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\begin{document}

\title{Vertical Transmission of SARS-CoV-2 is Plausible During Pregnancy and
Vaginal Delivery: A Prospective Cohort Study}



\author[1]{Julie Milbak}%
\author[1]{Victoria Holten}%
\author[1]{Paul Axelsson}%
\author[1]{Jane Bendix}%
\author[2]{Anna Aabakke}%
\author[3]{Lene Nielsen}%
\author[3]{Martin Barfred Friis}%
\author[1]{Ellen Løkkegaard}%
\author[1]{Claus Jensen}%
\author[4]{Tina Olsen}%
\author[5]{Line Rode}%
\author[1]{Tine Clausen}%
\affil[1]{Nordsjaellands Hospital}%
\affil[2]{Holbaek Hospital}%
\affil[3]{Herlev Hospital}%
\affil[4]{Rigshospitalet}%
\affil[5]{Rigshospitalet Glostrup}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective: To evaluate if SARS-CoV-2 is detectable in vaginal swabs and
whether antibodies against SARS-CoV-2 are present in maternal and
umbilical cord blood of pregnant women with COVID-19. Design:
Prospective cohort study. Setting: Department of Obstetrics and
Gynaecology, Copenhagen University Hospital -- North Zealand, Denmark.
Population: Pregnant women tested positive for SARS-CoV-2 in a
pharyngeal swab between August 20th, 2020 and March 1st, 2021 who gave
birth during the same period. Methods: Maternal blood sample and vaginal
swabs were collected at inclusion. If included during pregnancy, these
samples were repeated at delivery in addition to an umbilical cord blood
sample. Swabs were analysed for SARS-CoV-2 and blood samples for
SARS-CoV-2 total antibodies. Placental and neonatal swabs were performed
on clinical indications. Main outcome measures: SARS-CoV-2 in vaginal
swabs and SARS-CoV-2 total antibodies in maternal and umbilical cord
blood. Results: We included 28 women, hereof 4 serious maternal or fetal
outcomes including 1 neonatal death. Within the first eight days after a
maternal positive pharyngeal swab, SARS-CoV-2 was detectable in two
vaginal (2/28) and two placental swabs (2/4), whereas SARS-CoV-2
antibodies were detected in 1/13 women. After eight days, SARS-CoV-2 was
not detectable in vaginal swabs and SARS-CoV-2 antibodies were observed
in 19/21 of women. Antibodies in cord blood of seropositive mothers
appeared after 16 days. Conclusion: Vertical transmission of SARS-CoV-2
seems plausible since SARS-CoV-2 is detectable in the vagina up to eight
days after a positive pharyngeal swab at which time the neonate is not
yet protected by antibodies.%
\end{abstract}%



\sloppy


\textbf{Vertical Transmission of SARS-CoV-2 is Plausible During
Pregnancy and Vaginal Delivery: A Prospective Cohort Study}

\textbf{AUTHORS}

Julie Milbak\textsuperscript{1}*, Victoria Holten\textsuperscript{1}*,
Paul Bryde Axelsson\textsuperscript{1}, Jane Marie
Bendix\textsuperscript{1}, Anna JM Aabakke\textsuperscript{2, 3}, Lene
Nielsen\textsuperscript{4}, Martin Barfred Friis\textsuperscript{4},
Claus AJ Jensen\textsuperscript{5}, Ellen Christine Leth
L\selectlanguage{ngerman}økkegaard\textsuperscript{1, 3}, Tina Elisabeth
Olsen\textsuperscript{6}, Line Rode\textsuperscript{7}, Tine Dalsgaard
Clausen \textsuperscript{1, 3}

*Shared first authorship

\textbf{AFFILIATIONS}

1. Department of Obstetrics and Gynaecology, Copenhagen University
Hospital -- North Zealand, Hillerod, Denmark

2. Department of Obstetrics and Gynaecology, Copenhagen University
Hospital -- Holbaek, Holbaek, Denmark

3. Department of Clinical Medicine, University of Copenhagen,
Copenhagen, Denmark

4. Department of Clinical Microbiology, Copenhagen University Hospital
-- Herlev and Gentofte, Herlev, Denmark

5. Department of Clinical Biochemistry, Copenhagen University Hospital
-- North Zealand, Hillerod, Denmark

6. Department of Pathology, Copenhagen University Hospital --
Rigshospitalet, Copenhagen, Denmark

7. Department of Clinical Biochemistry, Copenhagen University Hospital
-- Rigshospitalet, Glostrup, Denmark

\textbf{CORRESPONDENCE} Tine Dalsgaard Clausen, MD, PhD, Senior
Consultant, Clinical Associate Professor

Address: Department of Obstetrics and Gynaecology, Copenhagen University
Hospital -- North Zealand, Dyrehavevej 29, 3400 Hillerod, Denmark.

Telephone number: +45 22 81 13 33.

E-mail: tine.clausen@regionh.dk

\textbf{RUNNING TITLE}

Maternal vertical transmission of SARS-CoV-2 is plausible

\textbf{WORD COUNT:}

Introduction (max 400 words): 338 words

Discussion and conclusion (max 1200 words): 1200 words

Manuscript (max 3500 words): 3418 words

\textbf{ABSTRACT}

\textbf{Objective:} To evaluate if SARS-CoV-2 is detectable in vaginal
swabs and whether antibodies against SARS-CoV-2 are present in maternal
and umbilical cord blood of pregnant women with COVID-19.

