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Severe acute respiratory syndrome coronavirus 2 detection in the female lower genital tract

  • Author Footnotes
    1 These authors contributed equally to this work.
    Pengfei Cui
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Zhe Chen
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Tian Wang
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Jun Dai
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Jinjin Zhang
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Ting Ding
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Jingjing Jiang
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Jia Liu
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Cong Zhang
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Wanying Shan
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Sheng Wang
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Yueguang Rong
    Affiliations
    Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China
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  • Jiang Chang
    Affiliations
    Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China
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  • Xiaoping Miao
    Affiliations
    Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China
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  • Author Footnotes
    2 These authors contributed equally to this work.
    Xiangyi Ma
    Footnotes
    2 These authors contributed equally to this work.
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Ave., Hankou, Wuhan 430030, China
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  • Author Footnotes
    2 These authors contributed equally to this work.
    Shixuan Wang
    Footnotes
    2 These authors contributed equally to this work.
    Affiliations
    Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Ave., Hankou, Wuhan 430030, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    2 These authors contributed equally to this work.
      Click Supplemental Materials under article title in Contents at ajog.org

      Objective

      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 million people, caused thousands of deaths, and become a worldwide pandemic. To effectively block its transmission, all possible transmission routes must be determined. SARS-CoV-2 has been identified previously in throat and anal swabs, urine, and tears.
      • Wang L.
      • Wang Y.
      • Ye D.
      • Liu Q.
      Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence.
      However, little has been reported about SARS-CoV-2 in the female genital tract, which may provide direct evidence on sexual and mother-to-child transmission. This study aimed to determine whether SARS-CoV-2 exists in the lower female genital tract (including vaginal fluid and cervical exfoliated cells).

      Study Design

      In this study, we recruited 35 women with coronavirus disease 2019 (COVID-19) from Jan. 28, 2020, to Feb. 18, 2020, in 3 branches of the Tongji Hospital: Sino-French New City Branch (16 cases), Optical Valley Branch (16 cases), and Hankou Main Campus (3 cases). Patients received a diagnosis of COVID-19 based on the New Coronavirus Pneumonia Prevention and Control Program (5th edition) published by the National Health Commission of China (NHCC).
      National Health Commission of China
      New coronavirus pneumonia prevention and control program. 5th ed.
      Written informed consent was obtained from each enrolled patient.
      A total of 27 patients had a positive result for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) analysis on samples from the respiratory tract, which were consistent with the interim guidelines of the World Health Organization (WHO).
      World Health Organization
      Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected. Interim Guidance.
      Eight patients received a clinical diagnosis of COVID-19 based on the NHCC guidelines, as mentioned previously.
      National Health Commission of China
      New coronavirus pneumonia prevention and control program. 5th ed.
      It was a special situation in Wuhan, China, that many patients received a clinical diagnosis of COVID-19 and were admitted to COVID-19–specific hospitals based on the NHCC guidelines.
      National Health Commission of China
      New coronavirus pneumonia prevention and control program. 5th ed.
      Patients had typical epidemiologic histories, symptoms, and computed tomography scans but lacked throat swabs with positive results. These patients were included to investigate if SARS-CoV-2 could be found in the genital tract considering that it was difficult to detect in the upper respiratory tract.
      To avoid false-negative results, 3 different types of samples were obtained from each patient, including vaginal fluid, exfoliated cell, and anal swab. Each type of sample was collected twice and tested at 2 separate laboratories. Vaginal fluid samples were obtained from the posterior vagina fornix using a speculum. Swabs were rotated for 5 seconds and extracted while rotating (sampling kit from Yocon, Beijing, China). Exfoliated cell samples were collected from the cervix (or vaginal residue of patients who had undergone hysterectomy) according to the protocol of the ThinPrep cytologic test (Hologic, Marlborough, MA). The anal swab was inserted 3 cm into the anal canal and rotated for 5 seconds (sampling kit from Yocon, Beijing, China). None of the patients were admitted to the intensive care, and none had invasive ventilation; all had the ability to cooperate completely and to assume a lithotomy position, to follow the standard gynecologic examination protocol during sampling. Following the WHO guidelines for real-time RT-PCR, all samples were tested for SARS-CoV-2 using the recommended Chinese Center for Disease Control and Prevention kit (Daan Gene, Guangzhou, China, or BioPerfectus Technologies, Jiangsu, China). All the samples were processed separately and simultaneously at Tongji Hospital, Department of Clinical Laboratory, Wuhan, China, and Wuhan KDWS Biological Technology Co, Ltd, Wuhan, China. Sample collection, processing, and laboratory testing followed WHO guidelines. Positive cases were defined as patients with a positive test result from either laboratory.

