# Fetal death and placental lesions after two COVID-19 episodes in single pregnancy in unvaccinated woman

Charlotte Dubucs, Marion Groussolles, E. Brazet, Monique Courtade-Saidi,

Nathalie van Acker, J. Ousselin, Christophe Pasquier, J. Aziza

► To cite this version:

Charlotte Dubucs, Marion Groussolles, E. Brazet, Monique Courtade-Saidi, Nathalie van Acker, et al. Fetal death and placental lesions after two COVID-19 episodes in single pregnancy in unvaccinated woman. Ultrasound in Obstetrics and Gynecology = Ultrasound in Obstetrics & Gynecology, 2022, 60 (6), pp.814-816. 10.1002/uog.26029. hal-04758914

HAL Id: hal-04758914

https://hal.science/hal-04758914v1

Submitted on 29 Oct 2024

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Fetal death and placental lesions after two
COVID-19 episodes in single pregnancy in
unvaccinated woman

Schwartz and Morotti showed that severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection in pregnant women can generate specific and
severe histopathological placental lesions¹. According
to Kotlyar *et al.*, around 20% of SARS-CoV-2-positive
unvaccinated mothers harbor placental lesions with
positive immunohistochemistry for SARS-CoV-2 in
villous trophoblasts². SARS-CoV-2 placental lesions have
been associated with intrauterine fetal demise (IUFD) via
functional placental insufficiency, with histological man-
ifestations of trophoblast necrosis, massive perivillous
fibrin deposition, chronic intervillositis and extensive
hemorrhagic changes³,⁴. We observed previously that
IUFD occurred 1–3 weeks after the mother tested
positive for SARS-CoV-2 by real-time polymerase chain
reaction (RT-PCR), in the second and third trimesters of
pregnancy⁵. Severe placental lesions were noted despite
mild maternal coronavirus disease 2019 (COVID-19)
symptoms. In a few cases, we found that placental
lesions became less inflammatory and richer in fibrin
deposits over time, with only focal or even negative
immunostaining for SARS-CoV-2, making histological
confirmation of infection difficult⁵. We illustrate this
statement with a case in which the mother developed
COVID-19 twice during a single pregnancy.

A 33-year-old woman, gravida 2, with no relevant medi-
cal history and no prior vaccination against SARS-CoV-2,

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<figure><img src="image_2.png" /><figcaption>**Figure 1** Histological images of placental lesions suggestive of recent (a,c) and historic (b,d) SARS-CoV-2 infection. (a,b) Immunohistochemistry using anti-SARS-CoV-2-nucleocapsid antibody, showing intense brown staining (a) and negative staining (b) of trophoblasts at periphery of chorionic villi. (c,d) Hematoxylin and eosin staining, showing: (c) intervillous hemorrhagic lesions with extensive trophoblast necrosis and chronic intervillosis (lymphohistiocytic infiltrate) and (d) massive perivillous fibrin deposition with villous infarctions in the absence of hemorrhage and significant inflammatory infiltrate.</figcaption></figure>

tested positive for SARS-CoV-2 at 16+5 weeks of gestation and exhibited mild symptoms of COVID-19, mainly asthenia and dyspnea. The pregnancy progressed normally and findings on routine ultrasound assessment at 32+5 weeks were unremarkable, with fetal weight estimated at 2100 g. At 33+4 weeks, the patient was infected with SARS-CoV-2 for a second time, with mild maternal symptoms. Maternal symptoms were assessed every 48 h. Nine days after testing positive, the patient became symptomatic with fever and influenza-like syndrome. A further 48 h later, she was clinically stable with antipyretics and hydration. Ultrasound and clinical assessment showed fetal biometry on the 75th percentile with normal fetal cardiac rhythm, amniotic fluid volume and umbilical artery Doppler.

Unexpectedly, IUFD occurred at 36+6 weeks of gestation. Standard diagnostic tests were negative, including array comparative genomic hybridization, cytomegalovirus and parvovirus B19 screening on amniotic fluid and maternal autoimmune analysis, thereby excluding other causes of IUFD. A stillborn male was delivered with a birth weight of 2880 g. Macroscopic examination of the placenta revealed abnormal cross-sectional slices with highly heterogeneous and hemorrhagic sections of parenchyma. Histological examination of the placenta showed extensive lesional areas characterized by trophoblast necrosis with confluent perivillous fibrinous deposits and inflammatory

histiocytic/lymphocytic infiltrate (CD68+/CD3+) mixed with cellular debris in the intervillous chamber, suggestive of both historic and recent lesions (Figure 1). Interestingly, immunohistochemical staining with anti-SARS-CoV-2-nucleocapsid antibody (clone BSB-134; Diagnostics, Blagnac, France) was heterogeneous, with difuse and intense labeling of cytotrophoblasts and villous syncytiotrophoblasts in lesional areas and no labeling in non-lesional areas. There was an absence of labeling in some areas of trophoblast necrosis, raising the possibility of sequelae from the first episode of COVID-19.

The presence of organized lesions linked to SARS-CoV-2 but with negative or only focally positive viral immunostaining highlights the potential for lesions to become antigen-negative over time. Indeed, RNA of the SARS-CoV-2 delta variant was detected by RT-PCR in lesional areas regardless of whether they were labeled with anti-SARS-CoV-2 antibody. Moreover, the fact that two successive maternal SARS-CoV-2 infections occurred during one pregnancy could suggest that immunity is not acquired systematically following maternal infection with the delta variant and highlights the significant immune-evasion capability of this variant.

C. Dubuc$^{1,2*}$, M. Groussolles$^2$, E. Brazet$^3$, M. Courtade-Saïdi$^1$, N. Van Acker$^4$, J. Ousselin$^1$, C. Pasquier$^5$ and J. Aziza$^1$

$^1$Department of Cytology and Pathology, IUCT Oncopole, Toulouse, France;
²SPHERE - Equipe Constitutive du CERPOP, UMR1295, Unité Mixte INSERM – Université Toulouse III Paul Sabatier, Toulouse, France;

³Department of Gynecology and Obstetrics, Paule de Viguier Maternity Hospital, CHU de Toulouse, Toulouse, France;

⁴Imag'IN Platform, Department of Cytology and Pathology, CHU, IUCT Oncopole, Toulouse, France;

⁵Virology Department, Federal Institute of Biology, CHU de Toulouse, Toulouse, France

*Correspondence.

(e-mail: dubucs.charlotte@iuct-oncopole.fr)

DOI: 10.1002/uog.26029

References

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