Clinical characteristics and intrauterine vertical transmission potential of COVID-19

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

Lancet 2020; 395: 809–15
Published Online
February 12, 2020

Reviewed by Dr Appu Gopalakrishnan

Authors
Huijun Chen*, Juanjuan Guo*, Chen Wang*, Fan Luo, Xuechen Yu, Wei Zhang, Jiafu Li, Dongchi Zhao, Dan Xu, Qing Gong, Jing Liao, Huixia Yang,Wei Hou, Yuanzhen Zhang

Conducted by

1. Department of Gynaecology and Obstetrics and Department of Paediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
2. Clinical Medicine Research Centre of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, Hubei, China
3. State Key Laboratory of Virology/Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China
4. Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China
5. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Summary

Background: Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection.

Methods: Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation.

Findings: All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1・0 × 10⁹ cells per L).

Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8–9 and a 5-min Apgar score of 9–10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus.

Interpretation: The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy.

Introduction
The type of pneumonia caused by the 2019 novel coronavirus disease (COVID-19) is a highly infectious disease, and the ongoing outbreak has been declared by WHO as a global public health emergency.1,2 COVID-19 pneumonia was first reported in Wuhan, Hubei Province, China, in December, 2019, followed by an outbreak across Hubei Province and other parts of the country.1,2 A study in The Lancet by Huang and colleagues2 reported the epidemiological, clinical, laboratory, and radiological characteristics, as well as treatment and clinical outcomes,

Of patients with laboratory-confirmed COVID-19 pneumonia.However, Huang and colleagues’ report mainly focused on non-pregnant adults. The clinical characteristics and vertical transmission potential of COVID-19 pneumonia in pregnant women is unknown. Urgent questions that need to be addressed promptly include whether pregnant women with COVID-19 pneumonia will develop distinct symptoms from non-pregnant adults, whether pregnant women who have confirmed COVID-19 pneumonia are more likely to die of the infection or to undergo preterm labour, and whether COVID-19 could spread vertically and pose risks to the fetus and neonate. Answers to these questions are essential for formulating the principles of obstetric treatment for pregnant women with COVID-19 infection. Therefore, to facilitate efforts, both in China and globally, to prevent and control COVID-19 pneumonia in children and pregnant women,3 we retrospectively collected and analysed detailed clinical data from pregnant

women with laboratory-confirmed COVID-19 infection at Zhongnan Hospital of Wuhan University, Wuhan, China. In this study we present clinical features of pregnant women with confirmed COVID-19 pneumonia and examine the vertical transmission potential of COVID-19.

Methods

Study design and patients
They did a retrospective review of medical records from nine pregnant women with COVID-19 pneumonia admitted to Zhongnan Hospital of Wuhan University from Jan 20 to Jan 31, 2020. Diagnosis of COVID-19 pneumonia was based on the New Coronavirus Pneumonia Prevention and Control Program (4th edition) published by the National Health Commission of China.4 All nine pregnant women with COVID-19 pneumonia tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract.This study was reviewed and approved by the Medical Ethical Committee of Zhongnan Hospital of Wuhan University (approval number 2020004). Written informed consent was obtained from each enrolled patient.

Data collection
They  reviewed clinical records, laboratory findings, and chest CT scans for all nine pregnant women. All information was obtained and curated with a customised data collection form. Two study investigators (JG and XY) independently reviewed the data collection forms to verify data accuracy.

Maternal throat swab samples were collected and tested for SARS-CoV-2 with the Chinese Center for Disease Control and Prevention (CDC) recommended Kit (BioGerm, Shanghai, China), following WHO guidelines for qRT-PCR. Amniotic fluid samples from patients with COVID-19 pneumonia were obtained via direct syringe aspiration at the time of delivery. Cord blood and neonatal throat swab samples were collected immediately after delivery

in the operating room. Additionally, breastmilk samples from patients with COVID-19 pneumonia were collected after their first lactation.

All samples were processed at the State Key Laboratory of Virology/Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, for further testing. All samples, as described above, were tested for SARS-CoV-2 by use of qRT-PCR with the CDC recommended Kit.

Statistical analysis
Statistical analysis was done with SPSS, version 20.0. Continuous variables were directly expressed as a range. Categorical variables were expressed as number (%).

