Brief Reports
cells express CD34, CD10, HLA-DR, CD19, CD56 and cyCD79α)
FIRST CASE OF CORONAVIRUS DISEASE 2019 IN
CHILDHOOD LEUKEMIA IN CHINA
Yang Zhao, MM,* Weihong Zhao, PhD,† Aibin Wang, MM,‡
Fang Qian, MM,‡ Sa Wang, MD,‡ Liwei Zhuang, MM,‡
Fujie Zhang, MD, PhD,‡ Delin Sun, PhD,§¶ and
Guiju Gao, MD,‡
Abstract:  We report the first case of coronavirus disease 2019 (COVID-19)
comorbid with leukemia in a patient hospitalized in Beijing, China. The
patient showed a prolonged manifestation of symptoms and a protracted diag-
nosis period of COVID-19. It is necessary to extend isolation time, increase
Downloaded from https://journals.lww.com/pidj by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD36tKOuhuKL2wddhB9W43Bc28mNyh13VCuUFE8UKE9Jto= on 05/21/2020
the number of nucleic acid detections and conduct early symptomatic treat-
ment for children with both COVID-19 and additional health problems.
Key Words: coronavirus disease 2019, acute lymphoblastic leukemia,
cough, fever, liver dysfunction
Accepted for publication April 23, 2020.
From the *Department of Pediatrics, Beijing Ditan Hospital, Capital Medical
University, Beijing, China; †Department of Pediatrics, Peking University
First Hospital, Beijing, China; ‡Department of infection, Beijing Ditan Hos-
pital, Capital Medical University, Beijing, China; §Brain Imaging and Anal-
ysis Center, Duke University, Durham, North Carolina; and ¶Department of
Veteran Affairs (VA) Mid-Atlantic Mental Illness Research, Education and
Clinical Center, Durham, North Carolina.
The authors have no funding or conflicts of interest to disclose.
Address for correspondence: Guiju Gao, Department of Infection, Beijing Ditan
Hospital, Capital Medical University, Beijing 100015, China. E-mail: guiju.
gao@163.com.
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/INF.0000000000002742
T he coronavirus disease 2019 (COVID-19) is a severe acute res-
piratory disease caused by a 2019 novel coronavirus (nCoV).1
COVID-19 was first identified in China during late December
20192,3 and has since been detected in over 100 international loca-
tions.3,4 On March 11, 2020, the World Health Organization char-
acterized COVID-19 as a pandemic.5 COVID-19 is spread through
rapid transmission, generally susceptible to crowds, and is charac-
terized with atypical clinical symptoms that can be easily missed or
misdiagnosed.6–8 As of March 15, 2020, a total of 153,517 global
cases have been confirmed resulting in 5735 deaths.4
People with underlying diseases are more vulnerable to COVID-
19.9 Although children infected with COVID-19 only account for a
small portion of the confirmed cases,9 children with tumors or auto-
immune diseases are more susceptible to various infections.10 Thus,
it is urgent to know whether these underlying diseases affect the clini-
cal manifestations in children with COVID-19 infection. Leukemia
accounts for nearly one-third of childhood cancer cases, and according
to the International Agency for Research on Cancer and the Interna-
tional Association of Cancer Registry, it is the most common cancer in
children.10 We report a case of acute lymphoblastic leukemia comorbid
with COVID-19 in Beijing, China. The patient presented with a pro-
longed manifestation of symptoms and a protracted diagnosis period
of viral infection of COVID-19 compared with adult patients.
CASE PRESENTATION
Underlying Disease of Acute Lymphocytic
Leukemia
The young male patient was diagnosed with acute lympho-
cytic leukemia (ALL) developed from the precursor B-cell (tumor
The Pediatric Infectious Disease Journal  •  Volume XX, Number XX, XXX XXX www.pidj.com | 1
Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
on February 12, 2018, at the age of 1 year and 10 months. He dis-
played hyperdiploidy, and his common ALL fusion genes, mixed
lineage leukemia, and Philadelphia-like screening were negative
and clinically dangerous. He achieved complete remission with
minimal residue detected in neutrophil count on day 33 (2.8 × 10−4)
after a course of treatment of vincristine, daunomycin, L-aspara-
ginase, prednisone induction chemotherapy. His minimal residue
was reduced to 0.9 × 10−4 after the cyclophosphamide cytarabine
6-mercaptopurine course and shifted negative on the fourth month
after his diagnosis. Afterward, he was administered chemotherapy
according to the Recommendations for the Diagnosis and Treat-
ment of Cell Leukemia: Fourth Edition.11 He received methotrexate
(25 mg/m2, once per week) and 6-mercaptopurine (50 mg/m2, once
per night) maintenance chemotherapy from January 7, 2019, until
he was diagnosed with COVID-19.
Time Course of COVID-19
The time course of his COVID-19 infection is shown in
Figure 1. The patient (3 years and 10 months) and his parents visited
his grandfather in Hebei province, China, between January 22 and
24, 2020, and returned to their home in Beijing, China, on January
25. The patient developed a cough on January 23, 1 day after visiting
his grandfather. His cough persisted after treatment with azithro-
mycin, oseltamivir and Feire Kechuan oral solution. Feire Kechuan
oral solution is a traditional Chinese medicine for cough relief. The
ingredients include ephedra, bitter almond, gypsum, licorice, honey-
suckle, forsythia, Anemarrhena, astragalus, isatis root, Ophiopogon
and Houttuynia. On February 1, 2020, the patient’s grandfather was
diagnosed with COVID-19. The patient was suspected to be infected
with COVID-19, but results from nucleic acid reverse transcription-
polymerase chain reaction were negative at the outpatient clinic of
Beijing Children’s Hospital, Beijing, China, on February 8 and 9.
On February 10, he developed a fever that reached a body tempera-
ture of 38.2°C, but the patient did not exhibit symptoms of chills,
chest tightness or asthma. On February 11, he tested positive for
COVID-19 and was hospitalized in Beijing Ditan Hospital. During
his hospitalization, he received interferon aerosolized inhalation
treatment, as well as oral solutions of Feire Kechuan and compound
sulfamethoxazole tablets. His temperature subsided on February
12, yet his cough continued. On February 18, he tested negative for
COVID-19 and was discharged home. The patient tested negative on
March 7 and during re-examination on March 14.
Auxiliary Examination and Treatment
When he was admitted to the hospital on February 11,
2020, the patient exhibited lower white blood cell, lymphocyte,
and CD4+ T lymphocyte counts, as well as higher alanine ami-
notransferase (ALT), aspartate aminotransferase (AST), C-reactive
protein (CRP) and serum amyloid A (SAA) (see Table 1). These
indices turned to normal level after the patient had administered
recombinant human interferon α1b nebulization, Feire Kechuan
oral solution, vitamin C tablets, compound sulfamethoxazole tab-
lets and compound glycyrrhizin tablets. His lymphocyte counts,
ALT, AST, CRP and SAA were in normal range. Additional tests
including influenza A/B antigen, procalcitonin, myoglobin, tro-
ponin, blood coagulation, renal function, serum amylase, lipase,
electrolytes and plasma levels of ammonia were all normal. His
transabdominal ultrasound showed normal liver size, but his chest
computed tomography (CT) revealed heavy texture in both sides
of his lungs (see Fig. 2). The patient’s blood type was A RhD posi-
tive. Blood testing results including white blood cell, lymphocyte
count, lymphocyte percentage, CD4+ T lymphocyte count, hemo-
globin, CRP, SAA, ALT and AST are listed in Table 1.
Zhao et al The Pediatric Infectious Disease Journal  •  Volume XX, Number XX, XXX XXX

