Title: Coronavirus Disease 2019 (COVID-19) During Pregnancy: A Case Series
Title: Coronavirus Disease 2019 (COVID-19) During Pregnancy: A Case Series
Title: Coronavirus Disease 2019 (COVID-19) During Pregnancy: A Case Series
Weiyong LIU PhD1*; Qianli WANG PhD2*; Qi ZHANG PhD3*; Ling CHEN MD1*; Junbo
CHEN PhD2; Bo ZHANG MS1; Yanjun LU PhD1; Shaoshuai WANG MD1; Liming XIA
MD1; Lu HUANG MD1; Kai WANG BS2; Lu LIANG BS4; Yongli ZHANG MS5; Lance
TURTLE PhD6,7; David LISSAUER PhD8,9; Ke LAN PhD3†; Ling FENG MD1†; Hongjie
Affiliations:
4. West China School of Public Health and West China Fourth Hospital, Sichuan
China
8. Women’s and Children’s Health, Institute of life course and medical sciences,
Malawi
† Corresponding author.
College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China; phone
Science and Technology, Wuhan, 430030, Hubei, China; phone number: 8627-
Hongjie Yu, School of Public Health, Fudan University, Key Laboratory of Public
Yingle Liu, State Key Laboratory of Virology, Modern Virology Research Center,
College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China; phone
Science and Technology, Wuhan, 430030, Hubei, China; phone number: 8627-
Financial support The financial support from the National Mega Project on
Science Fund for Distinguished Young Scholars (No. 81525023), National Science
Liverpool School of Tropical Medicine. The views expressed are those of the
author(s) and not necessarily those of the NHS, the NIHR, the Department of
Health, or PHE.
AJOG at a Glance
limited. Only two studies reporting 18 mothers and 19 infants have been published.
observed.
B. Key findings
pregnancy and both caesarean and vaginal birth without adverse outcomes for
the mother, infant and healthcare staff. Our findings reinforce the need for the
Abstract
their newborn infant, and we sought to explored whether the SARS-CoV-2 can be
Study Design: The study was a case series study conducted in the obstetric ward
infection using oropharyngeal swab, placenta tissue, vaginal mucus, and breast
milk of mothers. and oropharyngeal swab, umbilical cord blood, and serum of
hospitalization. The clinical course and outcomes of three pregnant women who
dyads. Two had caesarean delivery in their third trimester. All patients showed
transmission in the case series and further in-depth study is needed. Both the
pregnancy woman and infant showed fewer adverse maternal and neonatal
outcomes.
Introduction
other countries1-3.
infections, with the potential for adverse maternal and perinatal outcomes.4 This
which were found to be associated with worse outcome during pregnancy. 5-8
infections caused by the coronavirus family, but at present this is still unknown
pregnancy are limited. Two recent publications by Chen et al. and Zhu et al.
patients who acquired the infection during the last trimester in Wuhan, with a
longer period of clinical observation and outcomes described in the mothers and
Prevention and Control Program (Trail 5th edition) published by the National
tertiary hospital in Wuhan. No cases were missed during this period. Informed
consent was obtained from each pregnant woman. For the newborn infant, proxy
oral informed consent was provided by a parent or legal guardian. The case
series study was approved by the institutional ethics board of Tongji Hospital
TJ-C2030).
data from the participants electronic medical records. Data available included
with participants and their families. If data were missing or unclear from the
doctors. The clinical outcomes were followed up to Feb 13, 2020. The data were
disease onset date was defined as the day when the symptom related to COVID-
19 was noticed.
Specimens were stored between 2°C and 8°C until testing. Total RNA was
TianLong Science and Technology Co., Ltd., Xi’an, China). Real-time reverse
of the National Institute for Viral Disease Control and Prevention, Chinese Center
frame 1ab gene (ORF1ab) and nucleocapsid gene (N) were amplified and tested
using the following primers and probes: ORF1ab forward primer 5'-
TAMRA-3'. Five μL of RNA solution was added into the 20 μL reaction mixture.
