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\begin{document}

\title{Case report of COVID-19 in pregnancy and viral presence in the vagina --
recommendations for obstetric practice}



\author[1]{Paul Axelsson}%
\author[1]{Ellen Løkkegaard}%
\author[1]{Victoria Holten}%
\author[1]{Julie Milbak}%
\author[2]{Jane Bendix}%
\author[3]{Line Rode}%
\author[4]{Tine Clausen}%
\affil[1]{Nordsjællands Hospital}%
\affil[2]{Nordsjaellands Hospital, Hillerod; University of Copenhagen}%
\affil[3]{Rigshospitalet Glostrup}%
\affil[4]{Department of Gynecology and Obstetrics, University of Copenhagen, Nordsjaellands Hospital, Hillerod, Denmark}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\textbf{Title page}

\textbf{Title:} ''Case report of COVID-19 in pregnancy and viral
presence in the vagina -- recommendations for obstetric practice''

\textbf{Authors:}

\begin{enumerate}
\tightlist
\item
  Paul Bryde Axelsson, Dyrehavevej 29, 3400 Hiller\selectlanguage{ngerman}ød, Denmark,
  Department of Gynaecology and Obstetrics Nordsjællands Hospital
  Hillerød
\item
  Ellen Christine Leth Løkkegaard, Dyrehavevej 29, 3400 Hillerød,
  Denmark, Department of Gynaecology and Obstetrics Nordsjællands
  Hospital Hillerød
\item
  Victoria Maria Foldbjerg Holten, Dyrehavevej 29, 3400 Hillerød,
  Denmark, Department of Gynaecology and Obstetrics Nordsjællands
  Hospital Hillerød
\item
  Julie Milbak, Dyrehavevej 29, 3400 Hillerød, Denmark, Department of
  Gynaecology and Obstetrics Nordsjællands Hospital Hillerød
\item
  Jane Marie Bendix, Dyrehavevej 29, 3400 Hillerød, Denmark, Department
  of Gynaecology and Obstetrics Nordsjællands Hospital Hillerød
\item
  Line Rode, Valdemar Hansens Vej 13, 2600 Glostrup, Department of
  Clinical Biochemistry, Rigshospitalet Glostrup
\item
  Tine Dalsgaard Clausen, Dyrehavevej 29, 3400 Hillerød, Denmark,
  Department of Gynaecology and Obstetrics Nordsjællands Hospital
  Hillerød
\end{enumerate}

\textbf{Name and contact details corresponding author:}

Tine Dalsgaard Clausen, tine.clausen@regionh.dk

\textbf{Running title} : ``COVID-19 in pregnancy and a positive vaginal
swab''

\textbf{Case report}

A 36-year old woman, para 3, and pregnant in gestational week 26+5
presented to the Emergency Department with shortness of breath and
vomiting. She tested positive for SARS-CoV-2 by a pharyngeal swab and
was admitted. She was a non-smoker, obese, and treated with
Levothyroxine for hypothyroidism.

She had previously contacted the antenatal ward with vaginal bleeding in
gestational week 24+5, and again at 25+1 with bleeding, in addition to
headache, shortness of breath, and calf tenderness. Deep vein thrombosis
of the left femoral vein was confirmed by ultrasound, and she started
treatment with daily injections of Tinzaparin. The vaginal bleeding was
from a varicose vein in the left labium minus. She had a negative
pharyngeal swab for SARS-CoV-2 and as symptoms improved shortly
thereafter she was discharged.

Eleven days later (26+5) she contacted the Emergency Department due to
coughing, shortness of breath, and vomiting and was subsequently
admitted to the Department of Cardiology, where she tested positive for
SARS-CoV-2 in a pharyngeal swab. Her respiration rate was 22 breaths per
minute, pulse 130 per minute, saturation of 97\% without oxygen, and a
temperature of 37.6 degrees Celsius. The following day (26+6) the
obstetrician was asked for a consult and decided to do a vaginal swab
for SARS-CoV-2, in case of need for urgent delivery. During admission
there were normal fetal movements, a normal cardiotocography, and no
signs of preeclampsia. Two vaginal swabs both came back positive. Cycle
threshold values for all swabs can be seen in Table 1. Temperature had
increased to 38.0 degrees Celsius, but as pulse decreased to 87 per
minute and saturation increased to 99\%, and there were no signs of
severe COVID-19 infection or pulmonary embolism, she was discharged from
the Department of Cardiology to recuperate at home. A couple of days
thereafter, her partner and daughter tested positive for SARS-CoV-2. The
patient had had coitus three or four days prior to testing positive for
SARS-CoV-2 in the vaginal swab. A serum antibody test (VITROS
Anti-SARS-CoV-2 total serology assay by Ortho Clinical Diagnostics)
performed at week 26+6 gestation was negative for SARS-CoV-2 antibodies.

We followed up with the patient, with complete remission of symptoms in
gestational week 28+0. A repeat pharyngeal swab in gestational week 29+0
was still positive but two vaginal swabs were negative. However, the
serum antibody test had turned positive. In week 32+0 both pharyngeal
and vaginal swabs were negative and serum antibody test still positive.
The patient was clinically well with no signs of preeclampsia and with
normal biophysical profile and growth of the fetus.

\textbf{Discussion}

Despite very few reported cases of neonatal COVID-19, it is an ongoing
discussion whether SARS-CoV-2 can be vertically transmitted from the
mother to the child during labor. As symptomatic women with COVID-19
have often been delivered by caesarean section it is still difficult to
evaluate whether vertical transmission is harmless or constitutes a
potential threat to the newborn which could be prevented by delivery by
caesarean section (1). Previously, three cohort studies with a total of
76 women, have reported three cases where SARS-CoV-2 was detected in
vaginal swabs (4--6), where only one of the three women was pregnant.

