Our objectives were to determine 1) the prevalence and description of placental pathologic lesions in pregnancies complicated by SARS-CoV-2 infection compared to healthy controls and 2) whether the prevalence and/ or pattern of placental pathologic lesions differed in the few neonates who tested positive for SARS-CoV-2 in the first 48 hours of life at a busy urban county hospital.
METHODS:
This study included all pregnant mothers who tested positive for SARS-CoV-2 and delivered at our institution from March 2020 to June 2021, while control placentas were collected from term pregnancies without complications.
RESULTS:
Approximately 90% (n = 380/425) of placentas from pregnancies complicated by SARS-CoV-2 infections had placental pathologic lesions, compared to 32% (n = 16/50) of controls. The predominant lesions were acute histologic chorioamnionitis with or without fetal response (n = 209/380, 55%), maternal vascular malperfusion (n = 180/380, 47%), and other inflammatory lesions (n = 148/380, 39%). Only 14 (2.5%) infants tested positive for SARS-CoV-2 within the first 48 hours of life. There were no significant differences in placental histopathology between infants who tested positive vs. those that were negative for SARS-CoV-2. Placental lesions in mothers who tested positive for SARS-CoV-2 during the first vs. second vs. third pregnancy trimesters, were significantly different in the incidence of inflammatory placental pathologic lesions (n = 9/19, 53% vs. n = 37/98, 49% vs. n = 102/439, 31%, respectively; p < 0.01).
CONCLUSION:
A significant proportion of women with SARS-CoV-2 infection during pregnancy at a single county hospital have inflammatory and vascular placental lesions at birth, raising questions regarding their downstream effects and clinical consequences.
CDC. COVID Data Tracker 2021 [Available from: https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-updates%2Fspecial-populations%2Fpregnancy-data-on-covid-19.html#pregnant-population.
2.
AngelidouA, SullivanK, MelvinPR, ShuiJE, GoldfarbIT, BartolomeR, et al. Association of maternal perinatal SARS-CoV-2 infection with neonatal outcomes during the COVID-19 pandemic in Massachusetts. JAMA Netw Open. 2021;4(4):e217523.
3.
D’AntonioF, SenC, MascioDD, GalindoA, VillalainC, HerraizI, et al. Maternal and perinatal outcomes in high compared to low risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection (phase 2): The World Association of Perinatal Medicine working group on coronavirus disease 2019. Am J Obstet Gynecol MFM. 2021;3(4):100329.
4.
Di MascioD, SenC, SacconeG, GalindoA, GrünebaumA, YoshimatsuJ, 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;49(1):111–5.
5.
Martinez-PortillaRJ, SotiriadisA, ChatzakisC, Torres-TorresJ, Espino Y SosaS, Sandoval-MandujanoK, et al. Pregnant women with SARS-CoV-2 infection are at higher risk of death and pneumonia: propensity score matched analysis of a nationwide prospective cohort (COV19Mx). Ultrasound Obstet Gynecol. 2021;57(2):224–31.
6.
OakesMC, KernbergAS, CarterEB, FoellerME, PalanisamyA, RaghuramanN, et al. Pregnancy as a risk factor for severe coronavirus disease 2019 using standardized clinical criteria. Am J Obstet Gynecol MFM. 2021;3(3):100319.
7.
SismanJ, JaleelMA, MorenoW, RajaramV, CollinsRRJ, SavaniRC, et al. Intrauterine transmission of SARS-COV-2 infection in a preterm infant. Pediatr Infect Dis J. 2020;39(9):e265–e7.
8.
HechtJL, QuadeB, DeshpandeV, Mino-KenudsonM, TingDT, DesaiN, et al. SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: A series of 19 placentas from COVID-19-positive mothers. Mod Pathol. 2020;33(11):2092–103.
9.
BahadurG, BhatM, AcharyaS, JangaD, CambellB, HuirneJ, et al. Retrospective observational RT-PCR analyses on 688 babies born to 843 SARS-CoV-2 positive mothers, placental analyses and diagnostic analyses limitations suggest vertical transmission is possible. Facts Views Vis Obgyn. 2021;13(1):53–66.