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Real-time RT-PCR was performed using the following cycling parameters: reverse
39.2, a positive result was defined as a Ct-value <35. Results were reported
positive when both ORF1ab gene and N gene tested to be positive. Specimens
tested as Ct-value of >=35 and <39.2 were retested for confirmation, a retest Ct-
Results
Between the 2nd and 5th February 2020, the obstetrics ward admitted a
total of 17 pregnant women, of which three (17.6%) were diagnosed with COVID-
19. All the three patients were from Wuhan city. The patient’s ages ranged from
30 to 34 years. All three pregnancies were infected in the third trimester and
delivered at term. The newborn infants survived and were uninfected. The three
patients had previously been cared for in different obstetric wards during the
same period. All the Healthcare Personnel (HCP) in the obstetric and newborn
current guidance12.
11
hypothyroidism for 4 years and epiglottic cysts. The potential exposure to SARS-
examination on Jan. 27, 2020. She reported the initial onset of fever (37.8℃) on
1st February 2020 (40 weeks gestational age), eight hours before presentation to
computed tomography (CT) of the chest and serial RT-PCR assays. On admission
worse on the left, including involvement of the upper lobe of left lung, localized
emphysema in the right lower lobe and a few linear fibrotic changes in the
middle lobe of the right lung (figure 1). Repeat CT scans of the chest, performed
on 8th February (eight days after onset) and 13th February (13 days after onset),
showed progression of the changes compared with the previous study (Figure 1).
specimens were positive on 5th February, and turned negative on the 7th and 9th
February. SARS-CoV-2 RT-PCR tests were performed on breast milk, placenta, and
vaginal mucus from the 2nd February 2 to 12th February and all results were
negative. A positive result for SARS-CoV-2 PCR performed on faeces was obtained
on 7th February and was negative on 12th February (on an anal swab). A
respiratory sputum specimen was obtained from her husband tested negative for
12
incubator with a separate air exchange system in the neonatal ward and received
initial care from HCP completely protected according to the current PPE
maternal blood and neonate washing was conducted in neonate ward. The infant
was not breast fed. The neonate presented chronic fetal distress in utero,
cord blood, plasma serum and whole blood collected at 34min after birth,
oropharyngeal swab collected on one day after delivery. The clinical details of
The patient was transferred back to the maternity ward after delivery.
(40μg, bid) and ganciclovir (0.25g, IV). She did not require ventilatory support.
13
was identified and she had consistently worn a mask for protection. Her family
fever on 30th January 2020 (37 weeks gestational age). She visited the outpatient
department of Tongji Hospital on 30th January and was admitted to the obstetric
patient 1. CT of the chest was performed on 30th January and showed bilateral
ground glass opacity (GGO), consolidation, nodules in the left lower lobe and
patchy consolidation in the right middle lobe. A repeat chest CT scan, performed
on 13th February (15 days after onset), showed progression of the changes
collected on admission (5th February 2020, seven days after illness onset, one day
before delivery) tested positive for SARS-CoV-2 by RT-PCR with a CT value of 28,
The patient returned to the maternity ward after delivery. Oxygen therapy,
was administered (3g, qd). She did not require ventilator support.
(gestational age 38+4 weeks). Apgar scores at 1 and 5 minutes were 8 and 9,
respectively. After delivery, the biosafety protection and medical care was the
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same as Infant 1 and neonate washing was conducted in neonatal ward. The
oropharyngeal swabs, serum, whole blood, urine and faeces collected 27 minutes
after birth and all results were negative. Subsequent RT-PCR assays on
oropharyngeal swab, urine and faeces were again negative from 7th through 13th
February. The clinical details of mother and infant 2 are shown in Table 1 and
Figure 2.