\textbf{Design:} Prospective cohort study.

\textbf{Setting:} Department of Obstetrics and Gynaecology, Copenhagen
University Hospital -- North Zealand, Denmark.

\textbf{Population:} Pregnant women tested positive for SARS-CoV-2 in a
pharyngeal swab between August 20\textsuperscript{th}, 2020 and March
1\textsuperscript{st}, 2021 who gave birth during the same period.

\textbf{Methods:} Maternal blood sample and vaginal swabs were collected
at inclusion. If included during pregnancy, these samples were repeated
at delivery in addition to an umbilical cord blood sample. Swabs were
analysed for SARS-CoV-2 and blood samples for SARS-CoV-2 total
antibodies. Placental and neonatal swabs were performed on clinical
indications.

\textbf{Main outcome measures:} SARS-CoV-2 in vaginal swabs and
SARS-CoV-2 total antibodies in maternal and umbilical cord blood.

\textbf{Results:} We included 28 women, hereof 4 serious maternal or
fetal outcomes including 1 neonatal death. Within the first eight days
after a maternal positive pharyngeal swab, SARS-CoV-2 was detectable in
two vaginal (2/28) and two placental swabs (2/4), whereas SARS-CoV-2
antibodies were detected in 1/13 women. After eight days, SARS-CoV-2 was
not detectable in vaginal swabs and SARS-CoV-2 antibodies were observed
in 19/21 of women. Antibodies in cord blood of seropositive mothers
appeared after 16 days.

\textbf{Conclusion:} Vertical transmission of SARS-CoV-2 seems plausible
since SARS-CoV-2 is detectable in the vagina up to eight days after a
positive pharyngeal swab at which time the neonate is not yet protected
by antibodies.

\textbf{Funding:} The Research Foundation, North Zealand Hospital and
Ferring

\textbf{Keywords} : Severe acute respiratory syndrome coronavirus 2;
COVID-19; Obstetric delivery; Pregnancy complications; Pregnancy
outcome; Placental dysfunction; Vertical transmission; Cohort studies;
Prospective studies

\textbf{Tweetable abstract:} Vertical transmission of SARS-CoV-2 is
plausible within the first week of maternal COVID-19.

\textbf{ABBREVIATIONS}

BMI: Body Mass Index

CTG: cardiotocography

COVID-19: Coronavirus disease 2019

NICU: Neonatal Intensive Care Unit

SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2

\textbf{INTRODUCTION}

Whether vertical transmission of SARS-CoV-2 from mother to child may
occur during maternal infection in pregnancy is still unclear (1, 2).
Possible mechanisms of prenatal transmission between mother and child
include transplacental transmission and ascending infection from the
vagina through the cervix. Intrapartum and postpartum transmission might
happen through fetal ingestion or aspiration of vaginal and fecal
secretions during vaginal delivery, through respiratory droplets, or
breast feeding (1). Few studies have detected SARS-CoV-2 in vaginal
secretions (3-6). A recent case report from Sweden found evidence of
transplacental vertical transmission of SARS-CoV-2 in gestational week
35 (7).

The presence of antibodies in fetal blood might offer protection of the
fetus and child against COVID-19 during pregnancy, vaginal delivery, and
in the neonatal period. SARS-CoV-2 total antibodies have been detected
in less than 40\% of non-pregnant individuals within the first week
after infection (8). One study showed that the SARS-CoV-2 antibody titre
remained stable from infection in the first trimester until delivery,
but the exact timing of maternal seroconversion was not investigated
(9). Other studies have examined the presence of SARS-CoV-2 antibodies
at delivery in blood samples from the umbilical cord or the offspring of
mothers with COVID-19. Some found anti-SARS-CoV-2 IgG, others both IgM
and IgG (3, 10, 11). Since IgG is the only antibody class that
significantly crosses the placenta, findings of IgM in cord blood
indicates in utero infection, while IgM in neonates could be caused by
in utero infection as well as postnatal infection. Additionally, the
timespan between maternal SARS-CoV-2 diagnosis and the presence of
antibodies in umbilical cord has been assessed, however, findings have
been ambiguous (3). Together, previous studies may indicate that the
risk of vertical transmission is increased if the woman delivers less
than one week from onset of infection.

The objective of this study was to investigate if SARS-CoV-2 is
detectable in vaginal swabs of pregnant women diagnosed with COVID-19
and to study the presence and timing of SARS-CoV-2 antibodies in
maternal and umbilical cord blood during and after COVID-19 in
pregnancy.

\textbf{METHOD}

During the second wave of the COVID-19 pandemic in Denmark, we conducted
a prospective cohort study entitled the ``CareMum COVID-19 study'' from
August 20\textsuperscript{th}, 2020 to March 1\textsuperscript{st},
2021, at the Department of Obstetrics and Gynaecology, Copenhagen
University Hospital -- North Zealand with approximately 4000 annual
deliveries.

