In-Utero Mother-to-Child SARS-CoV-2 Transmission: Viral Detection and Fetal Immune Response

Abstract Pregnancy is known to increase the risk of severe illnesses in response to viral infections. Therefore, the impact of SARS-CoV-2 infection during gestational ages might be detrimental and the potential vertical transmission should be thoroughly studied.Herein, we investigated whether SARS-CoV-2 vertical transmission is possible and, in case, whether this results in a fetal involvement. Additionally, we analyzed the role of the antibody and the inflammatory responses in placenta and plasma from SARS-CoV-2-positive pregnant women and fetuses.31 SARS-CoV-2 pregnant women were enrolled. Real-time PCR was performed to detect the virus on maternal and newborns’ nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk. Maternal and umbilical cord plasma, and milk were tested for specific anti-SARS-CoV-2 antibodies. RNA expression quantification of genes involved in the inflammatory response was performed on four selected placentas. On maternal and umbilical cord plasma of the same subjects, secreted cytokines/chemokines were quantified.SARS-CoV-2 is found in at-term placentae and in the umbilical cord blood, in the vaginal mucosa of pregnant women and in milk. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in the umbilical cord blood of pregnant women, as well as in milk specimens. Finally, a specific inflammatory response is triggered by SARS-CoV-2 infection in pregnant women at both systemic and placental level, and in umbilical cord blood plasma.Our data strongly support the hypothesis that in-utero vertical transmission is possible in SARS-CoV-2 positive pregnant women. This is essential for defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.

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IN−UTERO MOTHER−TO−CHILD SARS−CoV−2 TRANSMISSION: viral detection and fetal immune response

10.1101/2020.07.09.20149591 ◽

2020 ◽

Cited By ~ 1

Author(s):

Claudio Fenizia ◽

Mara Biasin ◽

Irene Cetin ◽

Patrizia Vergani ◽

Davide Mileto ◽

...

Keyword(s):

Inflammatory Response ◽

Cord Blood ◽

Pregnant Women ◽

Umbilical Cord ◽

Vertical Transmission ◽

Umbilical Cord Blood ◽

In Utero ◽

Vaginal Mucosa ◽

Cord Plasma ◽

The Impact

Pregnancy is known to increase the risk of severe illnesses in response to viral infections. Therefore, the impact of SARS−CoV−2 infection during gestational ages might be detrimental and the potential vertical transmission should be thoroughly studied. Herein, we investigated whether SARS−CoV−2 vertical transmission is possible and, in case, whether this results in a fetal involvement. Additionally, we analyzed the role of the antibody and the inflammatory responses in placenta and plasma from SARS−CoV−2−positive pregnant women and fetuses. 31 SARS−CoV−2 pregnant women were enrolled. Real−time PCR was performed to detect the virus on maternal and newborns nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk. Maternal and umbilical cord plasma, and milk were tested for specific anti−SARS−CoV−2 antibodies. RNA expression quantification of genes involved in the inflammatory response was performed on four selected placentas. On maternal and umbilical cord plasma of the same subjects, secreted cytokines/chemokines were quantified. SARS−CoV−2 is found in at-term placentae and in the umbilical cord blood, in the vaginal mucosa of pregnant women and in milk. Furthermore, we report the presence of specific anti−SARS−CoV-2 IgM and IgG antibodies in the umbilical cord blood of pregnant women, as well as in milk specimens. Finally, a specific inflammatory response is triggered by SARS−CoV−2 infection in pregnant women at both systemic and placental level, and in umbilical cord blood plasma. Our data strongly support the hypothesis that in−utero vertical transmission is possible in SARS−CoV−2 positive pregnant women. This is essential for defining proper obstetric management of COVID−19 pregnant women, or putative indications for mode and timing of delivery.

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Analysis of SARS-CoV-2 vertical transmission during pregnancy

Nature Communications ◽

10.1038/s41467-020-18933-4 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 7

Author(s):

Claudio Fenizia ◽

Mara Biasin ◽

Irene Cetin ◽

Patrizia Vergani ◽

Davide Mileto ◽

...

