgium,38 the UK,43 Turkey,45 and France.52 We identified a
total of 114 pediatric patients with COVID‐19. All the patients had a
confirmed infection of SARS‐CoV‐2 by laboratory tests. The data related
to the demographic features and clinical characteristics of the pediatric
patients with COVID‐19 are presented in Table 2, including the clinical
symptoms and outcomes, chest radiological and echocardiographic find-
ings, and laboratory findings.
The age at onset of the SARS‐CoV‐2 infection was reported in all
included case reports and case series. Twenty‐nine patients (25.4%)
were infants including seven neonates, 61 patients (53.5%) ranged
from age 1 to 10 years, and 24 patients (21.0%) were older than 10
years. Forty‐three articles mentioned the sex of the cases (N = 107),
50 patients (46.7%) were boys and 57 patients (53.3%) were girls.
3.1 | Clinical signs, symptoms, and outcomes
The most common symptoms of 112 pediatric patients with COVID‐
19 were fever (N = 72, 64.2%) and cough (N = 39, 34.8%). rhinorrhea
(N = 18, 16.1%), sore throat (N = 10, 8.9%), sputum production (N = 3,
2.7%), and dyspnea (N = 12, 10.7%) were reported as less common
symptoms. Dyspnea was identified as a more frequent symptom in
the age group of less than 1 year. Gastrointestinal symptoms in-
cluding diarrhea (N = 15, 13.4%) and vomiting (N = 7, 6.3%) were
reported more frequent in the age group of 1 to 10 and more than 10
years. Headaches (N = 5, 4.5%) were reported mainly in the age group
of more than 10 years. Seventeen patients were asymptomatic
(N = 17, 15.2%). The proportions of asymptomatic patients were 7.4%
(N = 2), 19.7% (N = 12), and 12.5% (N = 3) for the age groups of less
than 1, 1 to 10, and more than 10 years, respectively. Both symp-
tomatic and asymptomatic patients were hospitalized.
Seventeen MIS‐C patients were included (N = 17, 14.9%) and two
patients exhibited symptoms resembling KD with concurrent SARS‐
CoV‐2 infections (N = 2, 1.8%). The median age of the MIS‐C cases
was 9 (5.5‐12.5). These MIS‐C patients presented with fever (N = 17,
100%), gastrointestinal symptoms (N = 9, 52.9%), shock (N = 10,
YASUHARA ET AL.
F I G U R E 1 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) flow diagram of study selection [Color figure can
be viewed at wileyonlinelibrary.com]
58.8%), and KD symptoms (N = 12, 70.6%) including skin rash, con-
junctivitis, swelling of the extremities, oral mucosal changes, and
cervical lymphadenopathy. Fourteen patients (12.3%), including 11
with MIS‐C (64.7%), were admitted to the intensive care unit (ICU)
because of hypotension. No deaths were reported among these
pediatric patients after SARS‐CoV‐2 infections.
3.2 | Radiology, echocardiography, and laboratory
findings
A chest X‐ray and chest CT were performed in 46 cases and 50 cases,
respectively. Mottling and ground‐like opacities suggesting pneu-
monia were identified in 16 patients (34.8%) by chest X‐ray and
27 patients (54.0%) by chest CT.
Echocardiography was performed in 19 cases with MIS‐C and
KD. Left ventricular (LV) systolic dysfunction which was defined as
depressed LV ejection fraction (EF) (<50%) or fractioning shortening
(<25%), was identified in nine patients (47.4%). LVEF was less than
30% in 1 patient (11.1%), 30% to 50% in two patients (22.2%), and
| 2567
LVFS was less than 25% in six patients (66.7%). However, complete
recovery of LV systolic function which was defined as LVEF more
than 60% or LVFS more tha 30%, was observed in eight patients
(88.9%) at a median time of 7.0 (5.0‐8.3) days after admission.
Coronary artery dilation was detected in two patients (10.5%) and
improved in the follow‐up echocardiography.
The blood tests revealed leukopenia (<5 × 109/L; N = 9, 11.7%),
lymphopenia (<1.55 × 109/L; N = 26, 32.5%), and thrombocytopenia
(<140 × 109/L; N = 10, 20.0%). The proportion of lymphopenia was
35.7% (N = 5), 24.4% (N = 11), and 20.5% (N = 10) for the age groups
of less than 1 year, 1 to 10 years old, and more than 10 years old,
respectively. The aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels were increased in 10 patients (22.2%
and 16.4%), especially in infants (N = 4, 57.1% and N = 3, 50.0%). The
creatinine level was increased in seven patients (22.6%). The D‐dimer
level was increased in 15 patients (51.7%). The proportion of an
elevated D‐dimer level was 100.0% (N = 3), 41.2% (N = 7), and 55.6%
(N = 5) for the age group of less than 1, 1 to 10, and more than
10 years, respectively. Elevated levels of C‐reactive protein (CRP) and
procalcitonin were reported in 32 patients (39.5%) and 14 patients
T A B L E 1 Results of the systematic review
2568
|

