Received: 16 February 2020 | Accepted: 26 February 2020

DOI: 10.1002/jmv.25740

REVIEW

Coronavirus disease (COVID‐19) and neonate: What

neonatologist need to know

Qi Lu MD, PhD | Yuan Shi MD, PhD

Department of Neonatology, Key Laboratory

of Pediatrics in Chongqing, Ministry of Abstract
Education Key Laboratory of Child
Development and Disorders, Children's Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) cause china epidemics
Hospital, Chongqing Medical University, with high morbidity and mortality, the infection has been transmitted to other coun-
Chongqing, China
tries. About three neonates and more than 230 children cases are reported. The disease
Correspondence condition of the main children was mild. There is currently no evidence that SARS‐
Qi Lu, MD, PhD and Yuan Shi MD, PhD,
Department of Neonatology, Key Laboratory CoV‐2 can be transmitted transplacentally from mother to the newborn. The treatment
of Pediatrics in Chongqing, Ministry of strategy for children with Coronavirus disease (COVID‐19) is based on adult experi-
Education Key Laboratory of Child
Development and Disorders, Children's ence. Thus far, no deaths have been reported in the pediatric age group. This review
Hospital, Chongqing Medical University, describes the current understanding of COVID‐19 infection in newborns and children.
Chongqing 400014, China.
Email: [email protected] (Q. L.) and
[email protected] (Y. S.)

1 | INTRODUCTION spike and envelope, virions are spherical, oval, or pleomorphic with
diameters of approximately 60 to 140 nm. Culture times were 4 days on
Since December 2019, patients with fever, dry cough, normal, or de- human airway epithelial cell lines and 6 days on Vero E6/Huh‐7 cell lines.
creased white blood cell counts who were initially diagnosed as “Fever The single‐stranded RNA was 29 903 bp in length. The organization of
of Unknown Origin with pneumonia” have been continuously in- the SARS‐CoV‐2 genome is 5′‐leader‐UTR‐replicase‐S (Spike)‐E
creasing in Wuhan.1 The causative agent of this unexplained infected (Envelope)‐M (Membrane)‐N (Nucleocapsid)‐3′‐UTR‐poly (A) tail with
pneumonia was identified as severe acute respiratory syndrome cor- unknown open reading frames.6 Its reference sequence (NC_045512.2)
onavirus 2 (SARS‐CoV‐2) which not only has a strong human‐to‐human is with an 80.26% sequence identity (and query coverage above 98%) to
2
transmission but also causes severe pneumonia to death. SARS‐ the human SARS‐coronavirus genome (NC_004718.3),7 however, the
CoV‐2 is so aggressive that the infection has been transmitted to other Middle East respiratory syndrome (MER) coronavirus is lower related to
countries and is seriously imperiling human life. World Health Orga- SARS‐CoV‐2 which is a group 2c β‐coronavirus. SARS‐CoV‐2 exhibits
nization has declared this disease to constitute a Public Health very high sequence similarity to the Guangdong pangolin coronaviruses
Emergency of International Concern on 30 January 2020.3 A total of in the receptor‐binding domain which indicates pangolins may be an
26 359 suspected cases and 31 225 confirmed cases with 639 deaths intermediate host of the virus before dissemination to humans.8 SARS‐
4
linked to this pathogen on 7 February 2020. Different age group are CoV‐2 has weak resistance, 56°C for 30 minutes, 75% ethanol, chlorine‐
generally susceptible to SARS‐CoV‐2. At present, neonates have been containing disinfectant, and peracetic acid can inactivate SARS‐CoV‐2.9
diagnosed with Coronavirus disease (COVID‐19). Neonatologists SARS‐CoV‐2‐S uses the SARS‐coronavirus receptor, angiotensin‐
should be vigilant assessing newborn babies delivered by infected converting enzyme 2 (ACE‐2) for entry host cells. ACE‐2 is a surface
mather or brought up by infected housemaid and improve the molecule highly expressed in AT2 cells of lung, along with esophageal
knowledge of prevention and treatment of COVID‐19. upper epithelial cells and absorptive enterocytes from ileum and colon
which indicated digestive system along with respiratory systems is a
potential route for SARS‐CoV‐2.10,11 The expression level of ACE‐2 in
2 | ET IOLOGY OF CO VID ‐19 Asian populations is significantly higher than that in European and
American populations, and ACE‐2 on male cells are higher than on fe-
SARS‐CoV‐2 is single‐stranded RNA viruses, belongs to subgenus Sar- male cells, which can partially explain the incidence rate of novel cor-
5
becovirus of the genus Betacoronavirus. SARS‐CoV‐2 particles contain onavirus pneumonia are higher in male and Asia.12,13

