Ma et al. BMC Medicine(2020) 18:123
https://doi.org/10.1186/s12916-020-01596-9

RESEARCH ARTICLE

Open AccessA single-center, retrospective study of
COVID-19 features in children: a descriptive
investigation
Huijing Ma1†, Jiani Hu2†, Jie Tian3†, Xi Zhou4, Hui Li5, Maxwell Thomas Laws2, Luke David Wesemann2, Baiqi Zhu1,
Wei Chen6,7, Rafael Ramos2, Jun Xia4* and Jianbo Shao1*

Abstract
Background: Compared to adults, there are relatively few studies on COVID-19 infection in children, and even lessfocusing on the unique features of COVID-19 in children in terms of laboratory findings, locations of computerized
tomography (CT) lesions, and the role of CT in evaluating clinical recovery. The objective of this study is to report
the results from patients at Wuhan Children’s Hospital, located within the initial center of the outbreak.
Methods: Clinical, imaging, and laboratory data of 76 children were collected retrospectively and analyzed with theFisher exact test and Cox regression statistical methods.
Results: Among 50 children with a positive COVID-19 real-time reverse-transcriptase polymerase chain reaction(PCR), five had negative PCR results initially but showed positive results in subsequent tests. Eight (16%) patients
had lymphopenia, seven (14%) with thrombocytopenia, four (8%) with lymphocytosis, two (4%) withthrombocytosis, ten (20%) with elevated C-reactive protein, four (8%) with hemoglobin above, and six (12%) withbelow standard reference values. Seven (14%) of the 50 had no radiologic evidence of disease on chest CT. For the
43 patients who had abnormal CT findings, in addition to previously reported patterns of ground-glass opacity(67%), local patchy shadowing (37%), local bilateral patchy shadowing (21%), and lesion location of lower lobes(65%), other CT features include that an overwhelming number of pediatric patients had lesions in the subpleuralarea (95%) and 22 of the 28 lower lobe lesions were in the posterior segment (78%). Lesions in most of the 15
patients (67%) who received chest CT at discharge were not completely absorbed, and 26% of these pediatricpatients had CT lesions that were either unchanged or worse.
(Continued on next page)* Correspondence: xiajun@email.szu.edu.cn; drshaojb@sina.com†
Huijing Ma, Jiani Hu, and Jie Tian are joint first authors.
4
Department of Radiology, Shenzhen Second People’s Hospital, The First
Affiliated Hospital of Shenzhen University Health Science Center, 3002
SunGang Xi Road West, Shenzhen 518035, China
1
Imaging Center, Wuhan Children’s Hospital (Wuhan Maternal and Child
Healthcare Hospital), Tongji Medical College, Huazhong University of Science& Technology, No.100 Hongkong Road, Wuhan 430016, China
Full list of author information is available at the end of the article© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate ifchanges were made. The images or other third party material in this article are included in the article's Creative Commonslicence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commonslicence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to thedata made available in this article, unless otherwise stated in a credit line to the data.

Ma et al. BMC Medicine(2020) 18:123

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Conclusions: There were a few differences between COVID-19 children and COVID-19 adults in terms of laboratory
findings and CT characteristics. CT is a powerful tool to detect and characterize COVID-19 pneumonia but has little
utility in evaluating clinical recovery for children. These results oppose current COVID-19 hospital discharge criteria
in China, as one requirement is that pulmonary imaging must show significant lesion absorption prior to discharge.
These differences between pediatric and adult cases of COVID-19 may necessitate pediatric-specific discharge
criteria.
Keywords: Children, Pediatric, Coronavirus, COVID-19, SARS-CoV-2, Epidemiology, Clinical features, Computerized
tomography

Background
Since initially identified in Wuhan city of China’s Hubei
province in December 2019, the coronavirus disease2019 (COVID-19) has resulted in 466,836 confirmed
cases and 21,152 deaths as of March 25, 2020. Twomonths prior, on January 23, 2020, there were only 581
reported cases. COVID-19 can rapidly spread fromhuman-to-human and is more contagious than othernotable members of the coronavirus family, such as severe acute respiratory syndrome (SARS) and Middle
Eastern respiratory syndrome (MERS) [1, 2]. The World
Health Organization recently declared COVID-19 a global pandemic, and the USA has declared a national
emergency. Even though the incidence of COVID-19 infection in children is less than it is in adults, the total
number of pediatric cases is expected to increase rapidly
in the coming weeks.
Compared to adults [3–7], there are a few studies on
the COVID-19 in children. Although mortality in children has been reported [8], studies have demonstrated
that COVID-19 is generally less severe compared toadults in terms of both symptoms and computerized
tomography (CT) manifestations [9–18]. The common
chest CT patterns are ground-glass opacities (GGO)
followed by local bilateral shadowing (LPS), in contrast
to a large percentage of bilateral patchy shadowing(BPS) pattern in adults [19, 20]. However, there are no
studies that quantitatively examine the location of lunglesions in COVID-19-positive pediatric patients [21].
Most of the pediatric patients are at the early stages ofthe disease when admitted to hospitals. Thus, a detailed
localization study is meaningful both clinically and scientifically, as it could help pinpoint lung regions that are
particularly susceptible to COVID-19 infection.
Several studies have reported on the laboratory findings of children infected with COVID-19. However, theinterpretations of these results vary substantially [15,
22–24]. The discrepancy in laboratory interpretations
could be attributed to the studies each referring to a different set of reference values. Of note, the range of normal lab values changes depending upon the age of thechild, i.e., a 1-year-old has a different set of reference

