Interpretation
Other studies have examined whether SARS-CoV-2 is detectable in vaginal
swabs. In contrast to our study, the majority of studies report negative
vaginal swabs for SARS-CoV-2 (1, 16-19). However, there are reports of
SARS-CoV-2 detected in vaginal swabs of both pregnant (n=3),
reproductive-aged (n=1), and post-menopausal (n=1) women, indicating
that transmission during vaginal delivery might be possible, although
the risk is likely to be low (3-6). In accordance with our findings,
other studies have also found positive placental swabs, indicating a
viral spread that is potentially either an ascending infection or
infection through the bloodstream (n=5) (3, 4, 6, 20). Other studies
have demonstrated SARS-CoV-2 in neonatal swabs of children born to women
with symptoms of COVID-19 (16, 17, 21, 22), which we did not find.
There are several potential sources for viral presence in the vagina.
The coronavirus binds to target cells through angiotensin-converting
enzyme 2 (ACE2) receptors, which are upregulated in vaginal epithelium
during pregnancy, making it possible for the virus to bind (23).
Alternatively, it is possible that SARS-CoV-2 is detected because of
exudation from the bloodstream rather than release from the epithelium
itself. Detection of SARS-CoV-2 in the vagina could also be due to fecal
or seminal contamination (15, 24).
Our study indicates that the neonate is not protected in the acute phase
of maternal COVID-19 (between 0-16 days after a positive maternal
pharyngeal swab) as there were no SARS-CoV-2 antibodies in cord blood
even though the mother had produced antibodies. However, after 16 days
94.1% of offspring had antibodies in cord blood. Other studies have
assessed the timespan between maternal SARS-CoV-2 diagnosis and the
presence of antibodies in cord blood, and a study found IgG in 11 cord
blood samples and both IgG and IgM in one case of 31 cases in total. In
one case IgG was found as early as one day after maternal SARS-CoV-2
infection (3). However, IgG is usually not detected before 1-2 weeks
after acute viral infection and the mother may therefore have been
infected several days before diagnosis. Another study found that 11
infants of 83 seropositive mothers (13%) did not have antibodies in
cord blood after a median time of six days (interquartile range 0-12
days) from diagnosis to delivery (25). This time span is shorter than we
report with a range of 0-16 days. In accordance with our study, they
found a positive correlation between the levels of maternal and
cord-blood IgG (25).
The adverse fetal outcomes of participant 5 and 6 in our study are
similar to a confirmed case of transplacental transmission of SARS-CoV-2
from Sweden, where a pregnant woman with a three-day history of COVID-19
presented with reduced fetal movements at GA 34w4d (7). After an
emergency caesarean section due to a pathological CTG the mother and
child were separated. Placental pathology was similar to the findings in
our study as well as other studies (4, 7, 26-28). Authors concluded that
the neonate had suffered from transient asphyxia attributed to
intrauterine hypoxia secondary to placental dysfunction. The case from
Sweden (7) and others (4), as well as participants 5 and 6 in our study,
suggests that reduced fetal movements during COVID-19 should be handled
with aggravated concern.
In our study, two cases did not have antibodies in neither maternal nor
umbilical cord blood (participants 25 and 26). Participant 25 had a low
CT value, but a negative pharyngeal swab four days later, while
participant 26 had no symptoms, a high CT value, and a negative
pharyngeal swab the day after testing positive. Possible explanations
could be either a false positive pharyngeal swab, a false negative
antibody tests or that the women did not have an antibody response. In
three other cases, antibodies were not detected in cord blood of
seropositive mothers, which in two of the cases was possibly due to a
short timespan from SARS-CoV-2 infection to delivery (8 and 16 days,
respectively).
In large cohort studies, the overall risk of severe neonatal outcomes as
well as neonatal infection related to maternal COVID-19 seems low (29).
However, our findings indicate that vaginal testing for SARS-CoV-2 in
women with COVID-19 within eight days before going into labour could be
considered. In case of a positive vaginal swab, mode of delivery should
be discussed with the woman as passive immunity of the neonate is not
guaranteed.