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Cross-posted to r/covidlonghaulers

As someone just coming out of long covid, I can't help but wonder how long that reduction in immunity lasts. Or is it permanent?

Anyone here know enough abt cytokines to tell us how "treatable" this is with modern technology?

Is it a matter of repurposing some other cytokine treatment, or do we need to develop a whole new technique?

> Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood.

So, many of the questions people will have about this are simply not going to have an answer yet, unfortunately. I see several for this submission already.

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Well, it's a step in the right direction.

At least we are finding significant differences to drive further research and testing. That’s usually how it begins.

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At work, can someone eli5 this for me for later?

In my case, I have IL-8 and IFN-Gamma in range

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Interleukin-8 (IL-8 o CXCL8) 4,56 pg/mL IN RANGE <13.87 pg/mL

Gamma interferon (IFN-gamma) 4,29 pg/mL IN RANGE <8.41 pg/mL

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How do you find these things out? I don't even know my blood type or how to find out.

>How do you find these things out? I don't even know my blood type or how to find out.

Private laboratory specialized in Spain does this type of analysis. I imagine that in advanced countries they will.

Lactoferrin has immune modulating properties. Among other benefits as an anti viral, bacterial, and fungal. Also gut modulating properties.

Get a micronutrient test done, check your Zinc and Vitamin C levels. They're likely depleted. Zinc and Vitamin C have fundamental roles in nourishing the gland which creates Cytokine molecules (Thymus Gland). Vitamin D also plays a crucial role. If we are insufficient in the nutrition that's responsible for Cytokine function, I would imagine that by bringing the nutrients to healthier levels would lead to higher cytokine levels. Issue is is that prolonged malnutrition of the Thymus gland actually leads it to have atrophy, which will mean lessened fundamental function. The sooner we replenish our Thymus, the better.

Virus's love to deplete Vitamin C and Zinc, because Vitamin C and Zinc are so readily necessary for Cytokine (immune fighting T Cells) to deploy and fight the virus. So not only will the virus deplete these key nutrients, but the key nutrients will be depleted leading to insufficient immune fighting function. Its a loop if you will.

For example, I have had a micronutrient panel done, I have resoundingly low levels of Zinc and Vitamin C. And now looking back realizing that during my last infection, I didn't even have a fever. It was extremely mild. Which is and could be in indication of a under functioning deployment of Killer T Cells to be sent out to fight the virus. As a indication that your T cells are busy fighting the virus is to have a fever, it is the body's natural process for killing viral material. Which makes me think, "Just think how many of us had "mild" or "asymptomatic" infections (no fever). Maybe even from the jab itself. Could our immune system of just been depleted? Hence leading to viral persistence within us still?"

GUY BELOW ME KNOWS MORE When a virus invades the host. The body's bacteria along with antibodies find and detect its existence. They then go to deploy Cytokine molecules from the Thymus gland to seek out and kill the viral matter through cells called "T cells", typically called "Killer T Cells". These cells engage the virus and begin to fight it. You usually experience symptoms like Fatigue, Fever, or other bodily dysfunctions during this time as your body is using natural processes to kill viral matter and protect itself.

In the above article it is stating that they are finding people with Long Covid don't have an overreactive immune system. But that they have an underreactive immune system. Specifically lessened Cytokine molecules aka T cells. T cells are the most crucial, when deployed they give the sensations of a "fever" and those other aforementioned bodily dysfunctions.

The Thymus gland produces Cytokine and T Cells. And it is fueled off of Vitamin C and Zinc. Vitamin C and Zinc are shown to be lessened in people with Long COVID. With insufficient nutrition the Thymus gland will have atrophy and shrink. This leading to a understrength baseline Immune System response in the future.

I'm now theorizing that our mild or asymptomatic infections are really red flags that our immune system was underprepared to fight off the virus. Or that our bodies did not have adequate antibodies or [gut] signaling bacteria to detect the existence of the virus for defense or deployment.

Thank you , I sincerely appreciate it.