Keyword(s):

Cord Blood ◽

Umbilical Cord ◽

Vertical Transmission ◽

Umbilical Cord Blood ◽

Inflammatory Responses ◽

Vaginal Mucosa ◽

Cord Plasma ◽

Expression Of Genes ◽

Obstetric Management ◽

The Impact

Abstract The impact of SARS-CoV-2 infection during gestation remains unclear. Here, we analyse the viral genome on maternal and newborns nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk from 31 mothers with SARS-CoV-2 infection. In addition, we also test specific anti-SARS-CoV-2 antibodies and expression of genes involved in inflammatory responses in placentas, and in maternal and umbilical cord plasma. We detect SARS-CoV-2 genome in one umbilical cord blood and in two at-term placentas, in one vaginal mucosa and in one milk specimen. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in one umbilical cord blood and in one milk specimen. Finally, in the three documented cases of vertical transmission, SARS-CoV-2 infection was accompanied by a strong inflammatory response. Together, these data support the hypothesis that in utero SARS-CoV-2 vertical transmission, while low, is possible. These results might help defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.

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An Immunological Perspective: What Happened to Pregnant Women After Recovering From COVID-19?

Frontiers in Immunology ◽

10.3389/fimmu.2021.631044 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sijia Zhao ◽

Ting Xie ◽

Li Shen ◽

Hong Liu ◽

Liling Wang ◽

...

Keyword(s):

B Cells ◽

Cord Blood ◽

Pregnant Women ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Peripheral Blood ◽

Immune Cell ◽

Immune Cell Subsets ◽

Significant Difference ◽

The Impact

The coronavirus disease 2019 (COVID-19) pandemic has been raging around the world since January 2020. Pregnancy places the women in a unique immune scenario which may allow severe COVID‐19 disease. In this regard, the potential unknown effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on mothers and fetuses have attracted considerable attention. There is no clear consistent evidence of the changes in the immune status of pregnant women after recovery from COVID-19. In this study, we use multiparameter flow cytometry and Luminex assay to determine the immune cell subsets and cytokines, respectively, in the peripheral blood and umbilical cord blood from pregnant women recovering from COVID-19 about 3 months (n=5). Our results showed decreased percentages of Tc2, Tfh17, memory B cells, virus-specific NK cells, and increased percentages of naive B cells in the peripheral blood. Serum levels of IL-1ra and MCP-1 showed a decreased tendency in late recovery stage (LRS) patients. Meanwhile, there was no significant difference in immune cell subsets in the umbilical cord blood. The placentas from LRS patients showed increased CD68+ macrophages infiltration and mild hypoxic features. The inflammatory damage of the placenta may be related to the antiviral response. Since the receptors, ACE2 and TMPRSS2, utilized by SARS-CoV-2 are not co-expressed in the placenta, so it is extremely rare for SARS-CoV-2 to cause infection through this route and the impact on the fetus is negligible.

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Costs of Hematopoietic Cell Transplantation: Comparison of Umbilical Cord Blood and Matched Related Donor Transplantation and the Impact of Posttransplant Complications

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2009.01.011 ◽

2009 ◽

Vol 15 (5) ◽

pp. 564-573 ◽

Cited By ~ 75

Author(s):

Navneet S. Majhail ◽

Jaya M. Mothukuri ◽

Claudio G. Brunstein ◽

Daniel J. Weisdorf

Keyword(s):

Cord Blood ◽

Cell Transplantation ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Hematopoietic Cell Transplantation ◽

Hematopoietic Cell ◽

Related Donor ◽

The Impact

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Transcriptional Activity of Human Endogenous Retroviruses in Response to Prenatal Exposure of Maternal Cigarette Smoking

American Journal of Perinatology ◽

10.1055/s-0038-1675768 ◽

2018 ◽

Vol 36 (10) ◽

pp. 1060-1065 ◽

Cited By ~ 4

Author(s):

Massimiliano Bergallo ◽

Ilaria Galliano ◽

Valentina Daprà ◽

Alice Pirra ◽

Paola Montanari ◽

...

Keyword(s):

Dna Methylation ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Tobacco Smoke ◽

Transcriptional Activity ◽

In Utero ◽

Endogenous Retroviruses ◽

Human Endogenous Retrovirus ◽

Human Umbilical Cord

Objective Transcription of human endogenous retrovirus (HERV) elements is usually suppressed by epigenetic factors such as DNA methylation and heterochromatin silencing by histone modifications. There is an association between maternal smoking during pregnancy and DNA methylation levels in placental tissue and in DNA from cord blood. Study Design We assessed the transcriptional activity of HERV-H, HERV-K, and HERV-W in umbilical cord blood from 47 term babies unexposed to tobacco smoke in utero and 23 term babies exposed to tobacco smoke in utero. Results In our population, the HERV-H, HERV-K, and HERV-W families were always transcriptionally active, and the levels of all HERVs (H, K, W) were significantly higher in unexposed than smoke-exposed babies. Conclusion This study provides preliminary information about the transcriptional activity of HERV-H, HERV-K, and HERV-W families in human umbilical cord blood.

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