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Figure.  Timeline and Imaging Findings of 3 Neonates Infected With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Timeline and Imaging Findings of 3 Neonates Infected With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Normal ranges: lymphocytes (L), 3000 to 8000 cells/μL (to convert to cells  × 109/L, multiply by 0.001); procalcitonin (PCT), <0.05 μg/L; white blood cell count (WBC), 8000-15000 cells/μL (to convert to cells × 109/L, multiply by 0.001). CBC indicates complete blood cell count; CT, computed tomography; NICU, neonatal intensive care unit; NIPPV, noninvasive positive-pressure ventilation; NRP, neonatal resuscitation program; RDS, respiratory distress syndrome; RT-PCR, reverse transcriptase–polymerase chain reaction.

Table.  General Information and Clinical Features of 33 Newborns With Mothers With COVID-19 Pneumonia
General Information and Clinical Features of 33 Newborns With Mothers With COVID-19 Pneumonia
1.
Zhu  H, Wang  L, Fang  C,  et al.  Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia.  Transl Pediatr. 2020;9(1):51-60. doi:10.21037/tp.2020.02.06PubMedGoogle ScholarCrossref
2.
Chen  H, Guo  J, Wang  C,  et al.  Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records.  Lancet. 2020;395(10226):809-815. doi:10.1016/S0140-6736(20)30360-3PubMedGoogle ScholarCrossref
3.
National Health Commission of China. New coronavirus pneumonia prevention and control program (4th edition). Accessed March 9, 2020. http://www.gov.cn/zhengce/zhengceku/2020-01/28/5472673/files/0f96c10cc09d4d36a6f9a9f0b42d972b.pdf.
4.
Wang  L, Shi  Y, Xiao  T,  et al; Working Committee on Perinatal and Neonatal Management for the Prevention and Control of the 2019 Novel Coronavirus Infection.  Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (first edition).  Ann Transl Med. 2020;8(3):47. doi:10.21037/atm.2020.02.20PubMedGoogle ScholarCrossref
5.
Wei  M, Yuan  J, Liu  Y, Fu  T, Yu  X, Zhang  ZJ.  Novel coronavirus infection in hospitalized infants under 1 year of age in China.  JAMA. 2020. doi:10.1001/jama.2020.2131PubMedGoogle Scholar
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    1 Comment for this article
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    Commentary: Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China
    Saba Alzabin, PhD, molecular immunology | Nabta Health
    I read with interest the report by Zeng and colleagues published on March 26th which assessed the likelihood of vertical transmission from 33 infected mothers with COVID-19 pneumonia. Whilst 30 of the 33 infants tested negative, 3 have tested positive, and presented with shortness of breath and pneumonia. The authors refer to previous studies (Lancet. 2020;395(10226):809-815 and Transl Pediatr. 2020;9(1):51-60) which show no clinical findings suggestive of vertical transmission and hypothesised based on the current study that it is indeed possible for COVID-19 to be passed to newborns from infected mothers. The authors correctly urge that the healthcare system and regulators should implement more strict infection control measures for pregnant women. However, what the authors did not highlight in their discussion is that 100% of the infected neonates were born by cesarean delivery, and that their symptoms appeared 2-4 days from delivery. All 30 non-infected neonates were born vaginally. A consideration should also be taken for the infection occurring as a result of the clinical environment. Implementation of more careful aseptic measures in delivery suites and theatres, combined with restriction of cesarean delivery only to cases where vaginal delivery is not possible for any health-related reason, are also factors that should be considered. The data to date is minimal and further investigation is required to implement more accurate guidelines.
    CONFLICT OF INTEREST: None Reported
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    Research Letter
    March 26, 2020

    Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China

    Author Affiliations
    • 1Department of Neonatology, Institute of Maternal and Child Health, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    • 2Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Wuhan, China
    • 3National Children's Medical Center, Children’s Hospital of Fudan University, Shanghai, China
    • 4Institute of Maternal and Child Health, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    JAMA Pediatr. Published online March 26, 2020. doi:10.1001/jamapediatrics.2020.0878

    The coronavirus disease 2019 (COVID-19) has spread rapidly across the world. With the sharp increase in the number of infections, the number of pregnant women and children with COVID-19 is also on the rise. However, only 19 neonates born to affected mothers have been investigated, and to our knowledge, no information on early-onset infection in newborns has been published in previous studies.1,2

    Methods

    In this cohort study, all neonates born to mothers with COVID-19 were recruited from Wuhan Children's Hospital, in Wuhan, Hubei Province, China. This study was approved by the local medical ethics committee. Written informed consent was obtained from the neonates’ parents. The diagnosis and management of newborns with or at risk of COVID-19 were in accordance with guidelines provided by the National Health Commission and the Chinese Perinatal-Neonatal SARS-CoV-2 Committee.3,4

    Data regarding demographic, epidemiologic, and clinical features were obtained from the medical records system. In addition, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase–polymerase chain reaction tests (Novel Coronavirus PCR Fluorescence Diagnostic Kit [BGI]) were conducted using nasopharyngeal and anal swab samples. Data were collected from January 2020 to February 2020. All statistical analyses were performed in Stata version 15.0 (StataCorp).

    Results

    Thirty-three neonates born to mothers with COVID-19, including 3 neonates with COVID-19, were identified (Table). The most common symptom was shortness of breath (4 of 33 neonates). Radiographic findings were nonspecific. No deaths were reported.

