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Placental SARS-CoV-2 viral replication is associated with placental coagulopathy and neonatal complications [Letter]

Tiozzo, Caterina; Manzano, Claudia; Lin, Xinhua; Bowler, Selina; Gurzenda, Ellen; Botros, Bishoy; Thomas, Kristen; Chavez, Martin; Hanna, Iman; Hanna, Nazeeh
PMID: 37952868
ISSN: 1097-6868
CID: 5610842

"Transplacental Transmission of the COVID-19 Vaccine mRNA: Evidence from Placental, Maternal and Cord Blood Analyses Post-Vaccination" [Letter]

Lin, Xinhua; Botros, Bishoy; Hanna, Monica; Gurzenda, Ellen; Manzano De Mejia, Claudia; Chavez, Martin; Hanna, Nazeeh
PMID: 38307473
ISSN: 1097-6868
CID: 5627002

Characterization of lipoproteins in human placenta and fetal circulation as well as gestational changes in lipoprotein assembly and secretion in human and mouse placentas

Nargis, Titli; Lin, Xinhua; Giordano, Elena; Ijaz, Laraib; Suhail, Sarah; Gurzenda, Ellen M; Kiefer, Daniel; Quadro, Loredana; Hanna, Nazeeh; Hussain, M Mahmood
In the maternal circulation, apoB-containing low-density lipoproteins (LDL) and apoA1-containing high-density lipoproteins (HDL) transport lipids. The production of lipoproteins in the placenta has been suggested, but the directionality of release has not been resolved. We compared apolipoprotein concentrations and size-exclusion chromatography elution profiles of lipoproteins in maternal/fetal circulations, and in umbilical arteries/veins; identified placental lipoprotein-producing cells; and studied temporal induction of lipoprotein-synthesizing machinery during pregnancy. We observed that maternal and fetal lipoproteins are different with respect to concentrations and elution profiles. Surprisingly, concentrations and elution profiles of lipoproteins in umbilical arteries and veins were similar indicating their homeostatic control. Human placental cultures synthesized apoB100-containing LDL-sized and apoA1-containing HDL-sized particles. Immunolocalization techniques revealed that ApoA1 was present mainly in syncytiotrophoblasts. MTP, a critical protein for lipoprotein assembly, was in these trophoblasts. ApoB was in the placental stroma indicating that trophoblasts secrete apoB-containing lipoproteins into the stroma. ApoB and MTP expressions increased in placentas from the 2nd trimester to term, whereas apoA1 expression was unchanged. Thus, our studies provide new information regarding the timing of lipoprotein gene induction during gestation, the cells involved in lipoprotein assembly and the gel filtration profiles of human placental lipoproteins. Next, we observed that mouse placenta produces MTP, apoB100, apoB48 and apoA1. The expression of genes gradually increased and peaked in late gestation. This information may be useful in identifying transcription factors regulating the induction of these genes in gestation and the importance of placental lipoprotein assembly in fetal development.
PMID: 37315736
ISSN: 1879-2618
CID: 5594982

Perinatal SARS-CoV-2 infection and vaccination: new insight [Meeting Abstract]

Hanna, N N
Cumulative data regardingCOVID-19 infection during pregnancy have demonstrated the ability of SARS-CoV-2 to infect the placenta. However, the mechanisms of SARS-CoV-2 placental viral entry are yet to be defined. SARS-CoV-2 infects cells by binding to the ACE2 receptor. However, SARS-CoV-2 cell entry also requires co-localization of spike protein cleavage by the serine protease TMPRSS2. However, the co-expression of ACE2 and TMPRSS2 in placental cells is debated, raising the question of whether potential non-canonical molecular mechanismsmay be involved in SARS-CoV-2 placental cells' viral entry. Although published data regarding the ability of the SARS-CoV- 2 to infect the fetus are contradicting, the placenta appears to be an immunological barrier to active SARS-CoV-2 infection and vertical transmission; however, the mechanism is unclear. Our experiments demonstrated the ability of the SARS-CoV-2 virus to directly infect the placenta and induce transcriptomic responses in COVID-positive mothers. These transcriptomic responses were characterized by differential expression of specific mRNAs and miRNAs associated with SARS-CoV-2 infection, with induction of specific placental miRNAs that can inhibit viral replication. Failure in such mechanisms may be associated with vertical transmission. Since the start of the COVID-19 pandemic, the COVID-19 mRNA vaccines have been widely used to reduce the morbidity and mortality of SARS-CoV-2 infection. Historically, non-live vaccines have not caused any harm to pregnant mothers; however, it is unclear whether our current understanding of the effects of non-live vaccines serves as a reliable precedent owing to the novel technology used to create these mRNA vaccines. Since there are no definitive data on the possible biodistribution of mRNA vaccines to the placenta, the likelihood of vaccine mRNA reaching the fetus remains uncertain. Little has been reported on the tissue localization of the lipid nanoparticles (LNPs) after intramuscular (IM) administration of the mRNA vaccine. The biodistribution of LNPs containing the mRNA vaccine has been investigated in animal models but not humans. In the murine model, the vaccine LNPs were rapidly disseminated to several organs, including the heart, liver, kidney, lung, and spleen, following IM administration. However, no traditional pharmacokinetic or biodistribution studies have been performed with the mRNA vaccines, including possible biodistribution to breast milk or the placenta
ISSN: 1600-0897
CID: 5514442

