Wont viruses just adapt and now we've got worse viruses as a result? Isn't this kind of why doctors don't like to prescribe antibiotics too often, because they become ineffective in the long run.
I'm genuinely asking, I'm a simple software dev not a doctor.
And the really, really bad part about abusing natural parts if the immune system to provoke pathogen resistance against them is that the resistance will target part of natural immunity.
My understanding is that there's often at tradeoff between fitness and antiviral resistance. The virus starts on a fitness local maximum, and it has to pay a fitness cost as it evolves resistance to the antiviral (due to stepping off the local maximum). If the antiviral is ineffective, and the virus continues reproducing, over time it will evolve "compensatory mutations" which allow it to regain some or all of the lost fitness.
So yeah, I wouldn't be super worried about the virus evolving to become worse in absolute terms as a result of antiviral exposure. Virii are evolving all the time anyways. Antivirals can also reduce evolution speed by fighting an infection: A more severe infection means more virions means greater evolution speed. I believe some new COVID variants were thought to have evolved in the body of someone who was severely infected. (However: Note that it's not necessarily beneficial for fitness for the virus to evolve greater infection severity, especially if that interferes with transmission.)
Probably, currently it's just 15 people that have it, but if you started giving it to more people there would be incredible advantages to any virus that could adapt and viruses mutate fast.
Interesting, and potentially very good. But I can't help but wonder, like at least one other commenter, that this might have unexpected effects if applied at a larger scale. I know some viruses kill bacteria for instance. I don't know, something about universal applicability makes me a little uneasy.
> When he and his colleagues looked at the individuals’ immune cells, they could see encounters with all sorts of viruses—flu, measles, mumps, chickenpox. But the patients had never reported any overt signs of infection or illness.
Given that the article goes on to talk about mild persistent inflammation, is it possible that these individuals are sometimes asymptomatic but still capable of carrying/transmitting viruses at least temporarily? The article talks about potentially immunizing healthcare workers during a future pandemic, but if this was just allowing people to never develop symptoms (and not have to leave work) while having low-grade infections, would we accidentally create a work-force of Typhoid Marys?
I would imagine the worker would be wearing protective gear. They're not walking around mask-off. Also, if you know you have gotten this treatment, you would obviously have to take different precautions.
Asymptomatic carriers are a concept I've always found interesting and honestly a bit confusing. When a pathogen can be present without ever causing symptoms it becomes much trickier to show causality.
This was a lynch pin of sorts in Koch's postulates. We can't properly go through those postulates with viruses like we can with biological pathogens, but it is odd to me that we don't have similar concerns when the presence of a replicable pathogen doesn't cause the symptoms they are expected to cause.
I wonder if enough of them exist to even do a study like that.
I have encountered side effects that probably no one has seen before, simply because of rarity and peculiarity of behavior. You don't run into a ton of people using both interferon and doing karate, so if bruising more easily happens 10% of the time... would anyone notice?
Personally I would be more worried about persistent inflammation causing inflammatory disorders, of which there are many. If there are like 10,000 individuals with this trait then there just aren't enough to detect. But that seems direct... wouldn't you expect something like this to potentially even destroy viral reservoirs over time?
The fact that this is short term in the treatment made me 1000x more comfortable with the idea in any case.
Broad-based inflammation delivered by lipid nanoparticle chock full of mRNA: what could possibly go wrong? I'll stick with monoclonal antibodies, thanks.
Oh, and here's what the ISG15 deficiency (the condition these mRNAs are there to simulate) does:
> Patients present...with infectious, neurologic or dermatologic features. Basal ganglia calcification is observed in all patients... The basal ganglia calcifications may cause epileptic seizures... The IFN-I inflammation may also manifest early in life as ulcerative skin lesions in the armpit, groin and neck regions. Finally, ISG15-deficiency leads to mendelian susceptibility to mycobacterial disease... [t]hese infections present as fistulizing lymphadenopathies and respiratory symptoms following BCG vaccination.
And the part where he says people with this mutation are more prone to bacterial infections is not worrying, because…?
In a world of more and more antibiotic resistant bacteria, that does not seem like a good trade-off…
This is researched as a potential treatment to an acute viral infection. For the duration of the treatment, you can accept the increased risk of bacterial infections.
