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.