values than a 9-year-old. Confounding these results isthe fact that the reference values used among the studies
lack consistency and appear to be hospital-self-definedvalues [15, 22–24]. This inconsistency of reference
values makes any systemic review of the published data
less meaningful [23].
There is also no research on the role of CT in monitoring clinical recovery in children. CT has been widelyused in the clinical management of adult patients due toits ability to reveal detailed features of pneumonia [25–28]. Because of how many unknowns there were about
the disease, particularly at the beginning of the COVID19 outbreak, CT was frequently used in the clinical management and diagnosis of children in China. Notably, repeated use of CT can be harmful, particularly forchildren [29, 30].
The objective of this study is to report relevant findings from the COVID-19-positive patients treated at
Wuhan Children’s Hospital. Specifically, we attempt toanswer three questions based on the patient’s clinical, laboratory, diagnostic, and treatment outcome data. The
questions are, in hospitalized COVID-19 children, (i)what are the typical laboratory findings, (ii) is there any
unique CT feature, and (iii) is CT necessary for evaluating clinical recovery?

Methods
Study design and patient selection

For this retrospective, single-center study, patients wererecruited from January 21 to February 14, 2020, at Wuhan Children’s Hospital in Wuhan, China. Real-timereverse-transcriptase polymerase chain reaction (PCR)
was performed on children 16 years of age and under
who had a family or social history of COVID-19 exposure. Subsequently, these patients received a chest CT
examination to evaluate lung pathology. Based on the
PCR and CT results, these patients were stratified into
groups A–C (Fig. 1). This study was approved by the
Ethics Committee of Wuhan Children’s Hospital(Wuhan Maternal and Child Health Care Hospital #WHCH 2020005). Written informed parental/guardianMa et al. BMC Medicine(2020) 18:123

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Fig. 1 Flow chart for patient selection. Group A: 43 children with COVID-19 exposure history, positive CT, and positive PCR. Group B: sevenchildren with COVID-19 exposure history, negative CT, and positive PCR. Group C: 26 children with COVID-19 exposure history, positive CT, andpersistently negative PCR resultsconsent and child assent (where appropriate) were obtained prior to enrollment in the study.
Procedures

We obtained demographic information, clinical symptoms, laboratory results, management, and outcome datafrom each patient’s electronic medical records. Clinicaloutcomes were followed up to February 17, 2020.
Chest CT without intravenous contrast was performed on all patients using a Siemens SOMATOM
Definition AS128 or GE Optima CT 660 with a 1mm or 0.625-mm slice thickness, respectively.
Children under 5 years old, as well as uncooperative
children, received oral chloral hydrate sedation (0.5 ml/kg)
prior to CT. Cooperative children above 5 years old weretrained with breathing exercises prior to CT.
All CT images were reviewed by at least two radiologists with more than 10 years of experience. Imaging
was reviewed independently. When the opinions on the

CT features were inconsistent, the two radiologists discussed and decided together. Only final decisions
reached by consensus are reported. No negative control
cases were examined.
PCR confirmation of COVID-19 was performed at
two different institutions: Hubei Center for Disease
Control and Prevention and Wuhan Children’s
Hospital.
Patient discharge

Criteria for discharging pediatric patients in this hospitalwere normal body temperature for 3 days, two negative
PCR results at 24-h intervals, and resolution of all clinical symptoms.
Statistical analysis

The Fisher exact test method was used to determine
whether there is a significant difference in CT image
characteristics and lesion locations between group A andMa et al. BMC Medicine(2020) 18:123

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group C. The Cox regression analysis was used to determine whether changes in CT images during treatment
were associated with clinical outcomes for children with
COVID-19 infection. All analyses were performed using
EmpowerStats (http://www.empowerstats.com) and thestatistical package R (version 3.2.3). p value of less than
0.05 was considered to indicate a statistically significant
difference.

