In my experience with immune related diseases, and reading about the immune system, the takeaway from all of it is "The immune system is ridiculously convoluted, and nothing necessarily makes sense or doesn't make sense"

Given that I can totally understand why they would investigate something that seems self-evident. I wouldn't have been even slightly surprised if they found that high antibody count meant higher susceptibility to re-infection. The immune system really is a spaghetti code mess of a system, and has seemingly as many intuitive as counter-intuitive behaviors.

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There was a time when I worked in the intersection of peripheral neuroscience and the immune system, studying the immune response of mammals to optogenetic therapies. It was a widely held belief that, in that problem space, the complexity of the immune system outpaced ambiguities and unknowns we had surrounding the PNS.

Basically, what I'm saying is take every statement you've seen in the media and documentaries about how complex the nervous system is, and consider that the immune system is considered equally incomprehensible today.

Not only is the immune system spaghetti code, but it likes to break all the time and, to our perspective, is full of weird and undefined behaviors.

Well, if my bio 200 class taught me anything, it's that we don't have bodies that are created with cells all united to single goals or purposes.

Our bodies are microservice hell :D. We have a bunch of cells all performing their complicated jobs and duties working together in a crazy complex distributed system. Even the internals of the cells are a bunch of horribly stitched together glue code that just happens to work because of billions of years of pruning off the glue that doesn't work.

It's an incredibly complex chain of chemical reactions which has been selected of eons based on which chains of chemical reactions produce more of the same chains. It's madness.

Maybe one way to think about biology is: "An ongoing exercise in systems documentation." :P

Evolution is a billion years of kludges.

No refactoring whatsoever…

Yeah. I did a lot of work with blood measures and every disease had some characteristic spike in n immune function. I worked in a lab with a ton of immunologists and we never knew what was going on. All we could say was activation of complement or strong TNF response or something else descriptive but not really helpful. Just too much dark matter in the immune system. My big hope is that the silver lining of COVID will be a much deeper understanding of the immune system. Certainly a ton of money is being poured into it. Fingers crossed, we could be entering a golden age for immuno-therapeutics.

Here here to the possibility of starting a golden age of immune related research and investment. IMO (as an autoimmune patient who reads a bunch about my disease/immune system and has done some computation biology work during my CS masters, but otherwise unqualified), immune system research is severely underfunded in relation to how involved it is in virtually ever bodily function.

I kinda feel like with other organs that are tangible and you can like see and feel (brain, kidney, heart, etc) are much more obvious choices to study and examine for pathology (ie plaque in the arteries, kidney stone). But an ephemeral system of on/off switches that communicate with each other to attack or not attack stuff? kinda makes sense that it is elusive and poorly understood.

my great hope is we are starting to enter a golden age of immuno-therapies, and it's not just because of COVID. Immunotherapy is genuinely the most exciting area of cancer therapies right now (again, IMO). between CAR-T cell therapies, proposed NK cell therapies, PD-1 inhibitors, etc, whats not to be excited about?

As someone who is currently considering IL-17 inhibitors for psoriasis, this kind of comment fills me with dread. The claims for products like skyrizi make it seem like they have a very good idea of why it works and what the potential risks are, but if things are as complex as you say then how could that be true?

Ankylosing Spondylitis patient here who has tried and failed most NSAIDS, Sulfasalazine, and 3 TNF inhibitors. Don't feel dread towards this notion! The immune system is definitely super complex and spaghetti code like, but rheumatology and science in general is working it's way through reverse engineering it. Since TNF inhibitors have come out, lots of data on these monoclonal antibody drugs that inhibit specific parts of the immune system have been gathered. The short term and long term side effects are noted and increasingly understood. If your rheumatologist has a good bedside manner, they should give you some comfort in how widely many of these drugs are used, what is known, and what is unknown.

I'm not trying to make any claims that we are close to a full or maybe not even good understanding of how the immune system works, but science is definitely advancing towards reducing the unknowns. I've been through the ringer of all the treatments and currently am not able to find relief in any, but I'm just trying to offer some hopeful empathy as someone who has at times felt dread from having very rare side effects to a whole bunch of the medicines and I rarely feel dread in general despite the uncertainty and my pain.

As always, talk things through with your rheumatologist and GP if you have concerns.

I'm glad they're confirming this, and it could be useful for determining who needs a booster the most, but yeah, it would be more surprising if this _weren't_ true.

It's a step in that direction, which is more than we had previously. It doesn't establish a cutoff threshold, but it does allow a doctor to say whether somebody's antibody level is closer to the group that got infected or the group that didn't. They could warn that person to be extra cautious and theoretically save lives based on this study alone. I find that newsworthy.

A main difference in this research is that it's very difficult to actually measure the levels of neutralizing antibodies. Traditional antibody tests aren't able to tell if you have high neutralizing antibody levels yet, as a BSL3 lab is needed to perform these experiments with live virus. Antibody levels aren't always a clear indication of level of immunity, so this was still an open question with COVID.

This study has serious implications for a recommendation for a third dose. It was known for a while that a 3rd dose increases levels of neutralizing antibodies, but this study now ties that increase to a significant boost in immunity which has implications for the new variants like Delta. It means that likely we don't need to wait 3-6 months for approval for a new strain specific booster. We can just use the doses we already have to bump up the neutralizing antibody level.

It also has implications for how long the 2-dose or 1-dose regimens are good for, since it has been known that the neutralizing antibody level does tend to dip after around 6-9 months, so this gives more evidence for the benefit of getting a booster after around 6 months to keep neutralizing antibody levels high.