      Results

      The age range of the 35 patients was 37–88 years. Most patients were natives of Wuhan, China. More than 50% of patients had chronic diseases. The interval from the first symptoms of COVID-19 to the time of taking the samples varied between 8 and 41 days. Twenty-eight patients had entered the menopause stage. One patient was postpartum and had just undergone a cesarean delivery. As a consequence, the sampling covered women who were postpartum and postmenopausal and women of reproductive age (Table).
      TableSARS-CoV-2 test by RT-PCR for vaginal fluid, cervical exfoliated cells, and anal swab samples
      Patient no.Age, yMenopauseDays from first symptoms to samplingThroat swabVaginal fluidCervical exfoliated cellsAnal swab
      174Yes24+
      260Yes27+
      359Yes36+
      464Yes31+
      560Yes21
      675Yes23+
      788Yes26+
      846No26+
      956Yes27+
      1069Yes26+
      1156Yes25+
      1255Yes25
      1370Yes31+
      1448No28+
      1537Postpartum28
      1671Yes31+
      1771Yes41
      1856Yes20+
      1941No23+
      2073Yes22+
      2163Yes14
      2267Yes21
      2351No24
      2444No21
      2576Yes22+
      2663Yes13+
      2769Yes9+
      2865Yes11+
      2944No14+
      3064Yes8++
      3153Yes15+
      3266Yes26+
      3367Yes29+
      3467Yes26+
      3566Yes26+
      The “+” symbol stands for positive results, and “−” symbol stands for negative results.
      RT-PCR, reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
      Cui. Severe acute respiratory syndrome coronavirus 2 detection in the female lower genital tract. Am J Obstet Gynecol 2020.
      Results from all samples of vaginal fluid, cervical exfoliated cells, and anal swab are presented in the Table. One anal swab sample was positive for SARS-CoV-2, which is consistent with previous research, and indicated that the digestive tract was a possible transmission route.
      • Wang L.
      • Wang Y.
      • Ye D.
      • Liu Q.
      Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence.
      All samples from the lower genital tract were negative for SARS-CoV-2. This negative result might be explained by the negative expression of angiotensin-converting enzyme 2, the receptor of SARS-CoV-2, in the vagina and cervix.
      • Uhlén M.
      • Fagerberg L.
      • Hallström B.M.
      • et al.
      Proteomics. Tissue-based map of the human proteome.
      We obtained breast milk from the 1 postpartum patient on the third day after delivery. A neonatologist helped to obtain neonatal throat swab samples. All the samples were negative for SARS-CoV-2, consistent with a previous study in which no SARS-CoV-2 was found in amniotic fluid, umbilical cord blood, and neonatal throat swabs.
      • 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.
      The strengths of our study include that both reproductive-age and postmenopausal women were included, multiple sites of the vagina were sampled, and all samples were double tested. Similar results were reported recently in a smaller study (n=10) in which no SARS-CoV-2 was detected in vaginal fluid.
      • Qiu L.
      • Liu X.
      • Xiao M.
      • et al.
      SARS-CoV-2 is not detectable in the vaginal fluid of women with severe COVID-19 infection.
      Our study was limited largely by sample size. Larger studies including many young patients and the mildly or moderately ill are needed to confirm the results. Furthermore, because samples from sex partners of the patients enrolled were missing, including anal swabs, semen, and urethral orifice swabs, we could not study whether sexual activity is a mode for transmission.

      Conclusion

      SARS-CoV-2 was not found in vaginal fluid and cervical exfoliated cells. Our results showed that the lower female genital tract may not be a transmission route for SARS-CoV-2. These results may help in the selection of the method of delivery for pregnant women with SARS-CoV-2 infection.

      Acknowledgments

      The authors thank all patients involved in the study.

      Supplementary Data

      References

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      Linked Article

      • Vaginal delivery in COVID-19 pregnant women: anorectum as a potential alternative route of SARS-CoV-2 transmission
        American Journal of Obstetrics & GynecologyVol. 223Issue 4
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          In a recently published article in the Journal, Cui et al1 reported that they did not find severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the genital tract of 35 patients of reproductive and postmenopausal age who received a diagnosis of coronavirus disease 2019 (COVID-19). All vaginal and cervical swabs were reportedly negative for SARS-CoV-2, whereas 1 anal swab sample tested positive. The authors concluded from these findings that the lower female genital tract may not be a transmission route for SARS-CoV-2 and that such evidence may guide the choice of delivery method in women with COVID-19.
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