Results
From January 21 to February 14, 2020, 158 children at
Wuhan Children’s Hospital were radiologically examinedwith chest CT, and respiratory secretions were obtained
and subsequently tested for COVID-19 with PCR. A CT
scan was considered positive when at least one lesion
was identified. Among them, 43 had a positive CT andpositive PCR (group A), 7 had a negative CT and positive

Table 1 Demographics and characteristics of patients
Characteristics

Group AGroup B

Group A + B

Group C

Age, years

3.0 (0.9–7.5)

1.0 (1.0–4.5)

2.5 (0.9–7.0)

2.5 (1.2–9.8)> 2.5

22/43 (51%)

3/7 (43%)

25/50 (50%)

13/26 (50%)≤ 2.5

21/43 (49%)

4/7 (57%)

25/50 (50%)

13/26 (50%)

Male

23/43 (53%)

5/7 (71%)

28/50 (56%)

14/26 (54%)

Female20/43 (47%)

2/7 (29%)

22/50 (44%)

12/26 (46%)

Discharged patients

33/43 (77%)

5/7 (71%)

38/50 (76%)

26/26 (100%)

Hospitalization duration

11.0 (9.0~13.0)

13.0 (7.0~14.0)

11.0 (8.2~13.8)

10.5 (8.0~12.0)

Sex

Type of care

Clinical status
Asymptomatica

0/43 (0%)

2/7 (29%)

2/50 (4%)

0/26 (0%)

Very mild

0/43 (0%)

5/7 (71%)

5/50 (10%)

0/26 (0%)

Mild

41/43 (95%)

0/7 (0%)41/50 (82%)

26/26 (100%)

Severe0/43 (0%)

0/7 (0%)0/50 (0%)

0/26 (0%)

Critically ill

2/43 (5%)

0/7 (0%)2/50 (4%)

0/26 (0%)

Fever

29/43 (67%)

3/7 (43%)

32/50 (64%)

21/26 (81%)

Cough

21/43 (49%)

1/7 (14%)22/50 (44%)

19/26 (73%)

Myalgia or fatigue

2/43 (5%)

0/7 (0%)2/50 (4%)

0/26 (0%)

Sore throat (pharyngalgia)

1/43 (2%)

0/7 (0%)1/50 (2%)

0/26 (0%)

Symptoms

Diarrhea

3/43 (7%)

0/7 (0%)3/50 (6%)

0/26 (0%)

Abdominal pain

2/43 (5%)

0/7 (0%)2/50 (4%)

0/26 (0%)

Rhinorrhea

7/43 (16%)

1/7 (14%)8/50 (16%)

2/26 (8%)

Loss of appetite

2/43 (5%)

0/7 (0%)2/50 (4%)

0/26 (0%)

Chest pain

0/43 (0%)

0/7 (0%)0/50(0%)1/26 (4%)

Intussusception

1/43 (2%)

0/7 (0%)1/50 (2%)

0/26 (0%)

No symptoms

4/43 (9%)

2/7 (29%)

6/50 (12%)

0/26 (0%)

Mortality

0/43 (0%)

0/7 (0%)0/50 (0%)

0/26 (0%)

Cardiac damage

4/43 (9%)

1/7 (14%)5/50 (10%)

3/26 (12%)

Appendicitis

1/43 (2%)

0/7 (0%)1/50 (2%)

0/26 (0%)

Foreign body in bronchus

1/43 (2%)

0/7 (0%)1/50 (2%)

0/26 (0%)

Mycoplasma infection

5/43 (12%)

0/7 (0%)5/50 (10%)

11/26 (42%)

Respiratory syncytial virus infection

1/43 (2%)

0/7 (0%)1/50 (2%)

0/26 (0%)

ComorbidityaRenal failure

1/43 (2%)

0/7 (0%)1/50 (2%)

0/26 (0%)

Intestinal necrosis in MODS

1/43 (2%)

0/7 (0%)1/50 (2%)

0/26 (0%)

No clinical symptoms and no abnormal CT findings

Ma et al. BMC Medicine(2020) 18:123

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PCR (group B), and 26 had a positive CT and at least two
negative consecutive PCR results (group C, Fig. 1).
PCR-positive groups A and B (n = 50) were chosen tointerpret clinical and chest CT features because group C
patients were not deemed COVID-19 positive by PCR.
Over half of the patients were males (56%, Table 1). The
most common symptoms at the onset of illness (Table 1)
were fever (64%) and cough (44%); less common symptoms were rhinorrhea (16%), abdominal pain (4%), diarrhea (6%), fatigue (4%), and pharyngalgia (2%). Six
children (12%) were asymptomatic. After treatment, 38(76%) children were discharged.