FIGURE 1.  Time course of symptoms and test outcomes of the family.

Table 1.  Blood Routine, Lymphocyte Count, CD4T

Lymphocytes, CRP and SAA

Pretreatment Posttreatment Follow-up

Index (February 13) (February 18) (March 14) Normal

WBC (≈10 /L)

9
5.70 5.50 8.22 8–11
L (%) 23.70 46.00 0.49 40–60
L (≈109/L) 1.35 2.53 4.03 1.5–4.0
CD4+ (cells/μL) 451 735 1023 900–2000
Hb (g/L) 121 124 137 110–140
CRP (mg/L) 22.0 1.7 0.6 0–5
ALT (U/L) 74.8 26.3 31.3 15–40
AST (U/L) 51.0 24.0 12.1 9–40
SAA (mg/L) 346.8 17.1 2.1 0–10
Hb indicates hemoglobin; L, lymphocyte; WBC, white blood cell.

Given that the patient was immunocompromised during

the treatment of COVID-19, he did not receive chemotherapy. The
patient had normal hemoglobin, normal coagulation and no ten-
dency to bleed, resulting from no detection of skin spots, petechiae,
gum inflammation or nosebleeds. A re-examination of the blood
test on March 14 was normal. His CRP, SAA, ALT and AST were
also normal.