We present a single case of a pregnant woman who was clinically affected
by COVID-19 in week 26 gestation, where SARS-CoV-2 was also detected in
two vaginal swabs. This case raises concern that SARS-CoV-2 could be
vertically transmitted during labor, however the clinical implications
of the findings should be discussed.

The cycle threshold values were markedly higher for the vaginal swabs
than for the pharyngeal swabs, indicating that there was a lower
presence of viral DNA. A week after the symptoms had resolved,
SARS-CoV-2 could still be detected in a pharyngeal swab but not in
vaginal swabs. This might imply that intrapartum transmission is most
likely when the mother is symptomatic, and the infant is not yet
protected by maternal antibodies.

In the present case, there are several potential sources for the viral
presence in the vagina. Theoretically, the vaginal epithelium is not
abundant in angiotensin-converting enzyme 2 (ACE2) receptors, but they
are upregulated during pregnancy (2). Hence, viral replication in the
vaginal epithelium itself is possible as the coronavirus binds to their
target cells though the ACE2 receptors. Further, as the patient was
being treated with anticoagulants at the time and had a history of
vaginal bleeding during pregnancy, it is possible that viral RNA was
being exudated from the blood stream, instead of actually being released
by the vaginal epithelium itself. There is also potential of seminal
contamination (3), however the patient had had coitus three to four days
before the vaginal swab and her partner first tested positive a couple
of days after the patient experienced the first symptoms.

Despite the risk of vertical transmission of COVID-19 during labor
presumably being low (7,8) and with infants being very likely to have a
mild course of the disease should they become infected (1), we recommend
all women testing positive for SARS-CoV-2 in pharyngeal swabs to be
routinely tested with a vaginal swab to gain more knowledge regarding
presence and level of the viral load in both symptomatic and
asymptomatic women with active COVID-19 infection. We also suggest that
mode of delivery should be discussed with women at risk of going into
labor with a recently discovered COVID-19 infection, where passive
immunity of the baby is unlikely, especially in more severe cases, where
caesarean section may be preferable due to potentially higher viral load
in the vagina.

\textbf{Acknowledgements:}

We deeply thank the staff at the department of Gynaecology and
Obstetrics for their support and hard work during the COVID-19 pandemic.

\textbf{Disclosure of Interests:}

All authors report no conflicts of interest.

\textbf{Contribution to Authorship:}

TDC conceived the presentation of the case report. PA wrote the first
manuscript draft with subsequent amendments and critical feedback by
TDC, ECLL, VMFH, JM, JMB, and LR. LR performed antibody analyses. VMFH
and JM followed up with the patient with additional vaginal and
pharyngeal swabs. All authors approved the final version of the
manuscript.

\textbf{Details of Ethics Approval:}

The patient has given verbal and written consent to have her case
published in BJOG.

\textbf{Funding:}

Not applicable.

\textbf{References:}

1. Di Toro F, Gjoka M, Di Lorenzo G, De Santo D, De Seta F, Maso G, et
al. Impact of COVID-19 on maternal and neonatal outcomes: a systematic
review and meta-analysis. Clin Microbiol Infect. 2020 Nov

2. Narang K, Enninga EAL, Gunaratne MDSK, Ibirogba ER, Trad ATA,
Elrefaei A, et al. SARS-CoV-2 Infection and COVID-19 During Pregnancy: A
Multidisciplinary Review. Mayo Clin Proc. 2020 Aug;95(8):1750--65.

3. Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical Characteristics and
Results of Semen Tests Among Men With Coronavirus Disease 2019. JAMA
Netw Open. 2020 May 7;3(5):e208292.

4. Schwartz A, Yogev Y, Zilberman A, Alpern S, Many A, Yousovich R, et
al. Detection of severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) in vaginal swabs of women with acute SARS-CoV-2 infection:
a prospective study. BJOG Int J Obstet Gynaecol. 2021;128(1):97--100.

5. Qiu L, Liu X, Xiao M, Xie J, Cao W, Liu Z, et al. SARS-CoV-2 Is Not
Detectable in the Vaginal Fluid of Women With Severe COVID-19 Infection.
Clin Infect Dis. 2020 Jul 28;71(15):813--7.

6. Fenizia C, Biasin M, Cetin I, Vergani P, Mileto D, Spinillo A, et al.
Analysis of SARS-CoV-2 vertical transmission during pregnancy. Nat
Commun. 2020 Dec

7. Pettirosso E, Giles M, Cole S, Rees M. COVID\selectlanguage{english}-19 and pregnancy: A
review of clinical characteristics, obstetric outcomes and vertical
transmission. Aust N Z J Obstet Gynaecol. 2020 Oct;60(5):640--59.

8. Dumitriu D, Emeruwa UN, Hanft E, Liao GV, Ludwig E, Walzer L, et al.
Outcomes of Neonates Born to Mothers With Severe Acute Respiratory
Syndrome Coronavirus 2 Infection at a Large Medical Center in New York
City. JAMA Pediatr. 2020 Oct 12

\textbf{Table Caption List:}

Table 1: Course of patient HS's COVID-19 infection and results of
pharyngeal and vaginal swabs, as well as antibody tests.

\textbf{Hosted file}

\verb`Table1.docx`  available at \url{https://authorea.com/users/469115/articles/562204-case-report-of-covid-19-in-pregnancy-and-viral-presence-in-the-vagina-recommendations-for-obstetric-practice}

\selectlanguage{english}
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