Results
The nine pregnant women were all in their third trimester, and all underwent caesarean section. All patients had a history of epidemiological exposure to COVID-19. The age range of the patients was 26–40 years, and the range of gestational weeks at admission was 36 weeks to 39 weeks plus 4 days. None of the patients had underlying diseases such as diabetes, chronic hypertension, or cardiovascular disease. One patient, however, had gestational hypertension since 27 gestational weeks, while another developed pre-eclampsia at 31 gestational weeks. Both of these patients were in a stable condition during pregnancy. Additionally, one patient was found to have influenza virus infection upon admission to hospital.

CONCLUSION
In the current study, they treated nine pregnant women with COVID-19 pneumonia in 11 days from Jan 20 to Jan 31, 2020. Considering that SARS-CoV-2 has up to 85% sequence similarity with SARS,although none of our patients developed severe pneumonia or died of COVID-19 infection, they should be alert to the possibility that the disease course and prognosis of COVID-19 pneumonia could follow the same trend as SARS in pregnant women. However, their observations are based on a small number of cases and the time between illness onset and delivery was short.

According to their study, pregnant women with COVID-19 pneumonia showed a similar pattern of clinical characteristics to non-pregnant adult patients, as recently reported.2,15 Common symptoms at the onset of COVID-19 pneumonia for these women included a fever and cough, whereas less common symptoms were myalgia, malaise, sore throat, diarrhoea, and shortness of

breath. Laboratory tests indicated that lymphopenia is also likely to occur. Additionally, increased concentrations of ALT or AST might be one of the clinical manifestations. The symptoms of pregnant women with COVID-19 pneumonia were diverse, with the main symptoms being fever and cough. And in the study,they found no evidence for vertical transmission in late pregnancy.

MY CRITICAL REVIEW ON CURRENT STUDY
This study is limited by the small sample size and retrospective method. Several considerations should be taken into account when interpreting the findings. First, all enrolled patients were in the third trimester. The effect of COVID-19 infection on the fetus in the first or second trimester of pregnancy remains to be clarified. Second, whether vaginal delivery increases the risk of mother-to-child intrapartum transmission, and whether uterine contraction could increase the possibility of the virus ascending, needs to be further investigated. whether COVID-19 could damage the placenta, which represents an important link in vertical transmission, also needs to be further investigated . In the same way foeto placental circulation could have been evaluated for the presence of pro inflammatory substances like IL1,IL6 and TNF-alpha to check whether the placental or umbilical vessals are affected  .Further follow up was not done to check the health status of mother and neonates exposed to COVID -19. Asymptomatic carrier state is an important concern about COVID-19 infection,in that perspective the study should have been followed up for atleast two months for both mother and baby. Most of the anti viral medications have side effects, in this study they did not considered such an aspect, especially for the neonate.

CROSS- REFERENCES AND OTHER  RELEVANT PUBLICATIONS CONSULTED

1 Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; published online Jan 24. DOI:10.1056/NEJMoa2001017.

2 Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; published online Jan 24. https://doi.org/10.1016/S0140-6736(20)30183-5.

3 The State Council’s Joint Prevention and Control Mechanism for Pneumonia Epidemic in Response to New Coronavirus Infection. Notice on prevention and control of pneumonia in children and pregnant women with new coronavirus infection. Feb 3, 2020. http://www.ljxw.gov.cn/news-93789.shtml (accessed Feb 4, 2020; in Chinese).

4 National Health Commission of China. New coronavirus pneumonia prevention and control program (4th edn). Jan 22, 2020. http://www. gov.cn/zhengce/zhengceku/2020-01/28/5472673/files/0f96c10cc09d4d 36a6f9a9f0b42d972b.pdf (accessed Feb 4, 2020; in Chinese).

5 WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. Interim guidance. Jan 12, 2020. https://www.who.int/docs/default-source/ coronaviruse/clinical-management-of-novel-cov.pdf (accessed Feb 4, 2020).

6 WHO. Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases. Interim guidance. Jan 17, 2020. https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-20200117 (accessed Feb 4, 2020).

7 Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill 2020;25: 2000045.

8 Gottfredsson M. The Spanish flu in Iceland 1918. Lessons in medicine and history. Laeknabladid 2008; 94: 737–45 (in Icelandic).

9 Jamieson DJ, Honein MA, Rasmussen SA, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009; 374: 451–58.

10 Wong SF, Chow KM, Leung TN, et al. Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. Am J Obstet Gynecol 2004; 191: 292–97.