PMC8740284_01
Radiological course in the triplets: Chest radiographies taken on days 1, 2, 6, and 13 after birth in triplet I; on days 1 and 2 in triplet II and on days 2 and 6 in triplet III (selected radiographs shown). Images are windowed in order to optimize visualization of the relevant findings.
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F1
In all triplets, chest radiographies showed bilateral, diffuse, multifocal cystic and linear radiolucencies and signs of lung hyperinflation, clearly distinct of prematurity-related acute respiratory distress syndrome (pmARDS) but resembling pulmonary interstitial emphysema (Figure 1).
Panel 1 (Region A_5x): Focal chronic histiocytic intervillositis is seen in the center of the picture. Panel 2 (Region A_40x): Higher magnification of the center of Panel 1 showing intervillous histiocytic aggregates. Panel 3 (Region B_5x): Focal chronic histiocytic intervillositis is seen in the center of the picture. Compared to Panel 1 the changes seem a bit more pronounced. Panel 4 (Region B_40x): Higher magnification of the center of Panel 3 showing intervillous histiocytic aggregates.
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F2
Histologically, placental villi revealed different maturation status, discrete intervillous fibrin deposition (Figure 2), and focal degeneration of the villi. Additionally, focal intervillous histiocytic aggregates were seen, compatible with chronic histiocytic intervillositis (Figure 2).
Immunohistological stainings for the detection of SARS-CoV-2- N-protein of the placenta of the COVID-19 positive triplets. Syncytiotrophoblast cells reveals strong membrane positivity for the viral N-protein. Scattered positive macrophages, Hofbauer cells and stroma cells are also virus positive. Control placenta of healthy triplets was consistently negative in immunohistochemistry (magnification x25 and x200).
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F3
Placenta tissue of healthy triplets was completely negative (Figure 3). ACE2 receptor was stained by using the mouse anti-ACE2 antibody (Novusbio/R&D Systems, clone #171606, 1:2000) and the ultraView detection system (Ventana) mentioned above. ACE2 was found to be expressed in syncytiotrophoblasts, villous cytotrophoblasts, villous stromal cells, and some stromal cells and macrophages within the decidua, corresponding well to the SARS-CoV-2 infected cell types within the placenta (Figure 3).