We included pregnant women who tested positive for SARS-CoV-2 in a
pharyngeal swab at a test centre or during a routine test when entering
the antenatal clinic or labour ward. Women were eligible if they were to
deliver within the study period and were able to give written and oral
informed consent in English or Danish. Inclusion took place either
during pregnancy at the antenatal clinic or when women were admitted for
delivery. All participants had vaginal swabs and maternal blood samples
done at the time of inclusion. If included during pregnancy, the samples
were repeated at delivery where an umbilical cord blood sample was also
taken. At the time of delivery, two vaginal swabs were done -- the
first, during the initial vaginal examination, and the second, during
the active phase of delivery or immediately after. Vaginal swabs were
frozen at -20°C until analysis (0-30 days, median 5 days). A maternal
blood sample was taken just before or immediately after delivery, and an
umbilical cord blood sample was performed immediately after birth. Blood
samples were frozen at -80°C until analysis.

In some cases, swabs from the neonate and the placenta, as well as a
placental histopathological examination and one fetal autopsy, was
performed on clinical indications. Placental swabs were done from both
the maternal and the fetal side, and neonatal swabs from the axillary
fold, naso-, and oropharynx. These samples were not part of the study
protocol, but results are described when present.

Pharyngeal swabs as well as vaginal and placental swabs were analysed by
RT-PCR as part of the routine diagnostics (see supporting information,
appendix S1, for further information).

Total SARS-CoV-2 antibodies in maternal and cord blood samples were
analysed using a qualitative (reactive/non-reactive) biochemical assay,
The VITROS Immunodiagnostic Product Anti-SARS-CoV-2 Total (CoV2T),
developed by Ortho-Clinical Diagnostics. The test result (S/C) = (signal
for test sample / signal at cutoff value) \selectlanguage{english}[?] 1.00 is considered reactive
(i.e. positive for antibodies) and result \textless{} 1.00 is considered
non-reactive (i.e. negative for antibodies).

We obtained demographic and clinical data of participants as well as
non-participants in the ``CareMum COVID-19 study'' from the Danish
``COVID-19 in pregnancy'' database, which contains information based on
medical records on all women diagnosed with COVID-19 during pregnancy in
Denmark as described elsewhere (12). Non-participants were women who
tested positive for SARS-CoV-2 and gave birth within the study period
but who for various reasons were not included in this study (e.g. women
did not understand and read Danish/English, did not want to participate
or were not asked due to busyness at the maternity ward). Case
completeness was secured by a retrospective registry linkage to national
databases covering information on results from SARS-CoV-2 pharyngeal
swabs. Furthermore, participants were asked to complete a questionnaire
about COVID-19 symptoms at the time of inclusion. Symptoms of
non-participants were not systematically reported. ~\textbf{~}

Data was analysed using SPSS version 27 (SPSS Inc., Chicago, IL).
Categorical variables are presented as number with percentage and
continuous variables as mean with standard deviation (SD) or median with
interquartile range as appropriate. Analyses of differences between
means, medians and proportions were performed using Student's T-test,
Mann-Whitney, or Fischer's Exact test, respectively. The study was
approved by The Regional Committee on Health Research Ethics.

\textbf{RESULTS}

We included 28 of 36 (77.8\%) women, who had SARS-CoV-2 positive
pharyngeal swabs during pregnancy in the study period. Three
participants were not tested by RT-PCR. Participant 6 was tested by a
nasopharyngeal antigen-test, and participants 16 and 18 were tested at a
private test centre. Participants and non-participants did not differ
regarding baseline characteristics (table 1). Twenty-two participants
(78.6\%) were included at delivery (table 2), while six participants
were included and examined during pregnancy with examinations repeated
at delivery (table 3). Participants tested positive for SARS-CoV-2 by a
pharyngeal swab between gestational age (GA) 25 weeks (w) and 0 days (d)
to 41w4d, and the onset of symptoms was reported from 16 days before and
until three days after the positive swab.

Vaginal swabs were obtained from all participants, and SARS-CoV-2 was
detected in 2 of 28 cases -- at one and eight days, respectively, after
the positive pharyngeal swab (7.1\%). One vaginal swab test was
inconclusive. No positive vaginal swabs were found during vaginal
delivery, independently of the timing with onset of symptoms or a
positive pharyngeal swab (table 2 and 3).

Maternal antibodies were analysed in 28 women (table 2 and 3). Within 8
days of a positive pharyngeal swab, SARS-CoV-2 antibodies were detected
in only 1 (participant 6, table 2) of 13 women (7.7\%). Whereas,
antibodies were observed in 19 of 21 (90.5\%) women who had a positive
pharyngeal swab more than 8 days prior to the antibody test (table 2 and
3). Two women had no antibody response in blood samples at day 57 and 74
days after infection, respectively (participants 25 and 26).