I thought long haulers were over inflammed, yet (correct me if I am wrong) the wording of OP and what you state is saying there is no more inflammation whatsoever happening in regard to these two cytokines specifically.

So I guess perhaps there is an over expression in other ones?

A lazy immune system makes sense, but the lack of thymus being an attributor does not. I still have most of my thymus noted on my CT with contrast as "favored residual thymic tissue" as a 30 year old, yet still abysmally low specs and long covid.

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Glad you’ve recovered

How can I get tested for long Covid ? Like it seems regular doctors don’t even try.

How long did you have it?

Well, I’m in the USA so I guess I’m out.

I was first diagnosed in late August 2022.

exact same for me and i am finally getting my brain back to normalish. i was vaccinated too.

Yeah, that was pretty good, thank you.

That’s good! I believe that it can be misleading to assume that because your thymus appears healthy on a CT scan that your immune system is functioning to par. Be sure you have the vitamin C, D, and Zinc in optimal ranges. There are other residual effects from the virus as well such as gut dysbiosis which is cause a number of continuous downstream effects if gone untreated. I did not mean to say any thymus dysfunction is the explanation for long Covid in it’s entirety. There is malabsorption of vitamins, nutrients, and amino acids; gut permeability, organ inflammation, dysfunction in Short Fatty Chain Acid synthesis, neurotransmitter synthesis, and a likely overgrowth of bad bacteria and yeast.

Not to be a pooper of parades but the same thing happened to me, I thought i was better, I got a cold that other people got over in a few days. I was hacking up phlegm for over a month, had a hard time breathing for a few days. Also vaccinated. Best of luck staying healthy.

There aren’t agreed upon bio markers yet which is partially why research like this is so important

Because you basically can't test for it yet.

Permanezzy brezzy

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010314/ Might be an interesting read.

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Perhaps. I did a simple search for systemic lupus and covid immunity. I found data that suggested people with active lupus have superior immunity and less progression than people who are not currently flaring. I am not a doctor. I have sle however, and I found covid was an extremely minor cold for me that lasted a few days. In another study it showed lupus patients have poor results with vaccines and immunity. It is very interesting that they're finding association with elevated Anti double stranded DNA and increased immunity. Thank you for your comments. It is interesting.

That stat can’t be true. HALF? We’d see it all around us

I've seen many people that don't want to believe they have long covid because "it cannot last that long" etc, but have headaches, persistent fatigue etc.

I definitely don't think my immune system is performing normally. Just was specifically mentioning the thymus part cause they said its rare for people to have an intact thymus when most by 30 went through a full involution.

State your study here - I don't believe this stat...

lactoferrin significantly lowers all my symptoms

So less symptoms mean more likely to get long covid?

There is an uncanny correlation between this exact phrase you uttered. It’s based by no scientific basis, some speculative research articles are floating around out there that mention this exact same hypothesis. While I would say it is probable it is not entirely purely 100% accurate. There seems to be a heavier hit to highly cardio active individuals as well.

I see. That’s fully understandable. I don’t believe my immune system is performing well either. May I ask, what was your attributed “long Covid” infection like?

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america means selling your life kidney and firstborn for medical care so it’s technically possible

My friend hasn't tasted or smelled for 2 years. The fatigue is still quite prevalent too.

not half though

"Up to half" doesn't mean half. It means various studies have found different amounts and the highest was a half.

As someone who works in immunology, your explanation is very inaccurate. When an unknown virus invades the host, special cells known as dendritic cells (not antibodies or bacteria—antibodies can’t even be produced until B cells are activated) take up bits of the virus and travel to lymph nodes (not the thymus—the thymus is where T cells mature).

In the lymph node, a single T cell with a matching receptor recognizes the bit of the virus the dendritic cell is presenting. When it recognizes the virus, the T cell divides and multiplies. Certain kinds of T cells—killer T cells—destroy infected cells. Other kinds of T cells—helper T cells—activate B cells, which produce antibodies that neutralize virus. All the multiplication of T cells and activation of B cells occurs in the lymph nodes—it’s why doctors check to feel if they’re swollen when you’re sick to see if there’s an infection on.