Laboratory reference normal ranges were age- andgender-adjusted according to values in Reference Range
Values for Pediatric Care 2nd edition, pages 92–98 [31].
On laboratory assessment, eight (16%) and seven (14%)
patients had lymphopenia and thrombocytopenia, respectively. In contrast, four (8%) were noted to havelymphocytosis, and two (4%) had thrombocytosis.
Overall, leukopenia was observed in 19 (38%) patientsand elevated C-reactive protein in ten (20%) patients. A
small set of patients had hemoglobin abnormalities, four(8%) with elevated hemoglobin, and six (12%) withanemia (Table 2).

Table 2 Laboratory examination and CT radiographic characteristics
Characteristics

Group AGroup B

Group A + B

Group C

Hemoglobin count increase (↑)

2/43 (5%)

2/7 (29%)

4/50 (8%)

6/26 (23%)

Hemoglobin count normal

36/43 (83%)

4/7 (57%)

40/50 (80%)

18/26 (69%)

Hemoglobin count decrease (↓)

5/43 (12%)

1/7 (14%)

6/50 (12%)

2/26 (8%)

C-reactive protein level increase (↑)

10/43 (23%)

0/7 (0%)10/50 (20%)

8/26 (31%)

C-reactive protein level normal

33/43 (77%)

7/7 (100%)

40/50 (80%)

18/26 (69%)

Laboratory examinationa

Platelet count increase (↑)

1/43 (2%)

1/7 (14%)2/50 (4%)

1/26 (4%)

Platelet count normal

35/43 (82%)

6/7 (86%)

41/50 (82%)

18/26 (69%)

Platelet count decrease (↓)

7/43 (16%)

0/7 (0%)7/50 (14%)

7/26 (27%)

Lymphocyte count increase (↑)

2/43 (5%)

2/7 (29%)

4/50 (8%)

2/26 (8%)

Lymphocyte count normal

34/43(79%)

4/7 (57%)

38/50 (76%)

18/26 (69%)

Lymphocyte count decrease (↓)

7/43 (16%)

1/7 (14%)8/50 (16%)

6/26 (23%)

Blood leukocyte count increase (↑)

2/43 (5%)

0/7 (0%)2/50 (4%)

1/26 (4%)

Blood leukocyte count normal

23/43 (53%)

6/7 (86%)

29/50 (58%)

13/26 (50%)

Blood leukocyte count decrease (↓)

18/43 (42%)

1/7 (14%)19/50 (38%)

12/26 (46%)

CT radiographic characteristics
Overall patients with CT abnormalities

43/43 (100%)

0/7 (0%)43/50 (86%)

26/26 (100%)Ground-glass opacity

29/43 (67%)

0/7 (0%)29/50 (58%)

21/26 (81%)

Local patchy shadowing

16/43 (37%)

0/7 (0%)16/50 (32%)

7/26 (27%)

Bilateral patchy shadowing

9/43 (21%)

0/7 (0%)9/50 (18%)

5/26 (19%)

Interstitial abnormalities

3/43 (7%)

0/7 (0%)3/50 (6%)

0/26 (0%)

Pleural fluid

1/43 (2%)

0/7 (0%)1/50 (2%)

0/26 (0%)

Lymphadenopathy

0/43 (0%)

0/7 (0%)0/50 (0%)

0/26 (0%)

Lesion characteristics and locationba

Subpleural

41/43 (95%)

0/7 (0%)41/50 (82%)

21/26 (81%)

Parallel to the pleura

21/43 (49%)

0/7 (0%)21/50 (42%)

10/26 (38%)

Vascular thickening shadowing

10/43 (23%)

0/7 (0%)10/50 (20%)

10/26 (38%)

Upper lobe of the lung

22/43 (51%)

0/7 (0%)22/50 (44%)

14/26 (54%)

Middle lobe of the lung

9/43 (21%)

0/7 (0%)9/50 (18%)

6/26 (23%)

Lower lobe of the lung

28/43 (65%)

0/7 (0%)28/50 (56%)

19/26 (73%)

Posterior segment of lower lung lobes

22/43 (51%)

0/7 (0%)22/50 (44%)

12/26 (46%)

Data from the first laboratory examination of the patient admission. The normal range of laboratory examination is the standard of Reference Range Values for
Pediatric Care 2nd ed [31] released by the American Academy of Pediatricsb
How many patients have the following lesion location

Ma et al. BMC Medicine(2020) 18:123

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Of the 26 patients in group C, all had more than
two negative consecutive PCR results. However, they
all had a history of exposure to COVID-19 infection(or strongly suspected infection), and their chest CT
had similar patterns to confirmed patients in group A(Table 2). Fisher exact test results indicated that there
was no significant difference in CT characteristics(ground-glass opacity [p > 0.05], local patchy shadowing [p > 0.05], bilateral patchy shadowing [p > 0.05],
interstitial abnormalities [p > 0.05]) and lesion location(parallel pleura [p > 0.05], visible vascular thickening[p > 0.05], subpleural [p > 0.05], lower lobe of the lung[p > 0.05], middle lobe of the lung [p > 0.05], upper
lobe of the lung [p > 0.05]) between groups A and C(Table 3).

