Clinical Manifestations of Children With COVID 19: A Systematic Review
Clinical Manifestations of Children With COVID 19: A Systematic Review
Clinical Manifestations of Children With COVID 19: A Systematic Review
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REVIEW
1
Pediatric Intensive Care Unit, Department of
Pediatrics, State University of Campinas Abstract
(UNICAMP), Campinas, São Paulo, Brazil
2 Background: The coronavirus disease 2019 (COVID‐19) outbreak is an
Department of Pediatrics, School of Medicine
São Leopoldo Mandic, Campinas, São Paulo, unprecedented global public health challenge, leading to thousands of deaths every
Brazil
day worldwide. Despite the epidemiological importance, clinical patterns of children
Correspondence with COVID‐19 remain unclear. The aim of this study was to describe the clinical,
Tiago Henrique de Souza, MD, PhD, Pediatric
laboratorial, and radiological characteristics of children with COVID‐19.
Intensive Care Unit, Department of Pediatrics,
State University of Campinas (UNICAMP), 126, Methods: The Medline database was searched between December 1st 2019 and
Tessália Vieira de Camargo Street, Campinas—
April 6th 2020. No language restrictions were applied. Inclusion criteria were (a)
SP 13083‐887, Brazil.
Email: [email protected] studied patients younger than 18 years old; (b) presented original data from cases of
COVID‐19 confirmed by reverse‐transcription polymerase chain reaction; and (c)
contained descriptions of clinical manifestations, laboratory tests, or radiological
examinations.
Results: A total of 38 studies (1124 cases) were included. From all the cases, 1117
had their severity classified: 14.2% were asymptomatic, 36.3% were mild, 46.0%
were moderate, 2.1% were severe, and 1.2% were critical. The most prevalent
symptom was fever (47.5%), followed by cough (41.5%), nasal symptoms (11.2%),
diarrhea (8.1%), and nausea/vomiting (7.1%). One hundred forty‐five (36.9%) chil-
dren were diagnosed with pneumonia and 43 (10.9%) upper airway infections were
reported. Reduced lymphocyte count was reported in 12.9% of cases. Abnormalities
in computed tomography were reported in 63.0% of cases. The most prevalent
abnormalities reported were ground‐glass opacities, patchy shadows, and
consolidations. Only one death was reported.
Conclusions: Clinical manifestations of children with COVID‐19 differ widely from
adult cases. Fever and respiratory symptoms should not be considered a hallmark of
COVID‐19 in children.
KEYWORDS
Abbreviations: CDC, Centers for Disease Control and Prevention; COVID‐19, Coronavirus disease 2019; CT, Computed tomography; SARS‐CoV‐2, Severe acute respiratory syndrome
coronavirus 2; WHO, World Health Organization.
Two authors (THS and JAN) screened the titles and abstracts in-
dependently and in duplicate for potential eligibility. They subse- 3 | RE SU LTS
quently read the full texts to determine final eligibility. Discrepancies
were resolved through discussion and consensus, and if necessary, 3.1 | Study selection and characteristics
the assistance of a third author (MBB) was sought.
Eligible studies fulfilled the following criteria: (a) studied patients Of 293 potentially relevant articles identified by the search strategy,
younger than 18 years old; (b) presented original data from cases of 38 met the inclusion criteria. A total of 1117 descriptions of pediatric
DE SOUZA ET AL. | 3
Dong et al20 731 10 ya 420 311 94 (12.9%) 315 (43.1%) 300 (41.0%) 15 (2.5%) 3 (0.4%) 1 (0.1%)
Lu et al3 171 6 y (1 d‐15 y)a 104 67 27 (15.7%) 33 (19.3%) 107 (62.6%) 1 (0.6%) 3 (1.7%)
Total 1121 643 478 159 (14.2%) 406 (36.3%) 514 (46.0%) 25 (2.1%) 13 (1.2%) 4
3.3 | Clinical manifestations 29 (16.6%) were decreased, and 132 (75.8%) were within normal ranges.
