Supplementary Appendix
This appendix has been provided by the authors to give readers additional information about their work.
Supplement to: Lu X, Zhang L, Du H, et al. SARS-CoV-2 infection in children. N Engl J Med. DOI: 10.1056/
NEJMc2005073

Supplementary Appendix (20-05073)

Table of contents
Methods…………………………………………………………………………….... 2
Table S1. Age distribution of infected children and their respective diagnoses…….. 4
Table S2. Laboratory results of 171 infected children and their respective diagnoses 5
Figure S1. Chest CT scan images of representative patients………………………….7
Author Contributions………………………………………………………………… 8
Acknowledgement…………………………………………………………………… 8Declaration of interests……………………………………………………………......8References…………………………………………………………………………..... 8Page 1 of 8

Methods
Study Design and ParticipantsThis was an observational study that recruited children and adolescents confirmed to have severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection treated at the Wuhan
Children’s Hospital located in Wuhan, the epidemic center of this novel infection. The Wuhan
Children’s Hospital is the only designated hospital for treating patients under 16 years of age withSARS-CoV-2 infection in Wuhan assigned by the central government. Children with known
contact with individuals having confirmed or suspected SARS-CoV-2 infection would undergo
confirmatory testing. All the children tested positive for SAR-CoV-2 were recruited in this study.
This study included children presented to our hospital between January 28 to February 26, 2020.
The natural history and clinical outcomes were monitored up to March 8, 2020. This study wasapproved by the institutional ethics board of the Wuhan Children’s Hospital (Approval number
WHCH 2020003). Informed consent was obtained from parents or legal guardian of each patient.
Data Collection
Data from the medical records were extracted by members of the research team and were checkedby two independent researchers. Epidemiological data were collected through interviews with thepatients, their parents and legal guardians. Clinical presentation, comorbidities, laboratory results,
radiological findings including chest radiographs and computed tomographic (CT) scans,modalities of treatment (oxygen therapy, intensive care support, use of antiviral or antibacterialagents) and outcomes were extracted from the medical records and entered into our clinical record
form for subsequent analyses.
Real-Time Reverse Transcription Polymerase Chain Reaction Assay for SARS-CoV-2
Nasopharyngeal swabs from suspected children younger than 2 years of age and throat swabs
from children 2 years or older were obtained for detection of SAR-CoV-2 RNA. After
collection, the swabs were transported to the laboratory within 2 hours in a collection tube with150 microliter virus preservative medium. RNA from the respiratory specimens was extractedwith the High Pure Viral Nucleic Acid Kit (Zhongzhi, Wuhan, China). The extracted nucleic
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acids were tested for SAR-CoV-2 using real-time reverse transcription polymerase chain reaction(RT-PCR) assay as described previously. 1,2 In brief, the following sequences of SARS-CoV-2
were adopted for the RT-PCR assays: forward primer 5′-TCAGAATGCCAATCTCCCCAAC3′; reverse primer 5′-AAAGGTCCACCCGATACATTGA-3′;
probe 5′CY5-CTAGTTACACTAGCCATCCTTACTGC-3′BHQ1.
Amplifications were initially done at 50°C for 15 min and subsequently at 95°C for 3 min,followed by 45 cycles of 95°C for 15 s and 60°C for 30 s.
Results
The age distribution of patients and their respective diagnoses (asymptomatic infection, upper
respiratory tract infection, pneumonia) were summarized in Table S1. The median ages ofasymptomatic patients, patients with upper respiratory infections (URTI), and patients withpneumonia were 9.6, 3.9, and 5.9 years, respectively. The laboratory results of all children weresummarized in Table S2. Laboratory results were expressed as median (interquartile range) or n(%). The 6 (3.5%) patients with lymphopenia either had URTI or pneumonia. Figure S1 showsabnormalities of the chest CT images from representative patients.

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Table S1. Age distribution of infected children and their respective diagnosesn (%) or median (IQR)
AsymptomaticUpper respiratory
All patients
infection
tract infection(n = 171)(n=27)(n = 33)
Age -years
Median (IQR)
6.7 (2.0-9.8)
9.6 (7.6-12.6)
3.9 (1.4-8.4)<131 (18.1)
06 (18.2)
1-5
40 (23.4)
1 (3.7)
12 (36.4)
6-10
58 (33.9)
14 (51.9)
10 (30.3)
11-15
42 (24.6)
12 (44.4)
5 (15.2)

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Pneumonia(n =111)5.9 (1.2-9.3)
25 (22.5)
27 (24.3)
34 (30.6)
25 (22.5)

Table S2. Laboratory results of 171 infected children and their respective diagnoses

Measures
Blood routine (unit; normal range)
White blood cell count (×109/L; 5.5-12.0)<5.5
Neutrophil count (×109/L; 1.1-3.9)
Lymphocyte count (×109/L; 1.2-6.0)<1.2
Hemoglobin (g/L; 110.0-149.0)
Infection biomarkers (unit; normalrange)
Procalcitonin (pg/ml; 0-46) *>46
C-reactive protein (mg/L; 0.0-10.0)>10Blood biochemistry (unit; normalrange)
Lactate dehydrogenase (U/L; 120.0300.0)
Alanine aminotransferase (U/L; 7-45)
Increased
Aspartate aminotransferase (U/L; 10-50)>50
Alkaline phosphatase (U/L; 42.0-220.0)
Creatinine (μmol/L; 27.0-62.0)
Blood urea nitrogen (mmol/L; 2.9-7.1)