10.
Blasco SantanaL, Miraval WongE, Alvarez-TroncosoJ, Sanchez GarciaL, BarthaJL, Regojo-ZapataRM. Maternal and perinatal outcomes and placental pathologic examination of 29 SARS-CoV-2 infected patients in the third trimester of gestation. J Obstet Gynaecol Res. 2021;47(6):2131–9.
11.
KreisNN, RitterA, LouwenF, YuanJ. A message from the human placenta: Structural and immunomodulatory defense against SARS-CoV-2. Cells. 2020;9(8):1777.
12.
SharpsMC, HayesDJL, LeeS, ZouZ, BradyCA, AlmoghrabiY, et al. A structured review of placental morphology and histopathological lesions associated with SARS-CoV-2 infection. Placenta. 2020;101:13–29.
13.
BerteroL, BorellaF, BottaG, CarossoA, CosmaS, BovettiM, et al. Placenta histopathology in SARS-CoV-2 infection: analysis of a consecutive series and comparison with control cohorts. Virchows Arch. 2021;479(4):715–28.
14.
DebelenkoL, KatsyvI, ChongAM, PeruyeroL, SzabolcsM, UhlemannAC. Trophoblast damage with acute and chronic intervillositis: Disruption of the placental barrier by severe acute respiratory syndrome coronavirus 2. Hum Pathol. 2021;109:69–79.
15.
Di GirolamoR, KhalilA, AlameddineS, D’AngeloE, GallianiC, MatarrelliB, et al. Placental histopathology after SARS-CoV-2 infection in pregnancy: A systematic review and meta-analysis. Am J Obstet Gynecol MFM. 2021;3(6):100468.
16.
GaoL, RenJ, XuL, KeX, XiongL, TianX, et al. Placental pathology of the third trimester pregnant women from COVID-19. Diagn Pathol. 2021;16(1):8.
17.
GlynnSM, YangYJ, ThomasC, FriedlanderRL, CaginoKA, MatthewsKC, et al. SARS-CoV-2 and placental pathology: Malperfusion patterns are dependent on timing of infection during pregnancy. Am J Surg Pathol. 2022;46(1):51–7.
18.
GulersenM, PrasannanL, Tam TamH, MetzCN, RochelsonB, MeirowitzN, et al. Histopathologic evaluation of placentas after diagnosis of maternal severe acute respiratory syndrome coronavirus 2 infection. Am J Obstet Gynecol MFM. 2020;2(4):100211.
19.
JaiswalN, PuriM, AgarwalK, SinghS, YadavR, TiwaryN, et al. COVID-19 as an independent risk factor for subclinical placental dysfunction. Eur J Obstet Gynecol Reprod Biol. 2021;259:7–11.
20.
MenterT, MertzKD, JiangS, ChenH, MonodC, TzankovA, et al. Placental Pathology Findings during and after SARS-CoV-2 Infection: Features of Villitis and Malperfusion. Pathobiology. 2021;88(1):69–77.
21.
MoresiS, Dell’AquilaM, SalviS, RulloR, FruciS, StollagliF, et al. SARS-CoV-2 Infection in pregnancy: Clinical Signs, placental pathology, and neonatal outcome-implications for clinical care. Front Med (Lausanne). 2021;8:676870.
22.
RadHS, RöhlJ, StylianouN, AllenbyMC, BazazSR, WarkianiME, et al. The effects of COVID-19 on the placenta during pregnancy. Front Immunol. 2021;12:743022.
23.
RestaL, VimercatiA, CazzatoG, MazziaG, CicinelliE, ColagrandeA, et al. SARS-CoV-2 and placenta: New insights and perspectives. Viruses. 2021;13(5):723.
24.
ShanesED, MithalLB, OteroS, AzadHA, MillerES, GoldsteinJA. Placental pathology in COVID-19. Am J Clin Pathol. 2020;154(1):23–32.
25.
TascaC, RossiRS, CortiS, AnelliGM, SavasiV, BrunettiF, et al. Placental pathology in COVID-19 affected pregnant women: A prospective case-control study. Placenta. 2021;110:9–15.