Among the 50 children with positive PCR results, fiveof them (10%) had negative initial PCR results but
showed positive results in subsequent tests. Two of the
50 (4%) had no clinical symptoms and no radiologic
findings. Seven of the 50 (14%) were negative for any abnormal CT findings. The spectrum of COVID-19 severity was two (4%) had no symptoms or radiologic signs,
five (10%) very mild, 41 (82%) mild, and two (4%) critically ill with one having multiple organ dysfunction syndrome (MODS) and another with renal failure (Table 1).
There were no patient mortalities in this study. The critically ill patient with renal failure has since fully
recovered.
Among the 43 children with positive PCR results andabnormal CT findings, 41 patients had lesions present inTable 3 Differences in CT image characteristics between Groups A and C
Characteristics

Group AGroup CStandardize diff.

p value––

0.31 (− 0.18, 0.80)

0.230

No

14 (32.56%)

5 (19.23%)

–

–

Yes

29 (67.44%)

21 (80.77%)

–

–

–

–

0.22 (− 0.27, 0.71)

0.380

Ground-glass opacity

Local patchy shadowingNo

27 (62.79%)

19 (73.08%)

–

–

Yes

16 (37.21%)

7 (26.92%)

–

–

–

–

0.04 (− 0.44, 0.53)

0.865

No

34 (79.07%)

21 (80.77%)

–

–

Yes

9 (20.93%)

5 (19.23%)

–

–

–

–

0.39 (− 0.10, 0.88)

0.168

Bilateral patchy shadowing

Interstitial abnormalitiesNo

40 (93.02%)

26 (100.00%)

–

–

Yes

3 (6.98%)

0 (0.00%)

–

–

–

–

0.46 (− 0.03, 0.95)

0.095

No

2 (4.65%)

5 (19.23%)

–

–

Yes

41 (95.35%)

21 (80.77%)

–

–

–

–

0.05 (− 0.43, 0.54)

0.829

No

21 (48.84%)

12 (46.15%)

–

–

Yes

22 (51.16%)

14 (53.85%)––

Subpleural

Upper lobe of the lung––

0.05 (− 0.44, 0.54)

0.834

No

34 (79.07%)

20 (76.92%)

–

–

Yes

9 (20.93%)

6 (23.08%)

–

–

–

–

0.17 (− 0.31, 0.66)

0.492

No

15 (34.88%)

7 (26.92%)

–

–

Yes

28 (65.12%)

19 (73.08%)––

Middle lobe of the lung

Upper lobe of the lung––

0.21 (− 0.28, 0.70)

0.401

No

22 (51.16%)

16 (61.54%)

–

–

Yes

21 (48.84%)

10 (38.46%)

–

–

–

–

0.33 (− 0.16, 0.82)

0.177

No

33 (76.74%)

16 (61.54%)

–

–

Yes

10 (23.26%)

10 (38.46%)––

Parallel to the pleura

Vascular thickening shadowing

Using the Fisher exact test method, p < 0.05 was considered to indicate a statistically significant differenceMa et al. BMC Medicine(2020) 18:123

the subpleural area (95%) and lower lung lobes (65%),
especially in the posterior segment of the lower lung
lobes (22 [78%] of 28). Ground-glass opacities (GGO)
were the most common radiologic lesion identified onchest CT (67%). Local patchy shadowing (37%) was thesecond most common radiologic lesion, followed by local
bilateral patchy shadowing (21%, Table 2). Interstitial lesions were rare (7%). Pleural fluid was observed in one
case, and no lymphadenopathy was noted (Table 2). Appearances of lesions were irregular shaped, flaky, wedgeshaped, or strip-shaped. The long axis of some lesions(49%) was parallel to the pleura. However, lesions did not
follow the segment of the lung lobe, single or multiple,
and diffuse consolidation was rare. Bilateral lesions can beseen radiating around the bronchial blood vessels or
showing large areas of consolidation, which can be tracedby the lung segment into the bronchial tube.
Among the 50 confirmed children (groups A and B),
29 patients (including 23 discharged children) had morethan one chest CT. Nineteen of the 29 patients (65%)
had improved CT presentations after treatment, and lesions in two of the 19 patients completely disappeared.
Two of the 29 patients (7%) showed no change in CT lesions, and 8 of the 29 patients (28%) had more CT lesions after treatment.

Page 7 of 11

Figure 2 illustrates typical radiographic features of
COVID-19 pneumonia in children. Figure 3 shows
chest CT before and after treatment from three
COVID-19 children. Cox regression results (Table 4)
indicated that there is no association between changes
in CT lesions (completely absorbed [p > 0.05], partiallyabsorbed [p > 0.05], worse [p > 0.05]). Table 5 lists
changes in CT lesions during treatment. Table 6 lists
the normal ranges for children of different ages basedon Reference Range Values for Pediatric Care 2nd edition pages 92–98 [31].