DISCUSSION
This study reported the first case of childhood leukemia
with COVID-19. COVID-19 is caused by 2019-nCoV, a single-
stranded RNA virus from a subfamily of Coronavirus, β gene.1,12
Common signs of human infection include respiratory symptoms,
fever, cough, shortness of breath and dyspnea. Severe cases com-
bined with comorbid diseases are highly associated with pneu-
monia, severe acute respiratory syndrome, renal failure and even
death.1,2,13,14 Children are reported to show less severe symptoms of
COVID-19 compared with adults.9
Our patient had a clear history of epidemic exposure and
family clustering. This is consistent with previous reports that most
diagnoses in children develop from family clustering cases.9,14 Close
family contact is the main epidemiological feature of COVID-19 in
children, similar to the main transmission pattern of severe acute
respiratory syndrome and Middle East respiratory syndrome coro-
naviruses in children.6,13,14 The patient and his parents developed
symptoms of fever and cough after visiting the patient’s asympto-
matic grandfather during an incubation period of COVID-19. The
patient may have been infected by his grandfather given the pos-
sibility that COVID-19 is contagious during its incubation period.15
The patient exhibited symptoms earlier and milder than his parents,
although his father developed a similar cough.
FIGURE 2. Chest CT (taken on February 17, 2020). The
arc-shapedhigh-density shadow in the heart projection area
considers machine-induced artifacts. CT indicates computed
tomography.
The patient tested negative for COVID-19 on February 8 and 9,
several days after the onset of his cough. Before contact with his
grandfather, the patient did not present symptoms of this cough, yet
after contact his cough persisted for 33 days without relief. Because
his cough developed similarly to his father’s, and although he initially
tested negative for COVID-19, the patient was still highly suspected
to be infected by his grandfather due to the cough’s symptom pres-
entation only 1 day after contact with his grandfather. This cough
also continued for 33 days, a longer duration than adults diagnosed
with COVID-19.16 This lengthened symptom presentation may be
explained by the patient’s diagnosis of ALL. This disease may weaken
the patient’s immune response resulting in a prolonged duration of
cough induced by a low viral load. However, due to the patient’s uncol-
laborative responses including crying and struggling to avoid sampling
during specimen collection, we cannot exclude the possibility that the
result on February 8 and 9 was a false negative. These findings require
validation from future studies with more cases. The 20-day lag period