SARS-CoV-2 was she reported a visit to Tongji hospital for a routine obstetric
identified and she consistently wore a mask for protection. Her family members
25th January 2020 (37 weeks gestational age). She was admitted to the obstetric
GGO, subsolid patchy and linear fibrosis in the left lung, increased mediastinal
CT scan was performed on 10th February (16 days after onset) showed
improvement compared with the previous imaging (Figure 1). The SARS-CoV-2
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6th February. Follow up oropharyngeal swab specimens were collected and tested
positive on 10th February but turned negative on 11th February. SARS-CoV-2 RT-
PCR was performed on breast milk, anal swab, and vaginal mucus on 11th
maternal request on 9th February. Apgar scores at 1 and 5 minutes were 8 and 9,
respectively. After delivery, the biosafety protection and medical care was the
same as Infant 1 and 2, and neonate was washed in the neonatal ward. SARS-CoV-
urine and faeces from 10th and 11th February and all results were negative.
The patient was transferred back to the maternity ward after delivery.
Oxygen and antiviral therapy (Arbidol hydrochloride 3g, qid orally) were
Comment
Principal findings
16
infants at different time points after birth were all negative for SARS-CoV-2 by
RT-PCR.
Our patients initially presented with mild symptoms, only fever or cough,
and all showed chest CT abnormalities during infection. There was progression
Results in context
There are limited data concerning the clinical features and impact of SARS-
One of the infants in our study showed Meconium Stained Amniotic Fluid
(MSAF), but all outcomes were good. However, Zhu and colleagues10, reported 6
out of 10 neonates born pre-term, and Chen et al9, who reported 6 out of 9
COVID-19 pregnancy is not without risk, albeit less serious than SARS, in which
recovered.9 10
Research implications
17
In this case series, which we believe has performed the most comprehensive
are consistent with the finding the two previous studies on COVID-19 infection in
pregnancy women 9 10 and with observations in SARS. Two neonates with COVID-
19 have been reported, but in each case infection after birth cannot be
excluded.13
care for SARS-CoV-2 infected mothers during late pregnancy and both caesarean
and vaginal birth without adverse outcomes for the mother, infant and healthcare
staff. This information will benefit those planning care for non-infection related
should be noted, however, that we only report three mother-infant dyads, all of
whom were not severely affected and did not have any evidence of virus
detectable in blood.
This study has several limitations. First, due to the limited sample size of
18
Conclusion
that can occur during vaginal delivery are worthy of concern. Therefore,
transmission.
Beijing Taikang Yicai Foundation for their great support to this work. We thank
Contributors Dr. Ziyong Zhang, Dr. Yingle Liu, Dr. Hongjie Yu, Dr. Ling Feng and
Dr. Ke Lan conceptualised the study design. Dr. Yingle Liu, Weiyong Liu, Dr.
Shaoshuai Wang, Dr. LimingXia, Dr. Lu Huang, Dr. Junbo Chen, Mr. Kai Wang, Ms.
Liang Lu and Ms. Yongli Zhang acquired the data and interpreted the data; Dr.
Weiyong Liu, Dr. Qianli Wang. Dr. Qi Zhang and Dr. Ling Chen drafted the
manuscript; Dr. Lance Turtle and Dr. David Lissauer contributed to revising the
manuscript; Dr. Ling Chen and Dr. Shaoshuai Wang collected specimens; Dr.
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 25 February 2020
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Weiyong Liu, Mr. Bo Zhang and Dr. Yanjun Lu did the laboratory tests.
