ABSTRACT
INTRODUCTION We report a case of stillbirth in a 33-years-old Caucasian woman at 36+1 weeks of gestation (WG), with a positive nasopharyngeal swab (NFS) for COVID-19 and preterm labor in the absence of vertical transmission. METHODS Histologic examination of the placenta was performed after fixation in 10% buffered formalin. The fetal and placental samples underwent routine processing with paraffin embedding, and staining with hematoxylin and eosin for microscopic morphological evaluation. Additional maternal surface samples were later additionally fixed in 2.5% glutaraldehyde in 1X PBS pH 7.4, and processed for examination by transmission electron microscopy Paraffin embedded placental tissue sections were used for immunohistochemical staining with anti-platelets CD61 antibody and anti SARS-CoV Spike Antibody Viral infection of the placenta was assessed by the presence of SARS-CoV-2 RNA by real time RT-PCR assay. Swabs were obtained from fetal right and left main bronchus, small intestine and rectum to detect SARS-CoV-2 RNA by RT-PCR assay. RESULTS Sectioning and examination of the cut placental surface showed a diffuse marbled appearance and a focal hemorrhagic area. At light microscope, the placental tissue showed multiple areas of hemorrhagic/ischemic necrosis and thrombosis of several maternal and fetal vessels with mural/ luminal fibrin and platelet deposition defining a clear picture of fetal vascular malperfusion.SARS-CoV-2 RNA in placental tissue was revealed by real time rRT-PCR assay. Virus particles were uniquely identified by Electron Microscopy mainly within the cytoplasm of endothelial cells, in the cytosol and in cytoplasmic vacuoles, or adjacent to damaged endothelial cells. CONCLUSIONS In our case, fetal vascular malperfusion was likely casually associated with the infection;indeed, our unique Electron Microscopy images clearly showed that the marked SARS-CoV-2 endotheliotropism involved the intravillous fetal capillaries likely leading to cell dysfunction and procoagulant activity. Since placental infection does not always correlate with infection of the fetus, it is possible that a time interval may ensue between these two processes;a stillbirth that occurs in this time frame can be mechanistically explained by an overriding process of severe endothelial dysfunction occurring within intravillous capillaries or massive hypoperfusion of the intervillous space. The consequences of placentotropic COVID-19 include the possible occurrences of vertical transmission or fetal death resulting from maternal and/or fetal placental hypoperfusion the prevailing mechanism being dependent by unknown determinants. The diffuse thrombosis and subsequent ischemia of fetal capillaries induced by COVID-19 cannot be predicted by standard clinical surveillance nor prevented by anticoagulants and represent a severe burden of Sars-Cov-2 infection.
ABSTRACT
INTRODUCTION The ongoing global pandemic of Coronavirus disease 2019 (COVID-19) has dramatically impacted on public health in the lasts months. The aetiology of the disease is related to a thrombotic microangiopathy, that can occur in several body compartments. In literature, molecular analysis of placental tissues revealed that the barrier between mother and fetus, damaged by high viral load of COVID-19, showed massive fibrin deposition and necrosis of the syncytiotrophoblast layer of the villi, without evidence of vertical transmission. The first aim of our study is to evaluate materno-fetal hemodynamics in pregnant women affected by previous COVID-19. The second aim of our study is to assess the utility of placental magnetic resonance, as previously described for maternal infectious disease. METHODS A retrospective pilot study in a tertiary maternity unit within a university hospital was conducted. We included pregnant women affected by previous COVID-19 infection, who underwent blood tests (inflammatory markers, coagulation tests, antibodies rate), obstetric Doppler ultrasound monthly, for the evaluation of fetal biometry and maternal uterine arteries, fetal middle cerebral artery and umbilical artery blood flow, and fetal magnetic resonance, focused on the examination of placenta. Moreover, gestational age at first positive Real Time-PCR test, seroconversion time, fetal echocardiography, maternal lung ultrasound score and perinatal outcomes were assessed. RESULTS From March 2020 to March 2021, among 36 pregnant women selected, twenty patients met inclusion criteria and were enrolled. Patients mean age was 33.3 years and they were divided into two groups: the largest part of these (70%) was symptomatic, with two or more symptoms (the most common was fever), while 6/20 (30%) patients were asymptomatic. No difference in adverse obstetrical and perinatal outcomes between symptomatic and asymptomatic group was registered (35.71% [5/14] vs. 33.33% [2/6];p=.91). The most common pregnancy complication was gestational diabetes. The estimated fetal weight mean percentile was in normal ranges in both groups (37° in symptomatic group vs. 33.5°;p=.4). A good percentage of patients showed an altered fetal Doppler velocimetry (4/14 [28.57%] vs 3/6 [50%];p=.35). Fetal echocardiography was normal in 78.57% of symptomatic women and in 66.66% of asymptomatic (p=.57). Fetal magnetic resonance did not proved any placental or fetal anomaly. Mean gestational age at delivery was 39.5 weeks in symptomatic group and 38.2 in asymptomatic group (p=.14). None preterm birth occurred. The average baby weight at birth was 3600 g in the first group and 3250 g in the second one (p=.39). None had a pathological Apgar score at first and 5th minute. CONCLUSIONS No statistically significant differences between symptomatic and asymptomatic group were found in obstetrical and perinatal outcomes, ultrasound and radiological findings. The additional role of fetal magnetic resonance turned out to be not useful. A larger sample of patients would be necessary to better investigate materno-fetal hemodynamic aspects after COVID-19 infection.