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If you have been reading The Pulse, then you probably know that the effects of SARS-CoV-2 (the virus that causes COVID-19) are not limited to the lungs but occur throughout the body. Infection with SARS-CoV-2 causes cascades of events that disrupt various organ systems, but it all stems from a particular characteristic of the virus. Whereas the genome of the virus – the genetic instructions for making new virus particles – consists of a molecule called RNA that the virus wants to deliver into cells that it infects, the viral RNA is contained within a kind of capsule consisting of a membrane made of a fat-like substance plus proteins. One of the proteins sticks out from the virus like spikes, so it is called the spike protein. The spike protein happens to fit like a key into another protein, a protein that is present on the surface of many types of body cells. Known as ACE-2, this protein, into which the SARS-CoV-2 spike protein fits, acts like a door that opens to let the virus into the cell, but ACE-2 is an enzyme with a job to perform for the body, and the virus distracts ACE-2 from performing that job. Specifically, the job of ACE-2 is to convert a hormone, called angiotensin II into a different hormone called angiotensin 1-7. To see how this relates both to pregnancy and to COVID-19, we need to discuss how angiotensin II is produced and its role in blood pressure.
Like many other phenomena in the body, blood pressure has a kind of Goldilocks zone. If it goes up too high, that’s not good because it can cause numerous life-threatening problems, like strokes and heart attacks, as well as longer-term problems like damage to the retina of the eye. However, it’s also bad if blood pressure drops too low because blood cannot perfuse adequately through vital tissues. The body has various mechanisms for keeping blood pressure in the Goldilocks zone, and these mechanisms adjust during pregnancy to account for changes in the cardiovascular system, such as an increase in the volume of blood.
Whether you are pregnant or not, if your blood pressure suddenly drops (for instance if you lose a lot of blood from a big cut), there are certain cells that detect the drop in pressure and secrete a protein called renin. Most of these renin-secreting cells are located in the kidneys, but renin can also be secreted from other organs, including the placenta during pregnancy and the ovaries. Renin is an enzyme whose production sets off an assembly line of events that leads to the production of angiotensin II, which causes the blood pressure to rise through a few different mechanisms. These mechanisms include the constriction of blood vessels and the production of other hormones that cause the kidneys to increase their retention of water and sodium in the body, and the degree to which they occur depends on how much angiotensin II is circulating in the blood. The higher the concentration of angiotensin II, the higher the blood pressure will rise.
The production of angiotensin II requires renin, plus the rest of the angiotensin II assembly line consisting of enzymes and other proteins that are made in the liver and other organs, but also, like renin, in the placenta. If all of this makes you think that the placenta must affect blood pressure, your thinking is correct. The placenta does affect blood pressure hormones, both in normal conditions and also when things go wrong. Normally in pregnancy, the amount of renin in the body increases, leading to an increase in angiotensin II, due to processes in various organs, including the placenta. Furthermore, the placenta is involved in a serious complication of pregnancy called preeclampsia. In preeclampsia, blood pressure rises to dangerous levels, plus there are problems with organs, especially the kidneys. Scientists have proposed many hypotheses to explain why this happens, including an idea that the immune system produces antibodies that have an effect very similar to angiotensin II. Additionally, because of the involvement of the placenta, the increased blood pressure and other effects of preeclampsia tend to resolve after delivery. Thus, the treatment for preeclampsia is to deliver the baby as early as possible.
Despite some initial concern that taking blood pressure medications called ACE inhibitors and ARBs, which interfere with the production (ACE inhibitors) or action (ARBs) of angiotensin II, might help the virus get into cells by making more ACE-II receptors available, studies have not demonstrated that the concern is justified.
Now, at the beginning, we mentioned ACE-2, which sits on the outside of body cells and converts angiotensin II into angiotensin 1-7. This latter hormone is extremely important because it lowers blood pressure, basically doing the opposite of its precursor, angiotensin II. The more ACE-2 molecules that are available, the more angiotensin II is converted to angiotensin 1-7. This means that ACE-2 lowers blood pressure both by getting rid of angiotensin II and by creating angiotensin 1-7, so it’s a very powerful effect.
So what happens when the SARS-CoV-2 attaches to ACE-2 on the surface of cells? Along with utilizing the ACE-2 as a doorway into the cell, the virus also prevents ACE-2 from converting angiotensin II into angiotensin 1-7. While we might expect this to raise blood pressure, based on what is known so far, the connection between COVID-19 and blood pressure is complex. Rather than COVID-19 causing blood pressure to rise, what’s clear is that people who suffer from high blood pressure have an elevated risk of getting COVID-19 and especially of developing severe complications if they do become infected. Despite some initial concern that taking blood pressure medications called ACE inhibitors and ARBs, which interfere with the production (ACE inhibitors) or action (ARBs) of angiotensin II, might help the virus get into cells by making more ACE-II receptors available, studies have not demonstrated that the concern is justified. People who are taking ACE inhibitors or ARBs have thus been advised to remain on their medications. However, pregnant women are not able to take these drugs anyway, as they can damage the fetal kidneys.
Rather than having a direct effect on blood pressure, studies are showing that interference by SARS-CoV-2 with ACE-2 on cells that line the inside of blood vessels causes a cascade of events leading to inflammation as well disruption of the body’s blood clotting system. Relevant to such changes, a study was published in May by researchers who examined lungs from patients who died from COVID-19 and lungs from those who died of respiratory complications of the flu. Looking at the lungs on the microscopic level, the team found small blood vessels obstructed by clots and damaged by inflammation and much more in COVID-19 lungs compared with flu lungs. Possibly related to this, clinicians and researchers are investigating recent outbreaks of a condition featuring blood vessel inflammation, similar to Kawasaki disease, in children, some of whom have tested positive for SARS-CoV-2. This adds to the growing realization that COVID-19 can present as very different diseases in different infected people.