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Am J Otolaryngol
journal homepage: www.elsevier.com/locate/amjoto
Pediatric COVID-19: Systematic review of the literature
Neha A. Patel⁎
Cohen Children's Medical Center, Division of Pediatric Otolaryngology, New Hyde Park, NY, USA
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Otolaryngology-Head and Neck Surgery, Hempstead, NY, USA
ARTICLE INFO
Keywords:
Pediatric
COVID-19
Coronavirus 19 SARS-CoV-2 2019-nCoV 2019 novel coronavirus ABSTRACT
Objectives: There is limited data regarding the demographics and clinical features of SARS-CoV-2 infection in
children. This information is especially important as pneumonia is the single leading cause of death in children
worldwide. This Systematic Review aims to elucidate a better understanding of the global impact of COVID-19
on the pediatric population. Methods: A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting
Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric COVID-19 epide-miology. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant article with a focus on Pediatric Covid 19, Pediatric Covid-19, Pediatric SARS-COV-2, and Pediatric Coronavirus 19. References
within the included articles were reviewed. All articles that met criteria where analyzed for demographics,
clinical, laboratory, radiographic, treatment and outcomes data.
Results: Ten studies including two case series and 8 retrospective chart reviews, altogether describing a total of
2914 pediatric patients with COVID-19 were included in this systematic review. Of the patients whose data was
available, 56% were male, the age range was 1 day to 17 years, 79% were reported to have no comorbidities, and
of the 21% with comorbidities, the most common were asthma, immunosupression, and cardiovascular disease. Of pediatric patients that were tested and positive for an infection with SARS-CoV-2, patients were asympto-
matic, 14.9% of the time. Patients presented with cough (48%), fever (47%) and sore throat/pharyngitis
(28.6%), more commonly than with upper respiratory symptoms/rhinorrhea/sneezing/nasal congestion (13.7%), vomiting/nausea (7.8%) and diarrhea (10.1%). Median lab values including those for WBC, lympho-cyte count and CRP, were within the reference ranges with the exception of procalcitonin levels, which were
slightly elevated in children with COVID-19 (median procalcitonin levels ranged from 0.07 to 0.5 ng/mL.
Computed tomography (CT) results suggest that unilateral CT imaging findings are present 36% of cases while 64% of pediatric patients with COVID-19 had bilateral findings. Of the studies with age specific hospitalization
data available, 27.0% of patients hospitalized were infants under 1 year of age. Various treatment regimens
including interferon, antivirals, and hydroxychloroquine therapies have been trialed on the pediatric population but there are currently no studies showing efficacy of one regimen over the other. The mortality rate of children
that were hospitalized with COVID-19 was 0.18%.
Conclusion: In contrast to adults, most infected children appear to have a milder course and have better out-
comes overall. Additional care may be needed for children with comorbidities and younger children. This review also suggests that unilateral CT chest imaging findings were seen in 36.4% pediatric COVID-19 patients. This is
particularly concerning as the work-up of pediatric patients with cough may warrant a bronchoscopy to evaluate
for airway foreign bodies. Extra precautions need to be taken with personal protective equipment for these cases, as aerosolizing procedures may be a method of viral transmission.
Level of evidence: 4 (Systematic Review).
https://doi.org/10.1016/j.amjoto.2020.102573 Received 18 May 2020
Abbreviations: WHO, World Health Organization; 2019-nCoV, 2019 novel coronavirus; COVID-19, 2019 novel coronavirus disease; PRISMA, Preferred Reporting
Items for Systematic Reviews and Meta-Analyses; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; CDC, Center for Disease Control; RT-PCR, reverse-
transcriptase polymerase chain reaction assay; n/a, data not available; CT, computed tomography; CXR, Chest X-Ray; WBC, white b lood count; CRP, C-reactive
protein; Hg, hemoglobin; CKMB, Creatine Kinase-MB; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; PICU, Pediatric
Intensive Care Unit; IRB, Institutional Review Board
⁎430 Lakeville Road, New Hyde Park, NY 11040, USA.
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1. Introduction
An outbreak of unusual respiratory disease causing severe cases of
pneumonia initially in Wuhan, China was caused by a novel enveloped
RNA coronavirus. The World Health Organization (WHO) named the
virus, the 2019 novel coronavirus (2019-nCoV) on January 7, 2020 [1].
Soon after, the virus rapidly spread throughout the world. On February
11, 2020, WHO named the illness associated with 2019-nCoV the 2019
novel coronavirus disease (COVID-19) [2]. The International Com-
mittee on Taxonomy of Viruses later renamed the 2019-nCoV virus to
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [3].
In the United States, 22% of the population is made up of children
aged < 18 years. In comparison, the Center for Disease Control (CDC)
COVID-19 Response Team has reported that 1.7% (2572/149,082) of
the COVID-19 cases reported as of April 2, 2020, for which the age was
known, occurred in pediatric patients aged < 18 years [4]. The CDC
COVID-19 Response Team has estimated that 20% of all pediatric pa-
tients whose hospitalization status was known, were hospitalized,
compared to 33% among all adults aged 18–64 years [ 4].