Antibodies were analysed in 25 umbilical cord blood samples. Antibodies
were not detected in umbilical cord blood from pregnancies where the
woman delivered within 16 days of a SARS-CoV-2 positive pharyngeal swab
(n=7). However, antibodies were present in 16 of 17 (94.1\%) cord blood
samples of pregnancies where the woman was seropositive and delivered
more than 16 days after infection (table 2 and 3). The test results
(S/C) of antibodies in maternal and cord blood at delivery were highly
correlated (figure S3, R\textsuperscript{2}=0.64, p\textless{}0.00005).
There was a positive correlation between the test results (S/C) for
antibodies in cord blood and the number of days from SARS-CoV-2 positive
pharyngeal swab to delivery (figure S4, R\textsuperscript{2}=0.43,
p=0.002), whereas the correlation between the test result (S/C) for
antibodies in maternal blood and the number of days between diagnosis
and delivery was not statistically significant (figure S4,
R\textsuperscript{2}=0.20, p=0.054). Three cord blood samples from
children of nineteen seropositive mothers were without detectable
antibodies (15.8\%, participants 6, 8 and 10).

\textbf{Samples performed on clinical indication (table S1)}

\emph{Placental swabs}

Placental swabs were done on clinical indication in four cases (Table 2
and S1, participants 3, 4, 5 and 6). SARS-CoV-2 was detected in two
cases (participants 5 and 6), both of which had adverse fetal outcomes
(described in details below).

\emph{Placental pathology}

Two placental histopathological examinations and one fetal autopsy were
performed which are described below (participants 5 and 6).

\emph{Neonatal swabs and neonatal COVID-19}

Swabs from the neonates were done in two cases (participants 4 and 6).
Neither were positive for SARS-CoV-2 and overall, no children were
diagnosed with COVID-19 after birth.

\textbf{Clinical outcomes and complications in pregnancies with
COVID-19}

Participant 5 was diagnosed with SARS-CoV-2 at GA 29w1d. She presented
at the antenatal ward at GA 29w6d with reduced fetal movements and
vaginal bleeding. The neonate was delivered the same day by emergency
caesarean section due to a pathological cardiotocography (CTG) and was
born small for gestational age (birth weight 1235 g, Z-score -1.87).
APGAR was 8 after 5 minutes and umbilical cord blood with respiratory
compensated metabolic acidosis (arterial pH 7.23, Base Excess -10.4 and
venous pH 7.33, Base Excess -12.0). Microscopic examination of the
placenta showed severe acute and chronic intervillositis with necrosis
of the trophoblast (Figure S1). Swabs from the fetal side of the
placenta were positive for SARS-CoV-2. The results of the vaginal swabs
were inconclusive. The neonate was admitted to NICU for 40 days. The
mother had a complicated puerperal period with fever, fatigue, and
diarrhea. Yersinia enterocolitica was found in a maternal fecal sample.
Bacterial culture from the placenta was negative. SARS-CoV-2 antibodies
were not detected in either maternal or in cord blood. Eleven weeks
after delivery, anti-cardiolipin antibodies were found associated with
an increased risk of arterial and venous thrombosis. The findings could
be consistent with intrauterine SARS-CoV-2 infection, but bacterial
infection could not be ruled out.

Participant 6 tested positive for SARS-CoV-2 at GA 31w2d. Her partner
was tested positive the same day. She presented at the antenatal ward at
32w0d with a reduction in fetal movements but was discharged after a
normal CTG. At 32w3d, she presented with contractions. The neonate was
delivered shortly after by emergency caesarean section due to a
preterminal CTG with APGAR 0 after 5 minutes and arterial pH 6.82, Base
Excess -17.5 and venous pH 6.85, Base Excess -17.2. Birth weight was
2000 g and Z-score -0.29. One hour after delivery, the neonate was
declared dead after a prolonged neonatal resuscitation attempt. Autopsy
of the neonate showed no malformations, but signs of asphyxia from
petechiae and meconium aspiration. In addition, there was some
histologic evidence of acute thymic involution and adrenal
stress-related changes, but no signs of prolonged intrauterine stress or
growth restriction. Microscopic examination of the placenta showed
severe abnormality with acute and chronic intervillositis and abundant
perivillous fibrin deposits comprising 70\% of the parenchyma (Figure
S2). SARS-CoV-2 was detected in the vaginal swab at delivery and in
swabs from both the fetal and maternal side of the placenta. Neonatal
swabs were SARS-CoV-2 negative. The mother tested positive for
SARS-CoV-2 antibodies while umbilical cord blood tested negative. Blood
and urine culture at the time of delivery were negative. The placental
findings, potentially linked to intrauterine SARS-CoV-2 infection were
likely to have caused the fatal fetal outcome.

Participant 27 was diagnosed with gestational diabetes mellitus at GA
13w0d. She tested positive for SARS-CoV-2 at GA 27w2d and was
hospitalized at GA 28w0d due to COVID-19. During the admission, she was
diagnosed with three segmental lung embolisms and a secondary pneumonia
was suspected. She was treated with Low Molecular Weight Heparins,
Remdesivir, antibiotics, and prednisolone. Vaginal swabs analysed for
SARS-CoV-2 were negative. She gave birth by an uncomplicated planned
caesarean section at GA 38w0d. During admission, no antibodies were
detected in maternal blood eight days after the SARS-CoV-2 positive
pharyngeal swab, whereas at delivery, 75 days after the initial
infection, SARS-CoV-2 antibodies were detectable in both maternal and
cord blood samples.

