Covid-19 during Pregnancy – Histopathological Lesions of the
                    Placenta

Julia Kummer; Giada Ameli; Anja Jebens; Josefine Königbauer; Valentin Mihajlov; Anna Kaarina Nacke; My Hanh Pham; Christian Rickert; Luisa Simon; Tim Schellenberg; Lars Hellmeyer

doi:10.1055/a-2180-7302

Zeitschrift für Geburtshilfe und Neonatologie, Table of Contents

Z Geburtshilfe Neonatol 2024; 228(01): 49-56
DOI: 10.1055/a-2180-7302

Original Article

Covid-19 during Pregnancy – Histopathological Lesions of the Placenta

Authors

Julia Kummer

¹Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany
Giada Ameli

¹Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany
Anja Jebens

¹Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany
Josefine Königbauer

²Obstetrical Department, Charite Medical Faculty Berlin, Berlin, Germany
Valentin Mihajlov

¹Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany
Anna Kaarina Nacke

¹Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany
My Hanh Pham

¹Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany
Christian Rickert

³Department of Pathology, Vivantes Klinikum im Friedrichshain, Berlin, Germany
Luisa Simon

¹Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany
Tim Schellenberg

¹Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany
Lars Hellmeyer

¹Department of Gynecology and Obstetrics, Vivantes Klinikum im Friedrichshain, Berlin, Germany

Abstract

Introduction Pregnant women and their offspring represented a vulnerable patient collective during the Covid-19 pandemic. Beyond the direct effect of SARS-CoV-2 via vertical transmission, an indirect impact on the fetus can occur through placental lesions deteriorating placental villous function. We performed a histopathological analysis of placentas of parturients with SARS-CoV-2 compared to healthy controls.

Methods and materials Between February 2022 and July 2022 we conducted a prospective case–control study analyzing placental specimens of parturients with SARS-CoV-2 infection compared to specimens of placentas of healthy controls. Patient history, Covid-19-specific symptoms, and obstetric outcomes were recorded. Statistical analysis was performed.

Results During the observation period 71 patients were included with a gestational age 37 1/7–41 5/7 weeks. Thirty-six patients presented with SARS-CoV-2 infection. The control group consisted of 35 patients and showed no placental abnormalities. Among SARS-CoV-2-positive parturients, 66.7% of placentas of the case group showed histopathological abnormalities classified as vascular or inflammatory abnormalities. 22.2% of placentas showed acute ischemic infarction areas. 8.3% of placentas showed subchorionic layered thrombi. There was one case of severe acute subchorionitis. SARS-CoV-2 increased the risk of placental lesions significantly (OR 3.000, CI 1.890–4.762, p=0.0001). Placental lesions had no significant impact on perinatal acidosis (OR 0.455, CI 0.044–4.667, p=0.498) or number of cesarean sections (OR 2.314, CI 0.717–7.473, p=0.156).

Conclusion SARS-CoV-2 infection during labor and delivery increased the risk of adverse outcomes. Histopathological analysis indicated that the placenta as a maternal-fetal interface was affected by SARS-CoV-2, leading to systemic vasculopathy and inflammation.

Key words

SARS-CoV-2 - Covid-19 pandemic - Covid-infection during pregnancy - histopathological changes of the placenta