Coronaviruses (including 229E, OC43, NL63 and KHU1) are pre-
valent and cause a significant percentage of all common colds in im-
munocompetent adults and children [5]. The 2019 novel coronavirus,
SARS-CoV-2, can be transmitted directly from person to person by re-
spiratory droplets and potentially uses the ACE2 receptor to infect
humans. SARS-CoV-2 has a more variable clinical course than the
common cold [ 5].
Many of those who died of the SARS-CoV-2 have had underlying
health conditions such as hypertension, diabetes or cardiovascular
disease that may have compromised their immune systems. SARS-CoV-
2 is more likely to infect elderly men [5,6]. In contrast, the virus is
thought to have a milder effect on the pediatric population. A case
series of a total four infants born to mothers with COVID-10, Chen et al.
[7] in which none of three infants tested were positive for the virus nor developed clinical symptoms of disease, suggests a low likelihood of
vertical transmission of the virus. Yet, there is limited data regarding
the demographics and clinical features of SARS-CoV-2 in children [8].
This is especially important as pneumonia is the single leading cause of
death in children worldwide [ 9]. This Systematic Review was per-
formed to gain a better understanding of the global impact of Covid-19 on the pediatric population. The Northwell Health Institutional Review
Board (IRB) granted this study IRB exemption.
2. Methods
A systematic literature search was performed in accordance with
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-
Analyses) [ 10] guidelines to increase comprehensiveness and trans-
parency of reporting. Published studies were found using a thorough search strategy of the Pubmed and Google Scholar databases on April
10, 2020, with no language or regional restrictions. The following
search terms were used: Pediatric Covid 19, Pediatric Covid-19, Pediatric
SARS-COV-2, and Pediatric Coronavirus 19. References within the in-
cluded articles were reviewed and the corresponding abstracts and full
articles were accessed if relevant. Studies citing the included articles
were searched for using Pubmed and Google Scholar databases and
their corresponding abstracts and full articles also accessed if relevant.
No restriction was placed on the date of publication. The literature
search was originally performed in April 10, 2020 when this project
first took shape and was repeated in April 16, 2020 prior to submission
of the manuscript for accuracy.
Eligibility for inclusion in the review was a specific focus of COVID-
19 on the pediatric population. Studies that had no data, those with data on adults, those with repeat data points due to updates, and those
without data specific to patients with positive COVID-19 testing were
excluded. Children were defined as being < 18 years old. Only cases
with confirmed COVID-19 positive testing were included. Commentaries and editorials were excluded. Isolated case reports and repeat case series from the same region were excluded in an attempt to
avoid duplicate data from large retrospective chart reviews.
A large retrospective chart review of 728 COVID-19 positive pediatric
patients by Dong et al. [ 2] was rejected as the case data was mixed with
the demographics of 1407 suspect cases without confirmatory COVID-19 positive testing. Of note, in this study, most cases were mild and one
child died [2 ]. The data from Calvo et al. [ 11], was rejected as a more
recent update on the demographics of COVID-19 was included [ 12
] and
this article likely included duplicate data. For similar reasons the results
of Sun et al. [ 6], Yu et al. [ 13] and Xia et al. [14] were rejected. These
were case series from Wuhan Children's Hospital that likely replicated data from the larger Lu et al. [ 8] retrospective chart review of 171
children treated at Wuhan Children's Hospital. Likewise, the results of Wei et al. [15] was rejected as the data was likely repeated from Chil-
dren's Hospitals in other Chinese provinces included in studies by Cai
et al. [16] and Qiu et al. [ 17]. Finally, the data from a series of infants
born to COVID-19 positive mothers, Chen et al. was also rejected as all the infants that were tested were negative for the disease [7 ].
Asymptomatic was defined as “without any clinical symptoms and
signs or imaging findings or disease, whereas the 2019-nCoV/SARS-
CoV-2 testing result was positive”. Cases were defined as confirmed
COVID-19 positive if they met any one of the following criteria:
1. Nasal, nasopharyngeal, oropharyngeal swab, nasotracheal, or blood
samples tested positive for 2019-nCoV/SARS-CoV-2 nucleic acid by using real-time reverse-transcriptase polymerase chain reaction
assay (RT-PCR).
2. Genetic sequencing of respiratory tract or blood samples was highly
homologous with 2019-nCoV/SARS-CoV-2.
3. Reports to government agencies (Center for Disease Control) in-
dicating a positive case.
