One universal antiviral to rule them all?

> 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 am not a medical expert, but from what I read the last time I saw this being discussed, ISG15 deficiency also causes something called "infernopathy" that leads to inflammation across the entire body. I don't believe it's related to viral activity at all.

From TFA: "We only generate a small amount of these ten proteins, for a very short time, and that leads to much less inflammation than what we see in ISG15-deficient individuals,” Bogunovic says. “But that inflammation is enough to prevent antiviral diseases."

It seems that the goal is to learn to trigger the benefits, without triggering the bad parts. Which, should probably have been obvious to you without even bothering to read the article.

Excellent point, and it seems plausible in my opinion.

https://www.frontiersin.org/journals/immunology/articles/10....

The weird thing about this quote: is the inflammation enough to prevent viral diseases, or antiviral diseases?

Oh, and it's probably worthwhile pondering what the viruses will do if this mechanism comes into widespread use.

While I was looking for the reference above this also came up:

https://www.sciencedaily.com/releases/2020/02/200210144854.h...

when bat cells quickly release interferon upon infection, other cells quickly wall themselves off. This drives viruses to faster reproduction

Quite a way from whole-animal physiology in the referenced research, by all means, but it's a fair point, right.

Even worse, that type of chronic inflammation might cause premature death. Or cancer. Or other disease states.

> “In the back of my mind, I kept thinking that if we could produce this type of light immune activation in other people, we could protect them from just about any virus,” Bogunovic says.

This sounds terrifying. There's a reason our bodies do not regulate like this.

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.

To the extent the disease is due to factors hurting the virus, I guess it's viable as a perspective, but I'd be surprised if it's deliberate in this case.

It also sounds like an episode of some televised sci-fi series where someone was exhibiting remarkable immunity to all sorts of diseases (including some nasty ones deliberately added for testing); but it turned out that this was no super-cure but instead the limited natural resources of the immune system being used up all at once, leading to a horrific death when they ran out.

I can't remember which series it was, though.

But if this was something you could activate as needed..

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.

The article states:

>Bogunovic’s therapy is designed to mimic what happens in people with ISG15 deficiency, but only for a short time.

Given the choice between 2 weeks of a moderate COVID infection (fever but no hospitalization), and 2 weeks of this therapy, I would guess that the moderate COVID infection gets you at least 10x the inflammation.

Probably just a mistake. I don't believe there is such a thing as an "antiviral disease".

On the other hand, let's aim for the juiced up immune systems portrayed in one of the Star Trek series. It gets so powerful it can reject acquaintances.

I have always been a huge fan of the show but sitting here trying to figure out what you specifically are referencing?

You can show transmission pathways with a combination of epidemiological evidence and sequencing data.

I am sure it does cause concern to many. I mean how scary is it that you can run into someone seemingly healthy and next thing you know you are sick?

I know as a health care worker I actually think about things like this. MRSA is a good example. Most people don't react to exposure but some do. Those that do get long term infections that are hard to get rid of if ever. Most think of this as a hospital issue. But the reality is that there are literally thousands of people with MRSA all over the world and they are carriers of it and they do things like go to the bank machine and touch it, open the door at 7-11, pick up items at the store and then put them back on the shelf and so on and so on. MRSA is literally everywhere. Some people contact it and suffer problems others do not.

Epidemiology can never show causation or evidence, at best it shows correlation that is a useful indicator for future research.

With something like MRSA how do you determine that the virus is cause for disease when, as you said, many will be infected without showing symptoms?

That the root of the confusion for me. I haven't wrapped my head around how we can know a specific pathogen causes disease if a large number of people can be found to have that pathogen present without showing symptoms.

Yeah, constant low-grade inflammation is a hallmark of auto-immune disease, diabetes, etc. It's a glide path to degeneration and death.

Sounds very Outer Limits-esque, but I don't recall that specific episode. It's certainly at least an easy interpolation from many Outer Limits episodes, though.

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.

I wonder if large numbers of humans acquire this mutation, how viruses would adapt to this evolutionary pressure?

Statistics.

Not all smokers get lung cancer. But with large enough samples, smokers turn out to be much more likely to get lung cancer than non-smokers. That's why we say that smoking causes lung cancer. It's not as if someone has actually watched a particle of tobacco interact with someone's lung cells to turn them cancerous in real time.

If that was what the article said, your point would be on topic.

But the article didn't talk about imposing constant low-grade inflammation. In fact, they specifically said they were talking about 3-4 days.

They would still have too many other possible hosts.Or maybe they'd find a way to attack that very system, similarly how HIV attacks the immune system.

Smoking isn't a contagious pathogen.

Worse, what if they actually are sick, but don't have the immune response so it's not obvious they are sick until their organs fail?

(I may have watched too much House)

A virivore infection could count I guess? But probably not what they meant.

Second- and third-hand smoke mimic contagion.

I think it was one of the offshoots like Next Generation that had a visit to some research station where all the scientists were dead or dying of premature aging. It was the immune systems of some (bioengineered?) children that were killing them.

That has nothing to do with contagion, that's just a sign that the impact of smoke inhalation isn't limited to the one sucking on a cigarette.

Contagion would mean that the smoke can infect the host, replicate, and spread to others. That's not how second hand smoking works.

Why doesn't that get dismissed with the usual universal dismissal "correlation != causation"?

For one I'd assume its because contagions and physical damage are quite different. That's not to say that correlation between viral presence and disease can't indicate causation, but it is more clear when you are looking at the direct damage to lung tissue from inhaling hot cigarette smoke for years or decades.