A COVID Overview

We all probably understand the “basics” of COVID-19. It’s a respiratory illness, kind of like a cold, or the flu, although sometimes with unusual symptoms (loss of sense of smell?!). If you get it you may get sick, possibly very sick, although the vast majority of infections are very mild or produce no symptoms (asymptomatic). But this basic understanding neglects a lot of details. This explainer will walk through the path of SARS-CoV-2, the scientific name of the virus that causes COVID-19 (the name of the disease), infection from exposure (when the person gets in contact with the virus) to the end of the infection. We’ll try to be clear on what we know, and what we don’t, and where we hope to learn more. Step 1: Exposure COVID-19 spreads via respiratory droplets that are produced when an infected person talks, coughs, or sneezes. The droplets are relatively heavy and are thought to travel no further than 6 feet; they will then fall and deposit on the floor or other surfaces. This is the source of the 6 feet distancing rules. Is it exactly six feet, or could they possibly go farther or less far? This is a source of debate and ongoing research. What we can say with some confidence is they can certainly travel some distance, and there are also some clear limits. After an infected person coughs or sneezes the droplets, small droplets remain suspended in the air for 30 minutes while larger droplets fall onto nearby surfaces where they may survive for a short time. In the lab, studies have shown that COVID-19 can survive less than 4 hours on copper, less than 24 hours on cardboard, and less than 72 hours on plastic and stainless steel. This is in lab conditions; it may be less time in the real world. The virus can be killed by household disinfectants; if it lands on a surface and then someone washes that surface with Lysol, it’s dead. It should be noted that it is unlikely the small droplets floating in the air will get on your clothes as you walk by since natural aerodynamics will push these droplets around you, instead of on you, as you walk. Putting this together, there are a number of ways you can be exposed to the virus. By far the most common way to get significant viral exposure is through one on one contact. That is, through someone who is infected with COVID-19 sneezing, coughing, or breathing on you. Through someone coughing into their hand and then shaking yours. Through someone picking their nose or their teeth or licking their finger to turn the page of a book and then touching you. And then you touching your nose or mouth so the virus enters your airways. It is also possible to be exposed indirectly. Imagine that someone infected with COVID-19 at the grocery store coughs into their hand, picks up a box of salad, realizes it is not the one they want, and then you pick it up right after. Or the take-out delivery guy touches the bag with his hand and then you touch it. However, the probability of exposure here is simply much, much less than the direct person to person contact. With less contact time and less contact surface, there is less chance of picking up an infected virus particle (also called a “viron”). Much of the advice that we hear about avoiding COVID is also centered around lowering the probability of exposure, and therefore of infection. If you wash your hands regularly, it decreases the chance that a virus particle reaches your face. If you wear a mask, you lower the probability that you cough virus particles on others (if you are infected). Wearing a mask also discourages you from touching your face. In the salad box example, even if you touch the infected box, if you get home and wash your hands before you touch your face, no viral exposure. The mask lowers the probability. Social distancing recommendations work on probabilities the same way: if you are further away from people and do not touch them, you’re less likely to be in contact with an infected virus particle. Step 2: Infection Now let’s imagine that through one of these means an infectious virus particle enters your body. You are not automatically infected. Your body has a number of defensive barriers to prevent infection. For example, your upper respiratory tract contains mucus that sticks to and “grabs” unwanted particles such as dust, bacteria, and viruses. Hair-like structures called cilia line our airways and constantly move in a beating motion to expel the mucus and replace it with a new layer of mucus. Basically, your body works hard to get rid of viruses. In case a “virion” makes it to the lower airways it can be taken up by cells specialized to eat and degrade the virion, then alert the rest of your immune system. All of these defenses provide the first line of the host immune response against a range of airborne pathogens. This means that the more virions that get in, the more likely infection is to occur. Currently, it isn’t clear how many SARS-CoV-2 particles are necessary to enter our body in order to cause an infection and this number is likely to vary across individuals. In addition, we should note that in order to be infectious, virions must be intact. When a virion sits out in the world — say, on a milk carton or cereal box at the store — it degrades. Once it is no longer intact, it retains some of the genetic material of the virus, but is too damaged to be infectious. So, let’s say the virion makes it past our initial defenses — mucus and cilia — without getting expelled. Once it gets in, it’s got to get into your cells to reproduce. Why? A virus contains genetic material (either RNA or DNA — SARS-CoV-2 is an RNA virus) but it doesn’t have the machinery to copy itself. Instead, it needs to hijack the machinery of your cells to replicate. To do this, it needs to get hold of cells and unlock them. Viruses can do this with the different "keys" it has on its surface. Different viruses have individualized keys that can unlock different cells in the human body. In the case of SARS-CoV2, we strongly suspect that the "lock" it can bind to on human cells is the ACE2 receptor. This ACE2 receptor is present throughout our airway and lungs, and possibly in the gastrointestinal tract. This could explain why COVID-19 presents with such a wide variety of symptoms. The main target cells, though, are the cells that line our lungs. Once the virus locks onto a cell, it uses the cell's own machinery to fuse and enter the cell. And then it gets to work. The virus hijacks the cell’s machinery to replicate itself, by translating its genetic material (its RNA) into proteins that can assemble to form more viral particles. It uses parts of the cell (technically the “Golgi apparatus”) to package these proteins. The packages gather at the edge of the cell and then bud off to form new virus particles. As these new virus particles exit the cell, the human cell it infected dies. Your cells die and replace themselves all the time, but having too many die at once can be a problem. Step 3: Response + Recovery: Asymptomatic, Mild and Moderate Cases This may sound scary, but it is important to remember that our body is used to this. You’ve very likely been infected with viruses before! And you have tools to deal with it. Your immune system gears up to fight. In fact, there are two separate immune responses: the innate immune response and the adaptive immune response. Because