The information that was extracted were as follows: study data
(author, year, level of evidence, geographic area, study age group,
study design); demographics data (including age and gender, co-
morbidities); clinical data (presenting signs and symptoms, exposure
history and coinfection data); laboratory data [white blood count
(WBC), lymphocytes, hemoglobin (Hg), platelets, C-reactive protein
(CRP), Creatine Kinase-MB (CK-MB), D-Dimer, procalcitonin, alanine
aminotransferase (ALT), aspartate aminotransferase (AST), urea, crea-
tinine, lactate dehydrogenase (LDH), and SARS-CoV-2 testing results
(aerodigestive tract, serum, urine, and fecal)], radiographic data [chest
x-ray (CXR) and computed tomography (CT) scan results]; treatment
data (hospitalization, pediatric intensive care unit (PICU) admission,
oxygen therapy, antibiotic, antiviral and other medication regimen]
and outcomes data (mortality, length of admission, repeat SARS-CoV-2
testing results).
Due to the qualitative, summative nature of this review and sig-
nificant variations in study design and reporting, a meta-analysis and
statistical calculations were not performed.
3. Results 3.1. Review of the literature
A search of 202 articles was performed. 10 papers were identified
that were relevant to the research topic and met inclusion criteria. A
PRISMA flow diagram detailing the systematic search is presented
(Fig. 1). The results focused on demographics, clinical data, laboratory data, radiographic data, treatment data and outcomes data. The results
of the 10 studies are summarized in Tables 1–6 ([4,8,12,16–22]). The
10 studies selected represent retrospective chart reviews and case series published in 2020 with data collection between Jan to April 2020. Data
came from regions throughout the world including distinct regions of
China, United States, Iran, and Spain. N.A. Patel $P - 2WRODU\QJRO
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3.2. Demographics data
There were an overall of 2914 pediatric patients that tested positive
for COVID-19, and were analyzed in the 10 studies included in the
systematic review (Table 1 ). Gender was reported in all studies but data
was missing for 82 individuals [4]. Of the 2832 cases with gender data available, the percentage of males ranged from 33% to 100% with an
overall mean percentage of males of 56.4% (n = 1598). Patients'
median age varied across studies from 1 to 11 years. Of the studies with reported means, patients' mean age varied across studies from 6.2 to
11 years, with a composite mean age of 7.9 years (n = 74, age range
1 day- 17 years).
Only two studies had “negative” COVID-19 testing data available.
The retrospective chart review by Lu et al. [8] describes that of the 1391 pediatric patients that were tested for COVID-19 at Wuhan Chil-
dren's Hospital, 171 patients tested positive. The retrospective chart
review by Tagarro et al. [12], describes that of 365 pediatric patients
tested for COVID-19 in Madrid, 41 patients tested positive. Ad-
ditionally, the CDC COVID-19 Response Team describes 2572 pediatric
patients tested positive for COVID-19 between Feb 12- Apr 2, 2020, but
only 2470 patients have gender data available [4].
3.3. Clinical data
Across the studies, data about the incidence of comorbidities was
available for 444 children, and of these, 349 were reported to have no
comorbidities (78.6%, with individual study percentages ranging from 50% to 100%) and 95 out of 444 children had comorbidities (21.4%, with individual study percentages ranging from 8.7% to 50%) Of the 95
children reported to have comorbidities, only 84 children had specific
data available ( Table 2). Of these 84 children, 40 had asthma, 11 had
immunosupression and 28 had cardiovascular disease. One patient with cardiovascular disease also had malnutrition and suspicion for an un-
derlying metabolic disorder. Five patients out of the 84 patients with
data available had “other comorbidities” but the comorbidities were not
listed.
Information about COVID-19 presenting signs and symptoms in
children was available for 633 cases (Table 3). Of these, 51 out of the
342 cases with data available were asymptomatic (14.9%, with in-
dividual study percentages ranging from 0% to 53.3%), 296 out of 633
patients had fever (46.8%, with individual study percentages ranging
from 26.8% to 100%), 285 out of 592 patients had cough (48.1%, with
individual study percentages ranging from 11.1% to 100%), 91 out of
578 had shortness of breath, respiratory distress, or tachypnea (15.7%,
with individual study percentages ranging from 0% to 50%), 86 out of
629 had upper respiratory symptoms, rhinorrhea, sneezing or nasal
congestion (13.7%, with individual study percentages ranging from
6.5% to 40%), 161 out of 563 had sore throat or pharyngitis (28.6%,
with individual study percentages ranging from 8.3% to 46.2%), 47 out
of 605 had vomiting/nausea (7.8%, with individual study percentages
ranging from 0% to 10.7%), 19 out of 316 had abdominal pain (6%,
with individual study percentages ranging from 3% to 8%), 62 out of
614 had diarrhea (10.1%, with individual study percentages ranging
from 0% to 22.2%), 87 out of 358 had headaches (24.3%, with
Fig. 1. Pediatric COVID-19 search strategy using PRISMA flowchart [10]. N.A. Patel $P - 2WRODU\QJRO
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Table 2
Comorbidities: summary of articles identified in the systematic literature review.
