Discussion
We reported clinical features and perinatal outcomes from 25 pregnant women with COVID-19 including 11 in the first and second trimester and 14 in the third trimester. The common clinical characteristics were similar between the two groups. None of the patients developed critical ill pneumonia, requiring mechanical ventilation, or died of COVID-19. Notably, based on our findings, there may be a potential risk of vertical transmission in SARS-CoV-2.
According to our study, the most common onset clinical manifestations of COVID-19 in the first and second trimester group showed the typical symptoms, such as fever and cough, similar to those in the late stage of pregnancy group and reported by Liu and colleagues15, while were different from those with SARS who mainly showed fever, myalgia, chills and rigors et al11. But notably, a considerable proportion of patients are asymptomatic in both groups, similar to those of 28% (10/36) in children with COVID-19, which called “covert transmitter” and may propagate the virus transmit silently and make it more difficult to control infection16, 17. Similarly, Meng and colleagues showed abnormal CT images and clinical course of asymptomatic cases with COVID-19 at admission and highlight the vital role of CT for early detection of the highly suspicious, asymptomatic cases18. Although laboratory tests indicated that creatinine and D-Dimer were significantly higher in the third trimester group compared with the first and second trimester group, none of the patients developed critical disease or died of COVID-19. This can be well understood by complex physiological changes during pregnancy, for example, D-dimers can be increased to 50% above baseline during the third trimester19. The predominant pattern of abnormal chest CT findings observed was bilateral in both groups, which was similar to those observed in the non-pregnant patients20.
There is a theoretical risk of worse perinatal outcomes for infected pregnant women because of the unstable immune system and physiological adaptive changes, especially in the early stage of pregnancy. As showed in our study, the RNA clearance time of patients in the first and second trimester group was significantly longer than that in late pregnancy group. Additionally, take severe acute respiratory syndrome (SARS) as an example, fatality rate of 25%, Intensive Care Unit (ICU) admissions (50%) and mechanical ventilation (33%) were reported by Wong and colleagues in pregnant women compared with nonpregnant adult population11. Higher maternal mortality rate of 50% were reported during the epidemic Asian flu of 195721. However, our study reveals a case fatality rate of 0% in pregnant women with COVID-19 which is in line with those reported by Chen and colleagues10. Additionally, severe maternal complications were not observed in all women by our study. Our data do not show an increased risk of severe disease among pregnant women. The perinatal outcomes of pregnant women are more promising compared with SARS. Activation of different T-helper (Th) lymphocytes result in the different disease severity. Patients with SARS activated Th1 immunity preferentially which is proinflammatory chiefly, leading to elevation of proinflammatory cytokines, such as IL-6, a risk factor of mortality in COVID-19 patients. However, patients with COVID-19 showed activation Th2 immunity at the same time, promoting the expression of anti-inflammatory cytokines such as IL-4 and IL-102, 22, 23. The Th1-Th2 shift may contribute the lesser severity of perinatal outcomes of patients with COVID-19 compared to those with SARS.
In our study, no IUGR was observed and fetal surveillance was satisfactory during the study period. Wong and colleagues reported the spontaneous miscarriage of 57% (4/7) in pregnant women with SARS11. The higher rate of spontaneous miscarriage during the 1st trimester was probably attribute to hypoxia or maternal respiratory failure caused by SARS-related acute respiratory distress. Additionally, impact of severe maternal debilitating illness, such as renal failure, disseminated intravascular coagulopathy and cardiovascular collapse, maybe was another one reason11, 24.
There is an extremely possibility risk of vertical transmission based on our findings. Previously, no intrauterine fetal infections were reported by Chen et al10 in all nine pregnant women with COVID-19 who underwent a caesarean section during the late pregnancy, the results was similar to those showed by Zhang et al25 in a retrospective study which including 10 infants who were conceived by patients with COVID-19, all infants were negative using RT-PCR analysis of throat swabs. Little existing evidences for vertical transmission were based on positive results of IgM antibody in neonatal serum26, 27. So, more definitive evidence is needed to ascertain the possibility of intrauterine vertical transmission during pregnancy28. Cases in which both antibody and nucleic acid tests are positive have not been reported. According to our study, although the result of nasopharyngeal swab was negative, vertical transmission of SARS-CoV-2 from mother to her neonate was confirmed by the coincident positive results of anal swab and serum sample for IgG and IgM antibody against SARS-CoV-2 at one neonate. A possible reason for why nasopharyngeal swab was negative is that SARS-CoV-2 transmitted through oral–fecal route29. Because the days from onset to delivery were as long as 31days in our case, the infection had possibly shifted from oral to anal. As those reported by Zhang and colleague, the positive rate of anal swab was higher than that of oral swab in the later stage of infection30. So, the neonate may has already infected in the early stage, however, cord blood, amniotic fluid or breast milk test is needed to ascertain this deduction in the future.
There are a few limitations in our study. First, recall bias and selection bias are inevitable because of our retrospective method. Second, relatively small sample size of pregnant women with COVID-19 remind us interpret the findings cautiously. However, we believe our conclusions are valid because more results are in line with existing studies about pregnant women with COVID-19.
In conclusion, the clinical characteristics of women with COVID-19 in early and middle pregnant women were similar to those in late pregnancy, although RNA clearance time and length of stay were significantly different between the two groups. In addition, our results showed the important role of anal swab for SARS-CoV-2 in neonates for diagnosis of fecal-oral infection and the potential risk of vertical transmission in SARS-CoV-2.