ABSTRACT
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.
Subject(s)
COVID-19 , Chronobiology DisordersABSTRACT
BackgroundWhile the presence of SARS-CoV-2 in human breast milk is contentious, anti-SARS-CoV-2 antibodies have been consistently detected in the human breast milk. However, it is uncertain when the antibodies become present and for how long they last.Methods:This was a prospective cohort study including all consecutive pregnant women with confirmed SARS-CoV-2 infection during pregnancy, recruited at six maternity units in Spain and Hong Kong over a one-year period. Colostrum and mature milk were prospectively collected by manual expression with strict contact precautions and paired maternal blood samples were also collected. Colostrum samples were first tested with rRT-PCR-SARS-CoV-2 and skimmed acellular milk and maternal sera were tested against SARS-CoV-2 specific immunoglobulin (Ig) M, A and G reactive to receptor binding domain of SARS-CoV-2 spike protein 1 to determine the presence of immunoglobulins. Then, we examined how the presence of each immunoglobulin type in the colostrum was related to the time when infection was acquired by logistic regression analysis and how they were correlated to the immunoglobulins present in maternal serum and mature milk by Cohen’s kappa statistic.Results187 pregnant women with confirmed SARS-CoV-2 infection during pregnancy or at delivery were recruited. No SARS-CoV-2 was found in the human breast milk. IgA and IgG were present in 129/162 and 5/163 colostrum samples and in 19/74 and 3/74 mature milk samples, respectively. IgA was the predominant immunoglobulin found in the breast milk and its levels were significantly higher in the colostrum than in the mature milk. We did not find that the presence of immunoglobulins in the colostrum was correlated to their presence in maternal serum, the severity of the disease or the time when the infection had occurred. InterpretationSince antibodies are found in the colostrum irrespective of the time of infection and SARS-CoV-2 is not detected in human breast milk, all women should be encouraged to breastfeed, undertaking contact precautions when there is active disease.Funding This study was conducted thanks to scholarships granted by the Spanish Ministry of Health (Instituto de Salud Carlos III: COV20/00188) and by iMaterna foundation (www.imaterna.org). PerkinElmer® provided the laboratory reagents and Synlab Diagnósticos Globales (Madrid, Spain) provided human resources to conduct the analyses performed in Madrid.
Subject(s)
COVID-19ABSTRACT
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.