Two years after the outbreak of COVID-19 pandemic a lot of knowledge about the course of the disease, the viral pathogenicity, the therapies, and the prevention of the infection have been acquired. Nevertheless, we are still far away from the end of it.
The impact of the SARS-CoV-2 infection in pregnancy raises great concern about the possible risks for the mothers and their unborn children.
First published data has shown somewhat contradictory findings about the consequence of the infection for pregnancy outcome, but recent reports indicated an unequivocal higher rate of preterm delivery, preeclampsia and maternal mortality in SARS-CoV-2 infected mothers. On the other hand, the risk of vertical transmission is very low (0.3-3.2%), teratogenic effects have not been observed and the infected newborns mostly have a mild course of disease so that there is only little direct impact of the maternal infection on the unborn child [1–7].
In the last months, we observed an evolution of the pandemic not only due to the development of the new SARS-CoV-2 variants. The lack of data about the Covid-19-vaccination of pregnant women, and hence the vaccine hesitancy before and during pregnancy has left a big part of childbearing women unprotected from the infection. Thus, the number of infected pregnant women exploded.
The B.1.617.2 (delta) variant is circulating in Germany since March 2021 and from June 2021 till January 2021 has been the dominant one.
The CDC reported a 4-fold risk of abortion/stillbirth in infected mothers during the B.1.617.2 (delta) variant dominance, and the severely decreased placental function caused by SARS-CoV-2 placentitis seems to be a possible explanation [8–13].
Meanwhile pathognomonic histopathological patterns in cases of SARS-CoV-2 placental infection have been described (inflammatory intervillositis, increased perivillous fibrin, villous trophoblast necrosis): all these cases are associated with poor fetal outcome [8, 10–15].
We present two cases of acute placental insufficiency and fetal distress emerging about 14 days after the diagnosis of maternal SARS-CoV-2 infection with paucisymptomatic clinical course during the dominance of the B.1.617.2 (delta) variant of the virus.
Case 1
involved a 34-year-old healthy pregnant woman (2G,0P) at 23 weeks+ 6 days of gestation, who presented to our observation at the first day after her 14-day isolation due to a mild SARS-CoV-2 infection (B.1.617.2). Until that moment, the pregnancy had been uneventful. The fetal scan showed a FGR (fetal Growth Restriction) with pathological maternal and fetal arterial flow (AREDF), but still positive pulsatiliy of the DV (Ductus Venosus). No other risks for placental insufficiency were known, the NIPT (Not Invasive Prenatal Test) showed a low risk for Trisomy 21, 18 and 13, CMV and Toxoplasmosis serology were uneventful.
The patient was normotensive, asymptomatic and with normal blood values without any indication for HELLP-Syndrome. The sFlt/PLGF quotient showed a high risk for a preeclampsia. The parents were counselled about the very poor fetal outcome in case of delivery at that moment (23w+6d), so that they preferred an expectant management, being aware of the high risk for IUD (Intrauterine fetal Death). We induced the fetal lung maturation (betamethasone 12mg IM for two doses 24 hours apart), monitored the maternal arterial pressure and well-being without fetal monitoring. At 25 weeks of gestation, the earliest point at which delivery could be recommended, we started the fetal surveillance and found a deterioration of the DV velocimetry (AREDF) and a pathologic CTG tracing (FIGO: silent with decelerations). The patient was still fine, without clinical and laboratory signs of preeclampsia. After a repeated counselling by the neonatologists, she consented the urgent cesarean section in spite of the high risk of hypoxic-ischemic encephalopathy in the newborn. The patient delivered a 450g boy, APGAR score 2/4/7, umbilical artery pH 6.99. The initial neonatal course was complicated by respiratory distress syndrome and other complications consistent with the prematurity, the extremely low birth weight and the hypoxia-acidosis at delivery. The infant recovered slowly and could be dismissed after 3 months in a relatively good clinical condition appropriate to his extreme prematurity.
Macroscopically, the placenta was eutrophic, but diffusely affected by large irregular, solid, and whitish areas (Fig. 1). Microscopically, prominent villous trophoblastic necrosis (>60%) and increased perivillous fibrin deposition could be observed. A positive RT-PCR (high viral load) was obtained from the fetal side of the placenta, although the neonatal nasopharyngeal swab was negative and the maternal one weakly positive (low viral load), suggesting a viral infection of the placenta (SARS-CoV-2 Placentitis).
Case 2
a 31-year old healthy pregnant woman (1G,0P) at 35 weeks +1 day of gestation was referred to our clinic because of a non-reassuring fetal heart rate tracing 14 days after her positive nasopharyngeal swab RT-PCR result for SARS-CoV-2, at just the first day after her isolation. She reported an asymptomatic course of the COVID-19 disease, but she noticed a reduction of the fetal movements in the last few days. Being the B.1.617.2 (delta) variant dominant in this period, there was no sequencing of the SARS-CoV-2 genome. After few minutes of FHR-registration (fetal heart rate) we suspected a fetal acidosis. A quick ultrasound scan showed a hypotrophic fetus with a pathological Doppler flow of the umbilical artery, a cerebral vasodilatation, a high pulsatile flow in the DV and a reduced amount of amniotic fluid. Thus, we confirmed the suspicion of fetal acidosis and indicated an emergent cesarean section. We delivered a depressed, acidotic, hypotrophic girl (1800g, APGAR score 1/5/7, umbilical artery pH 7.06). After an uncomplicated first care she was transferred to the intermediate NICU for monitoring. She recovered quickly and could be dismissed after a few days.
Macroscopically, the placenta was mild hypotrophic (10° percentile) and inhomogeneously affected by large irregular, solid and whitish areas. Microscopically, prominent villous trophoblastic necrosis (40-45%) and increased intervillous inflammatory infiltration (villitis and intervillositis) could be observed (Fig. 2). A positive RT-PCR (high viral load) was obtained from the fetal side of the placenta even though the neonatal and maternal nasopharyngeal swab were negative, as well as in case 1, suggestive of a viral infection of the placenta (SARS-CoV-2 Placentitis).