First author No. of

(Ref #) Study type Country patients Age Symptoms Laboratory findings Radiological and echocardiographic findings
13
Cai et al Case report China 1 7y Fever, cough, rhinorrhea, dyspnea Elevated CRP Bronchial thickening
14
Zhang et al Case report China 1 3 mo Fever Normal Mottling
15
Wang et al Case report China 1 17 d Fever, cough, vomiting, diarrhea Normal Bronchial thickening
16
Zhang et al Case report China 2 1y Fever, cough Elevated CRP Mottling
17
Pan et al Case report China 1 3y Asymptomatic Normal NA
18
Wang et al Case report China 1 0d Asymptomatic Lymphopenia, elevated AST Nodular consolidation
19
Park et al Case report Korea 1 10 y Fever, sputum Normal Ground‐glass opacity

Kamali Aghdam Case report Iran 1 15 d Fever, dyspnea Elevated CRP Normal
et al20

Canarutto Case report Italy 1 1 mo Fever, cough Normal Normal

et al21

Lin et al22 Case report China 1 7y Cough, rhinorrhea Normal Normal

23
Li et al Case report China 2 4y Cough, rhinorrhea Elevated CRP Ground‐glass opacity

Mogharab Case report Iran 1 2 mo Fever, cough, rhinorrhea, dyspnea NA Ground‐glass opacity
et al24

Zhu et al25 Case series China 10 1‐17 y Asymptomatic, fever, cough, headache Elevated ALT pneumonia
26
Cai et al Case series China 10 3 mo‐ 10 y Fever, cough, rhinorrhea, sore throat Lymphopenia, thrombocytopenia, Ground‐glass opacity
elevated CRP, AST, ALT, D‐dimer

Wei et al27 Case series China 9 1‐11 mo Asymptomatic, fever, cough, sputum, NA NA
rhinorrhea

Xu et al28 Case series China 10 1‐15 y Asymptomatic, fever, cough, rhinorrhea, sore Lymphopenia, elevated CRP, Ground‐glass opacity
throat, diarrhea procalcitonin, D‐dimer

Tan et al29 Case series China 10 1‐12 y Fever, cough, vomiting Lymphopenia, Elevated CRP, Ground‐glass opacity

Le et al30 Case report Vietnam 1 3 mo Fever, rhinorrhea Normal Normal

See et al31 Case series Malaysia 4 4y Asymptomatic, fever, cough, sputum, NA NA

rhinorrhea, diarrhea

Jones et al32 Case report USA 1 6 mo Fever, rash, conjunctivitis, swelling of Elevated CRP Faint opacity
extremities, prominent tongue papilla

Rivera‐Figueroa Case report USA 1 5y Fever, conjunctivitis, erythematous lips, Elevated CRP, procalcitonin, ALT Enlarged heart silhouette
EI et al33 cervical lymphadenopathy, history of
rash and swelling of palms and soles
YASUHARA
ET AL.
TABLE 1 (Continued)

First author No. of

YASUHARA

(Ref #) Study type Country patients Age Symptoms Laboratory findings Radiological and echocardiographic findings
34
ET AL.