Participant 28 presented at the antenatal ward at GA 24w5d with vaginal
bleeding and at GA 25w1d with symptoms of deep vein thrombosis of the
femoral vein, which was confirmed by ultrasound. She started treatment
with Low Molecular Weight Heparin. The vaginal bleeding was derived from
a varicose vein in the left labium minor. Eleven days later (GA 26w5d),
she contacted the Emergency Department due to shortness of breath and
vomiting. There was no suspicion of pulmonary embolism or severe
COVID-19. She tested positive for SARS-CoV-2 by a pharyngeal swab and
was admitted for two days. At day one after the positive pharyngeal
swab, two vaginal swabs were positive for SARS-CoV-2, but no maternal
antibodies were detected.~Blood culture and urine culture taken after
admission to the hospital with COVID-19 were negative. She gave birth by
an uncomplicated planned caesarean section at GA 38w5d. On day 16 and 37
after the positive swab and at delivery (day 84), SARS-CoV-2 antibodies
were detected in maternal blood samples. At delivery, antibodies were
also detected in cord blood.

Besides the abovementioned four severe cases, a few other complications
were found among participants during pregnancy and delivery (table 1).

\textbf{DISCUSSION}

\textbf{Main Findings}

SARS-CoV-2 was detected in vaginal swabs of two pregnant women with
COVID-19 and in placental swabs of two severe fetal cases after maternal
COVID-19. Within the first eight days of a positive pharyngeal swab,
SARS-CoV-2 antibodies were detected in only 7.7\% of the women, while
SARS-CoV-2 antibodies were observed in 90.5\% women tested more than
eight days after a positive swab. Antibodies in umbilical cord blood
were not detected within the first 16 days after the mother was tested
positive, hereafter, antibodies were present in 94.1\% of cord blood
samples of seropositive mothers. We observed two severe fetal outcomes
both associated with maternal admittance due to reduced fetal movements,
pathological or preterminal CTG, delivery by emergency preterm caesarean
section, and abnormal placental histopathological examinations.

\textbf{Strengths and limitations~}

The prospective design is a strength of our study. Participants were
compared with all non-participants by a retrospective registry linkage,
enabling us to examine whether participants were representative of all
pregnant women with COVID-19 at the index hospital during the study
period. Additionally, tests for SARS-CoV-2 in Denmark are free of charge
and performed at public test centres reporting the results to national
databases, which reduced the number of undetected cases of COVID-19.
Finally, we used a serological assay with a high diagnostic accuracy
with a sensitivity of 95.3\% and a specificity of 100\% (13).

The study has several limitations. We included 77.8\% of eligible women.
However, participants and non-participants did not differ with regards
to background characteristics. We had no samples from mothers or cord
blood between eight and 16 days after a positive maternal pharyngeal
swab, entailing the exact timing of seroconversion among pregnant women
with COVID-19 unknown. Further, most vaginal swabs were kept at
-20\selectlanguage{english}\textsuperscript{*}C until analysis, possibly causing a deterioration
of SARS-CoV-2 during storage, decreasing our ability to detect
SARS-CoV-2 in the vaginal samples. However, a previous study found that
SARS-CoV-2 RNA was stable when stored at -20degC for up to 84 days (14).
Lack of infection status from the participants' partners is a
limitation, since it is not fully evaluated whether SARS-CoV-2 can be
transmitted through semen and cause detection of SARS-CoV-2 in the
vagina (15). We measured total antibodies and did not discriminate
between IgG and IgM. Finally, three participants were not tested by
pharyngeal RT-PCR (one by an antigen-test and two at private test
centres), thus exact details about analysis methods are lacking.
However, the participants were positive for SARS-CoV-2 antibodies.

\textbf{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.

\textbf{CONCLUSION}

Vertical transmission of SARS-CoV-2 during vaginal delivery seems rare,
but is plausible within the first week of infection, since SARS-CoV-2 is
detectable in the vagina and antibodies do not yet protect the neonate
at this time. Further, maternal COVID-19 may in rare cases cause
intrauterine infection and fetal asphyxia due to placental dysfunction.
We propose that reduced fetal movements in pregnancies affected by
COVID-19 should be handled with aggravated concern.

\textbf{Acknowledgements}

We would like to thank the participating women as well as the midwives
and other staff at the Department of Obstetrics and Gynaecology,
Copenhagen University Hospital -- North Zealand for their kind help and
collection of samples.

\textbf{Disclosure of Interests~}

None of the authors have any conflicts of interest to declare.

\textbf{Contribution to Authorship}

TDC, PBA, JMB, and EL designed the study. TDC applied for the ethical
approval. JM and VH recruited the participants and collected the
samples. LR was responsible for analysis of anti-SARS-CoV-2 in blood
samples. CJ was responsible for the initial handling of blood samples.
AA was responsible for providing baseline data on participants as well
as non-participants. TEO performed the pathological examination. LN and
MF were responsible for analysis of swabs for SARS-CoV-2. JM and VH
wrote the first draft of the manuscript with subsequent amendments by
all authors, who also approved the final version.