Full Text

References

References
1 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506
2 World Health Organization. WHO Director-Generalʼs opening remarks at the media briefing on COVID-19. Available from: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 Accessed: 21 September 2022
3 Knight M, Bunch K, Vousden N. et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ 2020; 369: m2107
4 Hein A, Kehl S, Häberle L. et al. Prevalence of SARS-CoV-2 in pregnant women assessed by RT-PCR in Franconia, Germany: First results of the SCENARIO Study (SARS-CoV-2 prEvalence in pregNAncy and at biRth In FrancOnia). Geburtshilfe Frauenheilkd 2022; 82: 226-234
5 Maier JT, Zickler D, Metz M. et al. Peripartum Covid-19 pneumonia with severe ARDS – A case report. Z Geburtshilfe Neonatol 2021; 225: 183-187
6 Pecks U, Mand N, Kolben T. et al. SARS-CoV-2 infection during pregnancy. An analysis of clinical data from Germany and Austria from the CRONOS Registry. Dtsch Arztebl Int 2022; 119: 588-594
7 Allotey J, Stallings E, Bonet M. et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ 2020; 370: m3320
8 Wang C, Zhou YH, Yang HX, Poon LC. Intrauterine vertical transmission of SARS-CoV-2: what we know so far. Ultrasound Obstet Gynecol 2020; 55: 724-725
9 Robbins JR, Bakardjiev AI. Pathogens and the placental fortress. Curr Opin Microbiol 2012; 15: 36-43
10 World Health Organization. Definition and categorization of the timing of mother-to-child transmission of SARS-CoV-2 scientific brief, 8 February 2021. Available from https://apps.who.int/iris/handle/10665/339422 Accessed: 29 September 2022
11 Burton GJ, Jauniaux E. Pathophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol 2018; 218: S745-S761
12 Shanes ED, Mithal LB, Otero S. et al Placental pathology in COVID-19. Am J Clin Pathol 2020; 8 154: 23-32
13 Robert Koch Institute. 02/2022 Wöchentlicher Lagebericht des RKI zu COVID-19 [Weekly Update from the RKI on COVID-19]. Available from: www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Situationsberichte/Wochenbericht/Wochenbericht_2022-03-03.pdf?__blob=publicationFile Accessed: 24 October 2022
14 Robert Koch Institute. 07/2022 Wöchentlicher Lagebericht des RKI zu COVID-19 [Weekly Update from the RKI on COVID-19]. Available from www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Situationsberichte/Wochenbericht/Wochenbericht_2022-08-25.pdf?__blob=publicationFile Accessed: 24 October 2022
15 Wong YP, Khong TY, Tan GC. The effects of COVID-19 on placenta and pregnancy: what do we know so far?. Diagnostics (Basel) 2021; 11: 94
16 Moltner S, de Vrijer B, Banner H. Placental infarction and intrauterine growth restriction following SARS-CoV-2 infection. Arch Gynecol Obstet 2021; 304: 1621-1622
17 Vedmedovska N, Rezeberga D, Teibe U. et al. Placental pathology in fetal growth restriction. Eur J Obstet Gynecol Reprod Biol 2011; 155: 36-40
18 Di Mascio D, Sen C, Saccone G. et al. Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19. J Perinat Med 2020; 48: 950-958
19 Watkins JC, Torous VF, Roberts DJ. Defining severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) placentitis. Arch Pathol Lab Med 2021; 145: 1341-1349
20 Schwartz DA, Mulkey SB, Roberts DJ. SARS-CoV-2 placentitis, stillbirth, and maternal COVID-19 vaccination: clinical-pathologic correlations. Am J Obstet Gynecol 2023; 228: 261-269
21 Bourne T, Leonardi M, Kyriacou C. et al. ISUOG consensus statement on rationalization of gynecological ultrasound services in context of SARS-coV‑2. Ultrasound Obstet Gynecol 2020; 55: 879-885
22 Zöllkau J, Hagenbeck C, Hecher K. et al. Aktualisierte Empfehlungen zu SARS-CoV-2/COVID-19 und Schwangerschaft, Geburt und Wochenbett [Update on Recommendations for SARS-CoV-2/COVID-19 During Pregnancy, Birth and Childbed]. Z Geburtshilfe Neonatol 2020; 224: 217-222
23 Redline RW. Extending the spectrum of massive perivillous fibrin deposition (maternal floor infarction). Pediatr Dev Pathol 2021; 24: 10-11
24 Feist H, Turowski G, Hussein K. et al. Massive perivillous fibrin deposition of an enterovirus A-infected placenta associated with stillbirth: a case report. Pediatr Dev Pathol 2019; 22: 142-145
25 Gestrich CK, Zhou YY, Ravishankar S. Massive perivillous fibrin deposition in congenital cytomegalovirus infection: a case report. Pediatr Dev Pathol 2021; 24: 47-50
26 Yu W, Tellier R, Wright JR. Coxsackie virus A16 infection of placenta with massive perivillous fibrin deposition leading to intrauterine fetal demise at 36 weeks gestation. Pediatr Dev Pathol 2015; 18: 331-334
27 Hosier H, Farhadian SF, Morotti RA. et al. SARS-CoV-2 infection of the placenta. J Clin Invest 2020; 130: 4947-4953
28 Vivanti AJ, Vauloup-Fellous C, Prevot S. et al. Transplacental transmission of SARS-CoV-2 infection. Nat Commun 2020; 11: 3572
29 Redline RW. Classification of placental lesions. Am J Obstet Gynecol 2015; 213: S21-S28
30 Khong TY, Mooney EE, Ariel I. et al. Sampling and definitions of placental lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab Med 2016; 140: 698-713
31 Chen S, Huang B, Luo DJ. et al. Pregnancy with new coronavirus infection: clinical characteristics and placental pathological analysis of three cases. Zhonghua Bing Li Xue Za Zhi 2020; 49: 418-423
32 Burton GJ, Jones CJ. Syncytial knots, sprouts, apoptosis, and trophoblast deportation from the human placenta. Taiwan J Obstet Gynecol 2009; 48: 28-37
33 Loukeris K, Sela R, Baergen RN. Syncytial knots as a reflection of placental maturity: reference values for 20 to 40 weeksʼ gestational age. Pediatr Dev Pathol 2010; 13: 305-309
34 Pecks U, Kuschel B, Mense L. et al Pregnancy and SARS-CoV-2 Infection in Germany–the CRONOS Registry. Dtsch Arztebl Int 2020; 4 117: 841-842
35 Hagenbeck C, Pecks U, Fehm T. et al. Schwangerschaft, Geburt und Wochenbett mit SARS-CoV-2 und COVID-19 [Pregnancy, birth, and puerperium with SARS-CoV-2 and COVID-19]. Gynäkologe 2020; 53: 614-623
36 Ward T, Glaser A, Overton CE. et al. Replacement dynamics and the pathogenesis of the Alpha, Delta and Omicron variants of SARS-CoV-2. Epidemiol Infect 2022; 151: e32