COVID Transmissions for 9-24-2020

What do my symptoms mean?

Sep 24, 2020

Good morning! It has been 311 days since the first documented human case of COVID-19.

Today I’m trying to get the newsletter back into its normal groove, along with an in depth piece that bridges us over from the past couple of days’ content by talking about some of the science underlying how I got sick. I’ve skipped headlines for today, however.

As usual, bolded terms are linked to the running newsletter glossary.

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Now, let’s talk COVID.

What am I doing to cope with the pandemic? This:

Doing nothing

It’s important to know when to do nothing and rest. Getting over how I’ve been feeling is one of those times to do nothing, and aside from keeping up with work, I’ve been keeping my activities as minimal as possible.

What did my symptoms mean?

My focus in graduate school was what’s called virus-host interactions, which is a catch-all term for almost everything that happens during virus infection. Specifically, it covers the way that the virus subverts host machinery to replicate itself, but it also focuses on the way that host immune pathways are triggered by virus infection. Building on that, people who study virus-host interactions also study evolved virus mechanisms that function to deactivate, mute, or suppress these immune responses.

This can make it very strange to be me when I am sick with something. I understand quite well—at least as well as our science currently can—what is happening to me at each step. This doesn’t change what happens, though in some cases it does allow me to make better decisions that might improve the course of the infection.

I think this knowledge might be helpful to you in understanding COVID-19, even if I’m not sure that’s what I was sick with still. So, I want to walk through the narrative of what I experienced and provide some insights on what was happening to me to make me feel this way.

On Friday night of last week, I started to experience a sore throat. This sort of symptom is often the first manifestation of virus infection. There are a few features that I want to highlight. The first reaction was localized, it was based around inflammation, and it increased over time. All of these features represent the early steps of the “innate immune response.” The innate response represents a set of pathogen-detection and hindrance mechanisms that are nonspecific to the pathogen that is responsible for the infection. Innate responses do have some specificity, but not to that particular pathogen.

The analogy for this that I like to use is the types of alarms that detect threats to your home, and that potentially deal with those threats. You may have a fire alarm, or a burglar alarm, or a carbon monoxide alarm—or all three. These things help to detect specific categories of threat and alert you to their existence. In the case of, say, a sprinkler system, they may even provide a slightly hindering response to the threat. However they are no replacement for a fire department that can identify the specific place that is on fire, the type of the fire, and the approach needed to fight it.

Instead, these systems warn you about the threat and impede it slightly. That is what the innate immune system generally does when combating viruses that you would notice getting infected with. I make this distinction because the innate immune system almost certainly does stop certain threats that we never even notice. Consider these to be like the thieves who see a burglar alarm sign and decide to move on to the next house, metaphorically.

In response to viruses, the key innate immune response is called the Type I interferon response. Interferons are inflammatory immune products that induce irritation and also alert the wider immune system to the presence of a threat. There are several types, but the earliest responders to virus infection tend to be these Type I molecules. They are produced in large quantities and they signal to nearby tissues and to the entire body that a threat is present.

In response to interferons, local cells activate hundreds of genes, a truly remarkable cascade that is induced in just a matter of hours. These genes produce additional alert molecules but also produce mechanisms that actively hinder virus replication. The interferon signal makes cells into more hostile territory for the incoming virus, which also happens to be harmful and irritating to the cells themselves. This irritation spreads locally, and is well represented by the sore throat that I felt at first.

What was happening was that at the site of infection, the innate response had been activated and interferons were being produced to make my throat a more hostile environment for this invader. It also happened to make my throat a more hostile environment for me, but this was a minor inconvenience compared to the potential consequences of an uncontrolled virus infection. This would have happened with COVID-19, and it would have happened with many other viruses. There is a reason I had to get a test to know what I had.

The inflammatory response is visible. If you’ve ever had a pimple, you’ve seen something like it. An irritant in the skin produces an inflammatory response, and that inflammatory response spreads out through the local tissue by the diffusion of chemicals, much in the way that a drop of food dye diffuses through a paper towel. That’s why the site is reddest in the center and this fades as your approach the edges; the chemicals producing the irritation have spread out from the source.

A similar pattern would probably have been visible in my throat, provided it weren’t so dark in there. This is one of the reasons that doctors look at your throat when you’re sick—the redness is a sign of an inflammatory response.

As my illness developed, I began to experience a fever, malaise, and systemic pain. Because I am an innate immunologist focused on interactions within cells, I understand these reactions slightly less well than I understand the interferon response, but I do know what they represent.

