Study explains why fetuses and newborns are mostly spared by COVID-19

By Angela Betsaida B. Laguipo, BSNJul 15 2020

Amid the coronavirus pandemic, it has been previously suggested that the most vulnerable individuals to developing severe coronavirus disease (COVID-19) include the elderly, those with underlying health conditions, and those who have weakened immune systems.

Meanwhile, younger people, children, pregnant women, and their unborn child, and infants are mostly spared by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). If they do get infected, they may only experience mild symptoms or no symptoms at all.

Now, a team of researchers at Wayne State University School of Medicine and the Perinatology Research Branch (PRB) of the National Institute of Child Health and Human Development/National Institutes of Health in Detroit shows how fetuses and newborns are mostly spared by the coronavirus infection.

This transmission electron microscope image shows SARS-CoV-2—also known as 2019-nCoV, the virus that causes COVID-19—isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the lab. The spikes on the outer edge of the virus particles give coronaviruses their name, crown-like. Image captured and colorized at NIAID's Rocky Mountain Laboratories (RML) in Hamilton, Montana. Credit: NIAID

How does SARS-CoV-2 infect cells?

Coronaviruses are single-stranded RNA viruses, which are about 120 nanometers in diameter. Usually, these viruses thrive in bats and wild birds and can spread to other animals. In some cases, the virus can jump from animals to humans, causing outbreaks in populations.

In the past, there had been two outbreaks of coronaviruses, the severe acute respiratory syndrome (SARS) in 2003, and the Middle East Respiratory Syndrome (MERS) in 2012.

To infect cells, the virus’s protein spikes bind to a protein on the surface of cells, called the angiotensin-converting enzyme 2 (ACE2). Typically, ACE2 plays a role in the regulation of blood pressure. However, when the coronavirus binds to it, it produces chemical changes that can connect the membranes around the cell and the virus together, allowing the RNA of the virus to enter the cell and trigger infection.

Once inside the cell, the virus hijacks the host cell’s protein-making machinery to translate its RNA into new copies of the virus. Within just hours, the cells will produce thousands of new virions, which go and infect other healthy cells.  This is how fast a viral infection can spread in the body.

Transcriptional map of the human placenta, including the decidua, in the three 689 trimesters of pregnancy. A. Uniform Manifold Approximation Plot (UMAP), where dots 690 represent single cells/nuclei and are colored by cell type (abbreviations used are: STB, 691 Syncytiotrophoblast; EVT, Extravillous trophoblast; CTB, cytotrophoblast; HSC, hematopoietic 692 stem cell; npiCTB, non proliferative interstitial cytotrophoblast; LED, lymphoid endothelial 693 decidual cell) B. UMAP plot with cells/nuclei co-expressing one or more transcripts for ACE2 694 and TMPRSS2, genes that are necessary for SARS-CoV-2 viral infection and spreading, in red.

Pregnancy and COVID-19

According to the researchers of the current study, published in the journal eLife, placental membranes that contain the fetus and amniotic fluid lack the messenger RNA (mRNA) molecule required to produce the ACE2 receptor, the primary cell surface receptor utilized by the coronavirus to trigger an infection.

Further, the tissues in the placenta also lack the messenger RNA required to produce the enzyme, known as TMPRSS2, which the SARS-CoV-2 uses to enter a cell. The receptor and enzyme are present in only small amounts in the placenta, which suggests that this might be the reason why the novel coronavirus rarely infects fetuses or newborns of women infected with the virus.

While pregnant women represent a potential high-risk population given that other viral infections like the Zika virus, rubella, and cytomegalovirus can be passed from the mother to the unborn child, the evidence for this type of transmission in SARS-CoV-2 infections is rare.

“The findings of this study help to understand why mother-to-fetus transmission is so rare (less than 2% of cases). The most likely explanation is that the cellular instructions for the production of the main receptor for SARS-CoV-2 are not expressed in the human placenta. In contrast, the receptors for other viruses known to cause fetal infection such as Zika and cytomegalovirus were found in placental cells,” Dr. Roberto Romero, chief of the PRB, said in a statement.

Rare transplacental transmission

At the same time, in a study published in the journal Nature Communications, researchers in France have described the first confirmed case of a newborn infected in the womb with the novel coronavirus disease by the mother.

“We report a proven case of transplacental transmission of SARS-CoV-2 from a pregnant woman affected by COVID-19 during late pregnancy to her offspring,” the researchers confirmed.

The infant, who was born in March, experienced brain swelling and neurological symptoms tied to COVID-19 in adults. The good news is, the baby has recovered.

The 23-year-old mother was admitted to a hospital in France with fever and severe cough. The mother was tested for the coronavirus, and it turned out positive. She delivered three days after via cesarean section. An hour after birth, the baby was tested for SARS-CoV-2 and again three and 18 days later. All the tests showed that the newborn is infected with the novel coronavirus.

“In conclusion, we have demonstrated that the transplacental transmission of SARS-CoV-2 infection is possible during the last weeks of pregnancy. Transplacental transmission may cause placental inflammation and neonatal viremia. Neurological symptoms due to cerebral vasculitis may also be associated,” the team concluded.