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.