ARBs and ACE inhibitors: Implications for COVID-19 and Pregnancy

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Note: The Pregistry website includes expert reports on more than 2000 medications, 300 diseases, and 150 common exposures during pregnancy and lactation. For the topic Coronavirus, go here. For the topic ACE Inhibitors, go here. For the topic Angiotensin Antagonists, go here. These expert reports are free of charge and can be saved and shared.

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If you are taking blood pressure medication belonging to a category called ARBs, or to a category called ACE inhibitors, then you will find that these drugs present issues both for pregnancy and for COVID-19.

Just to get some terminology out of the way, like many drugs, both of these classes of drugs work by interfering with an enzyme, a chemical that body cells manufacture to control biological processes. The term ACE stands for angiotensin converting enzyme, while ARB stands for angiotensin-receptor blocker. Blocker is basically another word for inhibitor and, basically, ARBs and ACE inhibitors throw a monkey wrench into the production and action of a series of hormones that normally has two effects. One effect is to constrict blood vessels, which causes blood pressure to increase. The other effect is to make the kidneys retain more sodium inside the body, which has the effect of raising the blood pressure.

If you are taking an ACE inhibitor or an ARB prior to pregnancy, you must consult with your doctor if you become pregnant or are trying to become pregnant. These drugs must be stopped during pregnancy, as they are notorious for damaging the fetal kidneys. However, anybody who is taking an ACE inhibitor or an ARB is doing so on account of a very serious health condition, such as high blood pressure (to lower blood pressure), congestive heart failure (to reduce the amount of fluid in the body), or diabetes mellitus (to help prevent serious complications in the nerves and retinas). Therefore, you should not stop taking these medications on your own. Instead, you should verify that the doctor who is managing your health condition (such as your cardiologist, endocrinologist, or primary care doctor) is aware of your pregnancy status, so he or she can replace your ACE inhibitor or your ARB with a different type of blood pressure drug that is safe during pregnancy. In nearly all cases, if you have visited an obstetrician or family doctor resulting in a positive pregnancy test, your other doctors will know about it immediately though the electronic health record (EHR), as will your pharmacist. However, if all you have is a result of a take home pregnancy test, or if you are trying to get pregnant and haven’t informed anyone on your healthcare team, you need to bring this to the attention of anybody who has prescribed you drugs.

By now, you may be wondering what is the deal with ACE inhibitors and ARBs and COVID-19? What I can tell you at this point is that there is a connection, but the details are still under investigation. Scientists have known for many years that human coronaviruses that cause severe complications in the lungs get into lung cells utilizing a protein called ACE 2, which is an enzyme, but not the same enzyme as ACE. The job of ACE is to convert a substance called angiotensin I into a hormone called angiotensin II, which does a lot of things throughout the body, including causing constriction of blood vessels, thus raising blood pressure. In contrast, the job of ACE 2 is to convert angiotensin II into yet another hormone called angiotensin 1-7, which does the opposite of angiotensin II; it dilates (opens up) blood vessels, causing blood pressure to decrease.

The ACE 2 enzyme is also called the ACE 2 receptor, because it happens that it sits on the surface of various body cells, including lung cells. Being on the surface of cells, while its minding its own business making lots of angiotensin 1-7 to lower blood pressure, ACE 2 also can serve as an attachment point for other things, such as drugs, but also viruses. Coronaviruses get their name from the word corona, meaning crown, because of a crown-like appearance that they have, due to proteins that stick out from the viruses like spikes. Although most coronaviruses do not make it down into the lungs of humans, SARS-CoV2 (the virus that causes COVID-19) is one of three exceptions. It can get down into the lungs and when this happens, the spiky proteins of the virus attach to the ACE 2 receptors and use them as entry points to invade the cells.

Based on how the production of ACE 2 is controlled, based on laboratory animal studies, and based on a limited number of studies of humans suffering from other coronavirus diseases (SARS and MERS), scientists suspect that taking ACE inhibitors and ARBs could increase the amount of ACE 2 receptors present on lung cells. Consequently, there has been some concern that the virus could have an easier time infecting lung cells of people who take these drugs, and such people have been active on social media, discussing whether they ought to stop their medications.

It turns out, however, that the situation involving interaction between the drugs, the ACE 2 receptors, and the virus is very complex. There is some evidence that these drugs actually lower the risk of the virus infecting the cells of the lungs’ air sacs, even while giving the virus more ACE 2 receptors to utilize as entry points into t he cell. There are different hypotheses that scientists are debating to explain it, one being that too many virus particles getting their genetic material into a cell might actually overwhelm cell machinery that the virus would otherwise hijack to make little baby viruses. Furthermore, a life threatening complication resulting from viral infection of the air sac cells, known as acute respiratory distress syndrome (ARDS), may be less likely in people taking ARBs and ACE inhibitors, because of the effects of these drugs opening up blood vessels.

Given all of the unknowns and the possibility that medications could hurt in one way, yet help in another, the current recommendation from experts is that people who are already taking an ACE inhibitor or an ARB should not be taken off the medication. That is, unless they need to come off the medication for a reason not related to COVID-19, such as the blood pressure dropping to low, or being pregnant.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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