Author: Michael Butler, Ph.D. Neuroscience
Co-Contributor: Austin Van Decar, B.S. HPS, EMT
Over the last few weeks there has been an unbelievable amount of misinformation being spread about the novel coronavirus that causes COVID-19 and what the world governments should do about it. The world seems extremely chaotic right now and everyone seems to be an infectious disease expert all of the sudden. While I’m not an infectious disease expert, or a virologist, epidemiologist, or a healthcare professional, I am a biological scientist. I have a PhD in Neuroscience and I work as a postdoctoral researcher at The Ohio State University Wexner Medical Center conducting research in Neuro-Immunology with a focus on nutrition and aging (disclaimer: this article is my own work and is not affiliated with OSU). Thus, I spend a lot of time reading about the immune system (usually how it impacts the brain) and have expertise in reading and interpreting peer-reviewed scientific literature. I am confident in my ability to help explain to my family and friends, and whoever else may read this, the science of what is currently happening in the world. In times of chaos, I usually find that correct information is comforting. In this article, I will attempt to summarize the basic biology behind the immune system, how it responds to threats like viruses, what a virus actually is, what a coronavirus is, how coronaviruses evoke an immune response, and what is special about the novel coronavirus that causes COVID-19 and the current pandemic that the world is dealing with.
Before we get to COVID-19, we need to go over some basic immunology. The human immune system is made up of two main parts: (1) the innate immune system and (2) the adaptive immune system.
The Innate Immune System
Some components of the innate immune system can actually be traced back to species that lived 500 million years ago. It’s been around a long time! It is made up of several different types of cells that all play a specific role in defending our bodies. The most famous cell of the innate immune system is the macrophage. Once a pathogen (something that is harmful to your body) enters our body, our macrophages are alerted to move towards the pathogen and destroy it. Here is an actual picture taken with an electron microscope of a macrophage destroying a bacterium.
Macrophages can recognize bacteria because the outside of bacterial cells are made up of fats and carbohydrates that are not natural to the human body. Macrophages have special receptors, which are proteins expressed on the surface of the cells, that can bind to these molecules and signal to the cell to destroy whatever they just came into contact with. While a macrophage is destroying something like a bacterium, it is also releasing specialized proteins called cytokines that are signaling to other macrophages and other types of immune cells that something is wrong and they may need help. In addition to the macrophage, the innate immune system contains several other types of cells that help out to destroy invaders, including natural killer (NK) cells (I think that’s an awesome name) that can destroy bacteria, parasites, some cancer cells, and virus-infected cells. Given that the world currently cares about viruses, I’ll say the innate immune system has some defense mechanisms against viruses when the virus is outside of a cell. With the help of different signaling mechanisms between innate immune cells (look up “the complement system” if you are interested in these signaling mechanisms), a virus can be engulfed and destroyed. However, as we will get to later, viruses actually enter the host’s cells and this is when the innate immune system is less effective and when we rely on the help of our adaptive immune system.
The Adaptive Immune System
The adaptive immune system is pretty unique to vertebrates (animals that have a spine), which includes all mammals and, of course, us humans! You may have heard of two types of cells that are pretty important for the adaptive immune system: B cells and T cells, both of which live in your lymph nodes and are called lymphocytes. B cells make and release antibodies. They have receptors on their surface that can sense very specific proteins on the surface of, say in this case, a virus. Once this contact happens, the B cell starts to make copies of itself over and over again for about a week until there are over 20,000 clones of that specific B cell that can all recognize the same antigen (the virus). Then they start making antibodies! Antibodies are similar to the receptor that initially found the virus but instead of hanging out on the surface of the B cell – they are actually released from the cell and stick to the virus. Other immune cells (like macrophages) will recognize the antibody-tagged virus and destroy it. This helps destroy pathogens that may otherwise be overlooked by the innate immune system. If viruses weren’t tagged with antibodies, some would go undetected. An antibody is like a GPS tracking device for pathogens!
However, this still does not solve the problem of when viruses get inside the host’s cells, which they need to do to reproduce. The adaptive immune system has a solution for that, though. T cells, specifically Killer T Cells (again, awesome name), can destroy cells that are infected with a virus so that both the cell and virus die together (the death of the cell is a good thing so it cannot further host the virus). They do this by receiving a signal from the infected cell and other immune cells and then making contact with that cell and signal for it to kill itself so the virus dies along with cell. It does sound rather sad but it is for the greater good of the entire organism, even if a few of its cells have to die in the process.