Díaz et al Case report Spain 1 0d Dyspnea Normal Ground‐glass opacity

35
Yin et al Case report China 1 9y Fever Elevated CRP Normal
36
Mansour et al Case report Lebanon 1 1y Fever, diarrhea Thrombocytosis, Elevated CRP Ground‐glass opacity
37
Mao et al Case report China 1 1y Fever, cough, rhinorrhea Normal Ground‐glass opacity
38
Piersigilli et al Case report Belgium 1 0d Dyspnea NA NA
39
Feld et al Case series USA 3 0 d ‐ 1 mo Fever, rhinorrhea, dyspnea Lymphopenia NA
40
Bush et al Case report USA 1 13 y ever, cough, rhinorrhea, dyspnea, diarrhea Lymphopenia Normal
41
Dumpa et al Case report USA 1 0d Fever Normal NA
42
Latimer et al Case report USA 1 16 y Fever, shock Lymphopenia, thrombocytopenia, Ground‐glass opacity, LV systolic dysfunction
elevated AST, ALT, creatinine, (LVEF 42%), improvement of LVEF on
Coagulopathy hospital day 9

Cook et al43 Case report UK 1 1 mo Dyspnea, shock Thrombocytopenia, Elevated CRP, Ground‐glass opacity
acute kidney injury, liver
dysfunction

Chiotos et al44 Case series USA 6 5‐14 y Fever, dyspnea, diarrhea, headache, Lymphopenia, thrombocytopenia, Ground‐glass opacity, LV systolic dysfunction
conjunctivitis, oral mucosal changes, rash, elevated CRP, procalcitonin, ALT, (LVFS 19%‐25%), complete recovery of
swelling of extremities, shock creatinine, D‐dimer LVFS on hospital day 5‐7, right coronary
artery dilation

Bekci et al45 Case report Turkey 1 7y Back pain Elevated CRP Ground‐glass opacity
46
Waltuch et al Case series USA 4 5‐13 y Fever, cough, diarrhea, vomiting, headache, Lymphopenia, thrombocytopenia, Ground‐glass opacity, LV systolic dysfunction
conjunctivitis, oral mucosal changes, rash, elevated CRP, procalcitonin, AST, (LVEF 47%), left coronary artery dilation
swelling of extremities, shock ALT, D‐dimer

Diercks et al47 Case report USA 1 4y Asymptomatic NA NA

48
Shaw et al Case report USA 1 3y Fever NA NA
49
Deng et al Case series China 2 2, 16 y Asymptomatic NA Normal
50
Li et al Case report China 1 3 mo Cough, rhinorrhea Elevated AST, ALT Ground‐glass opacity
51
Chen et al Case series China 2 8, 9 y Fever, cough, headache NA Ground‐glass opacity
52
Blondiaux et al Case series France 4 6‐8 y Fever, diarrhea, vomiting, rash, conjunctivitis, Lymphopenia, elevated CRP LV systolic dysfunction (LVEF <30%),
oral mucosal changes, swelling of complete recovery of LVEF on hospital
extremities, cervical lymphadenopathy day 4‐14

Greene et al53 Case report USA 1 11 y Fever, sore throat, rash, swelling of Lymphopenia, elevated CRP, LV systolic dysfunction, complete recovery of
|

extremities, shock procalcitonin, creatinine, D‐dimer systolic function before discharge

2569

(Continues)
2570 | YASUHARA ET AL.

(3.2%). All the MIS‐C patients had evidence of a marked inflammatory

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C‐reactive protein; d, days; EF, ejection fraction; FS, fractional shortening; LV, left ventricular; mo, months; NA, not
Radiological and echocardiographic findings
state such as an elevated CRP (166.5 [30.2‐302.5] mg/L) and procalci-
tonin (16.3 [15.1‐47.5] ng/mL). In addition, those MIS‐C cases demon-
strated liver dysfunction (N = 5, 29.4%), acute kidney injury (N = 7,
41.4%), and coagulopathy (N = 10, 58.8%).

