MedExpert Science & Research
By MedExpert | Apr 06, 2020
Q.
I am pregnant. I am following all guidelines to avoid getting COVID-19, but how careful do I need to be?
A.
Remain diligent and careful.
Consequences of infection with SARS-CoV-2 for third trimester pregnancies are favorable but unknown for early trimesters. Further, only a few small studies have reported any results. In a study by Dr. Hui Zeng published in Lancet on March 26, 2020, among six mothers with confirmed COVID-19, SARS-CoV-19 was not detected in the serum or throat swab in any of their newborns. However, virus-specific antibodies were detected in neonatal blood samples. As of March 6, 2020, all six newborns were healthy. In another study published in March in JAMA, of 33 newborns born to COVID-19 infected mothers, only three had any signs of the virus and their symptoms were mild. The newborns were healthy.
Pregnant women infected with SARS-CoV-2 need to inform their doctor to develop a plan for any drug management decisions that may become necessary and for understanding and planning of the delivery. Most SARS-CoV-2 infected mothers deliver their newborns by caesarian section to avoid transmitting the virus during delivery and mothers are asked to express and discard their breast milk until the milk is safe.
Studies appear to indicate that pregnancy is not considered a risk factor to predict a more severe course of illness. With that said, the risk of not being able to take medication puts the mom and baby at risk.
A group is beginning a study to learn more. UC San Francisco perinatologist Stephanie Gaw, MD, PhD, and pediatrician Valerie Flaherman, MD, MPH, are leading the newly launched PRIORITY study, which is enrolling pregnant and recently pregnant women with COVID-19 to fill in the many gaps in our knowledge.
See more information below
Management of pregnant women infected with COVID-19
Yongwen Luo, Kai Yin
Lancet Infectious Disease
March 24, 2020DOI:https://doi.org/10.1016/S1473-3099(20)30191-2
Since December, 2019, the outbreak of coronavirus disease 2019 (COVID-19), which originated in Wuhan, China, has become a global public health threat.
On Feb 28, 2020, WHO upgraded their assessment of the risk of spread and the risk of impact of COVID-19 to very high at global level. By March 10, 2020, 116 166 cases have been reported globally, causing 4088 deaths. The epidemic has spread to 118 countries around the world.
With immunocompromised status and physiological adaptive changes during pregnancy, pregnant women could be more susceptible to COVID-19 infection than the general population. As COVID-19 is rapidly spreading, maternal management and fetal safety become a major concern, but there is scarce information of assessment and management of pregnant women infected with COVID-19, and the potential risk of vertical transmission is unclear. In The Lancet Infectious Diseases, Nan Yu and colleagues
report the clinical features and obstetric and neonatal outcomes of pregnancy with COVID-19 pneumonia in Wuhan, China. Seven pregnant women with COVID-19 pneumonia were assessed and the onset symptoms were similar to those reported in non-pregnant adults with COVID-19. All patients received oxygen therapy and antiviral treatment in isolation. All patients had caesarean section after consultation with a multidisciplinary team and the outcomes of the pregnant women and neonates were good. Three neonates were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and one was found to be infected with COVID-19 36 h after birth. The findings of the study provide some indications for clinical assessment and management of pregnant women with COVID-19, but questions remain on how to manage pregnant women infected with COVID-19.
As Yu and colleagues
reported, five pregnant women were treated with steroids after caesarean section. Two were also treated with traditional Chinese medicine. However, no reliable evidence recommends any specific COVID-19 treatment for pregnant women. WHO guidance and some clinical evidence does not recommend the use of corticosteroids for COVID-19.
,
Use of drugs in pregnant women needs to be on the basis of solid evidence. Clinical trials are needed to prove the effectiveness of drugs and the effects on the fetus to establish a standardised treatment for pregnant women with COVID-19. More evidence of the safety of traditional Chinese medicine is also warranted.
The time of delivery in the study was 37 weeks to 41 weeks plus 5 days, all by caesarean section. In cases of pregnant women with COVID-19, more evidence is needed to establish when to deliver and when caesarean sections should be recommended. Previous treatment experience has been inconclusive about which delivery method is safer in this patient population. Zhu and colleagues
reported nine pregnant women with COVID-19. Seven of the women delivered their babies by cesarean section and two by vaginal delivery. All three neonates delivered vaginally (including two who were twins) had an Apgar score of at least 9 and negative nucleic acid test. Yudin and colleagues
reported a pregnant woman with SARS at 31 weeks of gestation; the patient stayed for 21 days in the hospital and did not require intensive care admission or ventilatory support, and a healthy baby girl was delivered by vaginal birth. It is unknown whether vaginal delivery increases the infection risk. Further research is needed to assess the risk and to produce guidelines for delivery times and methods in patients with COVID-19.
