Welcome to another MedCram COVID-19 update. As you  are probably aware, new daily cases are on the rise  

in the United States and it may be looking to  peak hopefully here soon in the next couple of  

weeks, although we can't be sure. Daily deaths,  which do lag behind, are coming up as well. And  

because of those extra cases, I'll remind you to  check out our "10 Tips If You Get COVID-19" video.  

We'll talk more about that. Have you ever  wondered why kids don't go to the hospital  

as often as adults do in terms of COVID-19?  Well, I thought this was a very interesting  

article that was put out by Nature Biotechnology,  titled "Pre-activated antiviral innate immunity  

in the upper airways controls early SARS-CoV-2  infection in children," and I think this article  

may actually give us some pretty good information  as to what we can do to improve our immune system. 

As we've talked about in previous videos, we tried  to see what it was that we could do that might  

prevent hospitalization, and the key to that is the  immune system and how there are two aspects to the  

immune system: the innate immune system on the  left and the adaptive immune system on the right.  

Now the innate immune system, which includes things  like macrophages and natural killer cells, all  

work together to eat up or phagocytize the viral  particles and viruses that infect people early on. 

The innate immune system is usually very strong in  young children and gets weaker with age. Interferon  

is a product of the innate immune system.  Interferon is very important in terms of fighting  

SARS-CoV-2 infection and so anything that we can  do to improve interferon levels would be important.  

So what you see here in this graph, on the left  side, which is the amount of interferon alpha  

2 and the activity on the right, is that as the  critical nature of SARS-CoV-2 or COVID-19 gets worse,  

that's associated with a lower amount or level  or activity of interferon. You can see here on the  

black bar, the baseline secretion of interferon,  and with mild disease, we see a very large  

increase in interferon levels and activity. Here in  the blue box, as it gets more severe and then even  

critical, in the red we can see there that there's  almost no interferon activity in those situations,  

so this leads us to believe that interferon levels  can basically predict the outcomes of COVID-19. So  

what they did in this study was they looked at  the upper respiratory tract cells in not only  

children and adults, but also in children that were  infected with SARS-CoV-2 and children that were not  

infected with SARS-CoV-2, and what they found was  that "children displayed higher basal expression  

of relevant pattern recognition receptors that  were involved with interferon and resulting in  

a stronger innate antiviral responses upon SARS-CoV-2." So what this showed was that "children  

displayed higher basal expression of relative  pattern recognition receptors, such as MDA5 and  

RIG-1 in upper airway epithelial cells, macrophages  and dendritic cells, resulting in stronger innate  

antiviral responses upon SARS-CoV-2 infection  than in adults." So what this is basically saying  

is that in children, they had more receptors for  the interferon antiviral response for SARS-CoV-2.  

In the article, they say "it's been shown that  an early cell intrinsic innate immune response  

mediated by pattern recognition receptors (PRRs) and the type I and type III interferon (IFN) system  

is crucial for the successful control  of SARS-CoV-2 infection. In line with these  

observations recent studies compared adults and  children with severe COVID-19 or those presenting to  

an emergency department and described an impaired  interferon response in pediatric COVID-19. However,  

the molecular mechanisms protecting against COVID- 19 in younger age groups, particularly in those  

with no or only mild to moderate symptoms, remains  unknown." And that was the purpose of this paper.  

So what they found using molecular  techniques were higher levels of genes  

and their proteins in the epithelial cells in  the upper airway in children as opposed to adults,  

and they say here that "this result suggests an  increased ability of the respiratory mucosa of  

children to respond to viral infections, which  is further supported by the highly increased  

amounts of innate immune cells in the upper  airways." So that key there is that there were  

more innate immune cells. Furthermore, they say  that following virus sensing, there was signaling  

through a number of different expression  and antiviral effectors, such that antiviral  

cytokines such as interferon beta and interferon  lambda, so these interferons act on epithelial  

cells in a autocrine and paracrine manner -- that  means on themselves and also on cells around them --

and all of this basically was shown to exhibit  strong antiviral activity against SARS-CoV-2.  