Just like you accept the risk of increased yeast infections while treating bacterial infections with antibiotics, or the risk of any infection while treating a cancer with chemotherapy.
What is the “current” scientifically approved and unbiased understanding about the negative effects of the COVID vaccines?
There seems to be a lot of information, misinformation, conspiracy theories, and information hiding at least in the perception, if not in reality.
I cannot imagine what society at large will have to deal with or what the reaction will be for or against an “everything” therapy, given what happened with Covid.
When you get a viral infection, immune cells make a signalling protein called a IFN-1 (Type I Interferon) cytokine, and this flips a boolean flag to True on a bunch of genes (interferon-stimulated genes or ISGs) that produce a bunch of proteins (hundreds) that control the infection. ISG15 is one of them and its role appears to be to downregulate and to limit the inflammation.
The paper title refers to a ISG15 deficiency, meaning if you are dificient in ISG15 that inflamation limitation goes away. But the paper is actually about how in people that naturally have a ISG15 deficiency, there is an always-on low level expression of some of these pro-inflamation genes. So they take that as a safe level.
The did RNA sequencing on experimental ISG15 deficient cells and from heatlhy individuals, identified the mutations, narrowed down to 10 genes (antiviral ones not inhibitors) that in combination significantly inhibited viral replication. They stuck the RNA for such genes in lipid nanoparticles such that they enter host cells, whose ribosomes happily read the RNA like a turing head reads a tape in base 20 and produce proteins encoded by these genes, similar to how the mRNA vaccine works.
So why not dose with the IFN-I directly? Three referenced papers show its "poorly tolerated with significant side effects" and all those downregulators that get expressed limit the inflammation response.
Disclaimer: IANAB (not a biologist) corrections might be due..
It was already invented [0], but the patents were bought by a small company in New Zealand (some kind of big pharma shell company?) who isn't seriously developing it and now appears to be defunct.
I always wonder this and maybe people in the comments here know the answer: If humans had the technology to eliminate all viruses on Earth, what would be the outcome? Do viruses keep other bad things in check? Would there be bad consequences if we eliminated all viruses?
Eliminate all viruses: Population issues in other organisms down to bacteria is my guess. We break a link in a significant food chain, basically.
Eliminate human-tropic viruses: We have to monitor for outbreaks when new viruses mutate and jump species to successfully infect humans. If there's zero mass immunity across the population at every outbreak, we're still in a high-risk situation.
Viruses have had a lot to do with the evolution of life and specifically us, where perhaps our distant ancestors were bestowed with a system of transcribing short term memory into long term memory via the hijacked machinery from a virus. This is only one example that I could remember off the top of my head, there are surely many more. Would that matter going forward? I feel like we'd better be sure that we aren't causing more problems than we are solving.
Loss of genetic diversity overtime will happen as well as a different path of evolution. Much of what you see on earth today is the result of virus-host interactions shaping evolutionary outcomes. Viruses are capable of providing horizontal inheritance of genetic material.
For one thing, viruses keep bacteria in check. Bacteria populations live in an equilibrium standoff with bacteriophages (viruses). The human gut contains more bacteriophage virions than bacterial cells. So eliminating all viruses could lead to bacteria overgrowth
Viruses are part of other biological processes as well as keeping things in check. For example, there is a bunch of viral activity involved in human pregnancy. A quick web search found this:
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[ 2.8 ms ] story [ 38.3 ms ] threadI'm genuinely asking, I'm a simple software dev not a doctor.
And the really, really bad part about abusing natural parts if the immune system to provoke pathogen resistance against them is that the resistance will target part of natural immunity.
See also https://news.ycombinator.com/item?id=35700881
Based on my recollections of this paper https://pmc.ncbi.nlm.nih.gov/articles/PMC5499642/
So yeah, I wouldn't be super worried about the virus evolving to become worse in absolute terms as a result of antiviral exposure. Virii are evolving all the time anyways. Antivirals can also reduce evolution speed by fighting an infection: A more severe infection means more virions means greater evolution speed. I believe some new COVID variants were thought to have evolved in the body of someone who was severely infected. (However: Note that it's not necessarily beneficial for fitness for the virus to evolve greater infection severity, especially if that interferes with transmission.)
