Increased DNA damage/repair response in placentas from women infected with COVID-19 in pregnancy

SARS-CoV-2 may induce DNA damage in infected cells. The objective of the study is to determine if maternal COVID-19 infection can induce cellular DNA damage in the placenta. We examined phospho-Histone H2AX (pH2AX) foci-positive cells, MRE11 expression, and telomere length (markers of DNA damage/repair) in placental specimens from women with or without COVID-19 infection during pregnancy.

A total of 61 placental formalin-fixed paraffin embedded (FFPE) tissue specimens were used in the study, 33 in the COVID-19 group and 28 in the control group. Expression of pH2AX (Ser-139) and MRE11 was determined by immunostaining. Telomere length was assessed using the relative Human Telomere Length Quantification qPCR Assay Kit. Maternal demographic data was obtained via electronic medical record review. Data were analyzed by unpaired t-test or Chi-square test. A p level <0.05 was set statistically significant.

pH2AX foci-positive cells in the placentas were significantly higher in the COVID group than in the control group, p < 0.01; Relative expression of MRE11 was significantly increased in the COVID group (15.68 ± 1.57) than in the control group (5.74 ± 1.21), p < 0.01. In contrast, relative telomere length was significantly shorter in the COVID group (0.839 ± 0.123) than in the control group (1.652 ± 0.285), p < 0.05. The correlation of telomere length with placental weight and gestational age at delivery and the correlation of placental/newborn ratio were also analyzed.

Both pH2AX and MRE11 are biomarkers of DNA double-strand breaks. Telomeres are targets of a persistent DNA damage response, and reduced telomere length is an indicator of cellular senescence and aging. Our findings of increased pH2AX foci-positive cells and MRE11 expression and reduced telomere length in placental cells from women infected with COVID-19 in pregnancy provide plausible evidence that increased placental cellular DNA damage could be associated with maternal COVID-19 infection in pregnancy.