Dear editor,
An emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) pandemic, imposes a great threat to global public health.1 The transmission and pathophysiology of SARS-CoV-2 gradually known among various populations, but public health effects of COVID-19 on women and their outcomes should not be ignored.1 , 2 In pregnant and perinatal women, vertical transmission of SARS-CoV-2 from an infected mother to her newborn is a controversial issue.2, 3, 4 SARS-CoV-2 was not detected in vaginal fluid from 10 women with COVID-195, however, no clear evidence regarding optimal delivery timing and safety of vaginal or cesarean delivery preventing SARS-CoV-2 vertical transmission has been reported.6 Thus, the management of COVID-19 in pregnancy based on obstetrical indications and maternal–fetal status is highly concerned. Here, we report clinical characteristics of COVID-19 pneumonia in puerperal women and evidence of SARS-CoV-2 shedding in her breastmilk.
Five hospitalized pregnant women clinically diagnosed with COVID-19 (according to the “pneumonia diagnosis protocol for novel coronavirus infection (trial version 5)”, gave birth to their babies. Of the five women, four were admitted to the Renmin Hospital of Wuhan University, Wuhan, China, while 1 was admitted to the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China from February 1 to March 25, 2020. The maternal information including clinical symptoms, epidemiological survey, puerperal data, radiological, and laboratory results, was obtained through electronic medical records or direct communication with patients and their families. SARS-CoV-2 infection of puerperal women was confirmed by series of investigations, such as clinical examination, laboratory tests, chest X-rays, and two independent RT-PCR tests. We used SARS-CoV-2 ORF1ab/N PCR detection kit (GeneoDx Biotech, Shanghai, China) for viral nucleic acid from nasopharyngeal swabs, vaginal secretion, and breastmilk, and SARS-CoV-2 antibody detection kit (YHLO Biotech, Shenzhen, China) for IgM-IgG antibody from blood serum, as previously reported.2
Between February 1 and March 25, 2020, five pregnant patients with COVID-19 were included to analyze this study (Table 1 ). The mean age of five mothers was 32 years (range 27 to 34 years), with the mean gestational age of 38 weeks plus 1 week (range 35 weeks to 40 weeks plus 1 week). All mothers' main onset symptoms were fever (40%), cough (20%), nasal congestion (20%), rhinorrhea (20%), poor appetite (20%), chest distress (40%), dyspnea (40%), and diarrhea (20%), that is consistent with clinical signs and symptoms, as previously described.7 Chest CT scan of all patients (except Patient 4) before delivery showed typical viral pneumonia, such as patchy and scattered ground-glass opacities, and blurred borders. Four patients (80%) had cesarean section delivery, while one patient (Patient 4) (20%) delivered her infant in vaginal mode. During hospitalization (range 6 to 41 days), the outcomes of puerperal women patients and their neonates were good, and patients underwent laboratory tests, recorded in detailed information (Fig. 1 A). Patient 3 with COVID-19 pneumonia had lymphopenia (<1 × 109 cells per L), while the other four patients (80%) had low lymphocyte ratio except one case (Patient 1). All patients (100%) had elevated concentrations of C-reactive protein (CRP) (>10 mg/L) with below the normal range concentrations of Procalcitonin (PCT). Two (40%) had slightly increased concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, four patients (80%) had normal white blood cell (WBC) count except Patient 4, who had mild increased WBC count (Table 1). None of the patients had co-infection with other common respiratory viruses (enlisted in Table 1).
Table 1.