Ground‐glass opacity

Ground‐glass opacity

Ground‐glass opacity
4 | D IS C U S S I O N

In this systematic review of 46 case reports and case series with

114 pediatric patients who had a confirmed SARS‐CoV‐2 infection,
we demonstrated that the main clinical features of COVID‐19 in
NA

NA

children were mild respiratory symptoms including a fever, cough,

and rhinorrhea, or without any symptoms. Dyspnea was more com-
elevated procalcitonin, D‐dimer
Elevated CRP, AST, ALT, D‐dimer

mon in infants as compared to the other age groups. Gastrointestinal

Lymphopenia, thrombocytosis,

symptoms including diarrhea and vomiting were reported in the older

age group. Our study described 17 MIS‐C patients associated with
COVID‐19 who developed a severe inflammatory phenotype, in-
Laboratory findings

cluding fever, gastrointestinal symptoms, shock, LV systolic dys-

Elevated CRP

function, liver and kidney dysfunction, and coagulopathy, as well as

Lymphopenia

clinical features that overlapped with KD, including rash, con-

junctivitis, swelling of the extremities, redness of the oropharynx, and
NA

coronary artery dilation.

Note: Complete recovery of LV systolic function which was defined as LVEF more than 60% or LVFS more than 30%.

Children with COVID‐19 have been reported to more often have

mild clinical symptoms than adults.6‐8,59‐61 In the review of the stu-
Asymptomatic, fever, cough, rhinorrhea

dies regarding COVID‐19 in children published before March 2020,

most children with COVID‐19 had mild symptoms, showing a good
prognosis, and recovered within 1 to 2 weeks.62 Liu X et al63 pro-
vided a summary of 171 confirmed pediatric cases in China, de-
scribing that most infected children had a milder clinical course, and
Fever, cough, rash

Fever, sore throat

Fever, rhinorrhea

asymptomatic infections were not uncommon (15.8%). There was

one death of a 10‐month‐old child with intussusception and multi-
Symptoms

organ failure. In the retrospective large cohort study of children with

Vomiting

COVID‐19 in China, 4% and 51% of the patients were diagnosed

without any symptoms or with mild symptoms, respectively, and only
1 child was reported to have died.6 Forty‐five percent of the patients
1‐15 y

2‐11 y

had moderate, severe, or critical symptoms such as pneumonia,

1 mo
13 y
Age

7y

hypoxia, or acute respiratory distress syndrome. In addition, the

proportion of severe and critical patients among the infants (11%)
patients

was higher than that among other age groups. Another retrospective
No. of

study reported two critical pediatric patients aged about 1 year who
1

required invasive mechanical ventilation, corticosteroids, and im-

Country

munoglobulin.64 That suggested that pediatric patients are generally

Case report China

China

Case report Italy

Case report USA

USA

available; RV, right ventricle; y, years.

less severe than adults, however, young children, particularly infants,

might have a higher risk with SARS‐CoV‐2 infection than older chil-
Case series

Case series
Study type

dren. Recently, the CDC COVID‐19 Response Team reported the

(Continued)

data about the current status in the United States.65 In that cohort,
73% of pediatric patients had symptoms of a fever, cough, or
58

shortness of breath as compared with 93% of adults. Between 5.7%

Del Barba et al
Jones et al54

56
First author

to 20% of pediatric patients were reported to be hospitalized, with

55

Chen et al
57
TABLE 1

Lee et al

Cai et al

0.58% to 2.0% admitted to the ICU. Three deaths were reported in

(Ref #)

this cohort of pediatric patients. That data suggested that respiratory

symptoms were less frequent among children than adults. Although
YASUHARA ET AL. | 2571

T A B L E 2 Epidemiological and clinical characteristics of pediatric patients confirmed with SARS‐CoV‐2 infections
Characteristics All cases (n = 114) Age <1 y (n = 29) Age 1‐10 y (n = 61) Age >10 y (n = 24)

Age, y 6.0 (1.0‐10.0) 6.0 (3.0‐8.0) 12.5 (11.8‐14.0)

Age, mo 2.0 (0.8‐3.8)

Sex
Female 57/107 (53.3%) 16/28 (57.1%) 27/56 (48.2%) 14/23 (60.9%)
Male 50/107 (46.7%) 12/28 (42.9%) 29/56 (51.8%) 9/23 (39.1%)

