How this coronavirus makes you sick

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This post will answer these questions:

1. How does the coronavirus that causes COVID-19 get into cells of the body?
2. What symptoms does the coronavirus cause?
3. Why does it cause those symptoms?
4. What is the time course of COVID-19?
5. How do I know if I’m one of the people with severe COVID-19 disease?

I think I may have turned the corner. Yesterday I woke up with chills and a fever after the tylenol wore off but this morning I had no fever. The cough is still keeping me up at night but I am a bit less achy. With a little help from heaven I’ll be coming out of this soon. I happen to have been quite busy researching for these posts and answering a flood of questions from friends and family which is prompting this post. One of the most common questions I have been getting is what to expect. Before we get to that we need to explore how and why viruses make us sick.

How viruses make us sick

Infection does not alway lead to disease. Infection occurs when the virus enters the body and begins to multiply. Disease, which typically happens in only a small proportion of infected people, occurs when the cells in your body are damaged as a result of the infection, and signs and symptoms of an illness appear. Even with long term close exposure to COVID-19, most people do not get the disease (more on that in a future post).

In response to the virus entering the body and starting to reproduce, the immune system is activated. After the virus enters the cells there are new proteins expressed on the surface of the cell that special immune cells recognize as foreign. White blood cells, antibodies, and other mechanisms are activated leading to the release of a multitude of chemicals that do a lot of different things. Indeed, many of the symptoms that make a person suffer during an infection—fever, malaise, cough, headache, etc. result from the activities of the immune system trying to eliminate the infection from the body. Other symptoms can come from the damage or disruption of your cells directly.

How does the virus that causes COVID-19 work?

Every virus has the ability to invade specific cell types in the body. The area of the body that these cells live will partially explain the symptoms that particular virus causes. For example, some viruses target cells in the GI tract and cause an infection that leads to GI symptoms. Some viruses infect the nervous system (like polio and west nile virus), some attack the immune system itself (like HIV). There is probably a virus for every part of the body. So the cell that the virus is able to infect determines the disease that it causes.

The virus that causes COVID 19 infects cells that line the entire respiratory tract (they are called alveolar epithelial cells). You may already be thinking how this explains the main symptoms of the disease which are primarily respiratory. The virus leads to damage to the lining of the lung which causes irritation and cough. (There have also been reports of people losing their sense of smell which makes sense because the nerve endings for smell are near the affected cells and may get injured as collateral damage.)

In addition to local injury from the virus causing symptoms, many of the chemicals created by the immune system are released into the body. These cause the general symptoms people get, things like fevers, body aches, and fatigue. If you remember from your primary schooling, the respiratory system is like a tree that starts at the nose and branches into smaller and smaller airways finally ending in tiny air sacs called alveoli. These sacs are surrounded by tiny blood vessels which is where oxygen enters into the bloodstream and carbon dioxide is cleared out.

When the immune response to COVID 19 becomes unregulated it can lead to an overwhelming response that damages the cells that make up these tiny air sacs. Fluid and protein then flood in which blocks oxygen getting into the blood stream. This is a condition called ARDS. ARDS leads to respiratory failure that requires a ventilator and can ultimately be fatal.

In ARDS the immune system overreacts and secretes a storm of chemicals that leads to severe damage to the lung itself. This is a bit confusing because people who have a depressed immune system are more likely to get ARDS. How can a depressed immune system lead to an overactive immune response? The reason is that to say someone has a weak or strong immune system is a vast oversimplification. When someone is immunocompromised it could be that they have problems regulating their immune system. The immune system is a mind boggling interaction of multiple cell types that secrete hundreds of chemicals in a precisely timed and tuned manner to protect us from the environment. Aging and chronic diseases can compromise that precise balance and make it difficult to ramp the system up but they could also impair the ability of the system to ramp itself down.

What are the symptoms

Most people start with a dry cough and then develop fever and body aches. People have misinterpreted this information to mean that if someone doesn’t have a cough or fever they don’t have the virus. This is a big mistake. FIrst, they may still be early in the course and infectious. Second, while those are the most common symptoms people with the infection have presented with other symptoms as well. As many as 10 out of every 100 patients presented with nausea, vomiting, or diarrhea and 14 out of every 100 had headaches. Up to 24 had runny nose. What all this means is that, if you have a dry cough, fever, and body aches you likely have the infection and, even if you don’t, you should assume you do to prevent spread (see my previous post on whether you should get tested). If you have other symptoms you should not assume that you are not infected and should avoid going out and spreading the virus around. It is less likely that you are infected but not a guarantee.

Fever is also tricky. Different studies have reported a different frequency of fever which may be due to how those studies were designed. They may have chosen from different populations of patients and/or at different times in their disease course. The important thing is that the absence of fever does not mean you don’t have COVID 19.

What is the time course?

The disease incubates for between 2 and 7 days. Incubation means that the person is infected but does not yet have symptoms. During this time it is possible for the disease to be spread unwittingly. This is why this virus can spread so effectively. It is being spread around by people that don’t know they have it. This is also why quarantine is so important if you have been exposed even if you don’t have symptoms.

So the virus incubates for 2-7 days and then symptoms develop. The thing people really want to know is ‘If I’m infected how do I know if I have severe disease?’ The way to answer that is to follow the time course of people who developed severe disease.

Looking back on those patients they usually started feeling short of breath on about day 6 after they started getting sick. Most were admitted to the hospital on day 8. They went into the ICU and were on life support on day 10.

This is not what happened with all patients, only the ones with severe disease. Out of every 100 patients with an infection that causes significant symptoms only about 20 will need to be hospitalized. Out of every 100 patients who are hospitalized only about 10-20 will need to be put on life support and only 2-5 will not survive.

As an aside, this was my course. I believe I was exposed on Saturday the 14th and developed symptoms the evening of the 19th, a little over 5 days later. I am now day 5 of illness and seem to be slowly improving. I’ve never been happier to be average.

What if I’m sick?

The real question people want answered is what will happen if I get sick. This is what is causing the greatest anxiety. If you watch the news it sounds really scary and there is a lot of fear but the information above puts things into a clearer perspective (One caveat is that, as more data about the disease is collected those numbers may change. There also seems to be a difference in severity in certain locations like northern Italy). But for the most part below is what I am telling people. As far as I know it is not in contradiction to what is being recommended by the CDC, WHO, or other governmental agencies.

1. Don’t go to an ER or hospital until you feel short of breath.
2. This will usually happen between days 5 and 7. If by day 5 and 7 your are feeling better this is a good sign but some people had severe symptoms later so still be on guard.
3. If you do feel short of breath, don’t panic! You should go to the ER that day, however. The disease seems to progress over a day or two on average but you want to be in the hospital in case it goes faster. Remember, there is still an 80% chance you’ll be OK. We also expect the survival rates to improve as the scientific community comes up with and tests new treatments.
4. If you’re not short of breath, don’t worry, you will most likely recover in 7-10 days.

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Sources:

1. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmunity. 2020 in press
2. Li X, Geng M, et al. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Analysis 2020: in press
3. Velevan TP, Meyer CG. THe COVID-19 epidemic. Top Med and Int Healthy 2020 in press.
4. https://www.youtube.com/watch?v=zFrghcp5pbY&feature=youtu.be
5. https://emcrit.org/ibcc/covid19/