Summary of clinical features and laboratory results of five puerperal patients with COVID-19
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | |
|---|---|---|---|---|---|
| Characteristics | .. | .. | .. | .. | .. |
| Age (years) | 29 | 29 | 34 | 27 | 32 |
| Interval between admission to hospital and symptom onset | 9 days | 6 days | 8 hours | 8 days | 1 day |
| Interval between delivery and admission to hospital | 1 day | 20 days | 3 hours | 10 hours | 6 hours |
| Gestation age (weeks) | 35+5 | 35 | 40 | 38+2 | 40+1 |
| Delivery mode | cesarean | cesarean | cesarean | vaginal | cesarean |
| CT findings | Patchy ground-glass opacities in both lungs | Scattered ground-glass opacities in both lungs | Blurred borders in left lung | Normal | Blurred borders in upper lobe and lower lobe of right lung |
| Symptoms and signs | .. | .. | .. | .. | .. |
| Fever | - | + | + | - | - |
| Cough | + | - | - | - | - |
| Nasal congestion | - | + | - | - | - |
| Rhinorrhoea | - | + | - | - | - |
| Poor appetite | + | - | - | - | - |
| Chest distress | + | + | - | - | - |
| Dyspnea | + | + | - | - | - |
| Diarrhoea | + | - | - | - | - |
| Body temperature (°C) | 36.0 | 37.9 | 37.8 | 37.2 | 36.8 |
| Clinical course | .. | .. | .. | .. | .. |
| Duration of fever | 0 | 6 days | 8 hours | 0 | 0 |
| Duration of hospitalization (days) | 28 | 41 | 18 | 6 | 6 |
| Laboratory test | .. | .. | .. | .. | .. |
| White blood cell count, × 109/L (normal range: 3.5-9.5) | 4.28 | 8.03 | 6.72 | 10.06 | 7.95 |
| Neutrophil count, × 109/L (normal range: 1.8-6.3) | 2.68 | 6.57 | 5.37 | 7.71 | 6.44 |
| Neutrophil ratio, % (normal range: 40-75) | 68.30 | 81.9 | 80 | 76.60 | 80.90 |
| Lymphocyte count, × 109/L (normal range: 1.1-3.2) | 1.01 | 1.08 | 0.97 | 1.64 | 1.08 |
| Lymphocyte ratio, % (normal range: 20-50) | 23.60 | 13.4 | 14.4 | 16.30 | 13.6 |
| CRP, mg/L (normal range: 0-10) | 53.2 | 57 | 11.5 | 74.8 | 43 |
| PCT, ng/mL (normal range: <0.1) | 0.075 | 0.086 | 0.03 | 0.004 | 0.003 |
| ALT, U/L (normal range: 7-40) | 13.0 | 40 | 50 | 13.0 | 15 |
| AST, U/L (normal range: 13-35) | 26.0 | 38 | 37 | 17.0 | 20 |
| PCR of nasopharyngeal swab | + Ct=36.8 | + Ct=33.3 | + Ct=37.2 | + Ct=36.1 | + Ct=34.3 |
| PCR of vaginal secretion | - | - | NA | - | NA |
| PCR of breastmilk | - | - | + | - | - |
| SARS-CoV-2 IgG, AU/mL (normal range: <10) | 128.79 | 107.89 | NA | 7.59 | 63.85 |
| SARS-CoV-2 IgM, AU/mL (normal range: <10) | 77.42 | 279.72 | NA | 0.62 | 20.96 |
| ADV DNA | - | - | - | - | - |
| Boca DNA | - | - | - | - | - |
| H1N1 RNA | - | - | - | - | - |
| H3N2 RNA | - | - | - | - | - |
| HCOV RNA | - | - | - | - | - |
| HMPV RNA | - | - | - | - | - |
| HPIV RNA | - | - | - | - | - |
| HRSV RNA | - | - | - | - | - |
| HRV RNA | - | - | - | - | - |
NA=not available; +=positive; -=negative; CRP=C-reactive protein; PCT=Procalcitonin; ALT=Alanine aminotransferase; AST=Aspartate aminotransferase; PCR, short for Real-time PCR against SARS-CoV-2 nucleic acid; Ct=Curve threshold value of SARS-CoV-2 N gene; ADV=Adenovirus; H1N1=Influenza virus A, H1N1; H3N2=Influenza virus A, H3N2; HCOV=Human seasonal coronavirus; HMPV=Human metapeumovirus; HPIV=Human parainfluenza virus; HRSV=Human respiratory syncytial virus; HRV=Human rhinovirus
Fig. 1.