Discussion
The symptoms in children with COVID-19 infection
have been well described in the literature [9–18]. Our
results are consistent with these previous reports. For
example, the clinical symptoms from our study versus
the recent study with the most pediatric patients are
similar [10]: fever, 64% versus 41.5%; cough, 44% versus
48.5%; diarrhea, 6% versus 8.8%; and fatigue, 4% versus
7.6%. Results including ours indicate that COVID-19
symptoms in children follow a similar pattern in adults,
albeit much less severe.
Our results of abnormal laboratory findings for children infected with COVID-19 contrast with recently

Fig. 2 Chest CT images depicting typical radiographic findings of COVID-19 pneumonia in children. 2A A unilateral chest CT from a 14-year-old
boy with a cough. Ground-glass opacities under and parallel to the pleura (thick green arrow) in the inferior lobes of the left lungs. Ground-glass
opacities distributed along the bronchovascular bundle (thin green arrow). 2B Bilateral ground-glass opacities with vascular thickening(arrowheads) in the subpleural area from a 13-year-old boy with a fever and a cough. 2C Local patchy shadowing (green arrow) image from a 6month-old girl with a fever and a cough. 2D Lesions in the lower lobe of both lungs (green arrows) on chest CT obtained from a 15-year-old boy
with a fever and a coughMa et al. BMC Medicine(2020) 18:123

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Fig. 3 Chest CT findings at initial presentation and at discharge. 3A, 3B Chest CT scans obtained from a 1-year-old boy, presenting with fever
and diarrhea, at arrival (3A) and after (3B) treatment. The first CT scan shows a large, patchy shadow in the left inferior lobe (green arrow). The
second CT scan shows no lesions. The patient was hospitalized for 17 days prior to discharge. 3C, 3D Chest CT scans from a 4-month-old girl,who presented with a fever and a cough at arrival. The first CT scan reveals multiple ground-glass opacities under the pleura in the left superior
lobe (green arrows). The second CT scan reveals that the range of original lesions was enlarged and extended to the center. The girl was
hospitalized for 13 days and subsequently discharged. 3E, 3F Chest CT scans from a 14-year-old boy, presenting with rhinorrhea and a cough, atarrival and discharge. The first CT scan reveals a patchy shadow in the left middle lobe (arrowhead). There were no obvious changes in the areasof pulmonary consolidation on the second CT scan. The boy was hospitalized for 11 days and then discharged

published ones [15, 22–24]. For example, our results
for lymphopenia compared to Zheng et al. are 16%
versus 40% [22]. Their normal reference values for
lymphocytes were (2.1–5.7) × 109/L (< 3 years), (1.4–
4.2) × 109/L (4–6 years), and (1.1–3.2) × 109/L (≥ 6
years). To date, this is the only paper that has explicitly listed the normal ranges for children of different
age ranges [22]. Thus, the differences between ours
and those in the literature are most likely due to different normal ranges used for children of different
ages or the small number of children who participated in their studies.

Like clinical symptoms, the laboratory findings in
COVID-19-positive pediatric patients can vary fromadult patients. Guan et al. [25] noted that 731 (82%) of
890 adult patients had lymphopenia, whereas only eight(16%) children had lymphopenia in this study. Similarly,
481 (61%) of 793 adult patients were found to have an
elevated C-reactive protein. In contrast, only ten (20%)
children in this study had elevated C-reactive protein.
Some laboratory findings were consistent between children and adult groups: leukopenia 38% versus 36% andthrombocytopenia 14% versus 18%. The mechanism behind the observations is unknown and might provide an

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Table 4 Association between CT imaging changes and clinicaloutcomea
Adjustb

Exposure
Changes in CT images during treatment
Completely absorbed

1.0

Partially absorbed

0.56 (0.25, 1.28), 0.168

No change

0.11 (0.01, Inf)cWorse

0.34 (0.10, 1.13), 0.08

aUsing the time-vary Cox regression method, p < 0.05 was considered toindicate statistically significant differencebAdjusted for gender, age, PCR positive and CT positivecThis model failed when analyzing “no change in CT image” due to thesmall sample