Cytokines like IFNy and IL-8 (among others mentioned in this paper) are produced by a wide array of immune and non-immune cells when they recognize viral infection. (Not the thymus, though. Once again, the thymus is just where T cells develop.) They activate dendritic cells to take up bits of virus and travel to the lymph node. They also direct T cells to develop in a certain way and for B cells to produce the right kind of antibodies. They also encourage migration of other kinds of immune cells to the site of infection to eliminate the virus.

The authors here believe that immune exhaustion is the cause of long COVID. Once cells stop producing these necessary cytokines, the immune system simply cannot function as it should anymore. This exhaustion doesn’t come from initial underreaction, though—it’s overreaction of the immune system that causes it.

Tons of studies have proven that high levels of pro-inflammatory cytokines like the ones in this paper actually correlate with worse outcomes. The inflammation they cause, when unchecked, can be very damaging to tissues. On the other hand, lack of reaction at all is also very dangerous. The immune system has to walk a tight line between over- and underreaction or risk either scenario. Long COVID is essentially dysfunction of this balance, likely due to initial overreaction.

I recommend How the Immune System Works by Lauren Sompayrac as a great primer to immunology. Cause it doesn’t work like how this person is describing it.

TL;DR: This explanation is absolute BS and any doctor or scientist would laugh their ass off about any number of things in it. Bacteria and antibodies taking virus to the thymus? Doesn’t happen and goes against the entire logic of how the immune system works. The thymus dying? The thymus shrinks with age, but that doesn’t cause what we see in long COVID. It usually just causes a weaker immune system in old age.

I asked ChatGPT to simplify the results of this study for me so I could understand it. Here's what it wrote. If someone is a scientist and understands this study, I'd love to hear if there are anything chatgpt got wrong. Here's the output:

"The study looked at 12 people who had long-lasting symptoms after having COVID-19, and compared them to 15 healthy people. They measured certain chemicals in their blood called cytokines, which help the body fight infections. They found that most of the cytokines were lower in the people with long-lasting symptoms compared to the healthy people. The cytokines that were the most different were Interferon Gamma (IFNγ) and IL-8, which were completely absent in the people with long-lasting symptoms. They also found that IL-6, IL-2, IL-17, and IL-13 were also lower in people with long-lasting symptoms, but not as much as IFNγ and IL-8.All of the people with long-lasting symptoms were women, so the researchers wanted to see if there was a difference between men and women in the healthy group. They found that there was no significant difference in cytokine levels between healthy men and women, except for one cytokine (IL-2) which was lower in healthy men than in healthy women. When they compared the women with long-lasting symptoms to the women in the healthy group, they found that the levels of IFNγ, IL-8, IL-6, IL-2, and IL-13 were lower in the women with long-lasting symptoms, but not IL-1β, IL-12, IL-10, IL-5, or TNFα. The decrease in IL-5 levels in women with long-lasting symptoms was only significant when comparing to other women, but not when comparing to men and women together."

The important part is:

>Based on our results we propose that immune exhaustion perpetuates long-COVID due to the seemingly complete reduction of IFNγ and IL-8, as well as significant decreases in IL-2, IL-4, IL-6, IL-13, and IL-17. Identifying these and other deficiencies will provide clues towards methods to intervene and possibly restore immune function in the context long-COVID. Although functional assays that test the ability of immune cells from individuals with long-COVID to respond to pathogenic stimuli will be required to support this theory.

From the paper:

>Also referred to as the neutrophil chemotactic factor, IL-8 recruit’s neutrophils and NK-cells to sites of inflammation where they can clear infected cells and promote wound healing.

>It is possible that the apparent lack of IL-8 in long-COVID patients may be responsible for at least some of the debilitating symptoms including post-exertional malaise, fatigue, and persistent cough, shortness of breath and chest pain.