\textbf{Details of Ethics Approval}

The Regional Committee on Health Research Ethics in the capital region
of Denmark approved the study on May 3\textsuperscript{rd}, 2020 with an
additional protocol approved November 17\textsuperscript{th}, 2020
(H-20028002). Written informed consent was collected from all
participants before inclusion in the study. Furthermore, a written
informed consent for publication was obtained from participant 5, 6, 27,
and 28. Demographic and clinical data of participants as well as
non-participants were extracted from the prospective national
observational study ``COVID-19 in pregnancy'', which was approved by the
Danish Patient Safety Authority on April 24\textsuperscript{th}, 2020
(reg. no. 31-1521-252) and the regional Data Protection Agency in Region
Zealand on March 23\textsuperscript{rd}, 2020 (reg. no. REG022-2020).

\textbf{Funding}

The Research Foundation at North Zealand Hospital, Hillerod and Ferring
Pharmaceuticals funded parts of the study. The Department of Clinical
Biochemistry at North Zealand Hospital, Hillerod and Rigshospitalet
Glostrup covered the expenses for analysis of blood samples. The funding
sources had no influence on the study design, data collection, analysis
and interpretation of data, preparation of the manuscript or decision to
submit the paper.

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\textbf{TABLE CAPTION LIST}

\textbf{Table 1} : Baseline characteristics (demographic and clinical
presentation)

\textbf{Table 2} : Pregnant women tested positive for SARS-CoV-2 during
pregnancy or delivery - data sampled at delivery only

\textbf{Table 3} : Pregnant women tested positive for SARS-CoV-2 during
pregnancy - data sampled at diagnosis as well as at delivery

\textbf{SUPPORTING INFORMATION}

\textbf{Appendix S1:} Method description regarding RT-PCR analysis of
swabs for SARS-CoV-2

\textbf{Figure S1} : Placental pathology, participant 5. (A) Transected
placenta, cut surface with patchy white fibrin deposit. (B) Acute and
chronic intervillositis with necrosis of the trophoblast layer (black
arrow) accompanied by fibrin deposits (white arrow). H\&E.

\textbf{Figure S2} : Placental pathology, participant 6. (A) Transected
placenta, cut surface with multiple white areas of confluent fibrin
deposits (white arrows). (B) Acute and chronic intervillositis (black
arrow) accompanied by abundant fibrin deposits (white arrow). H\&E.

\textbf{Figure S3:} Correlation between maternal and umbilical cord
blood test result (S/C) for total antibodies. Mothers non-reactive for
antibodies are excluded. Mother-infant pairs, where the umbilical cord
blood sample was missing, are excluded.

\textbf{Figure S4:} Test result (S/C) for total antibodies in maternal
and umbilical cord blood and the number of days between diagnosis and
delivery. Mothers non-reactive for antibodies are excluded.
Mother-infant pairs, where the umbilical cord blood sample was missing,
are excluded.

\textbf{Table S1:} Samples performed at delivery on clinical indications

\textbf{Table 1: Baseline characteristics (demographic and clinical
presentation)}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& \textbf{Participants (n=28)} & \textbf{Non-participants (n=8)} &
\textbf{P-value}\tabularnewline
\midrule
\endhead
\textbf{Maternal age (years)} & 30.0 (\selectlanguage{ngerman}±4.5) & 30.0 (\selectlanguage{ngerman}±7.9) &
0.99\tabularnewline
\textbf{Pre-pregnancy BMI (kg/m\textsuperscript{2})} & 24.25 (20.8;28.2)
& 27.93 (20.5;30.1) & 0.54\tabularnewline
\textbf{Current smoker} & 2 (7.1) & 0 & 1.00\tabularnewline
\textbf{Parity, nulliparous} & 11 (39.3) & 3 (37.5) &
1.00\tabularnewline
\textbf{Ethnicity, Caucasian} & 15 (53.6) & 4 (50.0) &
1.00\tabularnewline
\textbf{Pre-existing medical disorders*} & 7 (25.0) & 2 (25.0) &
1.00\tabularnewline
\textbf{Presenting symptoms} & \textbf{Presenting symptoms} &
\textbf{Presenting symptoms} & \textbf{Presenting
symptoms}\tabularnewline
Headache & 18 (64.3) & &\tabularnewline
Cough & 19 (67.9) & &\tabularnewline
Sore throat & 16 (57.1) & &\tabularnewline
Nasal congestion & 18 (64.3) & &\tabularnewline
Muscle soreness & 11 (39.3) & &\tabularnewline
Fever & 16 (57.1) & &\tabularnewline
Anosmia & 13 (46.4) & &\tabularnewline
Dyspnoea & 7 (25.0) & &\tabularnewline
Diarrhoea & 4 (14.3) & &\tabularnewline
Asymptomatic & 4 (14.3) & &\tabularnewline
\textbf{Maternal admission due to COVID-19} & \textbf{Maternal admission
due to COVID-19} & \textbf{Maternal admission due to COVID-19} &
\textbf{Maternal admission due to COVID-19}\tabularnewline
Medical ward & 3 (10.7) & 0 & 1.00\tabularnewline
ICU & 0 & 0 &\tabularnewline
\textbf{Pregnancy complications} & \textbf{Pregnancy complications} &
\textbf{Pregnancy complications} & \textbf{Pregnancy
complications}\tabularnewline
Gestational hypertension & 1 (3.6) & 0 & 1.00\tabularnewline
Preeclampsia & 0 & 1 (12.5) & 0.22\tabularnewline
Deep venous thrombosis & 1 (3.6) & 0 & 1.00\tabularnewline
Pulmonary embolism & 1 (3.6) & 0 & 1.00\tabularnewline
Gestational diabetes mellitus & 2 (7.1) & 1 (12.5) & 0.54\tabularnewline
\textbf{Delivery mode} & \textbf{Delivery mode} & \textbf{Delivery mode}
& \textbf{Delivery mode}\tabularnewline
Vaginal delivery & 19 (67.9) & 4 (50.0) & 0.42\tabularnewline
Vaginal, vacuum extraction & 1 (3.6) & 0 & 1.00\tabularnewline
Elective caesarean section & 4 (14.3) & 1 (12.5) & 1.00\tabularnewline
Acute caesarean section & 4 (14.3) & 3 (37.5) & 0.17\tabularnewline
\textbf{Perinatal outcomes} & \textbf{Perinatal outcomes} &
\textbf{Perinatal outcomes} & \textbf{Perinatal outcomes}\tabularnewline
GA (days) & 280.0 (269.8;285.8) & 269.5 (259.6;280.0) &
0.19\tabularnewline
Preterm delivery (\textless{} 37+0 weeks) & 2 (7.1) & 1 (12.5) &
0.54\tabularnewline
Offspring gender (girl) & 16 (57.1) & 4 (50.0) & 1.00\tabularnewline
Birth weight (Z-score) & -0.10 (-0.8;0.5) & -0.73 (-1.7;0.0) &
0.17\tabularnewline
Artery pH \textless{} 7.1 & 1 (4.5) & 0 & 1.00\tabularnewline
Apgar (5 min) \textless{} 7 & 1 (3.6) & 0 & 1.00\tabularnewline
NICU & 3 (10.7) & 2 (25.0) & 0.31\tabularnewline
Neonatal death & 1 (3.6) & 0 & 1.00\tabularnewline
\bottomrule
\end{longtable}