Diagnosis

All patients(n = 171)

Asymptomatic
infection(n=27)

Upper respiratory
tract infection(n = 33)

Pneumonia(n =111)

6.8 (5.5-8.2)
45/171 (26.3)
2.5 (1.8-3.7)

7.0 (6.1-8.1)
1/27 (3.7)
3.4 (2.9-3.9)

6.9 (5.5-8.6)
9/33 (27.3)
2.5 (1.7-3.9)

6.6 (5.3-8.2)
35/111 (31.5)
2.3 (1.6-3.5)

2.9 (2.2-4.4)
6 (3.5)126.0 (118.0-135.0)

2.8 (2.4-3.3)0(0)132.0 (125.0-135.0)

3.1 (2.6-4.6)
1(3.0)
128.0 (121.0-138.0)

2.9 (1.9-4.5)5(4.5)
125.0 (115.0-133.0)

50 (40-80)
105 (64.0)
4.0 (1.3-8.0)
33 (19.7)

40 (30-50)
10 (40.0)
2.0 (1.0-4.0)
2 (7.4)50 (40-80)
22 (68.8)
4.0 (1.3-6.8)
4 (12.1)

60.0 (40-90)
73 (68.2)
4.0 (1.7-9.0)
27 (24.3)

246 (207-305)

215 (181-254)

243 (215-323)

254 (216-329)

15 (11-27)
21 (12.3)
30 (24-42)
25 (14.6)
198.0 (156.0-245.0)
33.9 (26.1-42.7)
4.1 (3.3-4.8)

13 (11-20)
1 (3.7)25 (20-31)0 (0)202.0 (126.0-239.0)
42.6 (36.4-47.1)
4.7 (3.6-5.5)

13 (11-28)
4 (12.1)
30 (24-46)
5 (15.2)
186.0 (165.0-217.0)
29.0 (23.3-39.7)
4.1 (3.4-4.4)

16 (11-28)
16 (14.4)
32.0 (24-46)
20 (18.0)
198.0 (158.0-256.0)
31.7 (25.8-42.0)
4.1 (3.1-4.8)

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Coagulation markers (unit; normalrange)
Fibrinogen (g/L; 2.0-4.0)
D-dimer (mg/LFEU; 0.0-0.6) #>0.6
Prothrombin time (s; 10.2-13.4)
Thrombin time (s; 14.0-21.0)
Electrolytes (unit; normal range)
Potassium (mmol/L; 3.5-5.3)
Sodium (mmol/L; 137.0-147.0)
Chloride (mmol/L; 99.0-110.0)

2.1 (1.8-2.7)
0.2 (0.2-0.4)
21 (14.1)
10.9 (10.6-11.3))
18.4 (17.7-19.2)

1.8 (1.8-2.0)
0.2 (0.1-0.2)
0 (0)10.9 (10.6-11.1)
18.5 (17.9-19.0)

2.2 (1.9-2.8)
0.2 (0.2-0.4)
4 (16.0)
10.8 (10.6-11.5)
18.2 (17.7-18.7)

2.1 (1.8-2.8)
0.4 (0.3-1.0)
17 (17.5)
11.0 (10.6-11.3)
18.5 (17.7-19.4)

4.8 (4.3-5.2)
139.1 (138.0-140.5)
101.3 (99.7-103.0)

4.4 (4.3-4.7)
140.4 (139.5-141.6)
100.5 (99.9-102.9)

4.8 (4.3-5.6)
139.1 (138.2-140.2)
101.8 (99.7-103.1)

4.8 (4.4-5.2)
138.9 (137.6-140.1)
101.1 (99.5-103.0)*Procalcitonin was available from 164 patients (25 patients with asymptomatic infection, 32 patients with upper respiratory tract infection,
107 patients with pneumonia)#D-dimer was available from 149 patients (27 patients with asymptomatic infection, 25 patients with upper respiratory tract infections and97 patients with pneumonia.

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Figure S1. Chest CT scan images of representative patients.
Representative chest CT scan images from patients with different severity of the infection.
Bilateral ground glass opacities in a thirteen-month old boy with severe pneumonia requiring
ICU care (A, B). Chest CT scan image from a 14-year old girl showing basal infiltrates (C).
Chest CT scan image from a 15-year old asymptomatic boy showing ground glass opacity in theright posterior lung field.

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Author Contributions
XL, GW, KS, and SX conceptualized the study design. XL, JZ, YYL, DL, HD, JS, GW, and SX
analysed the data with input from JS, XP, YY, ZL, YX, YW, FZ, SB, LZ, HX, YL, CW, JQ,WZ, HL, YY. XL, JZ, GW wrote the first draft with all authors providing critical feedback forsubsequent revisions of the manuscript. All authors read and approved the final report.
Acknowledgement
We are very grateful to all the medical, nursing and supportive staff of the Wuhan Children’sHospital for their dedication in looking after the patients during this epidemic.
Declaration of interests
The authors have no competing interests to declare.
References
1. National Institute For Viral Disease Control and Prevention(http://ivdc.chinacdc.cn/kyjz/202001/t20200121_211337.html.)
2. World Health Organization- Novel Coronavirus (2019-nCoV)(https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance)

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