Signs and symptoms

Fever 72/112 (64.2%) 16/27 (59.3%) 37/61 (60.7%) 19/24 (79.2%)
Cough 39/112 (34.8%) 8/27 (29.6%) 24/61 (39.3%) 7/24 (29.2%)
Sputum production 3/112 (2.7%) 1/27 (3.7%) 2/61 (3.3%) 0/24 (0.0%)
Rhinorrhea 18/112 (16.1%) 7/27 (25.9%) 9/61 (14.8%) 2/24 (8.3%)
Sore throat 10/112 (8.9%) 1/27 (3.7%) 6/61 (9.8%) 3/24 (12.5%)
Dyspnea 12/112 (10.7%) 6/27 (22.2%) 3/61 (4.9%) 3/24 (12.5%)
Headache 5/112 (4.5%) 0/27 (0.0%) 1/61 (1.6%) 4/24 (16.7%)
Diarrhea 15/112 (13.4%) 1/27 (3.7%) 9/61 (14.8%) 5/24 (20.8%)
Vomiting 7/112 (6.3%) 1/27 (3.7%) 2/61 (3.3%) 4/24 (16.7%)
Rash 12/112 (10.7%) 1/27 (3.7%) 6/61 (9.8%) 5/24 (20.8%)
Conjunctivitis 9/112 (8.0%) 1/27 (3.7%) 6/61 (9.8%) 2/24 (8.3%)
Swelling of extremities 9/112 (8.0%) 1/27 (3.7%) 5/61 (8.2%) 3/24 (12.5%)
Oral mucosal changes 7/112 (6.3%) 1/27 (3.7%) 5/61 (8.2%) 1/24 (4.1%)
Cervical lymphadenopathy 3/112 (2.7%) 0/27 (0.0%) 3/61 (4.9%) 0/24 (0.0%)
Shock 10/112 (8.9%) 1/27 (3.7%) 4/61 (6.6%) 5/24 (20.8%)
Asymptomatic 17/112 (15.2%) 2/27 (7.4%) 12/61 (19.7%) 3/24 (12.5%)

Chest X‐ray findings

Ground‐glass opacity 16/46 (34.8%) 3/12 (25.0%) 8/25 (32.0%) 5/9 (55.6%)

Chest computed tomography scan

Mottling and ground‐glass opacity 27/50 (54.0%) 5/6 (83.3%) 15/33 (45.4%) 7/11 (63.6%)

Echocardiographic findings
LV systolic dysfunction 9/19 (47.4%) 0/2 (0.0%) 3/9 (33.3%) 6/8 (75.0%)
Complete recovery of LV systolic function 8/9 (88.9%) 0/0 (0.0%) 3/3 (100.0%) 5/6 (83.3%)
Time to recovery of LV systolic function, days 7.0 (5.0‐8.3) NA 7.0 (5.0‐7.0) 9.0 (7.0‐11.5)
Coronary artery dilation 2/19 (10.5%) 0/2 (0.0%) 1/9 (11.1%) 1/7 (14.3%)

Laboratory findings (normal range)