>In this scenario, the acute SARS-CoV-2 infection damages the lungs, the cytokine milieu unfolds as described above, recruiting cells to the site of damage where the cells can either (a) help control the infection and induce a wound healing environment and the individual recovers normally; or (b) the infection causes abundant cellular infiltration leading to a high concentration of immune cells in a relatively small physical space, ultimately causing more tissue damage, which is not efficiently repaired in the absence of IL-8.

>Predictably, under scenario ‘b’ the individual remains having difficulty with oxygen transfer from the lungs into the blood stream. Therefore, if the macrophages and other cells that secrete IL-8 become exhausted or are otherwise incapable of secreting IL-8, neutrophils will not be recruited to assist in the wound healing process in the lung once the infection has been cleared [63]. Scenario ‘b’ therefore emerges as a potential model to explain certain long-COVID complications based on lack of IL-8.

>IFNγ is secreted by the innate immune Natural Killer cells (NK) and Natural Killer T cells (NKT) as well as the adaptive immune CD4+ Th1 and CD8+ Cytotoxic T Lymphocytes (CTL) after the development of antigen-specific immunity [64]. Together with IL-12, IFNγhelps drive the differentiation of Th1 cells, which in turn can secrete IL-2, TNFα, and IFNγ [65]. The observed lack of circulating IFNγ (Figure 1 and Table 2) in the plasma of patients suggests either severe immune dysfunction or exhaustion.

The war in the lungs is over, but there are too many soldiers still there, hanging out, causing drama. What's not happening: they need to be transported away and the engineering+construction crews need to come in to start rebuilding.

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I don't fully understand your question. If you mean my acute infection, it was bad, 91% spo2 bilateral delta pneumonia. If you mean my long covid symptoms....2 years of pure hell....burning hands/feet, blurred vision, sob, chest pains, brain fog, dysmotility. To name a few.

We're talking about long COVID, not chicken pox. You've lived your whole life surrounded by people masking their problems so why would it surprise to know many people are sick?

yes, everyone is feeling terrible and they're all hiding it from me

Everyone would be ridiculous. The point is you don't see so you can't know.

I got sick for at most a day in Nov 21 and this all hit my suddenly end of Jan 22. They can’t even be sure I had COVID but given how I had sudden LC symptoms that’s what my doctor said was very likely. Always wondered why it came months after like a 1 day mild fever.

James Patterson MD does some blood testing but insurance doesn’t cover it and it’s expensive. Go over to r/covidlonghaulers there’s mixed reviews on him.

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What do you mean “state your study”? It’s a direct quote from the article the post is about

Here is a link to the study that this study cites about prevalence of long covid

It's this study.

Whoops - sorry - should have clarified. I meant any additional studies that validate this statement. This statement defies common sense from those of us in the real world who are surrounded by Covid victims of all age groups who have shown no long Covid symptoms 3 months after initial infection.

Honestly in my personal experience, half isn’t that surprising or far off. Of course, I’m not doing a study or anything, but I’d say more than half of the people I know who have had Covid experienced symptoms for months afterward, including myself - I finally have gone a couple weeks without noticing anything and I got Covid in August

I was meaning long Covid. And sorry to hear about these symptoms Man. I’m about to begin a long Covid podcast and we’re aiming at just bringing on people with long Covid for quality collaboration, and discussing our long Covid stories. At the least you make a friend in the community and have some meaningful helpful conversations, at the most you help others through the spread of awareness and knowledge and we blow the lid off this misunderstood illness

I see I do appreciate your correction. I’m regurgitating personal at home research from online doctors I’ve watched explaining it and pubmed papers. It looks like I’ve completely messed up the initial signaling from the dendritic cells. I never did say that bacteria or antibodies carried the virus to the thymus to correct you. But that they served a role in signaling to the T cells for response of the immune system. Which is a true scientific statement that I would be happy to share the research on. I was however incorrect about the thymus being the origin of the production of cytokines. I appreciate the correction again. My explanation also was missing the functionality of the dendritic cells, lymph node, and B cell activations for the pathology of immune response. I’d love to ask you more questions because I am fascinated to hear more and to learn more!

