Is that the hypothesis, IFNg? Strange since the type I interferons are usually considered stronger anti-viral immunity. There are a LOT of differences between children and adults, and even between children under 5 and those above 5 years old.

It's not inducing IFNg that you want, it's to induce a protective response. IFNg can be produced by a LOT of cells...and high IFNg is not a good thing. And no, there is no safe way to scale up induction...first it's not practical... Unless you want to just inject people with IFNg..which is also not advisable.. And there are a LOT of ways to vaccinate to induce IFNg... if you read the vaccine research that's what a lot of people go for depending on the disease area.

And no, you can't use catching the flu as a vaccine... first, they are not even the same virus. So there are no antigen overlap (probably). They are most likely trying to use an inactivated COVID-19 or a less pathogenic one (but considering it's so new, I doubt that they can find a way to grow it in vitro and make it less pathogenic before the first wave circles the globe). I mean there is also antigenic vaccines... but again... I'm not sure how far they are into identifying the protective target...And then there is adjuvant pairing that is needed.

The strategy that they are going for right now is therapeutic treatment with some anti-viral drug that is already developed...

Thanks for your answer dear Shen. My research criteria is not immunology, but as I've read, the most significant difference is the threshold of interferon-gamma production. If not, please elaborate (or send a link to an article please). As I've read, there may be ways to induce it better, like the addition of PHA to the diet. Of course, I'm not sure. By the way, it seems like uncooked red beans have high concentrations of PHA! The proposed way of induction of immune response (by catching other viral diseases such as measles or common cold) is not to stimulate the antigens of the COVID-19. It is to induce the wholistic immune response of interferon induction.

I know that the main immune response to viral infections is not interferon-gamma, but what if we've been looking at the problem from the wrong angle? To "prevent" the viral disease, we have to use the preventional means of the immune system, ie: interferon-gamma.

In general, there are large differences between kids and adults in terms of immune function (you can find hundreds of papers on this topic). This is not specific to COVID-19. For example, kids have less t cell function, and rely more on innate responses. Adults may have more memory t cells but as you age, less T cell variability in recognition of epitopes. In general, children's immune response is not as strong as adults, hence why with a lot of pathogens, children are more vulnerable (like with the flu, measles, etc). And IFNg can be made in large amounts by innate lymphocytes, so maybe that's where the lower threshold comes in. But to take that and leap to the hypothesis that IFNg is the protective response in kids is not logical. Especially if you read up on what IFNg actually does. And I have not seen any reports where they even have a guess at why COVID-19 infection is lower in kids. The closest related topic is that it's probably having to do specifically with coronavirus, since the other two related viruses (SARS and MERS) also had low infection rates in kids.

As for PHA... it doesn't just stimulate IFNg..it stimulates T cells. And depending on what your t cell population make up is, you will get different levels of IFNg from different people. Also. your gut is lined with regulatory T cells... so... the most likely effect from ingesting PHA is increasing your regulatory response. Just as a FYI, one method for people to tolerize against an allergic antigen is to ingest it frequently.

As for IFNg..it is not a protective response of the immune system as a whole. It is protective in certain areas...and pathologic in others. It's protective in certain cancers, and pathologic in certain autoimmune diseases. It's protective in TB but it is also pathologic. And this goes for most cytokines. IL-4 is protective against parasites, but it is pathologic in leprosy. Cytokines don't operate only in one direction. As for viral infections... there are 7 types of viruses, each with their own mechanism of entry replication, etc...

Catching a cold to prime interferon -- I don't think your idea is crazy. There are observations suggesting that you don't usually get the common cold and influenza at the same time, or in very short succession. They are completely different viruses. So it's not likely to be mediated by an adaptive immune response. There might well be a role for some kind of innate immunity priming underlying these observations.

But as far as COVID-19 is concerned, that's just a story. We don't know if it's true. One might as easily tell an opposing story. For example, if the common cold gives you just a little bit of pre-existing tissue damage, it could end up making all the difference between survival and death from COVID-19.

One could look at recombinant interferon. I'm sure many doctors are. There are several approved drugs. They're not normally given preventivly, due to the side-effects. But this is not a normal situation. I don't it would be crazy to try it in a high risk group with probable exposure.

There's a lot that could be tested, and looks like little time to do it for many of us.

While John is correct in that there are evidence that it is unlikely for the common cold and the flu to infect the same person at the same time, there is no evidence to suggest that one or the other offers protection. The study for that is correlative. While we can't rule out an innate response... it would take mechanistic studies to point in this direction. It could most likely be just viral competition.

Also... is there any suggestion that patients who are sicker have lower IFNs? I thought most, if not all, IFN therapy is for chronic diseases, not acute.

Thank you all for your responses. I have a better vision of immune response today.

Dear Shen: Actually there are studies based on IFN therapy for coronaviruses such as SARS (UpTodate). Besides, innate immune response is the key difference between adults and children as quoted"NK cytolytic function increases during gestation but is still only half of adult level at birth. Neonatal NK cells are less responsive to activation by IL-2 and IL-15, and produce limited IFN-γ concentrations. However, the cells' threshold for activation is lower, which provides some anti-viral protection"

Dear John: Wow that's great. As I've searched, there are substances like PHA who can induce IFNg production. PHA is highly concentrated in uncooked red kidney beans. Can we recommend people to use red kidney beans once daily?

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Hi Farbod, IFN therapy in patients? Most are on in vitro cultures. The few published studies on patients, the IFN therapy is in conjunction with corticosteriods. These patients already have an inflammatory response...you cannot add more inflammatory IFN gamma to that system. IFNa does not cause as much inflammation as IFN gamma.

Your statement clearly says that NK cell function in kids are half of adult level, and that IFNg production is limited. That lower threshold for activation will not make up for the reduced protection against viral infection in kids. It just states that the lower threshold is probably responsible for what little protection the kids have against viral infection. This does not support your original hypothesis that kids are less susceptible to COVID-19 because kids have a lower threshold for innate IFN gamma induction.

And you are focused on only ONE difference between kids and adults. Immune response does not work in a vacuum.

Greetings

In regard to this conversation, we have developed a therapeutic approach for stage-I of COVID-19. Here's the link: https://www.preprints.org/manuscript/202003.0206/v1

Thanks for your cooperations. It was very helpful.

infection with parasite helps CD4 T helper to differentiate to T helper 1 which become finally producing gamma interferon

Dear Farbod Shahabi

IFN-gamma already has been used as therpeutics in human.

IFN-gamma is now necessary to use as a major immunotherapuetic drug for viral epidemics including COVID 19.

You can see this aritcle.

Article IFN-γ as a Major Antiviral Therapeutic for Viral Epidemics, ...

Thank you.