The initial inflammatory signal in my infection called up a host of different responses within my body. Individual cells responded to consume virus particles, produce antibodies, and develop a specific response to the infection. The machinery involved requires a tremendous number of chemicals and cells, all of them with specific purposes. The timing of activation for each of these is also very important.

In past editions of this newsletter, we’ve talked a lot about antibodies, and how they sometimes take time to be created. In fact, a full-blown antibody response can take up to two weeks to really be solidified within the body. In that time, it is necessary to continue fighting the infection.

The systemic reactions that occur represent the body calling on far-flung resources to continue to fight infection while fine-tuning the antibody and cellular immune responses. Symptoms like fever, which I experienced, are thought to be a mechanism that systemically impacts infection. Living things, particularly microscopic ones, can be very sensitive to temperature. If you’ve baked bread, this is evident in the quality of rise that you get if you keep dough at a low 25 degrees celsius (77F) versus a more comfortable (for the yeast) 35 celsius (95F). Go up ten more degrees (113F) and your yeast will die.

For you, these three temperatures are comfortable spring weather, a hot summer day, and a cup of tea that’s gone lukewarm. Your body is very robust to changes in temperature. A microbe is not. Fever may represent our body taking advantage of this. It may also represent the inflammation and increased metabolism from the immune response causing us to overheat a little. There are mixed opinions on the matter, but everyone agrees that it represents the body doing something in response to infection.

The aches and pains that I experienced are almost certainly that inflammatory response manifesting itself in unexpected ways. A systemic inflammatory reaction is necessary to activate immune cells around the body, but it can have nasty unexpected effects.

Another symptom that I experienced was exhaustion. This is almost certainly because of the need to bring a bunch of metabolically “expensive” immune resources online and into the fight quickly. Your body is working hard when it is sick—which is why it is so important to rest.

While these new symptoms were happening, my sore throat began to subside. This can happen with some virus infections—the virus begins to spread more systemically and so the localized symptoms subside in favor of things that are more distributed.

In the meantime, the adaptive immune response is also working. In fact, the systemic responses manifest from chemicals that turn on this adaptive response. The adaptive response is the specific pathogen-recognition system. Antibodies are part of that response, as are T-cells. The analogy that I use for this response is that it is similar to the fingerprinting and wanted posters that are used by law enforcement. These are things that recognize specific threats, and respond to those threats only.

By three days into infection, the first antibodies would have been produced. These would have been the IgM antibodies that I mentioned in an earlier in-depth piece. They are lower-affinity and represent the earliest ability of the body to provide a specific, adaptive response. While the IgM antibodies are being made, the body is also further developing the antibody response, mutating the genes in antibody-producing B-cells to produce antibodies that are even better at recognizing the specific infection. Eventually, these matured antibodies, in the form of IgG, will replace the early IgM response.

That part hasn’t happened for me just yet, and usually takes 9 to 11 days to fully mature.

At the same time, T-cells will also be maturing to improve their population and provide support for my immune response—as well as potentially seek out and destroy infected cells.

The interesting thing about these adaptive responses is that I don’t really feel them. They do produce inflammatory chemicals that I feel as symptoms, but when a T-cell divides and produces a small army of descendants, I don’t feel those cells rushing through my body. I don’t feel my antibodies, either.

This will help me in the future if I see this infection again. It will be recognized more quickly, by a less strong interferon response. The parts of the adaptive response that I don’t feel will be stored in immune memory cells, and will quickly be activated when the infection is recognized. The end result will be that I may not ever know I was infected at all.

As I mentioned at the beginning, knowing this doesn’t help me to feel better faster necessarily. It does help me understand what’s happening and what may be unusual—if my fever spikes to a harmfully high degree, for example, I know this is a sign of struggle and that I need outside help. Still, though, it doesn’t make me get better any faster to have this knowledge.

What does make me feel better faster is rest, fluids, and medical care, and this knowledge did help me to understand that. I know that my body needs time and space to do its work, which meant I needed to sit back and let it do its job. I also knew that it could fail, and I would need to be ready to seek additional medical care. Thankfully that has not happened in this case, but understanding what’s happening when you’re sick can go a long way to knowing how to take care of yourself.

Join the conversation, and what you say will impact what I talk about in the next issue.

Also, let me know any other thoughts you might have about the newsletter. I’d like to make sure you’re getting what you want out of this.

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