I came across an article the other insinuating that a very possible potential bio marker is the microbiota layout within the gut microbiome.

I’m on mobile so pardon my formatting.

> The body’s bacteria along with antibodies find and detect its existence.

This is not true. Yes, there have been some studies that show that commensal bacteria are important for signaling to T cells. However, they do not activate T cells. T cell activation only occurs upon recognition of an antigenic peptide presented upon the MHC molecule of a dendritic cell in the lymph node. Signaling from commensal bacteria only has an effect once T cell activation occurs, when it can affect the differentiation of a T cell down different lineages. T cells can only then activate B cells, which produce antibodies. Antibodies for previously unknown viruses do not exist in the body yet—that’s why it takes so long to mount an immune response because it takes some time for a T cell with the correct receptor to recognize the virus as presented on a dendritic cell.

The initial recognition of a virus, though, occurs from innate immune cells that can recognize patterns present in lots of viruses. In response, these innate immune cells produce cytokines that begin the process of inflammation and activate dendritic cells to take up virus and travel to the thymus. These cytokines can affect the differentiation of T cells down different lineages (killer, helper types 1, 2, and 17, regulatory, follicular). These cytokines also affect the type of antibody produced, as different antibodies have different properties for better neutralizing different kinds of microbes.

Notice how the thymus isn’t involved in any of this. It’s very important but it doesn’t really play a role in the basics of the immune response.

I really wouldn’t rely off random internet doctors for immunology research, sorry. Way too many conspiracy theorists online. Research papers are also going to be way too advanced at this stage. Sompayrac is your best bet. I’ll even sell you my copy. Even Cells at Work (on Netflix) is going to be more accurate and helpful.

Haha we're saying the same thing about the commensal bacteria aspect. I never did say that commensal bacteria activated the T cells as you so put. I'd love to hear more from you. I'm a Long Covid struggler who's on the mend. A lot of people don't know what is going on, medical professionals especially, however, everyone has their theories.

I think through discourse like this we're only going to improve in knowledge and learn more. Obviously I do not have a background in immunology as you say you have. I've also been looking into starting a Long Covid Collaboratory podcast where we bring in other people struggling to share stories, share what helped us, and discuss symptoms. Would you ever be interested in saying some words?

Yep potentially good one there

Me too. Except for one pesky symptom. I didn’t see an effect until ramping up the dose though. I take Apolactoferrin which as I understand prevents the concern of high iron levels.

Agreed - no way it's half...

But is it half of your friends? Nowhere near half of the people in my network have ended up with LC.

It says "up to half". This is kind of a tough number to get a handle on and it depends on how you look at it and what time frame. At this moment, of the people who have had COVID, only 11% currently have long COVID symptoms and an additional 17% have HAD long COVID at some point, so that's 28%. Most people who get long COVID have their symptoms resolve within a year.

But in June of 22, that number was 35% (19% current 16% ever).

So it may be based on a specific time period during a certain outbreak.

But again, the vast majority of long COVID cases resolve within a year.

Source: Kaiser Family Foundation

Edit: I forgot to mention, there's also been some discussion that a large number of long COVID cases go unreported. My own daughter had long COVID and we never reported it. It was mild and it eventually resolved itself, but we never took her to a doctor for it, so it never ended up in the stats, so that might be factored in as well.

Same, rona was mild but I got a cold recently and I could not stop coughing phlegm for 3 weeks. I was sicker and nastier than when I had covid. Also had shortness of breath.

Yeah, biomesight who is one amongst many investigating this. If given a stool of long Covid in a mix of stool from common people, they could accurately identify who’s is the long Covid one. There are very specific imbalances in the microbiota species

That you know of. The impairments may not always be obvious.

Up to half in 3 months is simply not a believable figure/statement based on real world anecdotal experience - and how can "unrealized symptoms" not impacting life functions in any way as implied by some be measured from a practical perspective? Also agreed that "up to half" could technically mean anything less than 50% but implies something close to 50% or the statement is meaningless.