Timeline of puerperal women with COVID-19 in hospital after onset of illness. (A) During hospitalization after onset of illness, the recorded events of all patients undergoing laboratory tests and delivery were marked with different diagrams on the indicated date. (B) Main records of Patient 3 during hospitalization. Real-time PCR against SARS-CoV-2 nucleic acid (shortened to PCR) was tested for breastmilk from Patient 3 after delivery for two (a) and three (b) days, respectively. +, positive result for SARS-CoV-2 nucleic acid test; -, negative result for SARS-CoV-2 nucleic acid test; Ct, Curve threshold value of SARS-CoV-2 N gene.
Five (100%) nasopharyngeal swab samples from patients were tested positive for SARS-CoV-2 RT-PCR. All the available vaginal secretion samples were negative for SARS-CoV-2 RT-PCR test, which is similar as previously reported.5 During follow-up, three of four (75%) available serum samples from patients had significantly elevated concentrations of SARS-CoV-2 IgM and IgG (Table 1). More importantly, four out of five (80%) patient`s breastmilk samples were negative for SARS-CoV-2 RT-PCR, which is similar to previous observations,2 , 8 while one (20%) patient`s (Patient 3) breastmilk showed SARS-CoV-2 RNA test positive (Table 1). Additionally, the breastmilk samples from Patient 3 after delivery for two and three days, remained positive for SARS-CoV-2 (Fig. 1B). Of note, the Ct value of RT-PCR test results was relatively high as 38.2 and 38.5 (Fig. 1B, a and b), suggesting the persistent presence of SARS-CoV-2 in human breastmilk from a patient with COVID-19.
In brief, SARS-CoV-2 causes milder COVID-19 in children as compared to adults,9 while newborns are still vulnerable to SARS-CoV-2 infection through the maternal–fetal transmission. The breastmilk (containing antibodies and other antimicrobial factors) feeding to infants safely is highly concerned in puerperal women with COVID-197. it`s hard to ignore SARS-CoV-2 infection risk factors in breastfeeding.
Although some human milk samples from SARS-CoV-2 infected mothers in China resulted negative in puerperal stage,2 , 8 safe breastfeeding should be encouraged according to standard infant feeding guidelines and necessary precautions for IPC (infection protection and control),10 as breastmilk is rich in essential antibodies and nutrients to increase infant's immunity against infectious diseases. The existence of SARS-CoV-2 in breastmilk from COVID-19 puerperal patients highlights the risk of virus transmission through breastfeeding.
Based on our observations, the clinical characteristics of puerperal women (Patient 3) with breastmilk positive results for SARS-CoV-2 on two and three days post-delivery, were similar to those puerperal women having breastmilk negative results for SARS-CoV-2, which provides focused evidence of SARS-CoV-2 persistently presence in breastmilk from COVID-19 women. In fact, this study is limited by small sample size and retrospective method. Some considerations should be taken into account when interpreting the findings, such as the dynamic presence of SARS-CoV-2 in breastmilk or confirmation of live SARS-CoV-2 in breastmilk.
Collectively, we reported detectable SARS-CoV-2 nucleic acid in human breastmilk from a puerperal woman with COVID-19. Although our conclusions are limited by the small sample size, we believe our findings are important for the concern of SARS-CoV-2 infection risk in breastfeeding of mother with COVID-19 to her neonate.
Authors’ Contributions
Conception and design: C Zhu, W Liu, Z Luo, and Y Xia, Obtaining written consent from patients and ethical approval, collecting samples: C Zhu, W Liu, Z Luo, and Y Xia, Acquisition, analysis, or interpretation of data: H Su, S Li, M Shereen, Z Lv, Z Niu, D Li, and F Liu, Confirming data accuracy: S Li, M Shereen, Z Lv, Z Niu, D Li, F Liu, Z Luo, and Y Xia, Drafting the manuscript: C Zhu, W Liu, and H Su, Revising the manuscript: Z Luo, and Y Xia, All authors had approved the final version of manuscript to be published, and agreed to be accountable for all aspects of the work.