J Med Virol. 2020;1–4. wileyonlinelibrary.com/journal/jmv © 2020 Wiley Periodicals, Inc. | 1

2 | LU AND SHI

3 | T R A N S M IS S I O N milk. In his family, the housemaid was the earliest case, subse-
quently, the mother was infected.21 The second newborn appeared
The symptomatic patients with Coronavirus disease are the main fever on 5 days after birth whose mother also confirmed infected.
disseminators, but the asymptomatic patients should not be under- The third one who was born by the infected mother was silent and
estimated. The current data show major transmission routes are diagnosed on 30 hours after birth by the viral nucleic acid test.
droplets transmission, contact transmission, and aerosol transmis- Short breath, vomiting milk, cough, and fever were present in
sion. fecal‐oral transmission cannot be ignored, because the nuclear neonates. The vital signs of those neonates were stable, there is no
acid of the SARS‐CoV‐2 is detected in the fecal samples of patients in severe emergency case until now.19,21‐23
14
the United States and China. Maternal‐infant vertical transmission
is doubtful—there have been no documented neonates of in-
trauterine vertical transmission occurring with SARS and MERS.15,16 5 | D IA G N O S IS
According to existing complete data, amniotic fluid, cord blood,
neonatal throat swab, and breastmilk samples from six newborn The diagnosis of COVID‐19 is based on comprehensive contact and
babies delivered by infected mothers were tested for SARS‐CoV‐2, travel history and precise laboratory tests. Current diagnostic tools
17
and all samples tested negative for the virus. were the nucleic acid or virus gene tests. Samples included naso-
pharyngeal swab, sputum, secretion of the lower respiratory tract,
blood, and feces. The nasopharyngeal swab is the most common
4 | CLINICAL PRESENTATION OF specimens, however, its detection positive rate is less than 50%.
COV I D‐ 19 Repeated detection is necessary for improving the positive rate. The
positive rate of bronchoalveolar lavage fluid was high, but it is not
The incubation periods of COVID‐19 were 1 to 14 days, and the suitable for most of the patients due to increased risk of cross‐
mean has been estimated to be 5.2 days (95% confidence interval infection.24,25
[CI]: 4.4‐6.0) and 97.5% of those who develop symptoms will do so
within 10.5 days (95% CI: 7.3‐15.3) of infection.18 From the
first confirmed child case who was reported in Shenzhen on 6 | INFECTION CONTROL AND
20th January 2020 to 6 February 2020, at least 230 COVID‐19 TREATMENT
cases in children (≤18 years) have been reported in China. The
SARS‐CoV‐2 rapid spread in children suggests that it has a strong Neonatologist must wear protective equipment (including hats,
transmission capacity in the special population (neonate, children). goggles, protective suits, gloves, N95 masks, etc) to resuscitate
SARS‐CoV‐2 infection can range from asymptomatic infection to neonates delivered by confirmed and/or suspected COVID‐19
severe respiratory distress in neonates and children. However, puerperant. If the puerperant is positive for SARS‐CoV‐2, the neo-
Respiratory distress occurs in children with underlying conditions. nate must be isolated, then detected SARS‐CoV‐2.26
One patient had severe malnutrition and survived surgery for Early identification and early isolation are imperative for
congenital heart disease, the other had bilateral hydronephrosis and COVID‐19 control. COVID‐19 neonates should be placed in nega-
left‐kidney calculi. The clinical course of COVID‐19 was generally tive pressure rooms or in rooms in which room exhaust is filtered
milder in children than adults.The most common clinical symptoms through high‐efficiency particulate air filters with reference to
of COVID‐19 included fever, fatigue, and dry cough. A few patients MERS management.16 No visiting is allowed for neonates of
showed upper respiratory symptoms such as nasal obstruction, COVID‐19. Treatment mainly depends on adult patients' clinical
nasal discharge, and sore throat. Gastrointestinal symptoms such as experience due to few cases in children. There is no specific drug
abdominal discomfort, vomiting, abdominal pain, and diarrhea may treatment for SARS‐CoV‐2 being similar to MERS‐CoV and
also occur. C‐reactive protein was normal or temporary upregula- SARS‐CoV.19,26 Symptomatic and supportive treatment is the
tion, ALT levels and myocardial enzyme were not obviously ab- mainstay of therapy for patients of SARS‐CoV‐2 infection including
normal changes. Chest imaging normalities were present in the supply of oxygen, the maintenance of water‐electrolyte, and
asymptomatic infected patients. SARS‐CoV‐2 can be mixed to dif- acid‐base balance. The supplement of water and electrolyte should
ferent pathogen including mycoplasma pneumonia, influenza A, in- be appropriate, so as to avoid aggravating the pulmonary edema
fluenza B, RSV, and EB virus. The clearance time of SARS‐CoV‐2 and reduced oxygenation.27 For newborns with severe acute re-
nucleic acid from nasopharyngeal swab was recorded in three spiratory distress syndrome, high‐dose pulmonary surfactant, in-
children, 9 days in two patients, 12 days in one patient.19 Thus far, haled nitric oxide, high‐frequency oscillatory ventilation, and
no deaths have been reported in the children which are similar to extracorporeal membrane lung may be useful. In the United States,
SARS.19,20 Three newborns have been diagnosed up to date who patients' conditions were improved apparently after the treatment
mainly belonged to family cluster cases. One 17 days old neonate with nucleoside analog‐remdesivir, but there was just one case, the
diagnosed as COVID‐19 infection had a fever, cough, and vomiting efficacy needs further verification.28 Interferon‐α2b nebulization
LU AND SHI | 3

