PMC8415358_01
Fetal-placental magnetic resonance imaging (MRI); pathology of the placenta and lung histopathology. (A) 3.0 Tesla MRI of placenta and fetus, using two 18-channel abdominal coil, showing the umbilical cord with no evident flow, no evident signal void (red arrow), and heterogeneous placenta, with ill-defined cotyledons, with contours having fewer lobulations than usual and wedge-shape or round-shape hypointense signal areas in T2 Haste sequence (orange arrowhead and orange arrows, respectively). The placental image showed insertion in the posterior wall, with a "cake" aspect, and the uterine insertion base is smaller than usual, which gave it a "shrinkage" aspect (coronal and sagittal T2 Haste images). Altered habitual T1 and T2 placental signals with hyposignal plate in T2 along its entire length of the fetal face, appearance of a line drawn in pencil (green arrows), presence of large and dilated vessels with massive thrombosis characterized by the unusual hyperintense signal in T2, and also blood lakes between the placental tissue (areas of hypointense signal in T2 and hyperintense signal in T1, predominating in the periphery) (white arrows). Diffusion-weighted image (DWI) sequence shows higher restriction than the usual pattern, and this is more evident in the right posterolateral portion of the placenta (black arrowheads), where vascular dilation and thrombosis are more pronounced. There are also areas of necrosis characterized by the facilitation mechanism more evident in the left placental portion (black arrows). (B) Placenta pathology. Left: maternal surface is wrinkled, compact, and yellow-tan with patchy hemorrhages. Middle: cut surfaces with extensive and diffuse fibrin deposition and recent infarcts. At the level of the umbilical cord insertion, there is a large subchorionic thrombus (arrow). Right: histological section with villitis, intervillositis, and massive fibrin deposition with intervillous thrombosis. (C) Histological sections of the lung. Left: thick alveolar septa with aggregates and scattered lymphocytes in pleura (hematoxylin and eosin). Middle: immunohistochemistry showing CD3+ T lymphocytes in the pleura and alveolar septa. Right: immunohistochemistry showing no lymphocytes in a normal control lung (patient without COVID-19).
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F1
A timeline of the case evolution is presented in Supplementary Figure 1. The main findings are presented in more detail in Figure 1A and Supplementary Figure 2 and consisted mainly of a substantial placental impairment (appearance of a collapsed placenta with no viability). The placenta weighted 470 g (80th percentile for gestational age) and had a paramarginally inserted three-vessel umbilical cord with a reddish color, and the chorionic plate vessels were highly dilated and congested and had magistral distribution; the fetal surface was reddish, and the membranes were hypotransparent (Figure 1B, left and middle). Histologically, it showed massive diffuse inflammatory alterations in regions with a predominance of acute and chronic intervillositis (Supplementary Figures 3F,G) and intervillous neutrophilic microabscesses associated with chronic and proliferative villitis and acute deciduitis (Figure 1B, right; and Supplementary Figure 3F). Histology of the lungs showed mild thickening of the pleura and alveolar septa, with mild infiltration of lymphocytes (Figure 1C, left) without signs of fibrosis as seen with Gomori's staining. They were CD3 T lymphocytes (Figure 1C, middle) and can be compared with a negative control lung of a patient without COVID-19 (Figure 1C, right).
Fetal tissues immunostained for SARS-CoV-2 spike protein (SP) (green) counterstained with nuclear marker DAPI (blue). Images were acquired with a confocal microscope Leica TCS SP8 using a x 63 objective lens. Scale bar for all pictures is 50 mum. Top pictures: pulmonary immunodetection of SP (the three on the left) and negative control of immunofluorescence without primary antibody (right) in the present case. Lower images: immunodetection of SP in the brain and heart of this case (the two on the left), negative control immunofluorescence without primary antibody in a section of the brain, and lack of immunodetection of SP in a non-COVID fetal lung (right).
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F2
The main findings are presented in more detail in Figure 1A and Supplementary Figure 2 and consisted mainly of a substantial placental impairment (appearance of a collapsed placenta with no viability). As a result, positive immunolabeling was identified in the fetus's lung, brain, and heart and was absent in the immunofluorescence negative lung control of a non-COVID case (Figure 2).