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Reference
1. Chan JF-W, Yuan S, Kok K-H, et al. A familial cluster of pneumonia associated
6736(20)30154-9
2. Holshue ML, DeBolt C, Lindquist S, et al. First Case of 2019 Novel Coronavirus
10.1056/NEJMc2001468
5. Wong SF, Chow KM, Leung TN, et al. Pregnancy and perinatal outcomes of
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10.3201/eid2203.151049
6736(20)30360-3
10. Zhu H, Wang L, Fang C, et al. Clinical Analysis of 10 Neonates Born to Mothers
prevention and control program (Trail 5th edn) Feb 4, 2020. Available from:
http://www.gov.cn/zhengce/zhengceku/2020-
02/05/5474791/files/de44557832ad4be1929091dcbcfca891.pdf (accessed
12. The State Council's Joint Prevention and Control Mechanism for Pneumonia
13. Qiao J. What are the risks of COVID-19 infection in pregnant women? The
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Table 1 Demographics, Clinical characteristics, Treatment and Laboratory Findings of Three Pregnant Women and Newborn Infant
Subject No. 1 2 3
Pregnant Women
Age (Years) 34 34 30
Occupation Employee Self-employed Self-employed
Hypothyroidism for 4 years / Gestational
Underlying comorbidities None
Epiglottic cysts diabetes
Other medical histories during pregnancy None Scarred uterus / Accreta placenta None
Gravidity 2 3 3
Parity 0 1 1
History of abortion Yes Yes Yes
Start of pregnancy Apr.29, 2019 May.11, 2019 May.7, 2019
Date of delivery Feb. 2, 2020 Feb. 6, 2020 Feb. 5, 2020
End of pregnancy, gestational age, Week/trimester 40/third 38+4/third 39+5/third
Vaginal delivery at
Delivery details Cesarean delivery at term Cesarean delivery at term
term
Remained in
Maternal outcome Remained in hospital Remained in hospital
hospital
Survived / Chronic fetal distress in
Fetal outcome Survived Survived
utero/ Chorioamnionitis
Clinical characteristics and treatment
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Newborn Infant
Demographics
Gender Male Female Male
Gestational age (Weeks) 40 38+4 39+5
No. of embryo Singleton Singleton Singleton
Birthweight (g) 3250 3250 3670
1 min Apagr score 8 8 8
5 min Apagr score 9 9 9
Meconium Stained Amniotic Fluid Slight decreased responsiveness and
Clinical characteristics None
(MSAF) muscle tension
Laboratory results
Leucocytes (× 10⁹ per L; normal range 5–20) 13.24 22.19 18
Neutrophils (× 10⁹ per L; normal range 2–10) 9.52 16.4 11.7
Lymphocytes (× 10⁹ per L; normal range 3–8) 2.43 3.31 3.8
Eosinophils (× 10⁹ per L; normal range 0.2–2) 0.11 0.35 0.88
Basophil (× 10⁹ per L; normal range 0.0–0.2) 0.01 0.2 0.1
Platelets (× 10⁹ per L; normal range 150.0–300.0) 218 137 208
Haemoglobin (g/L; normal range 148.0–190.0) 160 158 195
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Blood biochemistry
Albumin (g/L; normal range 38.0–54.0) 38.3 32.6 32.1
Alanine aminotransferase (U/L; normal range 0.0–41.0) 11 18 24
Aspartate aminotransferase (U/L; normal range 0.0–40.0) 143 28 150
Infection-related biomarkers
Procalcitonin (ng/mL; normal range 0.0–5.0) NA 0.23 0.33
C-reactive protein (mg/L; normal range 0.0–5.0) <0.5 <0.1 NA
Abbreviations: NA, not available; COVID-19, 2019 novel coronavirus disease; Abnormal value are of laboratory results are highlighted in bold.
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Figure legend
infection.
A: Patient 1 at two days after illness onset (A1) and eight days after onset (A2). CT
compared to A1.
B: Patient 2 on the illness onset (B1) and 15 days after onset (B2). CT images shows
compared to B1.
C: Patient 3 at 11 days after illness onset (C1) and 16 days after illness onset (C2).
CT images show GGO, subsolid patch and linear fibrosis. C2 showed absorption
(A) Patient 1and her newborn; (B) Patient 2 and her newborn; (C) Patient 3 and
her newborn.
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Figure 1
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Figure 2