were be applied in MERS‐CoV and SARS‐CoV, so it could be con- entry into target cells. bioRxiv. 2020. https://doi.org/10.1101/2020.
sidered to use in SARS‐CoV‐2 infection.29,30 In addition, three po- 01.31.929042
11. Zhang H, Kang Z, Gong H, et al. The digestive system is a potential
tential drug combinations (sirolimus plus dactinomycin,
route of 2019‐nCov infection: a bioinformatics analysis based on
mercaptopurine plus melatonin, and toremifene plus emodin) are single‐cell transcriptomes. bioRxiv. 2020. https://doi.org/10.1101/
candidate repurposable drugs.31 Moreover, convalescent sera from 2020.01.30.927806
SARS‐CoV‐2‐recovered patients may be useful for SARS‐CoV‐2 in- 12. Zhang Q, Cong M, Wang N, et al. Association of angiotensin‐
converting enzyme 2 gene polymorphism and enzymatic activity with
fection, because of a significant reduction in the mortality following
essential hypertension in different gender: a case‐control study.
convalescent sera from SARS‐recovered patients treatment.32 Medicine. 2018;97(42):e12917.
13. Zhao Yu, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single‐cell RNA
expression profiling of ACE2, the putative receptor of Wuhan 2019‐
nCov. bioRxiv. 2020. https://doi.org/10.1101/2020.01.26.91998510
7 | C O NC LUSION S
14. Zhang W, Du RH, Li B, et al. Molecular and serological investigation of
2019‐nCoV infected patients: implication of multiple shedding routes.
COVID‐19 can result in asymptomatic to severe illness, fortunately, Emerg Microbes Infect. 2020;9(1):386‐389.
children without underlying diseases appeared to have mild disease. 15. Principi N, Bosis S, Esposito S. Effects of coronavirus infections in
The disease condition of the neonates was also minor. Though this children. Emerg Infect Dis. 2010;16(2):183‐188.
16. Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome.
new virus comes out without specific antiviral drugs treatment,
Lancet. 2015;386(9997):995‐1007.
neonatologist needs to more virological, epidemiological, and clinical 17. Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine
data to treat and manage COVID‐19. vertical transmission potential of COVID‐19 infection in nine
pregnant women: a retrospective review of medical records. The
Lancet. 2020.
CO NFLICT OF I NTERE STS
18. Lauer SA, Grantz KH, Bi Q, et al. The incubation period of 2019‐nCoV
The authors declare that there are no conflict of interests. from publicly reported confirmed cases: estimation and application.
Med Rxiv. 2020. https://doi.org/10.1101/2020.02.02.20020016
A UT HO R C ONT RI BU TIO NS 19. Recommendation for the diagnosis and treatment of novel cor-
onavirus infection/pneumonia in children in Hubei (Trial version 2).
Qi Lu and Yuan Shi conceived this review, Qi Lu wrote the manu-
20. Li AM, Ng PC. Severe acute respiratory syndrome (SARS) in neonates
script, Yuan Shi revised the manuscript. and children. Arch Dis Child Fetal Neonatal Ed. 2005;90(6):F461‐F465.
21. Lingkong Z, Xuwei T, Wenhao Y, Wang J, Liu X, Liu Z. First case of
OR CID neonate infected with novel coronavirus pneumonia in China. Chin
J Pediatr. 2020;58:E009.
Qi Lu http://orcid.org/0000-0002-5428-4032
22. Cai J, Wang X, Ge Y, et al. First case of 2019 novel coronavirus
infection in children in Shanghai. Zhonghua Er Ke Za Zhi. 2020;58(2):
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