So far, there have been no studies with a large sample size to convincingly summarize the clinical features of COVID-19 in pregnancy. Based on the data of 9 cases, we demonstrated that pregnant patients with COVID-19 had the comparable symptoms as non-pregnant adults2. In the current report, we described more comprehensively the clinical characteristics of COVID-19 patients with pregnancy with an expanded patient cohort of 23 cases in their third trimester. Fever and cough were still the most common symptoms, consistent with our previous findings. However, nearly half of the patients manifested no typical symptoms of SARS-CoV-2 infection. Instead, they just showed abnormal CT images (43.5%), which was the only clue for us to discover these asymptomatic infections. The results of laboratory examination were also atypical. It was showed that 39.1% of the patients had increased leukocytes, 65.2% had increased neutrophils, and 21.7% had decreased lymphocytes, showing some differences from what was reported by Chen et al8. Although the nucleic acid test is still used as the “gold standard” for the diagnosis of COVID-19, it is not unusual that patient compliance and the way of sampling as well as storage of throat swabs may lead to false negatives. Furthermore, there is a so-called "window period" for the detection of virus serology, which can be affected by the differences of individual immune response and other factors. In contrast, chest CT showed a better sensitivity than nucleic acid test in the early detection of SARS-CoV-2 infection9. Thus, we suggested that CT should be included in routine screening for pregnant women requiring hospitalization, as the safety of chest CT in pregnancy has been verified10. Moreover, in order to avoid the adverse consequences of patients with asymptomatic infection, it is necessary to adopt the highest level of protective measures for emergency patients who did not complete the screening in time.
Mother-to-child transmission, which is the most serious adverse effect for pregnant women with pathogen infection, can take place through several channels. With regard to vertical transmission, various viruses behave differently. Before the discovery of SARS-CoV-2, six coronaviruses were known to infect human beings, four of which, including HCoV-229E, HCoV-OC43, HCoV-NL63, as well as HCoV-HKU1, usually showed common cold symptoms and could be transmitted vertically11. On the contrary, there is no evidence to support the vertical transmission of SARS-CoV or MERS-CoV12-14. Our previous study demonstrated no evidence for the existence of SARS-CoV-2 in amniotic fluid, cord blood and newborn throat swabs by RT-PCR2. Similar results have been reported in subsequent studies independently15. However, limited samples were reported so far, and the data with placenta was still inadequate and controversial. Here, in addition to the negative results of SARS-CoV-2 in cord blood, amniotic fluid and newborn throat swab samples from 23 cases, we also demonstrated that no viral nucleic acids could be detected in placenta tissue, which provided stronger evidence for the absence of vertical transmission. The damage of placenta structure is also the reason for adverse pregnancy outcomes. In the current study, no virus inclusion bodies were found in placenta, and no obvious destruction of placenta structure were observed.
In the context of the WHO's efforts to promote vaginal delivery16, it is of great significance to clarify whether SARS-CoV-2 can transmit to the newborn through vagina during delivery. However, it is not appropriate to expose the newborn and medical staff in an environment that may cause infection for a long time, in the case of without knowing the risk of intrapartum transmission. Because COVID-19 is a severe respiratory infectious disease, and trial labor is a time-consuming and energy consuming dynamic process with variable outcomes, pregnant women may open their masks to breathe because of oxygen consumption, or cry out for pain, both of which can result in generation of viral aerosols. Two cases in this study chose caesarean just because they were not able to tolerate wearing masks anymore. To give a preliminary risk assessment about intrapartum transmission of SARS-CoV-2, we detected the samples of vaginal secretions for SARS-CoV-2and obtained negative results from all cases. This provided us more supporting evidence that neonates would not be infected during delivery due to the contacts with maternal birth canal. What's more, the newborn who was born through vaginal delivery had no signs of any SARS-CoV-2 infection. Thus, vaginal delivery should be taken into account, at least for those patients who have entered the stage of labor and can end the labor in a short time, because the risk of pathogens entering the fetus due to uterine contraction no longer can be eliminated. The prerequisite of vaginal trial is to strictly protect the area around the birth canal. After all, there have been studies in which the existence of virus from feces was detected17,18. Our study also showed a case with SARS-CoV-2 positive in her perianal secretion sample. In the process of delivery, protecting the birth canal from contamination, avoiding invasive operation, clamping the umbilical cord quickly and separating the newborn from maternal surrounding environment as soon as possible, may help to reduce the risk of newborn's exposure to virus and the possibility of infection.
Since the lack of evidence of vertical transmission and intrapartum transmission, we should put our focus of neonatal protection on postpartum transmission. However, during the process of early neonatal care after umbilical cord clamping, there was no protective measure for newborn. Besides that, because the newborns of infected mother were defined as suspected cases, they should be transferred through the patient channel. Although the total transit time was only a few hours, the possibility of exposure to the virus could not be completely ruled out. Recently, there have been reports about cases of neonatal infection, but they did not clarify the transport process after birth and the time of samples collection, so it is not appropriate to infer that these newborns were infected through vertical transmission. It has been recommended that, in the study of mother-to-child transmission, samples of placenta, amniotic fluid, cord blood and nasopharynx swabs should be taken for detection immediately after delivery in sterile environment. Only if we get the necessary samples correctly and carry out standard detection, can the scientific evidence be obtained. In other word, the positive nasopharynx swab results of newborns with transport experience do not indicate that the virus was obtained from their mothers. In this study, SARS-CoV-2 tests in several newborns were negative at birth, but positive after being transported to neonatal department for several hours. However, this positive result could not be repeated in the next few days. This may because these newborns were exposed to a small amount of virus during transport, or the results were false positive. Special neonatal transport system should be designed and used for newborns of COVID-19 patients.
The transmissibility of SARS-CoV-2 through breast milk is another issue of widespread concern of health practitioners and policy makers. If breastfeeding is wrongly discouraged, years of public health efforts to promote breastfeeding could be lost. Conversely, if breastfeeding is wrongly encouraged, many infants could be put at risk. For instance, Ebola virus has been found in the breast milk of mothers in acute and convalescent phases of Ebola Virus Disease (EVD) as well as in asymptomatic mothers19. Thus, breastfeeding should not be suggested in women with EVD. Consistent with our previous results, SARS-CoV-2 was not detected in the breast milk of infected women. However, other factors such as sucking of the newborn should also be taken into account for breastfeeding. Maternal saliva, respiratory droplets and even aerosols may cause neonatal infection. Taken together, we would like to advise mothers with SARS-CoV-2 infection to squeeze milk into sterile containers under protection, and the infants should be fed by healthy family members. Direct breastfeeding in COVID-19 patients should be opposed.
We acknowledge that the significance of this study is limited by several factors. First of all, none of the enrolled patients had been infected by SARS-CoV-2 for a long time and developed severe pneumonia before delivery. Thus, it could not rule out that the placental barrier of severe ill patients with viremia might be destroyed due to inflammation as well as necrosis, and the virus may enter uterine cavity to cause fetal infection. Secondly, the outcomes of infants from patients who were infected in the first or second trimester of pregnancy remain unclear. Thirdly, the risk of intrapartum infection should be assessed with more cases of vaginal delivery. Finally, the long-term prognosis of newborns of COVID-19 patients is not known and a systematic follow-up is needed.