Now this is very important in the discussion: they  say that "our data provides clear evidence that the  

epithelial and immune cells of the upper airways  or the nose of children are pre-activated and  

primed for virus sensing. This is likely a general  feature of the children's mucosal immune response,  

but of particular relevance for SARS-CoV-2. Very  recently, scRNA sequencing of fibroblasts infected  

with Chikagonya virus showed an extremely narrow  window of opportunity for the cells to express  

interferons before viral protein production shuts  off the antiviral system." You see here that there  

are viral proteins which can actually shut down  the body's antiviral system, and this is exactly  

what happens with SARS-CoV-2. "This likely also  explains the differences between SARS-CoV2 and  

other respiratory viruses, including respiratory  syncytial virus, influenza A virus or SARS-CoV,

in terms of the induced host response." Now notice  that "SARS-CoV-2 is characterized by extensive  

intracellular replication and a remarkable  absence of interferon production and secretion," 

and I think this is the key statement right  here that in SARS-CoV-2, where there should be  

a prolific response of interferon, there isn't, and  that's important because it says here, "on the other  

hand, SARS-CoV-2 is highly sensitive to treatment  with interferons before or after infection as  

shown in lung epithelial cells, even more so  than SARS-CoV." And as you maybe recall, SARS-CoV  

was in 2002 an epidemic in Asia and also in  Canada. So the bottom line here is that SARS-CoV-2, 

the proteins suppresses the body's ability to make  interferon, and this is important to understand  

because SARS-CoV-2 is very sensitive to interferon.  So if that's the case, is there a way to improve  

the body's ability to secrete interferon? And  the answer is yes, and this is nothing new. For  

those of you who have been following MedCram, we  talked about this way back in update 46 and 47  

over a year ago. So in this paper that was  published in 1988 in the Journal of Interferon  

Research, scientists took human subjects and  subjected them to different temperatures, and then  

measured the amount of interferon that was  secreted after stimulation from monocytes.  

And what they found is that as core body  temperature increased from 37 degrees  

celsius all the way up to 39, once it hit 39, the  amount of interferon released from lymphocytes  

after mitogen stimulation was 10-fold higher than  it was at 38.5. Now, this was an in vitro study, but  

it does seem to suggest that there are things that  you can do in terms of body temperature or indeed  

the benefits of fever in terms of boosting that  innate immune system. For those of you who want  

more information on this, I highly recommend update  47 on MedCram, and just to briefly review, we did  

talk about the Nobel Prize in Medicine winner  in 1927, Dr. Julius Wagnedr-Jauregg, who used fever  

to basically cure his patients of neurosyphilis  in his Austrian psychiatric ward. But as it says  

here in this article that was published back in  2013 in the journal, Psychiatriki, other things can  

be used, including immersion of the individual  in a hot bath or placing them in a heat cabinet.  

We also talked about the 1918 pandemic and also  the observations of Dr. Wells Ruble, who was the  

Medical Director of the Boston Sanitarium, and  these were Dr. Ruble's observations that were  

published but not peer-reviewed in a religious  periodical entitled Life and Health, May 1, 1919,

where it was shown that when used with other  modalities, such as sunshine, fresh air, ventilation,  

things of that nature, they were able to approach  an infection fatality ratio of about 1.1%,  

whereas those in the Army hospitals  who used aspirin to suppress fevers  

and did not expose their patients to sunlight  had an infection fatality ratio of 6.4%.  

Again, this is not a practice that I would do in  lieu of other things. We like to talk about the  

Swiss Cheese Respiratory Virus Pandemic Defense  model that has been shown multiple times, where  

each intervention that you do filters out more  and more of these viral particles, so that you are  

protected here at the end. I'd like to give credit  to Ian Mackey, who created this picture, but I'd  

also like to add a couple more slices of cheese  to this. So sleep, vitamin D, sunlight, fresh air,  

hydrotherapy. The more slices of cheese the better  protection you're going to have against SARS-CoV-2,

and not any of these is 100% effective. So in  this video, we talked about potential strategies  

for increasing your core body temperature and the  potential positive effects on interferon for doing  

that especially with COVID-19, and this practice is  often referred to as hydrotherapy or hyperthermia.  

And for those of you that are interested, we'll  put links in the description below for more  

information on hydrotherapy. And, again, even though  we don't have randomized controlled trials showing  

the efficacy of raising core body temperature in  SARS-CoV-2, briefly, this is one potential treatment  

that can be used in conjunction with other  medical treatments while the patient is at home  

after diagnosis, but not sick enough to be admitted  to the hospital. And of course the other thought  

is that maybe not treating fevers aggressively  unless they get over 102 degrees, that might be beneficial. 

Because here you have the innate immune system  that's producing a fever, and that fever is  

beneficial for getting rid of the virus, because as  we've shown, that increased core body temperature  

can activate interferon levels. And as it turns out,  this modality of treatment possibility has already  

been suggested and was published in Medical  Hypotheses in January of 2021, and we will put a  

link to this article also in the description below.  Don't forget to subscribe. Thanks for joining us.