White blood cell, ×109/L (5‐12) 7.8 (5.8‐10.5) 7.8 (5.1‐9.8) 7.7 (5.9‐11.7) 7.5 (5.1‐10.5)
<5 9/77 (11.7%) 2/12 (16.7%) 4/45 (8.9%) 3/20 (15.0%)
5‐12 57/77 (74.0%) 10/12 (83.3%) 32/45 (71.1%) 15/20 (75.0%)
>12 11/77 (14.3%) 0/12 (0.0%) 9/45 (20.0%) 2/20 (10.0%)
Neutrophils, ×109/L (2.0‐7.2) 2.7 (1.5‐5.2) 1.6 (1.0‐2.7) 3.3 (2.2‐8.4) 4.2 (2.3‐7.5)
>7.2 9/40 (22.5%) 0/12 (0.0%) 7/22 (31.8%) 2/6 (33.3%)
Lymphocytes, ×109/L (1.55‐4.80) 2.4 (1.2‐3.6) 2.6 (2.0‐5.1) 2.6 (1.5‐3.7) 1.4 (0.59‐2.0)
<1.5 26/80 (32.5%) 5/14 (35.7%) 11/45 (24.4%) 10/21 (20.5%)
Platelets, ×109/L (140‐440) 235.0 (152.8‐321.0) 351.0 (230.0‐494.0) 253.0 (181.0‐308.5) 167.0 (143.2‐211.8)
<140 10/50 (20.0%) 2/13 (15.4%) 6/27 (22.2%) 2/10 (20.0%)
Hemoglobin, g/L (105‐145) 125.0 (112.5‐137.5) 123.0 (112.5‐140.5) 126.0 (112.8‐133.5) 128.0 (117.3‐143.0)
ALT, U/L (9‐50) 20.0 (14.0‐34.8) 46.0 (40.0‐100.0) 19.4 (14.3‐27.8) 20.0 (12.8‐29.8)
>50 10/61 (16.4%) 3/6 (50.0%) 5/39 (12.8%) 2/16 (12.5%)
AST, U/L (5‐60) 28.5 (22.0‐43.0) 93.5 (53.2‐138.0) 28.3 (24.2‐34.5) 21.0 (16.3‐34.1)
>60 10/45 (22.2%) 4/7 (57.1%) 3/28 (10.7%) 3/10 (30.0%)
Creatinine, µmol/L (18‐62) 46.0 (29.0‐59.0) 15.0 (14.0‐15.5) 35.0 (29.0‐54.0) 69.5 (53.8‐138.0)
>62 7/31 (22.6%) 1/4 (25.0%) 3/19 (15.8%) 3/8 (37.5%)