Ok, so now that we have VERY general understanding of the immune system and a few of its few key players, let’s talk about why we’re all here – viruses – specifically, coronaviruses. A virus is a tiny pathogen that is only able to reproduce inside a living cell of a host organism. Viruses can infect all types of organisms, from plants to animals and even bacteria. There are several components of a virus. There is the genetic material that is made up of either DNA (like humans and other animals) or RNA. There is a coat of proteins that protect that genetic material and, in some cases, an outer layer of lipids (fats) called an envelope that further protects the virus (this is true for all coronaviruses). In order for a virus to replicate its genetic material, it needs to use the hosts’ cellular machinery. It does this by first attaching to the outside of the cell and penetrating through the cellular membrane. Once inside the cell, it sheds its protein coat to “release” its genetic material, which is then replicate by the cell’s own machinery. This is a cruel trick the virus plays on the host cell as the host cell is unaware it’s replicating viral (infectious) genetic material. Once replication of the genetic material has occurred, the new viral molecules are assembled in the cell and can be released (sometimes by literally exploding the cell open) to go infect other nearby cells.
Coronaviruses are a family of viruses. They are named for the crown-like (corona is Latin for crown) structures on the surface of the virus (pictured below).
There are several different strains of coronaviruses and 4 of them are common in humans. In fact, these 4 strains of coronaviruses (along with rhinoviruses) are the main causes of the common cold. It is important to point out that the common cold is different from the flu, even though the two terms are often used interchangeably. One does not have the flu unless they are actually infected with a strain of the influenza virus. Anyway, I digress. In humans, coronavirus cause an upper respiratory infection and are very common and normally pretty mild (hence the common cold). Humans are used to seeing the main 4 strains of coronavirus and our immune system does a pretty efficient job of clearing the virus and returning us to normal.
However, back in 2002 a new coronavirus was discovered, meaning this virus was genetically different from the other 4 strains previously known to infect humans and it was one that the human immune system had never been trained to defend against (remember that antibodies are made for killing pathogens AFTER being exposed to their specific receptors). This new virus was called SARS-COV and caused the Severe Acute Respiratory Syndrome (SARS) pandemic. Anytime a new virus infects a species it is alarming and needs to be taken seriously. Now, SARS-COV wasn’t technically a brand new virus – it was just new to humans. It had been reproducing in other animals (like bats) for a long time. Viruses evolve to reproduce in certain host species and cannot reproduce in other types of hosts. However, every now and then a zoonotic virus comes along. A zoonotic virus is one that can jump from a different animal species to the human species. This is alarming because normally viruses don’t really want to kill their host (unless that’s part of their replication mechanism but we don’t have the time for that in this article) because that means they die too. Thus, when a virus jumps to a different species it doesn’t normally reproduce in, it could have some terrible, unintended effects (death) on that new species. The SARS virus had an ~10% mortality rate and caused a severe illness in those who were infected. This actually made it easier to contain because it was easier to recognize, track, and isolate. The same was the case for Middle East Respiratory Syndrome (MERS), which had an even higher mortality rate of ~35%. This was also a zoonotic coronavirus that likely came from camels. So until recently there were 6 different coronaviruses that could infect humans (2 of which originated in other species), some producing worse effects than others.
Then comes COVID-19 (coronavirus disease of 2019) at the end of last year. The viral strain is officially called SARS-COV2 and the disease it produces is COVID-19. This is the 3rd type of coronavirus that made the jump from a different species to humans. While it is still unclear, scientists suspect that SARS-COV2 made the jump from bats to pangolins (a scaly ant-eater-like animal) and then to humans. It is believed this originated at an exotic animal market in Wuhan, China, which is where the outbreak began at the end of 2019. This virus causes an upper respiratory tract infection (like other coronaviruses) and is usually accompanied with a fever and body aches. So far, the mortality rate is hard to calculate as it has been extremely difficult to get an accurate number of total cases. Another important factor contributing to not being able to track the virus is that the symptoms can actually be very mild, much less severe than SARS or MERS. Because of this, some people may not even know they have it, but can still spread it to others who may not be so lucky.
Coronaviruses and the immune response
Coronaviruses are respiratory viruses, meaning they like to infect tissues of the respiratory tract (nose, throat, lungs, etc). When they get into the human body they bind to cells in these tissues and penetrate the cells just like I talked about before. Coronaviruses seem to be able to infect immune cells of both the innate and adaptive immune system, which is a pretty good viral strategy if they are able to suppress both the innate and adaptive immune response. However, the immune system typically responds within enough time to clear the virus. The typical immune response you probably think of is a fever, increased congestion due to increased mucus buildup, coughing, body aches, etc. These are all adaptive responses we experience to help get rid of a pathogen, in this case a coronavirus. Increased body heat can be unfavorable to a pathogen, increased mucus can help trap certain pathogens, and body aches can help us retreat and withdraw so our body can devote all energy to fighting the pathogen.