2  |  www.pidj.com © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
The Pediatric Infectious Disease Journal  •  Volume XX, Number XX, XXX XXX COVID-19 and Childhood Leukemia
between the onset of cough and positive result for nucleic acid sug-
gests that COVID-19 tests should be conducted on children who have
been exposed to individuals with a confirmed diagnosis of COVID-19,
especially for children with primary or secondary immune dysfunc-
tion, even if the child remains asymptomatic. On the other hand, the
patient showed normal hemoglobin during the treatment of COVID-
19. However, the patient did not receive chemotherapy during the
treatment of COVID-19 and could be harmed by the inability to treat
his ALL. Additional studies are needed to investigate the influences of
COVID-19 in individuals with dysregulated immune function.
The patient tested negative for influenza A virus and influ-
enza B virus and displayed no improvements after treatment with
oral azithromycin and compound sirolimus. Therefore, these obser-
vations were unrelated to influenza A/B viruses or bacterial infection.
However, we cannot eliminate the possible infection of a separate res-
piratory virus. Previously, we observed that children with COVID-19
usually have mild clinical symptoms (which findings are in prepara-
tion for submission; Li et al17). It is possible that children are easily
infected with various respiratory pathogens, including coronavirus
229E, OC43, and NL-63 and thus gain cross-immunity protection.
In addition, children may carry viruses for a longer time and become
a potential source of infection, even if they remain asymptomatic.
The laboratory tests showed lower peripheral blood lympho-
cyte count and lower CD4+ T lymphocyte count during the early stage
of COVID-19, suggesting that childhood leukemia comorbid with
COVID-19 exhausts lymphocytes. For this reason, it is important to be
aware of changes in T-cell subsets in children with both leukemia and
COVID-19. Finding the key mechanism for pathogens to destroy lym-
phocytes will inspire clinicians to improve treatment by regulating the
immune function of patients.9 This study speculates after 2019-nCoV
infection, the virus protein phenotype that recognizes CD4+ T cells is
instead modified to create CD4+ T cells during the process of replica-
tion in the host cells. Because these cells cannot recognize the virus cor-
rectly, they remain in a low activation state. To have an antiviral immune
effect, the body selects other immune cells who are able to recognize the
virus protein phenotype to activate and proliferate. This effectively kills
the virus. At this time, the immune bias in the body is more conducive
to the inhibition of CD4+ T-cell expression. For this conjecture, we need
to further explore and analyze the molecular mechanism.
Multiple clinical observations report that patients with
COVID-19 may have liver damage, and the proportion of liver
enzymes is significantly increased in critically ill and severe patients
with COVID-19.16 Human angiotensin I converting enzyme (pep-
tidyl-dipeptidase A) 2 is the receptor related to 2019-nCoV.18 Our
patient with acute lymphoblastic leukemia was in remission, and
under maintenance treatment, and his previous liver enzyme tests
were normal. After being infected with COVID-19, he exhibited
higher ALT and AST but showed normal liver enzymes after receiv-
ing oral liver protection therapy.
The patient also showed thick and fuzzy lungs on his chest
CT. This result is different from previous reports of patients with
COVID-19 showing multiple subpleural ground-glass shadows and
infiltrates in the lungs and even pulmonary consolidation in severe
cases.9 This finding suggests that, to avoid a false negative and
the delay of treatment, more attention should be provided to chil-
dren exposed to COVID-19, even if they do not display significant
symptoms or show expected changes on a chest CT. It is predicted
that the COVID-19 pandemic may be similar to seasonal influenza
(fatality rate close to 0.1%) or the pandemics of 1957 and 1968.19
CONCLUSION
Children with underlying diseases and suspected to be
infected by COVID-19 should be observed with extended isolation
time and tested with more nucleic acid detections. They should also
© 2020 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
receive early symptomatic treatment. Further attention should be
provided for patients experiencing complications such as abnormal
liver function, and greater active treatment should be implemented
to avoid exacerbations. The findings of this case study need to be
verified in a larger sample. A follow-up study of this patient may
also help to understand the long-term effects of COVID-19 and its
treatment on children with underlying diseases.
ACKNOWLEDGMENTS
We thank Ms. Heather Bouchard for her polishing the texts.
We also thank the anonymous reviewers.
REFERENCES
1. Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a
new coronavirus of probable bat origin. Nature. 2020;579:270–273.
2. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with
2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
3. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with
pneumonia in China, 2019. N Engl J Med. 2020;382:727–733.
4. World Health Organization. Coronavirus disease 2019 (COVID-19)
Situation Report – 55. Available at: https://www.who.int/docs/default-
source/coronaviruse/situation-reports/20200315-sitrep-55-covid-19.
pdf?sfvrsn=33daa5cb_6. Accessed March 15, 2020.
5. World Health Organization. WHO Director-General’s opening remarks at the
media briefing on COVID-19 - 11 March 2020. Available at: https://www.
who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-
media-briefing-on-covid-19---11-march-2020. Accessed March 11, 2020.
6. Phan LT, Nguyen TV, Luong QC, et al. Importation and human-to-
human transmission of a novel coronavirus in Vietnam. N Engl J Med.
2020;382:872–874.
7. Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV
infection from an asymptomatic contact in Germany. N Engl J Med.
2020;382:970–971.
8. Holshue M, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavi-
rus in the United States. N Engl J Med. 2020;382:929–936.
9. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized
patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China.
JAMA. 2020;323:1061–1069.
10. Allemani C, Matsuda T, Di Carlo V, et al; CONCORD Working Group.
Global surveillance of trends in cancer survival 2000-14 (CONCORD-3):
analysis of individual records for 37 513 025 patients diagnosed with one
of 18 cancers from 322 population-based registries in 71 countries. Lancet.
2018;391:1023–1075.
11. Gao C, Zhao XX, Li WJ, et al. Clinical features, early treatment responses,
and outcomes of pediatric acute lymphoblastic leukemia in China with or
without specific fusion transcripts: a single institutional study of 1,004
patients. Am J Hematol. 2012;87:1022–1027.
12. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of
2019 novel coronavirus: implications for virus origins and receptor binding.
Lancet. 2020; 395:565–574.
13. Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of
novel coronavirus-infected pneumonia. N Engl J Med. 2020;382:1199–1207.
14. Chan JF, Yuan S, Kok K, et al. A familial cluster of pneumonia associated
with the 2019 novel coronavirus indicating person-to-person transmission: a
study of a family cluster. Lancet. 2020;395:514–523.
15. Shao P, Shan W. Beware of asymptomatic transmission: Study on 2019-nCoV
prevention and control measures based on extended SEIR model. BioRxiv
manuscript. Available at: https://doi.org/10.1101/2020.01.28.923169.
Accessed January 28, 2020.
16. Lei C, Fu W, Qian K, et al. Potent neutralization of 2019 novel coronavi-
rus by recombinant ACE2-Ig. BioRxiv manuscript. Available at: https://doi.
org/10.1101/2020.02.01.929976. Accessed February 1, 2020.
17. Li B, Shen J, Li L, et al. Radiographic and clinical features of children
with 2019 novel coronavirus (COVID-19) pneumonia. Indian Pediatr.
2020;pii:S097475591600156.
18. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry
depends on ACE2 and TMPRSS2 and is blocked by a clinically proven pro-
tease inhibitor. Cell. 2020; pii:S0092–8674(20)30229-4.
19. Fauci A, Lane H, Redfield R, et al. Covid-19 - navigating the uncharted. N
Engl J Med. 2020;382:1268–1269.
www.pidj.com | 3