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At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, uncertainties about the virus and its dangers during pregnancy caused great uncertainty and fear, especially among pregnant women. New data suggest an increased risk of obstetric complications, including maternal complications, preterm labor, intrauterine growth restriction, hypertensive disorders, stillbirths, gestational diabetes and risk, of neonatal developmental disorders. In addition, preeclampsia (PE)-like syndromes were also induced by severe COVID-19 infection. Therefore, the aim of this study was to investigate the expression of CD68 and CD163 and PD-L1 on placental tissues from acute covid patients, patients who survived a covid-19 infection and normal term controls that are known to be dysregulated in preeclampsia cases. We examined a total of 60 placentas from women that had given birth to female or male offspring in the University Hospital Augsburg. We investigated ten acute COVID-19 females, ten acute COVID-19 males, ten post-COVID-19 females, ten post-COVID-19 males, ten female term controls, and ten male term controls. Immunohistochemical staining against CD68, CD163, and PD-L1 was performed and the expression of the markers was evaluated with an immunoreactive score (percentage score). Identity of CD163- or PD-L1 expressing cells was analyzed by double immune fluorescence analyses. In opposite to PE, CD163 positive maternal macrophages are significantly upregulated in the decidua of male acute COVID-19 placentas. PD-L1 is significantly upregulated on male acute- and post-COVID-19 decidual immune cells and on male post-COVID-19 extravillous trophoblast cells. Surprisingly the observed effects are related to the fetal gender as they were not observed in female offsprings. Further investigation is necessary to analyze especially the imprinting effect of this infection.
CD24 is a mucin-like glycoprotein expressed on trophoblast cells and endothelial tissue of first and third trimester placentas. As an immune suppressor, CD24 may contribute to maternal immune tolerance to the growing fetus. CD24 is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs), specifically siglec-10. The aim of this study was to investigate the expression of both, CD24 and siglec-10 on placental tissue slides from acute covid patients, patients who survived a covid-19 infection and normal term controls. For the evaluation of CD24 & siglec-10 we used a total of 60 placentas, 10 acute covid-19 female, 10 acute covid-19 male, 10 post-covid-19 female, 10 post-covid-19 male, 10 female term controls and 10 male term controls. Immunohistochemical staining against CD24 and siglec-10 was performed and the expression of both markers was done with an immunoreactive score (IRS). Identity of CD24- or siglec-10 expressing cells was analyzed by double immune fluorescence analyses. The expression of CD24 is significantly downregulated on the extravillous trophoblast and on Hofbauer cells of female acute covid placentas. In the contrary, CD24 is significantly upregulated on male post-covid-19 Hofbauer cells. The CD24-ligand siglec-10 is significantly downregulated in post-covid-19 Hofbauer cells independently of fetal sex, whereas it shows significant higher expression in control female Hofbauer cells. CD24 and its ligand siglec-10 are differentially expressed in placentas of patients who survived a covid-19 infection. Surprisingly this effect is related to the fetal gender. Further investigation is necessary to analyze especially the imprinting effect of this infection.