*Essential hypertension (n=1), Factor V Leiden mutation (n=1),
beta-thalassemia (n=1), hypothyroidism (n=3), PCOS (n=1), depression
(n=2).

Data presented as means (\selectlanguage{ngerman}±SD), medians (25;75\% percentiles) or
proportions (\%). For some of the variables, proportions are changing
because of missing data. Differences between means, medians and
proportions were analysed by Student's T-test, Mann-Whitney or Fischer's
Exact test, respectively. BMI: Body Mass Index. ICU: Intensive Care
Unit. GA: gestational age. NICU: Neonatal Intensive Care Unit.

\textbf{Table 2: Pregnant women tested positive for SARS-CoV-2 during
pregnancy or delivery - data sampled at delivery only}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
\textbf{Pt} & \textbf{Data sampled at delivery} & \textbf{Data sampled
at delivery} & \textbf{Data sampled at delivery} & \textbf{Data sampled
at delivery} & \textbf{Data sampled at delivery} & \textbf{Data sampled
at delivery} & \textbf{Data sampled at delivery} & \textbf{Data sampled
at delivery}\tabularnewline
& \textbf{Days between SARS-CoV-2 positive pharyngeal swab and delivery}
& \textbf{SARS-CoV-2 positive pharyngeal swab (GA)} & \textbf{Onset of
symptoms (GA)} & \textbf{Delivery (GA)} & \textbf{Mode of delivery
(VD/CS)} & \textbf{Vaginal swabs for SARS-CoV-2*} & \textbf{Total
antibodies (Test result (S/C))} & \textbf{Total antibodies (Test result
(S/C))}\tabularnewline
& & & & & & & \textbf{Maternal} & \textbf{Umbilical cord}\tabularnewline
1 & 0 & 38w1d & No symptoms & 38w1d & VD & -/-** & \textless{}1.00 &
N/A\tabularnewline
2 & 1 & 37w5d & 36w2d & 37w6d & VD & -/- & \textless{}1.00 &
\textless{}1.00\tabularnewline
3 & 1 & 41w0d & 41w1d & 41w1d & E-CS & -/- & \textless{}1.00 &
\textless{}1.00\tabularnewline
4 & 1 & 41w4d & 41w2d & 41w5d & VD & -/- & \textless{}1.00 &
\textless{}1.00\tabularnewline
5 & 5 & 29w1d & 29w4d & 29w6d & E-CS & Inconclusive & \textless{}1.00 &
\textless{}1.00\tabularnewline
6 & 8 & 31w2d & 31w0d & 32w3d & E-CS & +*** & 9 &
\textless{}1.00\tabularnewline
7 & 8 & 39w3d & 39w3d & 40w4d & VD & -/- & \textless{}1.00 &
\textless{}1.00\tabularnewline
8 & 16 & 38w6d & N/A & 41w1d & VD & -/- & 3 &
\textless{}1.00\tabularnewline
9 & 30 & 35w5d & 35w5d & 41w0d & VD & -/- & 24 & 16\tabularnewline
10 & 30 & 36w5d & 35w5d & 41w0d & VD & -/- & 2 &
\textless{}1.00\tabularnewline
11 & 35 & 35w3d & N/A & 40w3d & VD & -/- & 8 & 7\tabularnewline
12 & 38 & 31w4d & 32w2d & 37w0d & VD & -/- & 95 & 31\tabularnewline
13 & 51 & 34w5d & 34w5d & 41w3d & VD & -/- & 45 & 79\tabularnewline
14 & 61 & 31w4d & 31w3d & 40w2d & VD & -/- & 4 & 2\tabularnewline
15 & 63 & 30w0d & 30w0d & 39w0d & VD & -/- & 20 & 20\tabularnewline
16 & 64 & 30w5d & 30w5d & 39w6d & VD & -/- & 14 & 20\tabularnewline
17 & 66 & 30w4d & N/A & 40w0d & VD & -/- & 34 & 31\tabularnewline
18 & 69 & 30w6d & 30w5d & 40w5d & E-CS & -/- & 11 & N/A\tabularnewline
19 & 79 & 28w5d & 28w6d & 40w0d & E-CS & -/- & 73 & 115\tabularnewline
20 & 86 & 26w0d & 26w0d & 38w2d & VD & -/- & 13 & 13\tabularnewline
21 & 91 & 26w6d & 26w4d & 39w6d & E-CS & -/- & 42 & 134\tabularnewline
22 & 102 & 25w0d & No symptoms & 39w4d & VD & -/- & 124 &
522\tabularnewline
\bottomrule
\end{longtable}