Acknowledgments
Acknowledgements
This study was supported by the National Natural Science Foundation of China [81971936, 82041004, 81672079, and 31800147], the Guangdong Basic and Applied Basic Research Foundation [2019A1515011073], the Fundamental Research Funds for the Central Universities, Zhejiang University special scientific research fund for COVID-19 prevention and control [2020XGZX089], the National Mega Project on Major Infectious Disease Prevention [2017ZX10103005-007] and the National Key Research and Development Program of China [2018YFE0204500]. We frankly thank patients, researchers, and clinical staff who provided significant contributions to this study.
Disclosure statement
We declare no competing interests.
Ethics
The study was approved by the Ethics Committee and Institutional Review Board of the Renmin Hospital of Wuhan University (file no. WDRY2020-K066), and the Tongji Hospital of Huazhong University of Science and Technology (file no. TJ-IRB20200201). Written informed consent was obtained from each enrolled patient.
The data in this study can be provided after the Article is published with the permission of the corresponding authors. We can provide participant data without names and identifiers, but not the study protocol, statistical analysis plan, or informed consent form through an appointed email address for communication. The corresponding authors have the right to decide whether to share the data or not regarding to the research objectives and plan provided.
Contributor Information
Zhen Luo, Email: zhluo18@jnu.edu.cn.
Yuchen Xia, Email: yuchenxia@whu.edu.cn.
References
- 1.Mantovani A, Dalbeni A, Beatrice G. Coronavirus disease 2019 (COVID-19): we don't leave women alone. International journal of public health. 2020 Apr 10 doi: 10.1007/s00038-020-01369-4. PubMed PMID: 32277247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Dong L, Tian J, He S, Zhu C, Wang J, Liu C. Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn. Jama. 2020 Mar 26 doi: 10.1001/jama.2020.4621. PubMed PMID: 32215581. Pubmed Central PMCID: 7099527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020 Mar 7;395(10226):809–815. doi: 10.1016/S0140-6736(20)30360-3. PubMed PMID: 32151335. Pubmed Central PMCID: 7159281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J. A case report of neonatal COVID-19 infection in China. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2020 Mar 12 doi: 10.1093/cid/ciaa225. PubMed PMID: 32161941. Pubmed Central PMCID: 7108144. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Qiu L, Liu X, Xiao M, Xie J, Cao W, Liu Z. SARS-CoV-2 is not detectable in the vaginal fluid of women with severe COVID-19 infection. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2020 Apr 2 doi: 10.1093/cid/ciaa375. PubMed PMID: 32241022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Chen D, Yang H, Cao Y, Cheng W, Duan T, Fan C. Expert consensus for managing pregnant women and neonates born to mothers with suspected or confirmed novel coronavirus (COVID-19) infection. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. May 2020;149(2):130–136. doi: 10.1002/ijgo.13146. PubMed PMID: 32196655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Yu N, Li W, Kang Q, Xiong Z, Wang S, Lin X. Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. The Lancet Infectious diseases. 2020 Mar 24 doi: 10.1016/S1473-3099(20)30176-6. PubMed PMID: 32220284. Pubmed Central PMCID: 7158904. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Liu W, Wang J, Li W, Zhou Z, Liu S, Rong Z. Clinical characteristics of 19 neonates born to mothers with COVID-19. Frontiers of medicine. 2020 Apr 13 doi: 10.1007/s11684-020-0772-y. PubMed PMID: 32285380. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Liu W, Zhang Q, Chen J, Xiang R, Song H, Shu S. Detection of Covid-19 in Children in Early January 2020 in Wuhan, China. The New England journal of medicine. 2020 Apr 2;382(14):1370–1371. doi: 10.1056/NEJMc2003717. PubMed PMID: 32163697. Pubmed Central PMCID: 7121643. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Marinelli KA, Lawrence RM. Safe Handling of Containers of Expressed Human Milk in all Settings During the SARS-CoV-2 (COVID-19) Pandemic. Journal of human lactation: official journal of International Lactation Consultant Association. 2020 doi: 10.1177/0890334420919083. Apr 3:890334420919083. PubMed PMID: 32242762. [DOI] [PMC free article] [PubMed] [Google Scholar]