(Continues)
2572 | YASUHARA
TABLE 2 (Continued)
Characteristics All cases (n = 114)
D‐dimer, µg/L (<0.5) 0.6 (0.3‐3.8)
>0.5 15/29 (51.7%)
CRP, mg/L (0.0‐10.0) 7.4 (1.1‐22.3)
>10 32/81 (39.5%)
Procalcitonin, ng/mL (<0.1) 0.10 (0.06‐13.0)
>0.1 14/44 (3.2%)
Clinical outcomes
Admission to ICU 14/114 (12.3%)
Death 0 (0.0%)
Note: Data are the median (IQR), n (%), or n/N (%), where N is the total number of patients with available data.
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C‐reactive protein; ICU, intensive care unit; IQR, interquartile
range; LV, left ventricular; NA, not available; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; y, years.
most pediatric COVID‐19 patients were not severe, a serious
COVID‐19 illness could result in severe outcomes including an ICU
admission and even death in children. Our systematic review sup-
ports those previous findings that most pediatric patients were
asymptomatic or had mild symptoms, including a fever and cough,
followed by upper respiratory symptoms such as rhinorrhea and a
sore throat. In our analysis, the proportion of the patients with
dyspnea was lower than the proportion previously reported among
adults, nevertheless infants with COVID‐19 tended to present with a
greater chance of dyspnea. We have to take special care because
infants with COVID‐19 might develop a more serious condition than
that in older children.
The main radiological features in pediatric patients with COVID‐19
have been reported to be subpleural ground‐glass opacities and con-
61,66
solidations with surrounding halo signs, suggestive of pneumonia.
These findings were similar to those in adults, and most pediatric pa-
tients with these findings were asymptomatic or had mild symptoms. In
addition, Qiu H et al7 reported that the prevalence of pneumonia with
COVID‐19 (53%) was higher than that with H1N1 Influenza (11%). In
this present study, we demonstrated the similar results that 54% of the
pediatric patients had ground‐glass opacities, and most of them had
mild symptoms or were without any symptoms. Moreover, 83% of the
infants who underwent chest CT had abnormal radiological findings,
and the prevalence of pneumonia in infants was higher than that in the
other age groups. This suggests that the early detection of COVID‐19
pneumonia might be responsible for the optimum management of
pediatric patients, especially in infants.
Typical abnormal laboratory findings were reported such as
lymphopenia (31%), leucopenia (19%), and elevated creatine kinase‐
MB (31%) and procalcitonin (17%) levels in the cohort of pediatric
patients with COVID‐19.7 Xia W et al66 showed the laboratory
findings in pediatric patients with COVID‐19, including lymphopenia
(35%) and elevated ALT (25%), creatine kinase‐MA (75%), CRP (45%),
and procalcitonin (80%) levels. Although data regarding the coagu-
lation profile in children with COVID‐19 has not been sufficient to
date, the study of adult patients with COVID‐19 demonstrated that
ET AL.
Age <1 y (n = 29) Age 1‐10 y (n = 61) Age >10 y (n = 24)
0.84 (0.72‐7.1) 0.51 (0.31‐3.9) 1.0 (0.28‐3.4)
3/3 (100.0%) 7/17 (41.2%) 5/9 (55.6%)
1.0 (0.8‐5.7) 8.0 (1.8‐16.0) 11.9 (0.95‐152.6)
2/11 (18.2%) 21/49 (42.9%) 9/21 (42.9%)
0.1 (0.07‐0.12) 0.08 (0.03‐0.81) 15.8 (0.18‐18.8)
1/6 (16.7%) 7/27 (25.9%) 6/11 (54.5%)
1/29 (3.4%) 7/61 (11.5%) 6/24 (25.0%)
0 (0.0%) 0 (0.0%) 0 (0.0%)
the prothrombin time and D‐dimer levels were higher in ICU patients
than non‐ICU patients.3 In addition, Zhou et al67 reported that an
elevated D‐dimer level was 1 of the important risk factors of death in
adult patients after COVID‐19. Our study found similar laboratory
findings such as lymphopenia and elevated CRP, ALT, and AST levels
in children with COVID‐19. Also, the fact that an elevated D‐dimer
level was more frequent in infants than in the other age groups may
suggest that infants might become more serious than older children
after COVID‐19.
Recent observations raised concern about a new MIS‐C related
to SARS‐CoV‐2 infection, known as MIS‐C. Although children with
COVID‐19 are generally less severe or even asymptomatic compared
to adults, some children develop a significant systemic inflammatory
response and have symptoms resembling a severe form of KD. MIS‐C
shares similarities with KD but has some distinct features such as the
epidemiology, age of onset affecting older children and adolescents,
gastrointestinal symptoms, shock, cardiac dysfunction, acute heart
failure, and extremely high levels of inflammatory biomarkers and
brain natriuretic peptide.9,10,68‐70 Verdoni et al10 described 10 pe-
diatric patients with Kawasaki‐like disease in Italy. Five children
within the cluster had features similar to KD such as conjunctivitis,
polymorphic rash, mucosal changes, and swollen extremities, how-
ever, another five children presented with fewer than three diag-
nostic criteria of KD, and were older than the patients with KD. In
addition, 5 of 10 children presented with hypotension requiring a
fluid bolus injection, and 2 of 10 children required inotropic support.
Riphagen et al9 described eight children with COVID‐19 requiring
critial care in the UK and highlighted the severe form of the spectrum
of this disease. The clinical presentations of these patients were fe-
ver, rash, conjunctivitis, and peripheral edema with significant gas-