Abbreviations: CTG: cardiotocography; CS: cesarean section; GA:
gestational age; w: weeks; d: days; VD: vaginal delivery; E-CS:
emergency cesarean section; Pt: Participant; SARS-CoV-2: Severe acute
respiratory coronavirus-2; SGA: small for gestational age; N/A: not
available. Results of swabs analysed for SARS-CoV-2 are shown as ``+''
for a positive result and ``-`` for a negative result. Test result (S/C)
= (signal for test sample / signal at cutoff value) [?] 1.00 is considered
reactive (i.e. positive for antibodies) and result \textless{} 1.00 is
considered non-reactive (i.e. negative for antibodies). * = If emergency
cesarean section, then two vaginal swabs were performed at an initial
vaginal examination and immediately before/after the emergency CS
respectively. If vaginal delivery then two vaginal swabs were performed,
one before an initial vaginal examination and one during the active
phase of delivery or immediately after, respectively. ** = Vaginal swabs
performed 1 day postpartum. *** = only one vaginal swab was performed
due to E-CS.

\textbf{Table 3: Pregnant women tested positive for SARS-CoV-2 during
pregnancy - data sampled at diagnosis as well as at delivery}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllllll@{}}
\toprule
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Pt}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled during pregnancy}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled during pregnancy}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled during pregnancy}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled during pregnancy}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled during pregnancy}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled at delivery}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled at delivery}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled at delivery}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled at delivery}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled at delivery}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Data sampled at delivery}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Days between SARS-CoV-2 positive pharyngeal swab and sampled
data}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{SARS-CoV-2 positive pharyngeal swab (GA)}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Onset of symptoms (GA)}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Vaginal swabs for SARS-CoV-2*}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Maternal total antibodies} \textbf{(test result (S/C))}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Days between SARS-CoV-2 positive pharyngeal swab and
delivery}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Delivery (GA)}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Mode of delivery (VD/CS)}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Vaginal swab for SARS-CoV-2**}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Total antibodies} \textbf{(Test result (S/C))}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Total antibodies} \textbf{(Test result (S/C))}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Maternal}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textbf{Umbilical cord}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
23\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
37w1d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
No symptoms\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textless{}1.00\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
26\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
40w6d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
VD\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
7\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
24\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
35w6d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
35w6d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textless{}1.00\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
34\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
40w5d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
VD\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
10\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
25\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
31w0d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
28w4d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textless{}1.00\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
57\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
39w1d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
VD\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textless{}1.00\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textless{}1.00\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
26\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
28w3d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
No symptoms\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textless{}1.00\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
74\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
39w0d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
VD\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
N/A\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textless{}1.00\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
N/A\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
27\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
8\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
27w2d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
27w4d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textless{}1.00\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
75\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
38w0d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
P-CS\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
250\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
290\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
28\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
26wd5\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
26w4d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
+/+\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\textless{}1.00\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
84\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
38w5d\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
P-CS\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\emph{-/-}\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
484\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
463\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
16\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
42\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
37\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
-/-\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
158\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.06\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Abbreviations: GA: gestational age; w: week; d: days; VD: vaginal
delivery; P-CS: planned cesarean section; Pt: Participant; SARS-CoV-2:
Severe acute respiratory coronavirus-2; N/A: not available. Results of
swabs analysed for SARS-CoV-2 are shown as ``+'' for a positive result
and ``-`` for a negative result. Test result (S/C) = (signal for test
sample / signal at cutoff value) [?] 1.00 is considered reactive (i.e.
positive for antibodies) and result \textless{} 1.00 is considered
non-reactive (i.e. negative for antibodies). * = Two vaginal swabs
performed at the same time. **= If planned cesarean section, the vaginal
swabs were performed immediately before and after CS. If vaginal
delivery, two vaginal swabs were performed, one before an initial
vaginal examination and one during the active phase of delivery or
immediately after, respectively.

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