Normal or elevated lymphocytes counts were detailed in 28 studies,
The most prevalent symptom was fever, reported in 47.5% of the cases, involving 154 cases.11,13,16,17,19,21‐43,45 Normal lymphocyte counts were
followed by cough (41.5%), nasal symptoms (11.2%), diarrhea (8.1%), reported in 69.5% and elevated in 11.7% of cases. Reduced lymphocyte
nausea/vomiting (7.1%), fatigue (5.0%), and respiratory distress (3.5%). counts were reported in 45 of 350 (12.9%) cases.3,11‐13,16,17,19,21‐43,45
The nasal symptoms described were runny nose and nasal congestion, Zheng et al12 reported a median white blood cell count of 6.2 × 109/L
symptoms of loss of smell were not described. One hundred forty‐five (interquartile range [IQR]: 4.30‐9.85) and median lymphocyte count of
(36.9%) children were diagnosed with pneumonia and 43 (10.9%) upper 2.19 × 109/L (IQR: 1.15‐3.31) of 25 pediatric patients.
airway infections were reported. Amongst the most common clinical Normal or decreased platelet counts were detailed in 15 studies,
signs described were pharyngeal erythema (20.6%), tachycardia (18.6%), involving 32 cases.16,23‐25,27,29,31‐33,35,37,39‐41,45 Normal platelet
and tachypnea (13.4%) on admission. All the clinical manifestations re- counts were reported in 78.1% (22/32) and decreased in 3.2% (1/32)
ported in the selected studies and their relative frequencies are de- of cases. Increased platelet counts were reported in 6 of 63 (9.5%)
scribed in Table 2. All clinical manifestations described in each study are cases.11,16,23‐25,27,29,31‐33,35,37,39‐41,45
presented in E‐Table 1 in the Supporting Information. Elevated C‐reactive protein (CRP) levels were described in 59 of 305
cases (19.3%), reported in 25 studies.3,11,13,16,19‐24,26,27,29,31‐37,39‐42,45
Zheng et al12 reported a median CRP level of 15.5 mg/dL (IQR: 0.93‐
3.4 | Laboratorial characteristics 25.04) in 25 cases, and Cai et al5 a median of 7.5 mg/dL in 10 cases.
Procalcitonin levels were elevated in 139 of 279 cases (49.8%),
Twenty‐nine studies detailed the white blood cell count of reported in 16 studies.3,11,13,16,24,26,27,31,33,36,37,39‐43 Cai et al5
174 cases.11,13,14,16‐19,21‐43,45 Of these, 13 (7.5%) were elevated, reported a median procalcitonin level of 0.07 ng/dL in 10 cases.
Increased liver enzymes were described in 56 of 292 cases
T A B L E 2 Distributions of clinical manifestations of children with (19.2%), reported in 16 studies.3,11,13,16,21,24,27,29,31,33‐37,39‐41,43
COVID‐19 described in the selected studies Zheng et al12 reported a median alanine aminotransferase of
Clinical manifestations Frequency of occurrencea 12 U/L in 25 cases, and Cai et al5 a median alanine aminotransferase
and aspartate aminotransferase level of 18.5 U/L and 27.7 U/L,
Fever 187 (47.5%)
respectively, in 10 cases.
Cough 163 (41.5%) Nine studies described 70 cases tested for coinfections
Pneumonia 145 (36.9%) with other pathogens, of which 19 were positive
Pharyngeal erythema 81 (20.6%) (27.1%).5,12,13,16,19,26,34,37,41 Two patients were reported with
influenza A, five with influenza B, three with respiratory syncytial
Tachycardia on admission 73 (18.6%)
virus (RSV), one with cytomegalovirus, seven with Mycoplasma
Tachypnea on admission 53 (13.4%)
pneumoniae and one with Enterobacter aerogenes.
Nasal symptoms 44 (11.2%)
Diarrhea 32 (8.1%)
3.5 | Radiological features
Nausea/Vomiting 28 (7.1%)
Twenty‐seven studies reported 184 cases which underwent chest
Fatigue 20 (5.0%) CT.3,11‐14,16‐27,29,30,32,34‐36,39‐42 One hundred sixteen (63.0%)
Respiratory distress 14 (3.5%) CT scans presented abnormalities. The most prevalent abnormalities
Sore throat 10 (2.5%) reported were ground‐glass opacities, patchy shadows, and
consolidations. In the study of Lu et al3 involving 171 cases,
Respiratory failure 7 (1.8%)
ground‐glass opacities and patchy shadowings were observed in
Creptations 6 (1.5%) 32.7% and 31% of cases, respectively.3 Pleural effusion was observed
Sputum 6 (1.5%) in a 2‐month‐old child with simultaneous RSV and SARS‐CoV‐2
Hypoxemia 5 (1.3%) infections.19
Sneezing 2 (0.5%)
3.6 | Outcomes
Cyanosis 2 (0.5%)
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