Thanks to Brilliant for supporting this episodeof SciShow. Go to Brilliant. org/SciShow to check out theircourse on artificial neural nets. This episode was filmed on June 19th, 2020. You can find more info on the COVID-19 pandemicin 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 infectsour airways, and is thought to spread primarilythrough droplets we breathe out. COVID-19 patients have experienced some unexpectedsymptoms that affect more than just theirlungs — like GI problems, skin rashes, anda 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 moleculethe virus uses to infect our cells: the angiotensin-convertingenzyme 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 embeddedin their outer membrane. As their name suggests, they receivesignals and stuff from outside the cell — stufflike hormones, neurotransmitters, nutrients,and immune molecules. ACE2 is a surface receptor with a bunch ofimportant jobs throughout our bodies, not just our lungs. Unluckily for us, that also means SARS-CoV-2has 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 workingwith another protein, angiotensin II, to keepblood pressure in balance. Angiotensin II raises blood pressure, andwhen it gets too high, ACE2 breaks it downto lower blood pressure again. ACE2 does lots of other things, too, likeaccelerating tissue repair and modulatingthe microbes in our guts. And while there are lots of other kinds ofsurface receptors that viruses can use toget into cells and hold them hostage, ACE2just happens to be the one that SARS-CoV-2 uses to get in. Scientists think the infection most oftenstarts 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, whichcan invade those cells to replicate. At this point, the newly-infected host mightnot have any symptoms, or they may developa fever, sore throat, dry cough, or loss ofsmell and tasteThat loss of taste and smell might seem likethe odd one out, but it has ACE2’s fingerprints all over it. One study in mice from May of 2020 found thatACE2 is expressed in cells of the nose thathelp transfer odors from the air to neurons,so the infection could block those signals. The researchers also found that older micetend to have more ACE2 in nasal cells than younger ones. If this is true in humans, it could help explainwhy older people are more susceptible to COVID-19. Upon infection, the virus can make itsway to our lungs. When the virus binds to ACE2 in the lungs,scientists think that it disrupts the normalbreakdown of angiotensin II. Which means angiotensin II is free to runamok, leading to a vicious cycle of inflammation,cell death, and even blood clots that keepthe lungs from getting oxygen to the body. So it’s no wonder that many patients needhelp breathing. And that’s not where it ends. Because, like we said, ACE2 is expressed inall /sorts/ of cell types. Like the circulatory system. A series of case reports in the journal theLancet looked at three patients with severeinflammation and cell death in their endothelialcells — the cells that line the inside of blood vessels. Researchers are pretty sure that the viruscan directly infect these cells using theirACE2 receptors — though the significanceof that isn’t totally clear yet. And if that wasn’t enough, there’s theheart. In severe cases of COVID-19, doctors haveobserved cardiac injuries. And COVID-19 patients with severe heart injuriesalso had relatively high amounts of ACE2 in their heart cells. For example, one patient in Italy presentedat the ER with all of the symptoms of a heartattack, but doctors couldn’t find evidenceof a blockage in the coronary arteries thatwould normally cause such symptoms. The patient tested positive for COVID-19. And while researchers don’t yet fully understandthe cause, it’s possible that SARS-CoV-2’srelationship with ACE2 is contributing tocardiac symptoms. Then there’s the gut. The lining of the lower digestive tract isrich in ACE2 receptors, which could explainwhy up to half of people with COVID-19 havediarrhea. A study in the journal Science Immunologyshowed that the virus can directly infecthuman and mouse intestinal cells in culture. This study also suggested that the virus breaksdown before it exits the colon, making transmissionby that route less likely — but researchis still ongoing there. Researchers are still trying to get a clearpicture of COVID-19 and all its symptoms. This has just been the short list of thingswe’re pretty sure can be traced to ACE2. We’ve barely touched on the more indirecteffects that seem to be a result of our immunesystem going into overdrive. The good news, though, is that it also makesACE2 a potential target for therapies — whichopens up another potential treatment pathfor COVID-19. It takes incredibly smart humans to diagnosediseases and come up with treatments. Sometimes, they enlist artificial intelligencefor help. Those AIs are powered by artificial neuralnets, which you can learn about in a wholecourse from Brilliant. It’ll teach you all about how we teach computersto recognize patterns. And if you want to learn even more, Brillianthas tons of courses in math, science, computerscience, and engineering, all of which willhelp 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 willget 20% off an annual Premium subscription.