Immune function varies across the lifespan (this is where some of my actual research and expertise comes in!). As humans age, our immune system gets into a hyper-reactive state and we have a higher baseline level of inflammation (immune activity) in our bodies. This is low-grade inflammation in the absence of any disease or pathogen. Aging is accompanied by an increased number of certain innate immune cells as well as increased pro-inflammatory cytokines that are constantly sounding the alarm to the entire immune system. This increased baseline activity of the aging innate immune system results in an exaggerated response to any secondary challenge to the immune system (secondary meaning in addition to aging). This can come in the form of a virus, bacterial infection, or, in the case of my own research, even unhealthy diets. In addition to hyper-reactivity, the aged immune system is also less efficient at clearing pathogens from the body, resulting in prolonged immune activity and failure to resolve the inflammation. This is likely why we see the most severe cases of any bacterial or viral disease in older people. Their immune systems are hyper-reactive and so overwhelmed they eventually succumb to the invasion. The opposite is thought to be true for younger people: the immune response is appropriate because it is not already heightened at baseline, the immune system is efficient at clearing pathogens, and inflammation is resolved in a timely fashion.
If you take nothing else from this article, just keep re-reading this paragraph and the one before it. The elderly are the most vulnerable during this global pandemic. Most people under 50 or 60 will be able to handle this virus without much complication, though there are exceptions. Actually, new data from the CDC says as many as 1 in 5 people ages 20-44 who contract COVID-19 will need to be hospitalized. However, only 0.2% end up dying, which is higher than the flu. The older a person is, the less likely they are going to be able to fight off SARS-COV2. Also, I should point out that even in the elderly, most patients recover, statistically speaking. But the mortality rate is much higher as a person ages. In addition to the elderly, individuals with underlying conditions such as heart disease, lung disease, or diabetes are also at a greater risk of death from COVID-19 (see charts on COVID-19 mortality rates below).
While traditional antiviral drugs used to treat the flu are not effective against COVID-19, there have been a few reputable reports of antiviral drugs that have shown some efficacy against it. Unlike the flu, there is no approved, effective vaccine for SARS-COV2 or any other coronavirus. However, at the time of writing this article the U.S. has started a Phase 1 clinical trial for a SARS-COV2 vaccine, which was created in record time. It will still take at least 12-18 months to conduct the clinical trials and for it become approved for mass use like the influenza vaccine. Given the limited medical interventions available to prevent or treat COVID-19, the world must turn to behavioral interventions to stop the spread of the virus. This means – you guessed it – social distancing. The SARS-COV2 virus spreads via respiratory droplets. When a person carrying the virus coughs or sneezes these droplets containing the virus land on surfaces and can live on certain surfaces for days. When someone else touches that surface and then touches their face, they are now infected. This is why constantly washing your hands is so important. Also, social distancing is a proven method to stop the spread of an infectious disease and is done so to protect the most vulnerable and to not overwhelm the healthcare system. Limited interactions prevent viral transmission. It’s a technique that has been around for centuries and it’s simple and effective.
The U.S. does not have enough hospital beds or medical supplies to treat hundreds of thousands (maybe more) of patients needing hospitalization due to COVID-19 in general, and especially not on top of an already active flu season and other ER and ICU patients needing treatment for various issues. Furthermore, the U.S. is a generally unhealthy population with two-thirds of the country being overweight or obese and high rates of heart disease and diabetes. We are arguably the most unhealthy nation to be heavily impacted by this virus. An already unhealthy population and an unequipped healthcare system is a bad combination when a new pandemic occurs.
After a few months of extreme social distancing in China, their epidemic seems to be letting up and life is slowly getting back to normal. During the outbreak of the 1918 Spanish Flu in the WWI fronts, the practice of distancing soldiers in medical wards was mandated. Some medical historians argue that distancing soldiers with the Spanish Flu had a huge impact on the outcome of WWI. History shows us that there is hope, and between science and medical advancement we will see the other side of this pandemic.
Not all of us can know everything. As a scientist, I constantly have to rely on the expertise of other scientists we collaborate with. Just like they rely on me for my expertise. If you hear scientists and doctors, actual infectious disease experts, telling you this is serious, listen to them. It is time every single person in the United States takes it seriously. The quicker you do, the quicker we can beat this virus and get back to normal.
I’d like to thank Austin Van Decar, a friend and medical historian, for providing thoughtful feedback and suggestions for this article.
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Images taken from:
Sompayrac, L., 2012. How the Immune System Works. Wiley-Blackewll.