Article [reference] No comorbidities
(n=) Comorbidities (n=) Asthma (n=) Immunosuppression (n=) Cardiovascular disease (n=)
Cai et al. (2020) [16] n/a n/a n/a n/a n/a CDC update 2020 [4] 265 80 40 10 25 Eghbali et al. (2020) [18] 2 2 0 1 1
Feng et al. (2020) [19] n/a n/a n/a n/a n/a Lu et al. (2020) [ 8] n/a n/a n/a n/a n/a
Qiu et al. (2020) [ 17] n/a n/a n/a n/a n/a
Shen et al. (2020) [20] n/a n/a n/a n/a n/a Tagarro et al. (2020) [ 12] 30 11 n/a n/a n/a
Wang et al. (2020) [ 21] 31 0 0 0 0
Zheng et al. (2020) [22] 21 2 0 0 2
Overall systematic review data 349 95 40 11 28
n/a, data not available. Table 1
Demographics: summary of articles identified in the systematic literature review.
Article [reference] Level of evidence
Study type
Study age range Study period Study country
Region
Study period COVID-19 +
Patients
n= Male
n = (%) Female n = (%) Mean age (years) Median age (years) Age range
Cai et al. (2020) [16] 4
Case Series
ages 0–18 years Jan 11–Feb 3, 2020 China Anhui and Shandong Provinces Jan 11–Feb 3, 2020 10 4 (40%) 6 (60%) 6.2 6.5 3 months to
10.9 years
CDC Coronavirus Update
(2020) [4] 4 Retrospective Chart Review ages 0–18 years
Feb 12–Apr 2, 2020 United States
50 states, District of Columbia, 4 US territories
Feb 12–Apr 2, 2020 2470 1408 (57%)
a 1062 (43%)a n/a 11 0 years to
17 years
Eghbali et al. (2020) [18] 4
Retrospective Chart Review
ages 0–16 years n/a (prior to Apr 10, 2020) Iran Tehran n/a (prior to Apr 10, 2020) 4 4 (100%) 0 (0%) 11 11 8 years to
13 years
Feng et al. (2020) [19] 4
Retrospective Chart Review ages 0–18 years
Jan 16–Feb 6, 2020 China
Shenzhen and Guangdong Provinces
Jan 16–Feb 6, 2020 15 5 (33%) 10 (67%) 7.4 7 4 years to
14 years
Lu et al. (2020) [ 8] 4
Retrospective Chart Review
ages 0–16 years Jan 28–Feb 26, 2020 China Wuhan Children's Hospital, Hubei Province Jan 28–Feb 26, 2020 171 104 (61%) 67 (39%) n/a 6.7 1 day to
15 years
Qiu et al. (2020) [ 17] 4
Retrospective Chart Review aged 0–16 years
Jan 17–Mar 1, 2020 China
Zhejiang Province Jan 17–Mar 1, 2020 36 23 (64%) 13 (36%) 8.3 n/a 1 year to
16 years
Shen et al. (2020) [20] 4
Retrospective Chart Review Ages 0–16 years Jan 8–Feb 19, 2020 China Changsha and Hunan Provinces Jan 8–Feb 19, 2020 9 3 (33%) 6 (67%) 7.6 8 1 year to
12 years
Tagarro et al. (2020) [ 12] 4
Retrospective Chart Review
ages 0–17 years
Mar 2–Mar 16, 2020 Spain Madrid
Mar 2–Mar 16, 2020 41 18 (44%) 23 (56%) n/a 3 9 days to
15 years
Wang et al. (2020) [ 21] 4
Retrospective Chart Review
ages 0–18 years Jan 25–Feb 21, 2020 China Shaanxi, Gansu, Ningxia, Hebei, Henan, and Shandong Provinces Jan 25–Feb 21, 2020 31 15 (37%) 16 (52%) n/a 7 3 months to
17 years
Zheng et al. (2020) [22] 4
Retrospective Chart Review, ages 0–14 years Feb 1–Feb 10, 2020 China
Wuhan urban and peri-urban
area Public Hospitals, Hubei Province Feb 1–Feb 10, 2020 25 14 (67%) 11 (44%) n/a 3 3 months to
14 years
Overall systematic review
data 4 Systematic Review aged 0–18 years
Jan 11–Apr 2, 2020 China, US, Iran, Spain
Jan to April 2020 2812 1598 (57%) 1214 (43%) 7.9 1 day to
17 years
n/a, data not available.
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individual study percentages ranging from 8.3% to 27.8%), 16 out of
202 had fatigue (7.9%, with individual study percentages ranging from
2.5% to 9.7%), and 66 out of 291 had myalgia (22.7%, with individual
study percentages ranging from 10.4% to 22.7%). No studies reported
data points on the presence or absence of pediatric anosmia or dys-
geusia. Of the studies that reported a final clinical diagnosis, 171 cases
out of 318 were given the clinical diagnosis of a pneumonia or
bronchiolitis (53.8%, with individual study percentages ranging from
12.9% to 68.0%).
