Contracting COVID-19 during pregnancy can increase a woman’s risk of developing pre-eclampsia, researchers have demonstrated.
A review of scientific literature by researchers in Brazil has shown that pregnant women infected by SARS-CoV-2 have a higher risk of developing pre-eclampsia, which can cause serious harm to both the mother and baby.
The findings of the review feature in the journal Clinical Science.
Pre-eclampsia is a condition that affects some pregnant women, usually during the second half of pregnancy or soon after their baby is delivered. Early signs of pre-eclampsia include high blood pressure and protein in the urine. Although most cases of pre-eclampsia are mild, there is a risk that a mother will develop fits known as ‘eclampsia’ which can be life-threatening for both them and their baby.
SARS-CoV-2 and the ACE2 protein
The authors analysed a large set of published data and concluded that the presence of SARS-CoV-2 in the maternal organism can cause alterations in levels of angiotensin-converting enzyme 2 (ACE2) – the protein to which the virus binds in order to invade cells. This consequently impairs the functioning of systems that depend on ACE2 to regulate blood pressure. Besides serving as a receptor for the virus, ACE2 plays a key role in establishing blood flow in the placenta and in the cardiovascular adaptations that occur during pregnancy.
Nayara Azinheira Nobrega Cruz, first author of the article, who conducted the study as part of her PhD research at the Federal University of São Paulo’s Medical School (EPM-UNIFESP), said: “Based on the findings of studies conducted to date on infection by SARS-CoV-2 in pregnant women and the role of ACE2 in the placenta, it can be concluded that pregnant women run a higher risk of developing the severe form of COVID-19 than non-pregnant women. Mortality is higher among pregnant women with the disease, and Brazil has one of the world’s highest rates of mortality from COVID-19 among pregnant women. Furthermore, pregnant women with the disease are more susceptible to pre-eclampsia and premature delivery.”
Mariane Bertagnolli, Principal Investigator for the study, and a professor at McGill University, said: “ACE2 plays a very important adaptive role in the maternal and foetal circulatory system, and in placentation. However, because it’s also a receptor for SARS-CoV-2, it increases risk to the placenta in pregnant patients with COVID-19, because the organ becomes a target for the virus, alongside the lungs, kidneys, and heart. Our review showed that the response varies greatly from one patient to another, and manifestations take different forms.”
The study was part of a project supported by FAPESP and led by Dulce Elena Casarini, a professor at EPM-UNIFESP and thesis advisor for Cruz during her PhD research.
Apart from the fact that ACE2 is abundant in the placenta, the researchers suggested that the incidence of COVID-19 among pregnant women could be due to inhibition of the enzyme’s action by the viral infection. As the virus uses it to invade cells, it is likely that COVID-19 infection reduces the availability of ACE2 and its capacity to protect the organism during pregnancy.
Professor Casarini said: “A deficit of ACE2 can cause an imbalance in the renin-angiotensin system and an increase in the peptide angiotensin 2, a vasoconstrictor, driving up the mother’s blood pressure and leading to pre-eclampsia.”
The researchers stressed that further research is needed to determine with greater precision why pregnant women are more susceptible to COVID-19, and the role played by the disease in pre-eclampsia. They are collecting samples of placenta from women infected by the virus to perform a series of experiments to investigate the link further. Aside from pre-eclampsia, the researchers are interested in the role of infection by the novel coronavirus in placental inflammation and vascularisation.
Bertagnolli said: “We know endothelial cells in general are affected by SARS-CoV-2. Given their role in promoting placental vascularisation and nourishing placental tissue, it’s possible that infection by the virus causes placental and foetal malperfusion.
“If so, this could restrict foetal growth. Even in the absence of pre-eclampsia, which is a more severe manifestation, there may be less visible alterations.”