SARS-CoV-2 impacts the transcriptome and epigenome at the maternal-fetal interface in pregnancy (preprint)

During pregnancy, the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent works show increased incidences of adverse pregnancy outcomes in COVID-19 patients; however, the mechanism remains unclear. Here, we analyzed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from COVID-19 patients and control samples, we discovered aberrant immune activation and angiogenesis patterns in patients. Surprisingly, retrotransposons were dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of Pregnancy-Specific Glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced significant changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.

Relationship between anti-SARS-CoV-2-specific antibodies in human breast milk following SARS-CoV-2 infection during pregnancy: a prospective cohort study (preprint)

Objective: To determine the presence of anti-SARS-CoV-2 antibodies in colostrum and mature milk in women who had SARS-CoV-2 infection during pregnancy or at delivery; to investigate the correlation between anti-SARS-CoV-2 antibodies in milk with antibody in maternal blood, severity of infection and time-interval from active illness; and to evaluate immunoglobulin evolution from colostrum to mature milk. Design: prospective cohort-study Setting: six hospitals in Spain and Hong-Kong. Sample: pregnant women with confirmed SARS-CoV-2 infection during pregnancy or at delivery. Methods: Colostrum and mature milk were collected by manual expression with strict contact precautions. Colostrum samples were tested with rRT-PCR-SARS-CoV-2 and both, maternal milk and serum were tested against SARS-CoV-2 specific immunoglobulin M, A and G reactive to receptor binding domain of SARS-CoV-2 spike protein-1. Results: All rRT-PCR-SARS-CoV-2 tested negative. IgA and IgG were present in 111/135 (82.2%) and 2/135 (1.5%) colostrum samples and 27/81 (33.3%) and 0/81 mature milk samples, respectively. Concentrations of immunoglobulins were not associated with the timing of infection but women with SARS-CoV-2 pneumonia had higher levels of IgA and IgG in colostrum than those who were asymptomatic or had mild symptoms. Conclusion: No SARS-CoV-2 virus was found in human milk, however, high levels of antibodies were found in colostrum, specially IgA, irrespective of the time of infection. All women should be encouraged to breastfeed, undertaking strict contact precautions when there is active disease. Funding: Spanish Government grant (Instituto de Salud Carlos III: COV20/00188). Synlab Diagnostics’ Globales (Madrid, Spain). Perkin Elmer.