Across the studies, information about coinfections was only avail-
able in 3 studies. Cai et al. reviewed a series of 10 COVID-19 positive
pediatric patients, all of whom tested negative for influenza A and in-
fluenza B [ 16]. In the chart review of 41 COVID-19 positive children by
Tagarro et al., 2 children tested positive for influenza B [12]. Finally, in the chart review of 25 COVID-19 positive children by Zheng et al., 2
children tested positive for influenza B, 3 children tested positive for
Mycoplasma pneumonia, and 1 child tested positive for Enterobacter
aerogenes [22].
Of the studies that included exposure data on all patients, 289 out of
338 cases had known exposure with a COVID-19 positive person or lived in/traveled to a concerning area (85.5%, with individual study
percentages ranging from 39% to 100%), while 49 out of 338 have no
known exposure risk factors and transmission was likely from com-
munity spread (14.5%, with individual study percentages ranging from
0% to 61.0%). Only 2 studies ([ 16,20]) reported data regarding the
median interval from exposure to symptom onset. Of these 19 patients the median interval days from exposure to symptom onset ranged from
7 to 7.5 days.
3.4. Laboratory data
Information about median laboratory values was available from
various studies. All median lab values including those for WBC, lym-
phocyte count, Hg, CRP, CK-MB, D-Dimer, AST, ALT, urea, creatinine,
and LDH levels were within the reference ranges based on each study
(Table 4 ) for which the data was available, with the exception of pro-
calcitonin levels. The median procalcitonin levels ranged from 0.07 to 0.5 ng/mL. Notably, in the retrospective chart review by Lu et al. [8],
the median procalcitonin was slightly elevated 0.5 ng/mL (reference
range of 0.46 ng/mL). In this review, 105 out of 164 (64%) patients had
procalcitonin levels ranging from 0.5 to 0.8 ng/ml. The median WBC
ranged from 6 to 7.35 × 10
9/L. A total of 58 out of 184 patients
(31.5%) with data available had a low WBC of < 5.5 × 109/L. The
median lymphocyte count ranged from 2.2 to 2.9 × 109/L. A total of 20
out of 220 patients (9.1%) with data available had a lymphopenia (lymphocyte count of < 1.2 × 10
9/L).
One study, Cai et al. [16], was the only one to report on data from
patients regarding SARS-CoV-2 detection in fecal and urine samples
with time. Fecal testing was positive for SARS-CoV-2 RNA detection in 5
out of 6 patients that were tested and remained positive for 18 to
30 days after symptom onset. These patients are still under “close
follow-up” due to the positive results. Six out of 6 patients with urine
and serum testing were negative for virus detection within 2–3 days of
symptom onset.
3.5. Radiologic data
Of the studies that included CXR imaging data on COVID-19 positive
cases, 6 patients out of 14 that got CXRs had normal results (42.9%) and
8 out of 14 had abnormal findings (57.1%) (Table 5 ). Unilateral find-
ings were seen in 5 out of the 8 patients with abnormal CXR imaging
(62.5%). These findings included “unilateral patchy infiltrates” in 4
patients and a lung “opacification” in one patient. Bilateral findings of
subpleural ground glass opacities were seen in 3 out of the 8 patients
with abnormal CXR imaging (37.5%).
Of the studies that included complete CT imaging data (normal and Table 3
Presentation: summary of articles identified in the systematic literature review.
Article [reference] Presentation data
available (n=) Asymptomatic (n=) Fever (n=) Cough (n=) Shortness of breath Respiratory distress Tachypnea (n=) URI symptoms Nasal congestion Rhinorrhea Sneezing (n=) Sore throat Pharyngitis (n=) Vomiting Nausea (n=) Abdominal pain (n=) Diarrhea (n=) Headache (n=) Fatigue (n=) Myalgia (n=) Pneumonia Bronchiolitis Clinical diagnosis (n=)
Cai et al. (2020) [16] 10 0 8 6 0 4 4 0 n/a 0 n/a n/a n/a 5
CDC Update (2020) [4] 291 n/a 163 158 13 21 71 31 17 37 81 n/a 66 n/a
Eghbali et al. (2020) [18] 4 0 4 4 2 n/a n/a n/a n/a n/a n/a n/a n/a 2
Feng et al. (2020) [19] 15 8 5 1 n/a 1 n/a n/a n/a n/a n/a n/a n/a
Lu et al. (2020) [ 8] 171 27 55 83 72 33 79 11 n/a 15 n/a 13 n/a 111
Qiu et al. (2020) [ 17] 36 10 13 7 1 7 3 1 n/a 1 3 n/a n/a 19
Shen et al. (2020) [20] 9 2 4 1 n/a 2 1 n/a n/a 2 n/a n/a n/a n/a
Tagarro et al. (2020) [12] 41 0 11 n/a 1 14 n/a 1 n/a 1 n/a n/a n/a 13
Wang et al. (2020) [ 21] 31 4 20 14 n/a 2 3 1 n/a 3 3 3 n/a 4
Zheng et al. (2020) [22] 25 0 13 11 2 2 n/a 2 2 3 n/a n/a n/a 17
Overall systematic review
data 51 296 285 91 86 161 47 19 62 87 16 66 171
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Table 4
Laboratory data: summary of articles identified in the systematic literature review.