trointestinal symptoms. All the patients developed shock, requiring
acute body fluid supply as well as inotropic support such as with
noradrenaline and milrinone. Most of the patients initially presented
with no respiratory involvement, however, 7 of 8 children required
mechanical ventilation for cardiovascular stabilisation afterwards.
Belhadier et al68 reported 35 patients with MIS‐C in France and
YASUHARA ET AL.
Switzerland, presenting with cardiogenic shock or LV systolic dys-
function and a multisystem inflammatory state. The median age of
these patients was 10 (range: 2‐16) years and gastrointestinal
symptoms were prominent features (83%). Depressed LV systolic
function with EF below 30% was observed in 28% of patients, and EF
between 30% and 50% in 72% of patients. Follow‐up echocardio-
graphy showed complete recovery of LVEF in 71% of patients at a
68
median time of 2 days after admission. All patients received in-
travenous immunoglobulin, 80% of the patients required inotropic
support, and 28% of them required mechanical circulatory assistance
with extracorporeal membrane oxygenation (ECMO) that was suc-
cessfully weaned.68 Whittaker et al69 described 58 patients with
MIS‐C (9 [5.7‐14] years) in the UK. A wide spectrum of presenting
symptoms and disease severity, including fever, gastrointestinal
symptoms (45%‐53%), rash (52%), shock with myocardial injury
(50%), and the development of coronary artery aneurysms (14%) has
been reported. Greater elevation of the inflammatory markers such
as CRP (229 [156‐338] mg/L) was observed as compared with KD.
Inotropic support and ECMO were required in 47% and 5%, re-
spectively. Seventy‐one percent were treated with immunoglobulin
and 64% with corticosteroids. Cheung et al70 reported 17 patients
with MIS‐C (8 [1.8‐16] years) in the United States, presenting with
gastrointestinal symptoms (88%), shock (76%), and mucocutaneous
findings (53%‐71%). Eight met the criteria for KD and five for in-
complete KD. A total of 36% of MIS‐C patients had moderate or
more severe LV dysfunction and most patients had an improved
function on follow‐up echocardiography (range: 2‐18 days from ad-
mission). A total of 82% received steroid treatment and 76% received
immunoglobulins. The findings of our study were consistent with
those of the prior reports on MIS‐C. It is important to recognize that
SARS‐CoV‐2 infections might cause MIS‐C, and demonstrate similar
symptoms to KD as well as distinct features. Early diagnosis of MIS‐C
might provide a favorable outcome in preventing LV systolic dys-
function and acute heart failure. Further investigation will be needed
to elucidate the pathophysiological mechanisms, genetic suscept-
ibility, and detailed clinical outcomes of MIS‐C for appropriate
treatment and potential prevention.
This study had several limitations to be noted. The main limita-
tion of our approach was that we purposefully excluded retro-
spective studies. Those larger retrospective studies provided much
more of a cross‐sectional approach as has been noted. In contrast to
those larger studies, this study included a small number of pediatric
patients in case reports and case series mainly from China and the
United States, including the first cases in Korea, Iran, Vietnam,
Malaysia, Spain, and Lebanon. Since this study was a collection of
individual case reports or small case series, it is impossible to know
whether these cases were representative of all pediatric cases or
were published to highlight some novel feature of the individual
cases, including neonates with gastrointestinal symptoms, sepsis, and
possible vertical transmission, family cluster, or infected twins. Sec-
ond, we were not able to assess more detailed clinical information
including the treatment and outcome because those data were un-
available in our analysis. Third, nearly all the studies were reported
| 2573
from Asian countries. We could not assess the race or ethnicity data.
Further studies with large cohorts of pediatric patients are needed to
gain a better understanding of the severity, risk factors, outcomes,
and management of children with COVID‐19.
5 | C O N CL U S I O N
This systematic review of the current literature on pediatric COVID‐
19 provides insight into the clinical characteristics of COVID‐19 in
children. Although children with COVID‐19 generally present with
mild symptoms or are asymptomatic, infants might have a high risk of
severe illness, and SARS‐CoV‐2 infection might cause MIS‐C mani-
fested by gastrointestinal symptoms, LV systolic dysfunction, shock,
and multiorgan involvement in older children. We suggest that the
early identification of children with mild symptoms or even without
any symptoms and early diagnosis of MIS‐C are crucial for the
management of COVID‐19 in children and the prevention of SARS‐
CoV‐2 transmission and a severe inflammatory state.
AC KNO WL EDG M EN TS
The authors would like to thank Dr Vidu Garg for his helpful
comments on the manuscript.
CON F LI CT OF IN TE RES T S
The authors declare that there are no conflict of interests.
ORCI D
Jun Yasuhara http://orcid.org/0000-0002-7937-3699
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How to cite this article: Yasuhara J, Kuno T, Takagi H,
Sumitomo N. Clinical characteristics of COVID‐19 in children:
A systematic review. Pediatric Pulmonology. 2020;55:
2565–2575. https://doi.org/10.1002/ppul.24991