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.
I originally wrote up a whole rant but I’ll keep it simple.
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The position you have presented isn’t consensus at all. The exact opposite trend is happening: a recognition that immune effects are surprisingly common and long-lived. This is highly relevant to the ongoing bumper crop of respiratory virus infections this winter.
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I can’t see any positive outcomes from this “demystification”. We’re in the second highest peak of the pandemic, hospitals are getting overwhelmed, new variants are escaping immunity and vaccines, and liberal normalization of saying, “fuck it” is at an all-time high. At the same time, there’s very little research suggesting we have the knowledge to take more risks, and plenty showing scary shit. I want my comrades to know what’s going on and what’s uncertain so that when they do make choices, they’re informed.
I also have credentials btw.
Thanks for the effort post. Can you comment on how multiple infections increase the risks for long COVID? Frankly this is what’s scaring me, as one infection brought serious health problems to my partner, and we’re terrified of a second infection.
It would be good to have access to the study, and they don’t mention the name or DOI in the article, but one study also doesn’t equal hard fact. This will need to be backed up with further research.
Their methodology seems to have been to look at anonymous medical records or veterans, which is fine, but it doesn’t say whether the people who were more likely to be hospitalised or die prematurely were more likely to die or be hospitalised with sickness before they were infected with COVID as well. I’m assuming they weren’t, because this would be a pretty glaring error otherwise, but without the paper I don’t know for sure. Also, out of 443,000 who tested positive, only around 10 percent tested positive more than once. Reinfection is now more common because of Omicron, but presumably the people in the study all had Delta or some other early variant. Omicron is dangerous, but is it as dangerous as Delta? And in the same way? I don’t know, but it seems as though the jury is out on that one on this website. It was dangerous enough to make my dad’s brain swell up, so it’s not a laughing matter either way.
If OP is correct, damage to the endothelial cells isn’t permanent, so maybe it is the amount of time elapsed between infections that makes it more serious, as in >t = <d, where t is time between infections and d is damage caused to endothelial cells. Then again, OP doesn’t cite any sources either, so this could be complete bullshit.
Here’s the full article of the original study.
The study was probably the largest one for reinfection. 10% of 5 million is still a good number for statistical purposes. The authors state that it was limited that the test subjects were older than most of the population. But what bothers me is that this is the biggest and most comprehensive study on reinfections with long COVID, and it shows it to be pretty bad. Ideally, we’d live in a world where NIHR and NIH would be pouring money into research on long COVID, but that doesn’t seem to be the case.
If OP is correct, damage to the endothelial cells isn’t permanent
I didn’t see that anywhere. But again, this is a very complicated matter, and the research on it is very new. Honestly it could go either way. But that’s not much reassurance for those concerned about long-term effects.
After looking at weighted comparisons of infected and reinfected people, you’re right. There doesn’t seem to be a difference in any comorbidities, which means that the findings are legit. Time between infections doesn’t seem to make a difference either.
I guess this does reiterate how new this virus is though, and how strange this situation is. How often does a completely new virus turn up which we have absolutely zero (0) resistance to? One which is both deadlier and more transmissible than flu, to boot.
What is clear is that at least 35 million Americans (~10% of the population) are currently suffering from long Covid, this figure is likely an underestimation
Is there a source on this beyond “Someone told me?”
How many people in the U.S. have developed “long COVID”?
It could be in the range of 7.7–23 million, some estimates say.
This clearly doesn’t say 35 million people currently have long covid
Edit: think you might be taken out of context from your other comments so I was too harsh because there’s some talking past each other happening in this section.
That video at the 36 minute mark isn’t saying exactly what you claim it is, and the nature article you posted to back up your points also don’t prove what what you’re saying. It’s also not really relevant to the discussion about long-covid RATES on a population level.
the pre-print study in that video (that i cant find on medrxiv yet which has many papers in the pre-peer-review-stage but maybe it will pop up after they get more participants) is about comparing the SYMPTOMS of long covid and vaccine side-effect people, and demographics involved.
I think it’s slightly misleading when you say “emerging evidence is vaccine causes long-covid symptoms” vs what should be said which is “emerging evidence says long-term vaccine side effects and long-covid symptoms resemble each-other”.
This reminds me of the misleading happening around more people who die from covid are now vaccinated, even though a higher proportion of unvaccinated people die so clearly vaccination does help reduce deaths, although antivax people will take it out of context.
These are two very different things to say in regards to causation because the structure of the study in that video isn’t about making a judgment on rates of vaccine symptoms vs rates of long covid, it’s about trying to figure out if numbers/stats might point towards it being worth looking at if there’s a shared mechanism between the things that cause long-covid vs vaccine side-effects; since from that pre-print the people with long covid and people reporting side-effects share very similar demographic traits in age and other things.
It’s the difference between saying “people who get hit by an apple while sitting under a tree have their head hurt just like people who fall off skateboards” vs “sitting under an apple tree causes headaches”. The second can be misleading since sitting under a tree doesn’t imply you will be hit by an apple.
My disclaimer is that I know stats but not much biology, but also this is a study about stats instead of how biological mechanisms work so I felt like I could comment.
I’m careful about COVID, have made friends during the pandemic, and spend time with friends outdoors at least once every week, in various weather conditions.
It’s a false dichotomy that you can either be a hermit or say, “fuck it”. You can wear an N95 mask in shared indoor spaces with strangers or people where you don’t know they’re careful and testing. You can have no mask outdoors and do any outdoor thing, including eating, drinking, playing games, watching TV and movies, dating, organizing, hiking, playing sports, reading books…
I’ll acknowledge that it’s still a shift and still additional effort, especially if the way you are used to socializing is structural proximity (school, work, organizing) rather than planning things or seeking out new people in new experiences and that the latter is a lot more difficult for some people than others. There are also fewer places to spend time “for free” and maskless, especially during the winter. It’s a hassle, no doubt. I just want to communicate that the message isn’t, “don’t go outside” and that there are options beyond social isolation and what I fear comrades are at risk of doing, which is more or less giving up on being careful. I want my comrades, including you, as alive and healthy as possible. Spending time with good people and also mitigating their risk of getting sick from a 3-year (so far) pandemic virus with few signs of slowing down
If I’m understanding OP correctly, the idea is that Long COVID is not necessarily COVID literally lingering in the body for months, but symptoms of damage caused by COVID, like lung damage. So, a lack of naive T cells might make sense if there is no COVID for them to be fighting. I might be misreading that Nature study, though.
Naive T-cells are fucked by COVID, seemingly directly. There are low counts because of COVID, including among people who had mild symptoms, as well as a whole host of related dysregulation (transition: shit is fucked) of the immune system. A big part of this is that they’re dead. Naive T can counts are just down, and they’re down for as long as anyone has tried measuring them longitudinally.
What this means, together, is that there’s a good chance your immune system looks more like an older person’s after infection, i.e. closer to immune-compromised. It’s not unlikely that this is why it’s such a bad year for infectious diseases, and particularly respiratory viruses, i.e. those that are held at bay by the cells that are now decimated. We don’t really know what immune system recovery looks like for those affected. Also the dysregulation makes it even weirder, with people developing autoimmune disorders at greater rates post-infection.