your body hadn’t seen SARS-CoV-2 before — it’s “foreign” to your immune system — your body will not have a solid plan to deal with it right away. When it does recognize the virus, it deploys first the which consists of barrier defenses (such as the mucus and cilia and also tight junctions between cells), secreted chemicals, and white blood cells. There are several different types of key white blood cells — macrophages, dendritic cells, and neutrophils — and they all have slightly different methods of attack. In general, though, these white blood cells are able to broadly recognize and attack a wide variety of organisms that can cause disease, whether they be bacteria, fungi, or viruses (like SARS-CoV2). In some cases white blood cells can identify your own cells that have been infected and induce them to kill themselves before the virus can get out. The innate immune response causes some symptoms of illness. For example, our innate immune system produces a fever as both a means to kill the virus (higher temperature might make it harder for the virus to survive) and also as a signal to the rest of the immune system that it’s time to kick in. Several days later (typically 4 to 7 days after exposure), the “adaptive immune response” enters the fight to support the initial innate response. This response is targeted rather than general — that is, it is a response that is specific to this virus. The adaptive immune response involves, for instance, the production of antibodies to the virus. These come in a few variants, all starting with “Ig” (short for immunoglobulin) and distinguished by their last letter (so you’ve got IgM, IgG, IgA…). They all have slightly different functions, but in the end they work together to kill the virus. These immune responses are the same ones that your body deploys to fight all kinds of viruses (the flu, measles, etc, etc). And for a large share of COVID-19 cases, this immune response is enough to deal with the virus. This is especially true if the virus is contained to the upper respiratory tract (causing symptoms such as sore throat, cough, fever, etc.) You’ll get mild symptoms, the antibodies will fight the virus, you’ll feel kind of crummy (or maybe not — a large share of infections are asymptomatic) and then it will be over. It is important to be clear: the vast majority of COVID-19 cases are mild or moderate. Initial estimates from China suggested at least 80% were mild. When we look at kids (again, from China) it looks like over 90% have mild, moderate or asymptomatic cases. A variety of data — from pregnant women, cruise ships and so on — point to a very large share of cases being totally asymptomatic. Once you recover from the virus, your body retains some antibodies, plus the cells which know how to produce more if they are needed. This helps your body respond faster if exposed again. If you want to know more about this, head over to our Immunity Explainer. Step 3B: Response & Possible Recovery in Severe and Fatal Cases In many cases of COVID-19, both the innate and adaptive immune response effectively keep the virus at bay. In other cases, they can’t and as the virus continues to spread, the immune response becomes more frantic and problematic. This is more likely to happen for those who are immunocompromised (literally, their immune system is compromised and unable to respond effectively) or have pre-existing health conditions. It can also happen to those who are healthy, although much less frequently. We do not well understand why some people get sicker than others, although this is a topic for ongoing research. In these more serious cases, the virus infects the lower respiratory tract and moves into the lungs. Chest pain, shortness of breath, difficulty breathing, and a deep cough signal that the virus has resulted in damage within the lower respiratory tract. Infection and inflammation of the lungs is referred to as pneumonia, which can be severe and fatal. It’s typically diagnosed with a chest X-ray, although doctors can often tell by listening to a patient breathe if there is fluid in their lungs. This fluid is a result of inflammation triggered by infection and this fluid buildup in the lungs compromises your ability to breathe. The real danger happens at the very bottom of our respiratory tract in balloon-like structures called alveoli. Alveoli are surrounded by a net-like arrangement of blood vessels with which they exchange carbon dioxide and oxygen. The walls on our alveoli are extremely thin so that oxygen can diffuse into these blood vessels when we breathe in and carbon dioxide can diffuse from the blood vessels back into our alveoli when we breathe out. If alveoli don’t function properly, our body can’t get rid of carbon dioxide and is starved of oxygen. Serious complications from COVID-19 can happen for various different reasons. Some people do not have a sufficient adaptive or innate immune response to wrestle the virus under control. The virus can take over, too many cells die, and this causes serious complications for the lungs and other organs. This can also happen if a high quantity of viral particles enters the body and replicate to really high numbers before a sufficient immune response kicks in. In other people, the immune response can be too extreme. When your body produces antibodies, it also produces another type of molecule to fight the virus, called a cytokine. These cytokines are useful because they can help recruit and ramp up the activity of the cells which produce antibodies. This can be good, since it can get the immune response to go faster, to do more. On the other hand, it can be damaging: if you ramp up the immune system too much, it can lead to too much inflammation and unwanted damage to your own tissues. Your own cells die and the overall lungs infrastructure can be damaged. The alveoli (those really important balloon-like structures at the bottom of our lungs) can no longer exchange oxygen and carbon dioxide, and you go into respiratory failure unless you have a ventilator to help you breathe. The worst-case scenario is one where your immune system sends cells beyond the lungs, potentially bringing the uncontrolled inflammation elsewhere. These immune cells and their production of cytokines can start attacking other organs and lead to multiple organ failure. In this case, death can occur. But we should emphasize again: this happens in only a small share of cases. Most people have mild or moderate infection and the body’s innate immune response or the adaptive response successfully protects you against the virus. And even in severe cases, the science of treatment is improving all the time. There is a tremendous amount of active research on COVID-19 treatment options, and more innovations are coming online all the time. Many people who get very, very sick do go on to recover. Stage 4: Recovery & Immunity Once you recover from COVID-19, your body retains the memory of having had it. This is helpful since your cells are then ready to fight again if you are re-exposed. You don't have to ramp up as much of an immune response since you already have some antibodies and you have cells prepped to make more. To understand a bit more about how immunity works — what we know and what we don’t — head over to the Immunity Explainer.

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