Expression of CD68 by macrophages and histopathology of the placenta in COVID-19: association with obstetric and neonatal complications

Introduction. COVID-19 causes direct and indirect placental damage through inflammatory monocytes/ macrophages, increasing the risk of infectious and inflammatory diseases in newborns.
Aim. To analyze the expression of CD68 by macrophages and structural changes in the placenta, and to assess the risks of obstetric and neonatal complications in cases of moderate COVID-19 during the third trimester of pregnancy.
Materials and methods. A histological examination was conducted on 33 placentas from women with moderate COVID-19 in the third trimester of pregnancy and 30 placentas from women not infected with SARS-CoV-2. Tissue sections were analyzed using an automated microscopy system for histological studies. CD68 expression on placental macrophages was studied using flow cytometry. Detection of SARS-CoV-2 RNA in placental tissue samples, as well as in nasopharyngeal swabs from newborns, was carried out by real-time reverse transcription polymerase chain reaction (RT-PCR).
Results. An increase in the number of CD68-positive macrophages was observed in the placentas from women with COVID-19 (80.8 (78.2; 83.5) %; p<0.0001) compared to samples from women not infected with SARS-CoV-2 (19.6 (17.2; 21.8) %). All placental samples and nasopharyngeal swabs from newborns of mothers with COVID-19 tested negative for SARS-CoV-2, indicating a low risk of vertical transmission. Histological analysis revealed signs of infectious involvement of both maternal and fetal placental parts, including focal deciduitis, villitis, and histiocytic intervillositis. Circulatory disorders were characterized by decidual vasculopathy, accelerated villous maturation, perivillous fibrin deposition, thrombosis, villous necrosis, and an increase in syncytial knots. A link was established between structural placental abnormalities and the development of chronic placental insufficiency (relative risk (RR)=2.33), preterm birth and premature rupture of membranes (RR=4.26), and fetal growth restriction. Newborns from mothers with COVID-19 exhibited complications such as cerebral ischemia and respiratory distress syndrome.
Conclusion. Moderate COVID-19 in the third trimester of pregnancy can induce structural changes in the placenta, reflecting both compensatory-adaptive responses and inflammation driven by CD68-expressing macrophages. These alterations are associated with a high risk of obstetric and neonatal complications.

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