Article [reference] LABS (median) (reference
values) data available
(n=) WBC (4–10 × 10
9/L) WBC < 5.5 × 109/L
(n=) Lymphocyte count (1.1–3.2 × 10
9 cells/L) Lymphocyte count < 1.2x10
9L
(n=) Hg (mg/dL) CRP (< 8 to
< 25 mg/L)
(n=) Procalcitonin (< 0.46–0.5 ng/mL) CK-MB (< 18–25 U/L) D Dimer ALT
(< 40 U/L) AS(
<
Cai et al. (2020) [16] 10 7.35 n/a n/a n/a n/a 7.5 0.07 23 0.45 μg/nl 18.5 27
CDC Update (2020) [4] n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/ a
Eghbali et al. (2020) [18] 4 6 2 n/a 2 11.6 n/a n/a n/a n/a n/a n/ a
Feng et al. (2020) [19] n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/ a
Lu et al. (2020) [ 8] 171 6.8 45 2.9 6 12.6 4 0.5a n/a 1.2 (mg/LFEU)b 15 30
Qiu et al. (2020) [ 17] 36 6.1 7 2.4 11 n/a 5 0.24 19 0.29 μg/nl 21 30
Shen et al. (2020) [20] 9 6.06 9 2.65 1 n/a 1.78 n/a n/a n/a 15.66 28
Tagarro et al. (2020) [12] n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/ a
Wang et al. (2020) [ 21] n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/ a
Zheng et al. (2020) [22] 25 6.5 n/a 2.19 n/a n/a 14.5 n/a n/a n/a 12 n/ a
n/a, data not available; WBC, white blood count; CRP, C-reactive protein; Hg, hemoglobin; CKMB, Creatine Kinase-MB; ALT, alanin e aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase.
aData from 164 patients out of the 171 included in the study.
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abnormal results) on COVID-19 positive cases, 37 patients out of 82
that got CT chest scans had normal results (45.1%) and 45 out of 82 had
abnormal findings (54.9%) (Table 5 ). Of these 45 patients with ab-
normal imaging, 3 had “bilateral subpleural ground glass opacities,” 1 had an “opacification,” 9 had “ground glass opacities,” 2 had “uni-
lateral ground glass opacities,” 9 had “patchy ground glass shadows and
nodules,” 5 unilateral had “patchy shadows or lung consolidation” and
11 had “bilateral patchy shadows or lung consolidations.” These results
do not include the Lu et al. study [ 8] as the data was incomplete (total
number of patients sent for radiographs and number of patients with normal findings were not listed) however, in this study, of the 111
patients with abnormal CT imaging, (56 patients had “ground-glass
opacities” (50.5%), 32 patients had “local patchy shadowing” (28.8%),
21 patients had “bilateral patchy shadowing” (18.9%) and 2 patients had “interstitial abnormalities (1.8%). These results also do not include
the Qiu et al. [ 17] study as the data was incomplete (total number of
patients sent for radiographs and number of patients with normal findings were not listed) however, this study found that 19 out of the 19
patients with abnormal CT imaging findings had “ground glass ab-
normalities.” Of note, this study included results of CT imaging of
COVID-19 positive patients that were “asymptomatic,” with the reason
for imaging listed as being for “diagnostic” purposes. Finally, of the
studies with abnormal CT results specifically describing imaging later-
ality, unilateral CT imaging findings were seen in 8 out of 22 patients
(36.4%) and 14 out of 22 patients had bilateral findings (63.6%).
3.6. Treatment data
Across the studies, all but 2 were chart reviews of patients that were
already hospitalized. The retrospective chart review by Tagarro et al.
[12] and the CDC COVID-19 Response Team [4] describe patients that
were tested but not necessarily admitted to be hospitalized. 172 out of
786 patients that tested positive in these 2 studies (21.9%, percentages
ranging from 19.7% to 60.1%) were hospitalized. Of the studies with
age specific hospitalization data available (Table 6 ), 172 out of 786
patients were children < 1 years old (27.0%, with individual study percentages ranging from 0 to 40.1%).
Of the studies with PICU admission data, 26 out of 382 hospitalized
patients (6.8%) received PICU level care. Of these 26 patients, data
regarding comorbidities was not available for 19 patients. Of 7 children
in the PICU that had data available, all 7 had comorbidities (2 were
immunosuppressed, 3 had cardiovascular disease, 1 had hydrone-
phrosis and 1 had intussusception). Of the studies with PICU age data, 6
out of 19 PICU patients (31.6%) were < 1 year of age.
Across the studies, data about oxygenation regimen was variable. Some studies report not needing any oxygen for patients while other
studies report the use of nasal cannula, high flow nasal cannula, and
non-rebreather face masks. Of the studies with intubation data avail-
able, 7 out of 327 (2.1%) of hospitalized children with COVID-19
needed intubation.
