Interpretation
According to the data of 118 cases of COVID-19 pregnancy in
Wuhan2, 64% of the cases occurred during late
pregnancy, and the rate of severe disease in all patients with COVID-19
pregnancy was 8%, which was lower than the average level of the general
population (15.7%). There were no deaths reported. It has been
suggested that pregnancy might confer potential immunity. This was
consistent with our study wherein even severe COVID-19 improved after
proper treatment (Case A).
Among the three confirmed patients (Case A, B, C), only two (Case A and
C) showed elevated liver enzymes possibly because of COVID-19-related
hypoxia augmenting the inflammatory factors. Additionally, we found a
pro-inflammatory state in COVID-19 (elevated CRP and IL-6 levels). The
liver was also affected as seen from the abnormal liver function tests.
Finally, after the administration of antiviral therapy (umifenovir and
interferon atomisation) and liver supplements,liver function profile
improved.
None of the patients showed significant foetal malformation or foetal or
placental virus infection. Even Case C, which was prematurely
terminated, had crown-lump length (CRL) at 12 weeks at par with age.
Placental pathology suggest chronic placental injury, hence has the
possibility of decreasing maternal blood perfusion into the villi, thus,
hindering maternal-foetal exchange2. This may be
secondary to the hypoxic and inflammatory condition during COVID-19
affecting the placenta. Massive perivillous fibrin deposition and large
agglomeration of necrotic villi suggested placental infarction was also
found in Case B. The preterm premature rupture of membrane in Case B may
be not only due to transverse presentation but also associated with the
chronic ischemia and increased cytokines. Fortunately, only significant
placental infarction was associated with SGA
foetuses13. In the present study, although placental
damaged was noted, the outcomes of were relatively ideal. The placental
potency may be enough to overcome the villi impairment. However, if a
mother had some complications associated with placental dysfunction
(preeclampsia, fetal growth retardation, et al), COVID-19 may severely
affect the placenta and foetus and result to adverse pregnancy outcome.
These studies indicated that pregnancy with COVID-19 during the first
and second trimester may result to full recovery allowing the
continuation of pregnancy to term with good maternal and foetal
outcomes.
All the placenta tests were negative for SARS-CoV-2 nucleic acid. In our
previous study, same negative results were found in the three cases who
had COVID-19 just before delivery9. The recent study
cannot provide definite evidence to support intrauterine infection with
COVID-19.
Vertical transmission includes intrauterine infection during pregnancy,
intrapartum infection, and transmission through close contact and
breastfeeding after delivery. ACE2 is a functional receptor for
SARS-CoV-2 infection14. Theoretically, ACE2 provides
the opportunity for SARS-CoV-2 infection. SARS-CoV-2 attaches to the
cells using S protein and enter cells through binding to ACE2. It was
suggested that the distribution and expression of ACE2 may be critical
for the target organs affected by SARS-CoV-215,16. The
available evidence suggests that ACE2 is widely expressed in female
reproductive system and the maternal-foetal interface, which includes
the stromal cells and perivascular cells of decidua, cytotrophoblasts
and syncytiotrophoblasts14,17. Our results showed that
both the placenta and decidua expressed ACE2 during early pregnancy with
significantly higher levels than those during late pregnancy. However,
the histologic and real-time PCR of the placenta had the negative
results. Therefore, organs with high ACE2 expression may not always be
the target of SARS-CoV-2.
During vertical transmission, high viral loads of SARS-CoV-2 is
necessary. The placental villi may have more opportunities for
SARS-CoV-2 to enter the maternal blood allowing the virus to infect the
trophoblast cells. SARS-CoV-2 may then pass through the placental
villous lobules to enter the foetal capillaries and infect the foetus.
According to some reports, the lungs and the intestine may be major
viral target organs of SARS-CoV-218. Studies have
shown a high expression of ACE2 and TMPRSS2 in the lungs of
newborns19. This places neonates at high risk for
SARS-CoV-2 infection.
A Lamouroux et al20 reported three swabs positive for
SARS-CoV-2 in 11 placental or membrane swabs sent following delivery in
women with moderate to severe COVID-19. None of the infants tested
positive for SARS-CoV-2 on days 1 to 5 of life, and none demonstrated
COVID-19 symptoms. While there were no clinical signs of vertical
transmission, they postulated on possible intrapartum viral exposure.
For infants delivered vaginally, viral contamination may be from room
air, vaginal secretions, maternal blood, or amniotic fluid. In our
study, no virus or viral infection was found in the placenta. Wang et
al21 reported a case of positive SARS-CoV-2 throat
swab test in a newborn 36 hours after delivery. Airborne transmission
possibility after delivery cannot be excluded. The risk of neonatal
infection from postpartum exposure via respiratory secretions and close
contact should be avoided. The neonate throat swab tests and placenta
tests were negative in our cases. This reminds obstetricians that
although there is no clear evidence of intrauterine infection, careful
attention to protect the neonate from exposure to SARS-CoV-2 during and
after delivery should be observed.
In clinical studies, most of the neonates were negative of
SARS-CoV-22,4. The placenta may not be the main target
organ of SARS-CoV-2. There is no clear evidence of intrauterine
infection, which requires further study regarding the specific
mechanisms involved.