Given that the article goes on to talk about mild persistent inflammation, is it possible that these individuals are sometimes asymptomatic but still capable of carrying/transmitting viruses at least temporarily? The article talks about potentially immunizing healthcare workers during a future pandemic, but if this was just allowing people to never develop symptoms (and not have to leave work) while having low-grade infections, would we accidentally create a work-force of Typhoid Marys?
https://www.frontiersin.org/journals/immunology/articles/10....
This was a lynch pin of sorts in Koch's postulates. We can't properly go through those postulates with viruses like we can with biological pathogens, but it is odd to me that we don't have similar concerns when the presence of a replicable pathogen doesn't cause the symptoms they are expected to cause.
I have encountered side effects that probably no one has seen before, simply because of rarity and peculiarity of behavior. You don't run into a ton of people using both interferon and doing karate, so if bruising more easily happens 10% of the time... would anyone notice?
Personally I would be more worried about persistent inflammation causing inflammatory disorders, of which there are many. If there are like 10,000 individuals with this trait then there just aren't enough to detect. But that seems direct... wouldn't you expect something like this to potentially even destroy viral reservoirs over time?
The fact that this is short term in the treatment made me 1000x more comfortable with the idea in any case.
(I may have watched too much House)
Oh, and here's what the ISG15 deficiency (the condition these mRNAs are there to simulate) does:
> Patients present...with infectious, neurologic or dermatologic features. Basal ganglia calcification is observed in all patients... The basal ganglia calcifications may cause epileptic seizures... The IFN-I inflammation may also manifest early in life as ulcerative skin lesions in the armpit, groin and neck regions. Finally, ISG15-deficiency leads to mendelian susceptibility to mycobacterial disease... [t]hese infections present as fistulizing lymphadenopathies and respiratory symptoms following BCG vaccination.
Yeah, about those antiviral superpowers...
Just like you accept the risk of increased yeast infections while treating bacterial infections with antibiotics, or the risk of any infection while treating a cancer with chemotherapy.
There seems to be a lot of information, misinformation, conspiracy theories, and information hiding at least in the perception, if not in reality.
I cannot imagine what society at large will have to deal with or what the reaction will be for or against an “everything” therapy, given what happened with Covid.
My summary for programmers:
When you get a viral infection, immune cells make a signalling protein called a IFN-1 (Type I Interferon) cytokine, and this flips a boolean flag to True on a bunch of genes (interferon-stimulated genes or ISGs) that produce a bunch of proteins (hundreds) that control the infection. ISG15 is one of them and its role appears to be to downregulate and to limit the inflammation.
The paper title refers to a ISG15 deficiency, meaning if you are dificient in ISG15 that inflamation limitation goes away. But the paper is actually about how in people that naturally have a ISG15 deficiency, there is an always-on low level expression of some of these pro-inflamation genes. So they take that as a safe level.
The did RNA sequencing on experimental ISG15 deficient cells and from heatlhy individuals, identified the mutations, narrowed down to 10 genes (antiviral ones not inhibitors) that in combination significantly inhibited viral replication. They stuck the RNA for such genes in lipid nanoparticles such that they enter host cells, whose ribosomes happily read the RNA like a turing head reads a tape in base 20 and produce proteins encoded by these genes, similar to how the mRNA vaccine works.
So why not dose with the IFN-I directly? Three referenced papers show its "poorly tolerated with significant side effects" and all those downregulators that get expressed limit the inflammation response.
Disclaimer: IANAB (not a biologist) corrections might be due..
[0] https://en.wikipedia.org/wiki/DRACO
Eliminate human-tropic viruses: We have to monitor for outbreaks when new viruses mutate and jump species to successfully infect humans. If there's zero mass immunity across the population at every outbreak, we're still in a high-risk situation.
* An increase in autoimmune diseases (related to the hygiene hypothesis).
* Decreased resistance to future viral pandemics, since the body wouldn't have practice since childhood in fighting viral disease.
It could be chaotic, I think.
https://m.youtube.com/watch?v=SbvAaDN1bpE
Are we also eliminating transposons? We would not survive that.
https://en.m.wikipedia.org/wiki/Transposable_element
https://pmc.ncbi.nlm.nih.gov/articles/PMC6177113/
Not saying this isn't worth researching but I'd expect big question marks around risk/reward.
I wonder how different it is from interferon therapy - interferons are used to signal viral infection, so they also activate immunity.