Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission

doi:10.1111/1471-0528.17132

Observational Study

. 2022 Jul;129(8):1361-1374.

doi: 10.1111/1471-0528.17132. Epub 2022 Apr 22.

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission

Mehreen Zaigham^{1

2}, David Gisselsson^{3

4}, Anna Sand^{5

6}, Anna-Karin Wikström⁷, Emma von Wowern^{2

8}, David A Schwartz⁹, Linda Iorizzo¹⁰, Maria Nelander⁷, Marie Blomberg¹¹, Nikos Papadogiannakis¹², Sandra Holmström¹³, Åsa Leijonhfvud¹⁰, Verena Sengpiel^{14

15}

Affiliations

¹ Obstetrics & Gynaecology, Institution of Clinical Sciences Lund, Lund University, Lund, Sweden.
² Department of Obstetrics and Gynaecology, Skåne University Hospital, Lund, Sweden.
³ Clinical Genetics and Pathology, Laboratory Medicine, Skåne University Hospital, Lund, Sweden.
⁴ Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
⁵ Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
⁶ Department of Obstetrics and Gynaecology, Karolinska University Hospital, Stockholm, Sweden.
⁷ Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
⁸ Perinatal and Cardiovascular Epidemiology, Institution of Clinical Sciences Malmö, Lund University, Lund, Sweden.
⁹ Department of Pathology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
¹⁰ Department of Obstetrics and Gynaecology, Helsingborg Hospital, Department of Clinical Science Helsingborg, Lund University, Lund, Sweden.
¹¹ Department of Obstetrics and Gynaecology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
¹² Department of Laboratory Medicine, Division of Pathology, Karolinska Institute and Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
¹³ Department of Obstetrics and Gynaecology, Halland Hospital, Varberg, Sweden.
¹⁴ Department of Obstetrics and Gynaecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁵ Region Västra Götaland, Sahlgrenska University Hospital, Department of Obstetrics and Gynaecology, Gothenburg, Sweden.

PMID: 35243759
PMCID: PMC9111112
DOI: 10.1111/1471-0528.17132

Observational Study

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission

Mehreen Zaigham et al. BJOG. 2022 Jul.

. 2022 Jul;129(8):1361-1374.

doi: 10.1111/1471-0528.17132. Epub 2022 Apr 22.

Authors

Affiliations

¹ Obstetrics & Gynaecology, Institution of Clinical Sciences Lund, Lund University, Lund, Sweden.
² Department of Obstetrics and Gynaecology, Skåne University Hospital, Lund, Sweden.
³ Clinical Genetics and Pathology, Laboratory Medicine, Skåne University Hospital, Lund, Sweden.
⁴ Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
⁵ Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
⁶ Department of Obstetrics and Gynaecology, Karolinska University Hospital, Stockholm, Sweden.
⁷ Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
⁸ Perinatal and Cardiovascular Epidemiology, Institution of Clinical Sciences Malmö, Lund University, Lund, Sweden.
⁹ Department of Pathology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
¹⁰ Department of Obstetrics and Gynaecology, Helsingborg Hospital, Department of Clinical Science Helsingborg, Lund University, Lund, Sweden.
¹¹ Department of Obstetrics and Gynaecology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
¹² Department of Laboratory Medicine, Division of Pathology, Karolinska Institute and Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
¹³ Department of Obstetrics and Gynaecology, Halland Hospital, Varberg, Sweden.
¹⁴ Department of Obstetrics and Gynaecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁵ Region Västra Götaland, Sahlgrenska University Hospital, Department of Obstetrics and Gynaecology, Gothenburg, Sweden.

PMID: 35243759
PMCID: PMC9111112
DOI: 10.1111/1471-0528.17132

Abstract

Objective: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress.

Design: Retrospective, observational.

Setting: Nationwide.

Population: Five stillborn and nine live-born infants from 13 pregnant women infected with SARS-CoV-2 seeking care at seven different maternity units in Sweden.

Methods: Clinical outcomes and placental pathology were studied in 14 cases (one twin pregnancy) of maternal SARS-CoV-2 infection with impaired fetal outcome. Outcomes were correlated to placental pathology in order to investigate the impact of virus-related pathology on the villous capillary endothelium, trophoblast and other cells.

Main outcome measures: Maternal and fetal clinical outcomes and placental pathology in stillborn and live-born infants.

Results: Reduced fetal movements were reported (77%) and time from onset of maternal COVID-19 symptoms to signs of fetal distress among live-born infants was 6 (3-12) days and to diagnosis of stillbirth 11 (2-25) days. Two of the live-born infants died during the postnatal period. Signs of fetal distress led to emergency caesarean section in all live-born infants with umbilical cord blood gases and low Apgar scores confirming intrauterine hypoxia. Five stillborn and one live-born neonate had confirmed congenital transmission. Massive perivillous fibrinoid deposition, intervillositis and trophoblast necrosis were associated with SARS-CoV-2 placental infection and congenital transmission.

Conclusions: SARS-CoV-2 can cause rapid placental dysfunction with subsequent acute fetal hypoxia leading to intrauterine fetal compromise. Associated placental pathology included massive perivillous fibrinoid deposition, intervillositis and trophoblast degeneration.

Keywords: COVID-19; COVID-19 maternal-fetal transmission; SARS-CoV-2; SARS-CoV-2 placental infection; chronic histiocytic intervillositis; coronavirus; fetal distress; maternal floor infarction; placental endothelial cells; placental pathology; vertical SARS-CoV-2 transmission; villous macrophages.

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Conflict of interest statement

None declared. Completed disclosure of interest forms are available to view online as supporting information.