explanation for the differences between pediatric andadult patients.
The most common pattern of chest CT is groundglass opacities, followed by local patchy shadowing andthen local bilateral patchy shadowing, which is consistent with published data [9–18]. Our study indicates thatchest CT manifested with a predominance of lesions inthe subpleural area (41 [95%] of 43) and in lower lung
lobes (28 [65%] of 43), especially in the posterior segment (22 [78%] of 28), an area with a relatively dense
amount of bronchioles, blood vessels, and alveoli. To thebest of our knowledge, these are the first quantitative results on the locations of chest CT lesions for COVID-19
children [21]. COVID-19 is less severe in children thanin adults, and the children infected with COVID-19 wereat the early stages of the disease when admitted to thehospital. The fact that an overwhelming percentage ofpediatric patients had lesions in the subpleural area suggests this site is the first target for the COVID-19 virus.
The current gold standard for the diagnosis of
COVID-19 is PCR. However, it has been documented
that patients with a negative PCR result cannot be definitively ruled out for COVID-19 infection [11, 26]. Our
results are consistent with the literature. Among the 50
hospitalized children with positive PCR results, five ofthem (10%) had negative initial PCR results but showed
positive results in subsequent tests. Moreover, 26 patients in group C never had a positive PCR result but
had histories of contact with COVID-19 patients. Mostof them exhibited clinical symptoms such as fever (81%)

and cough (73%). Although they received a negative
PCR result at least twice, all 26 patients had similar CT
patterns to the PCR-positive COVID-19 patients ingroup A. Twenty-one (81%) had ground-glass opacities(GGO). Seven (27%) had local patchy shadowing. Five(19%) had bilateral patchy shadowing. Furthermore, ourFisher exact analysis indicated that there was no significant difference in CT image characteristics and lesion
location between groups A and C. Although a positive
CT alone cannot rule out the possibility of other causesof virus-induced pneumonia [11, 26], all 26 children
were hospitalized and given immediate antiviral and supportive therapy. Whether or not a child presents withpneumonia is one of the key considerations for clinicalmanagement, and it is crucial to start treatment as earlyas possible, considering that many deaths in the adult
population are due to complications resulting from severe pneumonia [3–7].
It has been well documented that chest CT is a
powerful tool to identify and characterize pneumonia
for COVID-19 adult patients [25–28]. However, there
is no publication to study its usefulness in evaluating
clinical recovery for children with COVID-19 infection. To determine whether CT is necessary, we investigated the data of 23 patients who had beendischarged after effective treatment and had at least
two CT scans. All patients had normal body temperatures for more than 3 days at the time of discharge,
clinical symptoms disappeared, and PCR tests all
returned negative twice at 24-h intervals. Of the 23
children, eight patients did not receive CT scans
within the 2 days before their discharge. However, in
their most recent CT scan performed in the hospital,
most children either still had lesions (50%), or moredeveloped lesions since the previous scan (37%). The
remaining 15 discharged children had a CT obtained
within 2 days of discharge. Again, ten patients had lesions that were not completely absorbed (67%), twowere the same (13%), and lesions in another two became worse (13%). These results indicate that CT
may not be better than symptoms in evaluating
recovery. Our Cox regression analysis further showedthat there was no association between changes in CT
lesions and clinical outcomes. The results are

Table 5 Changes in CT presentation after treatment
ResultCompletely absorbed

Between the first and discharge CTa

Between the first and the nearest CTbc

Between the first and latest CTaPartially absorbed

No changeWorse

1/15 (7%)

10/15 (67%)

2/15 (13%)

2/15 (13%)

1/8 (13%)

4/8 (50%)

0/8 (0%)3/8 (37%)

2/29 (7%)

17/29 (58%)

2/29 (7%)

8/29 (28%)

Only for those discharged patients with at least two CT; discharge CT here means CT within 2 days of discharging; total 15 patients out of group A and group Bb
Only for those discharged patients with at least two CT but no CT within 2 days of discharging; the nearest CT means that the CT taken closest to the date ofdischarging; total 8 patients out of group A and group Bc
For all patients with at least two CT; total 29 patients out of group A and group B

(2020) 18:123

Ma et al. BMC Medicine

Page 10 of 11

Table 6 Laboratory examination reference ranges
Age

Sex

Hemoglobin (g/dL)

C-reactive protein (mg/L)

Platelets (× 109/L)

Lymphocytes (× 109/L)

Leukocytes (× 109/L)

1 to < 2 monthsM

102–127

0.09–10.41

221–471

2.22–5.63

8.36–13.66

F

111–137

184–430

2.49–6.26

7.34–12.32

M

105–130

215–448

2.57–7.54

7.91–13.41

F

107–134

147–423

2.22–7.11

6.85–12.84

M

104–125

185–399

2.47–6.41

7.73–13.12

F

108–126

211–408

2.34–6.44

7.05–12.98

M

114–143

187–444

1.60–5.30

4.40–12.9

F

114–143

187–444

1.60–5.30

4.40–12.9

M

115–143

186–400

1.40–3.90

3.80–10.4

F

115–143

186–400

1.40–3.90

3.80–10.4

M

118–147

186–400

1.40–3.90

3.80–10.4

F

118–147

186–400

1.40–3.90

3.80–10.4

M

124–157

176–381

1.00–3.20

3.80–10.4

F

119–148

176–381

1.00–3.20

3.80–10.4

M

133–169

138–319

1.00–3.20

3.80–10.4

F

119–148

158–361

1.00–3.20

3.80–10.4

2 to < 6 months

6 months to 2 years

3–5 years

6–8 years

9–10 years

11–14 years

15–19 years

From Reference Range Values for Pediatric Care 2nd edition pages 92–98 [31] released by the American Academy of Pediatrics

