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Go to Brilliant.org/SciShow to check out their course on artificial neural nets. [ ♪ INTRO ]. This episode was filmed on June 19th, 2020.

You can find more info on the COVID-19 pandemic in our playlist, linked in the description. At first, we were told to watch out for coughing, fever, and trouble breathing. That is still true.

But COVID-19 has a /lot/ of possible symptoms, not all of which scream “respiratory disease” -- even though the virus SARS-CoV-2 infects our airways, and is thought to spread primarily through droplets we breathe out. COVID-19 patients have experienced some unexpected symptoms that affect more than just their lungs -- like GI problems, skin rashes, and a loss of smell and taste. Some of this is due to our immune response to the virus.

But today we're going to focus on the molecule the virus uses to infect our cells: the angiotensin-converting enzyme 2 receptor, or ACE2 for short. This molecule lets certain coronaviruses, including SARS-CoV-2, affect us in a /ton/ of different ways. All cells have various surface receptors embedded in their outer membrane.

As their name suggests, they receive signals and stuff from outside the cell -- stuff like hormones, neurotransmitters, nutrients, and immune molecules. ACE2 is a surface receptor with a bunch of important jobs throughout our bodies, not just our lungs. Unluckily for us, that also means SARS-CoV-2 has the potential to infect a variety of cell types.

It still only causes the one disease -- COVID-19 -- but this helps explain some of its broader effects. One of ACE2's major functions is working with another protein, angiotensin II, to keep blood pressure in balance. Angiotensin II raises blood pressure, and when it gets too high, ACE2 breaks it down to lower blood pressure again.

ACE2 does lots of other things, too, like accelerating tissue repair and modulating the microbes in our guts. And while there are lots of other kinds of surface receptors that viruses can use to get into cells and hold them hostage, ACE2 just happens to be the one that SARS-CoV-2 uses to get in. Scientists think the infection most often starts when the virus is introduced to someone's nasal passages.

The nasal cavity has tons of ACE2 receptors, so it's fertile ground for the virus, which can invade those cells to replicate. At this point, the newly-infected host might not have any symptoms, or they may develop a fever, sore throat, dry cough, or loss of smell and taste. That loss of taste and smell might seem like the odd one out, but it has ACE2's fingerprints all over it.

One study in mice from May of 2020 found that ACE2 is expressed in cells of the nose that help transfer odors from the air to neurons, so the infection could block those signals. The researchers also found that older mice tend to have more ACE2 in nasal cells than younger ones. If this is true in humans, it could help explain why older people are more susceptible to COVID-19.

Upon infection, the virus can make its way to our lungs. When the virus binds to ACE2 in the lungs, scientists think that it disrupts the normal breakdown of angiotensin II. Which means angiotensin II is free to run amok, leading to a vicious cycle of inflammation, cell death, and even blood clots that keep the lungs from getting oxygen to the body.

So it's no wonder that many patients need help breathing. And that's not where it ends. Because, like we said, ACE2 is expressed in all /sorts/ of cell types.

Like the circulatory system. A series of case reports in the journal the Lancet looked at three patients with severe inflammation and cell death in their endothelial cells — the cells that line the inside of blood vessels. Researchers are pretty sure that the virus can directly infect these cells using their.

ACE2 receptors -- though the significance of that isn't totally clear yet. And if that wasn't enough, there's the heart. In severe cases of COVID-19, doctors have observed cardiac injuries.

And COVID-19 patients with severe heart injuries also had relatively high amounts of ACE2 in their heart cells. For example, one patient in Italy presented at the ER with all of the symptoms of a heart attack, but doctors couldn't find evidence of a blockage in the coronary arteries that would normally cause such symptoms. The patient tested positive for COVID-19.

And while researchers don't yet fully understand the cause, it's possible that SARS-CoV-2's relationship with ACE2 is contributing to cardiac symptoms. Then there's the gut. The lining of the lower digestive tract is rich in ACE2 receptors, which could explain why up to half of people with COVID-19 have diarrhea.

A study in the journal Science Immunology showed that the virus can directly infect human and mouse intestinal cells in culture. This study also suggested that the virus breaks down before it exits the colon, making transmission by that route less likely -- but research is still ongoing there. Researchers are still trying to get a clear picture of COVID-19 and all its symptoms.

This has just been the short list of things we're pretty sure can be traced to ACE2. We've barely touched on the more indirect effects that seem to be a result of our immune system going into overdrive. The good news, though, is that it also makes ACE2 a potential target for therapies -- which opens up another potential treatment path for COVID-19.

It takes incredibly smart humans to diagnose diseases and come up with treatments. Sometimes, they enlist artificial intelligence for help. Those AIs are powered by artificial neural nets, which you can learn about in a whole course from Brilliant.

It'll teach you all about how we teach computers to recognize patterns. And if you want to learn even more, Brilliant has tons of courses in math, science, computer science, and engineering, all of which will help you sharpen your scientific thinking skills. If you want to get started, head over to Brilliant.org/SciShow, where the first 200 people to sign up will get 20% off an annual Premium subscription. [ ♪ OUTRO ].