As discussed in the study, although all mothers and infants showed good outcomes, all enrolled pregnant women were in the third trimester, and all had only mild symptoms. Hence, the effect of SARS-CoV-2 infection on the fetus in the first or second trimester or in patients with moderate to severe infection is unknown. As a previous study reported, SARS coronavirus infection during pregnancy might cause preterm birth, intrauterine growth restriction, intrauterine death, and neonatal death.
Considering that the potential of SARS-CoV-2 to cause severe obstetric and neonatal adverse outcomes is unknown, rigorous screening of suspected cases during pregnancy and long-term follow-up of confirmed mothers and their neonates are needed.
In the study by Yu and colleagues,
three neonates were tested for SARS-CoV-2, of whom two were negative. One neonate was positive, but the viral nucleic acid tests of the placenta and cord blood in this case were negative. At the end of follow-up, no pneumonia and other clinical symptoms and signs were reported in any of the seven neonates. No reliable evidence has been provided in support of the possibility of vertical transmission of COVID-19 infection from mother to baby. The outcomes are consistent with previous reports.
,
But all these studies only assessed a small number of cases. Future studies should include a larger number of samples across multiple centres to establish whether vertical transmission can occur between mother and child.
Yu and colleagues'
report of the clinical features and obstetric and neonatal outcomes of pregnant women with COVID-19 provides a reference for clinical assessment and management of this patient population. However, understanding of SARS-CoV-2, especially the effect on pregnant women and neonates, is still insufficient. We need to further strengthen research to provide an evidence-based foundation for the medical management of pregnant patients with COVID-19.
References
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Date accessed: March 6, 2020
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Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study.
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https://doi.org/10.1016/S1473-3099(20)30176-6
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Pregnant women with new coronavirus infection: a clinical characteristics and placental pathological analysis of three cases.
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Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records.
Lancet. 2020; 395: 809-815
Article Info
Publication History
Published: March 24, 2020
Identification
DOI: https://doi.org/10.1016/S1473-3099(20)30191-2
Copyright
© 2020 Elsevier Ltd. All rights reserved.
Research Letter
March 26, 2020
Antibodies in Infants Born to Mothers With COVID-19 Pneumonia
Hui Zeng, MD1; Chen Xu, BS1; Junli Fan, MD1; et alYueting Tang, PhD1; Qiaoling Deng, MD1; Wei Zhang, MD, PhD2; Xinghua Long, MD, PhD1
JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4861
https://jamanetwork.com/journals/jama/fullarticle/2763854#243000281
Tests for IgG and IgM antibodies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became available in February 2020. On March 4, 2020, the seventh edition of the New Coronavirus Pneumonia Prevention and Control Protocol for the novel coronavirus disease 2019 (COVID-19) was released by the National Health Commission of the People’s Republic of China and added serological diagnostic criteria.1 A previous study of 9 pregnant women and their infants found no maternal-infant transmission of SARS-CoV-2 based on reverse transcriptase–polymerase chain reaction (RT-PCR).2 We applied these new criteria to 6 pregnant women with confirmed COVID-19 and their infants because serologic criteria would allow more detailed investigation of infection in newborns.
Methods
Clinical records and laboratory results were retrospectively reviewed for 6 pregnant women with COVID-19 admitted to Zhongnan Hospital of Wuhan University from February 16 to March 6, 2020, confirmed based on symptoms, chest computed tomography, and positive RT-PCR results.
Blood samples were collected from the mothers at delivery and neonatal blood and throat swab samples were collected at birth. Quantitative RT-PCR for SARS-CoV-2 nucleic acid (RT-PCR Kit, BioGerm) was conducted on neonatal serum and throat swabs. Inflammatory cytokines (CBA Human Th1/Th2 Cytokine Kit II, BD Biosciences) were tested on neonatal serum. Maternal and neonatal sera samples were used to test for IgG and IgM antibodies. All tests were performed by 2 researchers (Y.T. and Q.D.), with SARS-CoV-2 IgG and IgM samples from infants double checked (CLIA assays Kit, YHLO). Sample collection, processing, and laboratory testing followed guidance from the World Health Organization.3 The sensitivity and specificity reported by the manufacturer for IgM are 88.2% and 99.0% respectively, and for IgG are 97.8% and 97.9%.4
This study was approved by the Zhongnan Hospital of Wuhan University institutional review board, which waived informed consent because data in this retrospective study were retrieved from medical records.
