Lately I’ve seen a number of comments and posts about damage to the immune system caused by Covid-19. Some of these comments run contrary to my understanding of the current scientific consensus. That’s not exactly surprising to me though. The CDC isn’t exactly a reliable source when it comes to Covid information. They were cribbing infection numbers from a volunteer organization for over a year. Major news media aren’t reliable either. There were endless articles about Omicron being “weaker”. That assertion is pure conjecture and a likely misinterpretation of the data. In both cases, official sources and the media were biased and sought to minimize concern over pandemic. That leaves us to either wade through all the scientific data and analyze ourselves or try to find media sources that don’t appear to be minimizing the threat Covid still poses. As someone who has the luxury of sifting through the evidence for a living, I thought I would share what I know with you all and try to demystify the biology of Covid.

Note, I am a scientist who has been involved with a number of research projects involving immunology and covid. I am not an immunologist nor am I an epidemiologist and I am not here to minimize the effects of covid. As long as it exists, it will continue to be a serious health concern. I am also of the position that stronger measures and a coordinated worldwide response in line with China’s zero covid policy could have and still can work. Not to digress, but I want to make it clear that I take this thing seriously.

To start, I want to describe what makes covid unique. It’s a coronavirus that’s true, but we deal with many coronaviruses that elicit little more than a common cold. The reason why I believe covid-19 is so virulent and deadly is the receptor the virus chooses to bind to known as ACE2. This receptor is commonly found in two places, the airway and the endothelium. It’s found elsewhere but I think these tissues are the most consequential. For context, the endothelium is a cell layer that makes up the inner lining of the cardiovascular system. The infection of the airway allows the virus to spread while infection of the endothelial layer is likely what made it so deadly.

Infection of the endothelium is dangerous for a couple of reasons. One, when you get enough of the virus the endothelial cells will start to die using a process known as apoptosis. Cells do this on purpose and it’s a necessary part of clearing away cells infected with pretty much any virus. It becomes a problem when you start to get a significant amount of cell death. This can induce blood clot formation which is likely a reason why ICU deaths were so high early in the pandemic. As doctors figured this out we’ve ended up with fewer deaths but that leaves us with another problem, long covid.

Now to be clear, long covid is not one thing. It’s characterized by various symptoms caused by infection but that last well beyond 3 months. In effect, the virus should be long gone by then but symptoms persist. The reason why this happens isn’t entirely clear but we have some clues. One hypothesis that I find compelling is that covid can cause damage to a person’s vasculature by infecting that endothelial layer I mentioned earlier. If someone is prone to inflammation they may end up with fibrosis and thus reduced vascular function. That could explain a whole host of symptoms simply because all organs rely on a healthy vasculature. There is also the hypothesis that the virus may remain long term in immune privileged tissues. This would explain why people suffering long covid may test negative when they are in fact still fighting the disease. Lastly, there is also a hypothesis that suggests microclots may harbor some inflammatory compounds from early in the infection. As they break up these get released and cause symptoms. Personally, I’m less swayed by this hypothesis. Either way, a lot of these hypotheses need further investigation before we can understand what’s causing long covid and what risks there actually are.

Now onto the immune response, my favorite part. To start, it’s important to know that the vast majority of studies out there do not suggest that covid-19 is immunologically unique. It is not a retrovirus and can not avoid the immune system as herpes and HIV do. It also does not target a receptor specific to immune cells. HIV does this by targeting the CD4 receptor which is specific to a subtype of T cells. ACE2 on the other hand is not expressed very highly in any immune cells which means they aren’t particularly susceptible to infection by the Covid-19 virus.

Now at this point, I’m sure some of you are going “But wait, I’ve read that covid causes death to T cells in a way that’s similar to HIV?” That’s actually true, but we need to get into some of the specifics to understand what that means for most people.

When a person first gets infected with covid, their immune system does not know how to recognize the virus. Instead your body relies on your innate immune system to signal the alarm due to all the havoc an infection is causing. This is where T cells come in. Now T cells are kind of amazing little machines. They basically evolve and self-select on the fly to produce a protein that can recognize unique parts of viruses or bacteria. It’s mind bending and maybe one of my favorite parts of biology.

Once a T cell determines that it has recognized an infection it will rapidly proliferate at an exponential rate. The rate at which they divide is only hampered usually by two conditions. In the first case, the virus is defeated at which point these T cells stop dividing and begin to die off. A few will go on to become memory T cells in case of reinfection. In the second possible case, there is too much virus and the resulting inflammatory signaling causes T cells to prematurely become ineffective or die through the process of programmed cell death aka apoptosis. This is called immune exhaustion and it sometimes happens during the immune response to cancer and HIV. It can also happen during severe covid infections. However, it’s important to note that this is likely not a concern in the majority of cases.

This ultimately means that most people who contract covid are not likely to be immunocompromised by the infection. In most cases, people’s immune systems can and will recover. As such, any cell death induced by the virus does not lead to what some have described as cumulative damage. For severe patients, of which there are many, this may be a concern at least in the short term. Even so, I believe they are also likely to recover given enough time. That said, people are still dying and long covid is a concern. It’s silly not to demand a systemic response.

TLDR:

The CDC and media are biased and minimize Covid. Covid is bad and a serious global response is still a good idea. Covid targets airways and vascular in particular. The effects on the latter may explain Covid’s deadliness and at least some long covid symptoms. The risk of long covid is somewhat ambiguous and needs further study. The Covid virus is not immunologically unique like HIV. Immune cells, including T cells, are not very susceptible to the virus. T cells learn to recognize the virus, expand rapidly, and then die when infection is cleared. In severe cases, T cells may also die as a response to excess inflammation. This may potentially lead to immune impairment. However, the majority of cases are not this severe. Even so, Covid is still serious.