consistent with the knowledge that clinical improvement predates radiographic improvement by weeks
for children with community-acquired pneumonia.
When deciding whether to use CT on children, theharmful effects that radiation may have on a growing
body must be considered. Hong et al., in a study of
12,068,821 children aged 0 to 19 years, found a statistically significant increase in cancer in children exposed at least once to diagnostic low-dose ionizing
radiation after adjusting for age and sex [29, 30].
Based on our data, we do not recommend using CT
for determining clinical recovery unless it is necessary
to evaluate the status of pneumonia. For comparison,
the current criteria for discharging adult patients infected with COVID-19 in China are (1) normal bodytemperature for 3 days, (2) two negative PCR tests at
24-h intervals, (3) resolution of clinical symptoms(these three are the current criteria for discharging
pediatric patients in this hospital), plus (4) a chest
imaging requirement: pulmonary imaging must show
significant absorption of lesions. To date, there are no
child-specific discharge criteria for COVID-19 in
China.
Our study had a few limitations. First, this study has asmall sample size and was conducted at a single-centerin Wuhan, China, located at the center of the outbreak.
The clinical severity of pediatric patients outside Wuhan
may be less severe. Indeed, it is reported that there is alower death rate of adult patients outside Wuhan areas.
Second, long-term follow-up was not done because of
the short time for data collection.

Conclusions
The severity of COVID-19 infection in children is lessthan it is in adults in terms of symptoms, lung consolidation as visualized by CT, and laboratory abnormalities.
COVID-19 has a preference for subpleural areas of thelung in pediatric patients. Chest CT is an excellent tool
to detect and characterize COVID-19 pneumonia but
not to evaluate the resolution of illness for children.
Abbreviations
BPS: Bilateral patchy shadowing; COVID-19: Coronavirus disease 2019;
CT: Computerized tomography; GGO: Ground-glass opacities; LPS: Local
bilateral shadowing; MERS: Middle Eastern respiratory syndrome;
MODS: Multiple organ dysfunction syndrome; PCR: Polymerase chain
reaction; SARS: Severe acute respiratory syndrome
Acknowledgements
We would like to thank Pin He for her help in image processing.
Authors’ contributions
HM, JH, JT, JX, and JS had roles in the study design, data analysis, datainterpretation, literature search, and writing of the manuscript. XZ, HL, MTL,
LDW, BZ, WC, and RR had roles in the data analysis, data interpretation,
literature search, and writing of the manuscript. JS, HM, HL, and BZ had roles
in clinical management, patient recruitment, and data collection and had fullaccess to all of the data in the study and take responsibility for the integrityof the data. HM, JH, and JT contributed equally. The authors read andapproved the final manuscript.
Funding
The authors received no specific funding for this work.
Availability of data and materials
The datasets used and/or analyzed during the current study are available
from the corresponding author on reasonable request.

Ma et al. BMC Medicine(2020) 18:123

Ethics approval and consent to participate
This study was approved by the Ethics Committee of Wuhan Children’s
Hospital (Wuhan Maternal and Child Health Care Hospital # WHCH 2020005).
Written informed parental/guardian consent and child assent (whereappropriate) were obtained prior to enrollment in the study.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1
Imaging Center, Wuhan Children’s Hospital (Wuhan Maternal and Child
Healthcare Hospital), Tongji Medical College, Huazhong University of Science& Technology, No.100 Hongkong Road, Wuhan 430016, China. 2Departmentof Radiology, School of Medicine, Wayne State University, Detroit, MI 48201,
USA. 3Beijing Advanced Innovation Center for Big Data-Based Precision
Medicine, School of Medicine and Engineering, Beihang University, Beijing
100191, China. 4Department of Radiology, Shenzhen Second People’s
Hospital, The First Affiliated Hospital of Shenzhen University Health Science
Center, 3002 SunGang Xi Road West, Shenzhen 518035, China. 5Medical
department, Wuhan Children’s Hospital (Wuhan Maternal and Child
Healthcare Hospital), Tongji Medical College, Huazhong University of Science& Technology, No.100 Hongkong Road, Wuhan 430016, China. 6Departmentof Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai
200065, China. 7Pingshan District People’s Hospital, Pingshan General
Hospital of Southern Medical University, Shenzhen 518118, Guangdong,
China.
Received: 26 March 2020 Accepted: 16 April 2020

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