Messenger RNA Vaccine in Mother's Milk-Reply

Hanna, Nazeeh; Clauss, Christie; Krilov, Leonard R
PMID: 36804769
ISSN: 2168-6211
CID: 5433782

Is Lactoferrin Supplementation Beneficial for All Preterm Infants?

Nayak, Amrita; Tiozzo, Caterina; Lin, Xinhua; Mejia, Claudia; Gurzenda, Ellen; Kim, Maureen; Hanna, Nazeeh
OBJECTIVE: Human milk (HM) has antibacterial properties due to the presence of immune-modulators, including lactoferrin (LF). This study will determine effect(s) of HM maturation, fortification, and storage conditions on LF levels and its antibacterial properties. STUDY DESIGN/METHODS:. RESULTS: The highest level of LF in preterm HM was observed in the first week of lactation. However, storage of preterm HM at 4°C decreased LF levels significantly. Both LF levels and antibacterial activity in preterm HM was lower compared with term HM, but significantly higher than donor HM even after HM-based fortification. LF supplementation of donor HM improved its antibacterial activity. CONCLUSION/CONCLUSIONS: Preterm infants fed donor HM, formula, or stored HM at 4°C may benefits from LF supplementation to improve HM antibacterial properties. KEY POINTS/CONCLUSIONS:· Milk LF levels vary with storage and maturity.. · Donor milk is deficient in LF even after adding HM-based fortification.. · Donor HM and formula fed infants may benefit from LF..
PMID: 34058763
ISSN: 1098-8785
CID: 4891072

Extracellular Vesicle-microRNAs as Diagnostic Biomarkers in Preterm Neonates

Schiller, Emily A; Cohen, Koral; Lin, Xinhua; El-Khawam, Rania; Hanna, Nazeeh
Neonates born prematurely (<37 weeks of gestation) are at a significantly increased risk of developing inflammatory conditions associated with high mortality rates, including necrotizing enterocolitis, bronchopulmonary dysplasia, and hypoxic-ischemic brain damage. Recently, research has focused on characterizing the content of extracellular vesicles (EVs), particularly microRNAs (miRNAs), for diagnostic use. Here, we describe the most recent work on EVs-miRNAs biomarkers discovery for conditions that commonly affect premature neonates.
PMID: 36768944
ISSN: 1422-0067
CID: 5421072

Detection of Messenger RNA COVID-19 Vaccines in Human Breast Milk

Hanna, Nazeeh; Heffes-Doon, Ari; Lin, Xinhua; Manzano De Mejia, Claudia; Botros, Bishoy; Gurzenda, Ellen; Nayak, Amrita
PMID: 36156636
ISSN: 2168-6211
CID: 5328352

"Impact of the COVID pandemic on the incidence of prematurity: Critical role of gestational age and environment." [Letter]

Weinberger, Barry; Divers, Jasmin; Campbell, Deborah; Ham, Steven; Juliano, Courtney; Kurepa, Dalibor; Lagamma, Edmund; Mally, Pradeep; Nafday, Suhas; Sheri, Nemerofsky; Sridhar, Shanthy; Williams, Kim; Hanna, Nazeeh
PMID: 35218696
ISSN: 1097-6868
CID: 5172662


Abuso, S.; Choi, J. J.; Akerman, M.; El-Khawam, R.; Kamity, R.; Clauss, C.; Hanna, N.; Dumpa, V.
ISSN: 1081-5589
CID: 5243662