Figures

**FIGURE 1**
Histopathology of SARS‐CoV‐2 positive placentas. (A) Placental parenchyma stained with haematoxylin–eosin (HE) from Case 8 (live‐born) showing acute intervillositis manifested by a mixed inflammatory infiltrated dominated by polymorphonuclear granulocytes in the intervillous space (blue demarcation) along with degeneration of villous trophoblasts (arrows). (B) Positive stain for SARS‐CoV‐2 nucleocapsid protein in villous trophoblasts in the same region as in (A) from Case 8. (C) HE‐stain from Case 6 (live‐born) demonstrating massive fibrinoid deposition in the intervillous space (green demarcation). (D) Positive stain for SARS‐CoV‐2 nucleocapsid protein in villous trophoblasts from the same region as in (C) in Case 6. (E) HE‐stain of Case 3 (stillborn) showing acute intervillositis among reticulate deposition of fibrinoid (black demarcation) surrounded by degenerating villous trophoblasts (arrows). Inset shows positivity for SARS‐CoV‐2 nucleocapsid protein in the same region

See this image and copyright information in PMC

Comment in

The placenta in COVID-19 infection in pregnancy.
Ville Y. Ville Y. BJOG. 2022 Jul;129(8):1375. doi: 10.1111/1471-0528.17162. BJOG. 2022. PMID: 35352874 Free PMC article.

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References

1. Juan J, Gil MM, Rong Z, Zhang Y, Yang H, Poon LC. Effect of coronavirus disease 2019 (COVID‐19) on maternal, perinatal and neonatal outcome: systematic review. Ultrasound Obstet Gynecol. 2020;56(1):15–27. - PMC - PubMed
1. Zaigham M, Andersson O. Maternal and perinatal outcomes with COVID‐19: a systematic review of 108 pregnancies. Acta Obstet Gynecol Scand. 2020;99(7):823–9. - PMC - PubMed
1. Walker KF, O’Donoghue K, Grace N, Dorling J, Comeau JL, Li W, et al. Maternal transmission of SARS‐COV‐2 to the neonate, and possible routes for such transmission: a systematic review and critical analysis. BJOG. 2020;127(11):1324–36. - PMC - PubMed
1. Villar J, Ariff S, Gunier RB, Thiruvengadam R, Rauch S, Kholin A, et al. Maternal and neonatal morbidity and mortality among pregnant women with and without COVID‐19 infection: the INTERCOVID multinational cohort study. JAMA Pediatr. 2021;175(8):817–26. - PMC - PubMed
1. Chinn J, Sedighim S, Kirby KA, Hohmann S, Hameed AB, Jolley J, et al. Characteristics and outcomes of women with COVID‐19 giving birth at US academic centers during the COVID‐19 pandemic. JAMA Netw Open. 2021;4(8):e2120456. - PMC - PubMed

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[1] Juan J, Gil MM, Rong Z, Zhang Y, Yang H, Poon LC. Effect of coronavirus disease 2019 (COVID‐19) on maternal, perinatal and neonatal outcome: systematic review. Ultrasound Obstet Gynecol. 2020;56(1):15–27. - PMC - PubMed

[2] Juan J, Gil MM, Rong Z, Zhang Y, Yang H, Poon LC. Effect of coronavirus disease 2019 (COVID‐19) on maternal, perinatal and neonatal outcome: systematic review. Ultrasound Obstet Gynecol. 2020;56(1):15–27. - PMC - PubMed

[3] Zaigham M, Andersson O. Maternal and perinatal outcomes with COVID‐19: a systematic review of 108 pregnancies. Acta Obstet Gynecol Scand. 2020;99(7):823–9. - PMC - PubMed

[4] Zaigham M, Andersson O. Maternal and perinatal outcomes with COVID‐19: a systematic review of 108 pregnancies. Acta Obstet Gynecol Scand. 2020;99(7):823–9. - PMC - PubMed

[5] Walker KF, O’Donoghue K, Grace N, Dorling J, Comeau JL, Li W, et al. Maternal transmission of SARS‐COV‐2 to the neonate, and possible routes for such transmission: a systematic review and critical analysis. BJOG. 2020;127(11):1324–36. - PMC - PubMed

[6] Walker KF, O’Donoghue K, Grace N, Dorling J, Comeau JL, Li W, et al. Maternal transmission of SARS‐COV‐2 to the neonate, and possible routes for such transmission: a systematic review and critical analysis. BJOG. 2020;127(11):1324–36. - PMC - PubMed

[7] Villar J, Ariff S, Gunier RB, Thiruvengadam R, Rauch S, Kholin A, et al. Maternal and neonatal morbidity and mortality among pregnant women with and without COVID‐19 infection: the INTERCOVID multinational cohort study. JAMA Pediatr. 2021;175(8):817–26. - PMC - PubMed

[8] Villar J, Ariff S, Gunier RB, Thiruvengadam R, Rauch S, Kholin A, et al. Maternal and neonatal morbidity and mortality among pregnant women with and without COVID‐19 infection: the INTERCOVID multinational cohort study. JAMA Pediatr. 2021;175(8):817–26. - PMC - PubMed

[9] Chinn J, Sedighim S, Kirby KA, Hohmann S, Hameed AB, Jolley J, et al. Characteristics and outcomes of women with COVID‐19 giving birth at US academic centers during the COVID‐19 pandemic. JAMA Netw Open. 2021;4(8):e2120456. - PMC - PubMed

[10] Chinn J, Sedighim S, Kirby KA, Hohmann S, Hameed AB, Jolley J, et al. Characteristics and outcomes of women with COVID‐19 giving birth at US academic centers during the COVID‐19 pandemic. JAMA Netw Open. 2021;4(8):e2120456. - PMC - PubMed

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Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission

Affiliations

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission

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