26.
KhongTY, MooneyEE, ArielI, BalmusNC, BoydTK, BrundlerMA, et al. Sampling and definitions of placental lesions: Amsterdam placental workshop group consensus statement. Arch Pathol Lab Med. 2016;140(7):698–713.
27.
MirIN, ChalakLF, LiaoJ, Johnson-WelchS, BrownLS, LongoriaC, et al. Fetal-placental crosstalk occurs through fetal cytokine synthesis and placental clearance. Placenta. 2018;69:1–8.
28.
GreerLG, ZiadieMS, CaseyBM, RogersBB, McIntireDD, LevenoKJ. An immunologic basis for placental insufficiency in fetal growth restriction. Am J Perinatol. 2012;29(7):533–8.
29.
MirIN, Johnson-WelchSF, NelsonDB, BrownLS, RosenfeldCR, ChalakLF. Placental pathology is associated with severity of neonatal encephalopathy and adverse developmental outcomes following hypothermia. Am J Obstet Gynecol. 2015;213(6):849e1–7.
30.
RedlineRW, AbramowskyCR. Clinical and pathologic aspects of recurrent placental villitis. Hum Pathol. 1985;16(7):727–31.
LinehanL, O’DonoghueK, DineenS, WhiteJ, HigginsJR, FitzgeraldB. SARS-CoV-2 placentitis: An uncommon complication of maternal COVID-19. Placenta. 2021;104:261–6.
33.
SchwartzDA, BaldewijnsM, BenachiA, BugattiM, CollinsRRJ, De LucaD, et al. Chronic histiocytic intervillositis with trophoblast necrosis is a risk factor associated with placental infection from coronavirus disease 2019 (COVID-19) and intrauterine maternal-fetal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in live-born and stillborn infants. Arch Pathol Lab Med. 2021;145(5):517–28.
34.
PatbergET, AdamsT, RekawekP, VahanianSA, AkermanM, HernandezA, et al. Coronavirus disease 2019 infection and placental histopathology in women delivering at term. Am J Obstet Gynecol. 2021;224(4):382e1–18.
35.
AlgarrobaGN, RekawekP, VahanianSA, KhullarP, PalaiaT, PeltierMR, et al. Visualization of severe acute respiratory syndrome coronavirus 2 invading the human placenta using electron microscopy. Am J Obstet Gynecol. 2020;223(2):275–8.
36.
LevitanD, LondonV, McLarenRA, MannJD, ChengK, SilverM, et al. Histologic and immunohistochemical evaluation of 65 placentas from women with polymerase chain reaction-proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Arch Pathol Lab Med. 2021;145(6):648–56.
37.
CribiùFM, ErraR, PugniL, Rubio-PerezC, AlonsoL, SimonettiS, et al. Severe SARS-CoV-2 placenta infection can impact neonatal outcome in the absence of vertical transmission. J Clin Invest. 2021;131(6):e145427.
38.
EdlowAG, LiJZ, CollierAY, AtyeoC, JamesKE, BoatinAA, et al. Assessment of maternal and neonatal SARS-CoV-2 viral load, transplacental antibody transfer, and placental pathology in pregnancies during the COVID-19 pandemic. JAMA Netw Open. 2020;3(12):e2030455.
39.
SeymenCM. Being pregnant in the COVID-19 pandemic: Effects on the placenta in all aspects. J Med Virol. 2021;93(5):2769–73.
40.
DhaundiyalA, KumariP, JawalekarSS, ChauhanG, KalraS, NavikU. Is highly expressed ACE 2 in pregnant women “a curse” in times of COVID-19 pandemic?Life Sci. 2021;264:118676.
41.
ØstergaardL. SARS CoV-2 related microvascular damage and symptoms during and after COVID-19: Consequences of capillary transit-time changes, tissue hypoxia and inflammation. Physiol Rep. 2021;9(3):e14726.
42.
VargaZ, FlammerAJ, SteigerP, HabereckerM, AndermattR, ZinkernagelAS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–8.