    We provide details of the 3 infected neonates (Figure). Patient 1 was born at 40 weeks’ gestation. The delivery was by cesarean delivery because of meconium-stained amniotic fluid and confirmed maternal COVID-19 pneumonia. On day 2 of life, the infant experienced lethargy and fever, with unremarkable physical examination results, and was moved to the neonatal intensive care unit. A chest radiographic image showed pneumonia, but other laboratory tests (except procalcitonin) were normal. Nasopharyngeal and anal swabs were positive for SARS-CoV-2 on days 2 and 4 of life and negative on day 6.

    Patient 2 was born at 40 weeks’ and 4 days’ gestation by cesarean delivery because of confirmed maternal COVID-19 pneumonia. He presented with lethargy, vomiting, and fever. A physical examination was unremarkable. Laboratory tests showed leukocytosis, lymphocytopenia, and an elevated creatine kinase–MB fraction. A chest radiographic image showed pneumonia. Nasopharyngeal and anal swabs were positive for SARS-CoV-2 on days 2 and 4 of life and negative on day 6.

    Patient 3 was born at 31 weeks’ and 2 days’ gestation by cesarean delivery because of fetal distress and confirmed maternal COVID-19 pneumonia. Resuscitation was required. The infant’s Apgar scores were 3, 4, and 5 at 1, 5, and 10 minutes after birth. Neonatal respiratory distress syndrome and pneumonia confirmed by chest radiographic image on admission resolved on day 14 of life after treatment with noninvasive ventilation, caffeine, and antibiotics. He also had suspected sepsis, with an Enterobacter agglomerates–positive blood culture, leukocytosis, thrombocytopenia (11 cells × 103/μL; to convert to cells  ×  109/L, multiply by 1.0), and coagulopathy (prothrombin time, 21 seconds; activated partial thromboplastin time, 81.9 seconds), which improved with antibiotic treatment. Nasopharyngeal and anal swabs were positive for SARS-CoV-2 on days 2 and 4 of life and negative on day 7.

    Discussion

    Consistent with previous studies, the clinical symptoms from 33 neonates with or at risk of COVID-19 were mild and outcomes were favorable.1,2,5 Of the 3 neonates with symptomatic COVID-19, the most seriously ill neonate may have been symptomatic from prematurity, asphyxia, and sepsis, rather than SARS-CoV-2 infection.

    In this cohort, 3 of 33 infants (9%) presented with early-onset SARS-CoV-2 infection. Because strict infection control and prevention procedures were implemented during the delivery, it is likely that the sources of SARS-CoV-2 in the neonates’ upper respiratory tracts or anuses were maternal in origin. Although 2 recent studies1,2 have shown that there were no clinical findings or investigations suggestive of COVID-19 in neonates born to affected mothers, and all samples, including amniotic fluid, cord blood, and breast milk, were negative for SARS-CoV-2, the vertical maternal-fetal transmission cannot be ruled out in the current cohort. Therefore, it is crucial to screen pregnant women and implement strict infection control measures, quarantine of infected mothers, and close monitoring of neonates at risk of COVID-19.

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    Article Information

    Accepted for Publication: March 10, 2020.

    Corresponding Author: Wenhao Zhou, MD, National Children's Medical Center, Children’s Hospital of Fudan University, 399 Wanyuan Rd, Shanghai 201102, China (zhouwenhao@fudan.edu.cn).

    Published Online: March 26, 2020. doi:10.1001/jamapediatrics.2020.0878

    Author Contributions: Dr Zeng had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Zeng, Shao, Zhou.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: All authors.

    Critical revision of the manuscript for important intellectual content: Xia, Yuan, Xiao, Shao, Zhou.

    Statistical analysis: Zeng, Yuan, Yan, Xiao.

    Administrative, technical, or material support: Zeng, Xia, Yan, Shao, Zhou.

    Supervision: Shao, Zhou.

    Conflict of Interest Disclosures: None reported.

    Additional Contributions: We thank Shoo K. Lee, MD, Department of Obstetrics and Gynecology and Department of Public Health, University of Toronto, for editing assistance. He was compensated for his contribution. We thank the patients’ families for granting permission to publish this information.

    References
    1.
    Zhu  H, Wang  L, Fang  C,  et al.  Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia.  Transl Pediatr. 2020;9(1):51-60. doi:10.21037/tp.2020.02.06PubMedGoogle ScholarCrossref
    2.
    Chen  H, Guo  J, Wang  C,  et al.  Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records.  Lancet. 2020;395(10226):809-815. doi:10.1016/S0140-6736(20)30360-3PubMedGoogle ScholarCrossref
    3.
    National Health Commission of China. New coronavirus pneumonia prevention and control program (4th edition). Accessed March 9, 2020. http://www.gov.cn/zhengce/zhengceku/2020-01/28/5472673/files/0f96c10cc09d4d36a6f9a9f0b42d972b.pdf.
    4.
    Wang  L, Shi  Y, Xiao  T,  et al; Working Committee on Perinatal and Neonatal Management for the Prevention and Control of the 2019 Novel Coronavirus Infection.  Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (first edition).  Ann Transl Med. 2020;8(3):47. doi:10.21037/atm.2020.02.20PubMedGoogle ScholarCrossref
    5.
    Wei  M, Yuan  J, Liu  Y, Fu  T, Yu  X, Zhang  ZJ.  Novel coronavirus infection in hospitalized infants under 1 year of age in China.  JAMA. 2020. doi:10.1001/jama.2020.2131PubMedGoogle Scholar
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