Across the studies, information about medication regimen was
available for 105 patients. Lopinavir-ritonavir was the most common
medication used. Eghbali et al. [18] reported the use of azithromycin (1
out of 4 patients) and hydroxychloroquine (3 out of 4 patients and
oseltamivir (3 out of 4 patients). Qiu et al. [17] reported the use of
interferon alpha aerosolization twice a day in 36 out of 36 patients and
lopinavir-ritonavir syrup twice a day in 14 out of 36 patients. Wang
et al. [ 21] reported the use of “antibiotics” in 6 out of 31 patients, while
2 out of 31 patients received IV gamma globulin, and 29 out of 31
received antivirals (10 interferon alone, 19 received interferon in
combination with 2 or more antivirals (ribavirin, abidor, oseltamivir or
lopinavir/ritonavir). Shen et al. [20], reported that 9 out of 9 patients
received antivirals (lopinavir/ritonavir twice a day) and 1 out of 9 re -
ceived meprednisone and immunoglobulin for febrile convulsion. Zheng et al. [22] reported 13 out of 25 patients trialed “antibiotics,”, 12
out of 25 received interferon arbidol, oseltamivir, or lopinavir/litonavir
(alone or in combination) and 2 intubated patients received systemic
corticosteroids and IV immunoglobulin.
3.7. Outcomes data
Across 7 studies for which the information about mortality out-
comes was available, there were a total of 5 pediatric mortalities out of
2843 COVID-19 positive cases (0.18%). The causes of death were to be
determined. One mortality occurred in an 11 year old male with
aplastic anemia and a low WBC of 1.1 × 10
9/L. Another mortality oc-
curred in a 10 month old child with intussusception and multiorgan failure. The data for the other 3 mortalities was not available.
Of the studies with hospital discharge data, 209 out of 292 patients
were discharged (72.6%) and 81 out of 292 patients were still inpatient
(27.7%) at the time of study publication. The average length of stay was
only available for 38 patients and the average length of stay ranged
from 6.5 to 14 days (composite mean length of stay was 13.6 days). Of
the 16 patients with repeat COVID-19 testing that was negative prior to
discharge, the median days after illness onset to negative COVID-19
testing ranged from 12 to 14 days.
4. Discussion
This article is a comprehensive systematic review on COVID-19 Table 5
Imaging: summary of articles identified in the systematic literature review.
Article [reference] Radiologic data available
(n) CXR normal (n=) CXR abnormal (n=) CT normal (n=) CT abnormal (n=)
Cai et al. (2020) [16] 10 6 4 n/a n/a
CDC Update (2020) [4] n/a n/a n/a n/a n/a
Eghbali et al. (2020) [18] 4 0 4 0 4
Feng et al. (2020) [19] 15 n/a n/a 6 9
Lu et al. (2020) [ 8] 111 n/a n/a n/a 111
a
Qiu et al. (2020) [ 17] n/a n/a n/a n/a 19a
Shen et al. (2020) [20] 9 n/a n/a 7 2
Tagarro et al. (2020) [ 12] n/a n/a n/a n/a n/a
Wang et al. (2020) [ 21] 30 n/a n/a 16 14
Zheng et al. (2020) [22] 24 n/a n/a 8 16
Overall systematic review data Overall (n=) 6 8 37 45
n/a, data not available; CXR, Chest X Ray; CT, Computed Tomography.
aStudy missing data of normal imaging, results not included in overall percentages. N.A. Patel $P - 2WRODU\QJRO
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disease in children. The preliminary clinical findings suggest that
children with COVID-19 usually had a mild presentation, with common
symptoms being cough and fever. It is unclear why most children with
COVID-19 have less severe disease than adults it is speculated that
children often experience respiratory infections and may have higher
levels of antibody against the virus than adults or that their developing
immune systems may respond to pathogens differently than adult im-
mune systems [2].
It is important to note that while 21.9% of children that were tested
and were positive for SARS-CoV-2 were hospitalized, testing was not
universal and presumably more patients that were feeling unwell were
being tested compared to screening the general population. Of the
studies with age specific hospitalization data available, 27.0% of pa-
tients hospitalized were infants under 1 year of age. Many patients that
required PICU level care were under 1 year of age (31.6%) or had sig-
nificant underlying medical conditions.
Procalcitonin elevation was seen, across several patients with
COVID-19, which was important to note as it was not common for
adults to have elevated procalcitonin levels [14]. The significance of
this finding is unclear. It is important to note that while children with
COVID-19 could be coinfected with other viruses such as influenza B
and other bacteria such as Enterobacter aerogenes, they also have had
procalcitonin elevation without a bacterial superinfection.
