key: cord-0771633-pk9mu23p
authors: Akdemir, Yesim; Haciseyitoglu, Demet; Celebi, Guven; Aydemir, Cumhur; Bahadır, Burak; Cakir, Anil T.; Barut, Aykut; Ozmen, Ulku
title: Probable viremia and positive placental swabs for SARS‐CoV‐2 in a preterm pregnant woman with mild COVID‐19
date: 2021-07-28
journal: J Med Virol
DOI: 10.1002/jmv.27202
sha: 7f3a601a5ae0a42e5052fc2979c9d62a696cf3cd
doc_id: 771633
cord_uid: pk9mu23p

This study aimed to report a case of mild novel coronavirus disease (COVID‐19) in a pregnant woman with probable viremia, as reverse transcription‐polymerase chain reaction (RT‐PCR) testing of endometrial and placental swabs for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was positive. A 26‐year‐old multigravida at 35 weeks 2 days of gestation, who had extensive thigh and abdominal cellulitis, tested SARS‐CoV‐2 positive by RT‐PCR performed on samples from the endometrium and maternal side of the placenta. However, other samples (amniotic fluid, fetal side of the placenta, umbilical cord, maternal vagina, and neonatal nasopharynx) tested negative for SARS‐CoV‐2. This is one of the rare reports of probable SARS‐CoV‐2 viremia with the presence of SARS‐CoV‐2 in the endometrium and placenta, but not leading to vertical transmission and neonatal infection. Because knowledge about transplacental transmission and results is very limited, we conclude that more RT‐PCR tests on placental and cord blood samples are needed in order to safely make definite conclusions.

Since the novel coronavirus disease (COVID- 19) outbreak, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became a pandemic, numerous papers have reported pregnant women with both mild and severe COVID-19. [1] [2] [3] [4] Although early reports with limited numbers of patients showed that most pregnant women with COVID-19 had mild disease, 1 increased hospitalization rate (RR: 5.4), need for intensive care unit admission (RR:

1.5), and need for invasive mechanical ventilation (RR: 1.7) were found in the study conducted by the Centers for Disease Control and Prevention, which included 8209 pregnant women with COVID- 19. 5 Today, the effects of the disease on pregnancy are not completely understood.

One other important and the possible issue is vertical transmission, but data is scarce. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are essential for the fusion and entry of SARS-CoV-2 into host cells. Meanwhile, it was shown that ACE2 and TMPRSS2 expressions are present and increase from the first to the second trimester in maternal-fetal interface cells and multiple fetal organs. 6 Several case reports and series reported suspected cases of vertical transmission by testing for SARS-CoV-2 using placenta, amniotic fluid, maternal vaginal swab, neonatal cord blood, and neonatal nasopharyngeal and rectal swab samples or testing for specific neonatal antibodies, 7-16 whereas others could not. [17] [18] [19] [20] [21] [22] [23] Regardless of the concerns about the quality of evidence, the optimal definition of vertical transmission was not clear. Recently, Blumberg et al. 24 suggested a classification for SARS-CoV-2 vertical transmission as follows: intrauterine transmission, intrapartum or early postnatal transmission, and superficial exposure to SARS-CoV-2 or transient viremia.

Herein, we report a case of mild COVID-19 in a pregnant woman with probable viremia, as reverse transcription-polymerase chain reaction (RT-PCR) testing of endometrial and placental swabs for SARS-CoV-2 were positive. Institutional review board approval was obtained and patient information was obtained from medical records.

A 26-year-old woman, Gravida 2 Para 1, at 35 weeks and 2 days of gestation was transferred to our clinic on August 31, 2020, due to abdominal pain and pruritus. She was morbidly obese, with a body mass index of 37.47. She did not receive proper antenatal care due to her fears about the COVID-19 outbreak. She reported that her firsttrimester aneuploidy screening test was within the normal risk limits, but no second-trimester fetal ultrasound scan or oral glucose tolerance test was performed. Her fasting and postprandial blood glucose levels were normal, even though HbA1c was 6.2%. Her blood type was AB Rh (−) and there was no history of Rh sensitization during her current or previous pregnancies. She had a history of cough, malaise, and fatigue, which started 5 days before admission, and worsened with dyspnea and fever 1 day before admission. She had warm and reddish abdominal lesions below the umbilicus and bilateral posterior thigh pain, which had started 1 month prior. At admission, the temperature was 36.1°C, blood pressure was 105/80 mmHg, pulse rate was 92/min, respiratory rate was 20/min, and blood oxygen saturation was 98% in room air. She also had mild dyspnea and cough.

Obstetric examination revealed a macrosomic fetus (estimated fetal weight was 3548 g, 37 2/7 gestational weeks' average, >97th percentile) with normal levels of amniotic fluid. Nonstress test was reactive, no uterine contraction was observed, and fetal movements were normal.