Results
All 6 mothers had mild clinical manifestations. All had cesarean deliveries in their third trimester in negative pressure isolation rooms. All mothers wore masks, and all medical staff wore protective suits and double masks. The infants were isolated from their mothers immediately after delivery.
All 6 infants had 1-minute Apgar scores of 8 to 9 and 5-minute Apgar scores of 9 to 10. Neonatal throat swabs and blood samples all had negative RT-PCR test results. All 6 infants had antibodies detected in their serum. Two infants had IgG and IgM concentrations higher than the normal level (<10 AU/mL). One infant had an IgG level of 125.5 and IgM level of 39.6 AU/mL; the second infant, had an IgG level of 113.91 AU/mL and IgM level of 16.25 AU/mL (Table 1). Their mothers also had elevated levels of IgG and IgM (Table 2). Three infants had elevated IgG levels (75.49, 73.19, 51.38 AU/mL) but normal IgM levels; all 3 mothers had elevated IgG and 2 also had elevated IgM levels. Inflammatory cytokine IL-6 was significantly increased in all infants. None of the infants presented any symptoms as of March 8, 2020.
Discussion
Among 6 mothers with confirmed COVID-19, SARS-CoV-19 was not detected in the serum or throat swab by RT-PCR in any of their newborns. However, virus-specific antibodies were detected in neonatal blood sera samples. The IgG concentrations were elevated in 5 infants. IgG is passively transferred across the placenta from mother to fetus beginning at the end of the second trimester and reaches high levels at the time of birth.5 However, IgM, which was detected in 2 infants, is not usually transferred from mother to fetus because of its larger macromolecular structure. In a study6 of mothers with SARS, the placentas of 2 women who were convalescing from SARS-CoV infection in the third trimester of pregnancy had abnormal weights and pathology. Whether the placentas of women in this study were damaged and abnormal is unknown. Alternatively, IgM could have been produced by the infant if the virus crossed the placenta.
This study is limited by the small sample size, lack of cord blood, amniotic fluid, and breast milk and by incomplete information on the outcome of the infants. These findings are important for understanding the serological characteristics of infants whose mothers are infected with SARS-CoV-2 and further study is necessary.
Section Editor: Jody W. Zylke, MD, Deputy Editor.
Article Information
Corresponding Authors: Xinghua Long, MD, PhD (zhoulongxinghua@qq.com) and Wei Zhang, MD, PhD (zw6676@163.com), Zhongnan Hospital of Wuhan University, 169 Donghu Rd, Wuhan, China.
Published Online: March 26, 2020. doi:10.1001/jama.2020.4861
Author Contributions: Drs Long and Zhang had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. Dr Zeng and Ms Xu contributed equally to the study.
Concept and design: Zeng, Xu, Long.
Acquisition, analysis, or interpretation of data: Fan, Tang, Deng, Zhang.
Drafting of the manuscript: Zeng, Xu, Long.
Critical revision of the manuscript for important intellectual content: Fang, Tang, Deng, Zhang.
Statistical analysis: Zeng, Xu, Fan, Tang, Deng.
Obtained funding: Long.
Supervision: Zhang.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by grants 81272372 from the National Natural Science Foundation of China and znpy2016033 from Zhongnan Hospital of Wuhan University Science, Technology, and Innovation Seed Fund.
Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
References
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China NHC. New Coronavirus Pneumonia Prevention and Control Protocol. 7th ed. National Health Commission of the People’s Republic of China; 2020. Accessed March 4, 2020. http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989/files/ce3e6945832a438eaae415350a8ce964 .pdf
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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
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World Health Organization. Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases: interim guidance 2020. Posted January 17, 2020. Accessed February 4, 2020. https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases- 20200117
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Contribution to Wuhan with SARS-CoV-2 IgG/IgM Assays. News release. YHLO, March 4, 2020. Accessed March 4, 2020. http://www.szyhlo.com/en/news_detail.php?menuid=75&id=125&from=singlemessage&isappinstalled=0.
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Kohler PF, Farr RS. Elevation of cord over maternal IgG immunoglobulin: evidence for an active placental IgG transport. Nature. 1966;210(5040):1070-1071. doi:10.1038/2101070a0PubMedGoogle ScholarCrossref
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Ng WF, Wong SF, Lam A, et al. The placentas of patients with severe acute respiratory syndrome: a pathophysiological evaluation. Pathology. 2006;38(3):210-218. doi:10.1080/00313020600696280PubMedGoogle ScholarCrossref
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