Of the studies with abnormal CT results specifically describing
imaging laterality, unilateral CT imaging findings were seen in 36.4%
Ground glass opacities were commonly seen in CT imaging. Unilateral
imaging findings are a particular concern in pediatric patients with
cough and may warrant a bronchoscopy to evaluate for airway foreign
bodies. Extra precautions need to be taken with personal protective
equipment for these cases, as aerosolizing procedures may be a method
of viral transmission [23]. In addition, extra precautions need to be
taken when caring for children in the home or work setting. Several
studies suggest a slightly longer incubation period from exposure to onset of symptoms in children (6.5–7.5 days in children compared to
5.4 days in adults) [ 16,20]. There is evidence that children may shed
SARS-CoV-2 in the stool for a prolonged time (up to 30 days) [16].
Various treatment regimens including interferon, antivirals, and
hydroxychloroquine therapies have been trialed on the pediatric po-pulation but there are currently no studies showing efficacy of one re-
gimen over the other. The mortality rate of all children that were
hospitalized with COVID-19 was 0.18%. This mortality rate is likely
overestimated as it includes only patients who were tested positive and
in most cases, only children who were symptomatic enough to be
hospitalized were tested.
This review has several limitations, primary due to the nature of the
design of the selected studies. The data from case series may be biased
as the full population is not included. Many chart reviews were based
solely on data of children that were symptomatic and were hospitalized,
and do not represent the population as a whole. We attempted to re-
move any duplicate data from cases reports but it is possible that some
case series may have duplicate data with another series or retrospective
case review that was included from the same region.
Conclusions regarding the epidemiology of the COVID-19 global
pandemic are difficult to make so soon after the disease was discovered.
Future research should have a broader scope in terms of population
surveillance to understand the clinical characteristics and natural his-
tory of the disease in children. Another area of future research is on
manifestations of anosmia and dysgeusia in the pediatric population.
None of the studies included in this review collected data regarding
these symptoms in the pediatric population but they have been noted as
possibly the first or only symptom manifestation of COVID-19 in some
adults [24]. Early symptom identification may help decrease disease
transmission. Finally, it is unclear why children have a milder course
compared to adults. Further investigation may provide insight in de-
veloping treatment modalities for COVID-19. Table 6
Clinical course: summary of articles identified in the systematic literature review.
Article [reference] Hospitalization
(n=) Age < 1 year
hospitalized (n=) PICU level care (n=) Age < 1 year PICU level care (n=) NO oxygen (n=) Respiratory support Nasal
cannula (n=) High flow nasal cannula (n=) Nonrebreather face mask (n=) Intubation/mechanical ventilation (n=)
Cai et al. (2020) [16] 10 2 0 0 10 0 0 0 0 0
CDC Update (2020) [4] 147
a 59 15 5 n/a n/a n/a n/a n/a n/a
Eghbali et al. (2020)
[18] 4 0 2 0 1 2 1 n/a n/a 1
Feng et al. (2020) [19] 15 n/a n/a n/a n/a n/a n/a n/a n/a n/a
Lu et al. (2020) [ 8] 171 31 3 n/a n/a n/a n/a n/a n/a 3
Qiu et al. (2020) [ 17] 36 n/a n/a n/a n/a n/a 6 0 0 0
Shen et al. (2020) [20] 9 0 0 0 0 9 9 0 0 0
Tagarro et al. (2020)
[12] 25 n/a 4 n/a n/a 4 n/a 1 2 1
Wang et al. (2020) [ 21] 31 n/a n/a n/a n/a n/a n/a n/a n/a 0
Zheng et al. (2020)
[22] 25 n/a 2 1 n/a n/a n/a n/a n/a 2
n/a, data not available.
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5. Conclusion
There is limited data regarding the epidemiologic characteristics
and clinical features of SARS-CoV-2 in children [8]. This Systematic
Review represents the largest pooling of pediatric COVID-19 data
throughout the world. It was performed to gain a better understanding
of the global impact of COVID-19 on the pediatric population. This
study shows that children can be asymptomatic carriers of the virus and
suggests children may play a role in the community spread of COVID-
19. There are no studies regarding the presence of anosmia or dysgeusia
in the COVID-19 pediatric population. Hand-washing and preventive
behaviors are recommended when taking care of the pediatric popu-
lation to protect those are highest risk such as the elderly population
and those with underlying medical conditions. Additional care may also
be needed to care for COVID-19 positive children under 1 year of age
and children with comorbidities. This review also suggests that uni-
lateral CT chest imaging findings were seen in 36.4% pediatric COVID-
19 patients. This is particularly concerning as the work-up of pediatric
patients with cough may warrant a bronchoscopy to evaluate for airway
foreign bodies. Extra precautions need to be taken with personal pro-
tective equipment for these cases, as aerosolizing procedures may be a
method of viral transmission.
Declaration of competing interest
The authors have no conflicts of interest relevant to this article to
disclose. Acknowledgements
Special thanks to the Department of Otolaryngology clinical re-
search coordinator, Virginia Mullooly, RN, for her help in the IRB re-
search process. Special thanks to Sushil Reshamwala for his help with
table formating.
Financial disclosure
The authors have no financial relationships relevant to this article to
disclose. IRB
This study was granted IRB approval exemption by the Northwell
Health Human Research Protection Program. Funding
None. References
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