An RT-PCR of SARS-CoV-2 RNA was performed on a nasophar- Table 1 . One day after admission, she had regular uterine contractions with cervical effacement and dilatation of 1 cm. Emergency cesarean section was performed with maximal caution and protection because she had a history of previous cesarean birth. The patient wore a surgical mask throughout the cesarean section. The amniotic fluid sample was obtained via direct syringe aspiration before rupturing the amniotic membrane, and a male newborn weighing 4040 g was delivered, with Apgar scores of 7 and 8 at 1 and 5 min, respectively. The cord was clamped without delay, and skin-to-skin contact was not permitted.

Umbilical cord blood samples were collected by direct syringe aspiration after delivery. The fetal side of the placental swab was obtained from the amniotic surface near the umbilical cord after clearing the maternal blood. The maternal side of the placental swab was obtained inside of the nearest cotyledon in the level of the umbilical cord. Endometrium inner surface swabs were performed from all uterine walls and fundus.

The placenta was sent to the pathology department for a detailed mi- After delivery, she was put on favipiravir treatment for 5 days.

The mild dyspnea and cough disappeared in 2 days and the blood oxygen saturation remained normal (98%-99%). She was afebrile with normal vital and puerperal signs for 8 days until discharge.

However, the abdominal cellulitis area tended to expand and CRP levels increased to 232.1 mg/dl on postoperative day 2. Teicoplanin was added to the meropenem therapy. Inflammatory markers and liver enzymes gradually normalized (Table 1) One study found elevated IgG and IgM antibodies in 2-h newborns, but neonatal throat swab was negative. 15 Another study found that 50% of newborns (3/6) had elevated IgM antibodies, but all neonatal throat swabs were negative. 14 It is already known that IgG transfer begins as early as 13 weeks of gestation and the rate of transfer increases after the second trimester, but the IgM macromolecule unlikely crosses the placenta. 27 Sensitivity and specificity of SARS-CoV-2 IgM immunoassays were reported to be 48.1% and 100%, respectively; thus, the results should be interpreted cautiously. 28 11 in which the mother, both the fetal and maternal sides of the placenta, and repeated neonatal nasopharyngeal tests were positive for SARS-CoV-2, and the placenta showed multiple areas of histiocytic intervillositis and infarction. In an interesting case of a woman with COVID-19 in the second trimester who presented with severe hypertension, placental abruption, and an abortion, placenta and umbilical cord blood were positive for SARS-CoV-2 and the placenta showed intervillositis with SARS-CoV-2 spike glycoprotein, which was predominantly detected in syncytiotrophoblasts. 16 Authors suggested that COVID-19 might have worsened the placental dysfunction, leading to early-onset pre-eclampsia and placental abruption.

The placenta is the main barrier against viral infections, as it has an organ-specific antiviral mechanism. Fused and periodically re- creating an immunomodulatory defense. 30 Altogether, placental functions could protect the fetus; however, there may be cases where the placenta per se is insufficient. The defense layer formed by the syncytiotrophoblasts may be deficient in the first and early second trimesters due to improper lining or in late pregnancy, when syncytium formation starts to decline. 31 In addition, maternal systemic disorders or inflammatory and vascular changes could cause hypoxic or immune injury in the placenta, which further disrupts the placental integrity. 32 The relationship between viral load and disease severity, mortality, comorbidities (congestive heart failure, diabetes, and chronic kidney disease), and increasing age has been shown in adults. 33, 34 However, the relationship between SARS-CoV-2 viral load and vertical transmission is not fully understood. Demirjian et al. 10 suggested that high pulmonary viral load might increase maternal viremia and facilitate vertical transmission, as they detected SARS-CoV-2 in neonatal blood, neonatal upper respiratory tract, and feces in a case of a pregnant woman with severe COVID-19 who required extracorporeal membrane oxygenation support. Therefore, the placental viral load might be an important factor that must be addressed. Placental viral load was much higher than maternal upper respiratory tract, vaginal, blood, and amniotic fluid viral load in a woman in late pregnancy with COVID-19 and suspected SARS-CoV-2 vertical transmission. 7 We detected SARS-CoV-2 in the endometrium and maternal side of the placenta in a preterm pregnant woman with mild COVID-19.

There was no vertical transmission. Samples from the fetal side of the placenta and amniotic fluid, neonatal cord blood, neonatal nasopharynx, and breast milk samples were all negative. Other studies found similar findings along with our study. Hsu et al. 13 

The authors declare that there are no conflict of interests.

Yesim Akdemir and Demet Haciseyitoglu were responsible for the organization and coordination of the trial. Yesim Akdemir was the chief investigator and was responsible for the data analysis. Cumhur Aydemir, Burak Bahadir, and Guven Celebi developed the trial design. All authors contributed to the writing of the final manuscript.

https://orcid.org/0000-0002-8574-5065

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Probable viremia and positive placental swabs for SARS-CoV-2 in a preterm pregnant woman with mild COVID