terms of infections if you go to world ometer and sort by deaths per 1 million

population you can still see that the highest concentration of deaths are

occurring in italy at this point in terms of new cases USA is still leading

in the united states new york and new jersey lead and california is a distant

third and of course in new york and now in california we're starting to have

issues regarding saturation of health care delivery systems okay let's discuss

exactly what's going on right now with COVID-19 what we have here are

three different populations we have the entire population as a whole and we have

those that are going to be infected and we have those that are going to need

hospitalization and you may have noticed that the situation that we're having

right now in new york especially also in other parts of the country is that this

population of people who need hospitalization is not able to get into

our tunnel here which is in fact the hospital and because of that we're

having issues with shortages of ventilators of ICU beds etc and so right

now all of the work is going into trying to increase the capacity of the hospital

system to allow this type of bolus of patients if you will to get through and

to be treated effectively now of course these graphs are not drawn to scale

remember that there's only a certain amount of the population that will

become infected and the way to reduce that even more is with isolation but

there's a certain percentage of those people that become infected that will

need to go to the hospital and as it stands according to the data that we

have right now that's about twenty percent which means that eighty percent

of the people that get the infection won't need to go to the hospital and

that is almost totally related to that patient's immune system so the immune

system is rather complicated and that's why i want to talk

about a little bit imagine your immune system is like this country's armed

forces you have the army the Navy the Marines the Air Force they all have

specific functions but they all work together to protect the organism to

protect the country let's face it there are a lot of threats that can happen to

a human being but in this case the SARS cub to virus affects the human body in a

very specific way and so if we can learn what part of the immune system is being

diminished then we can learn potentially how to fight this virus effectively and

reduce the number of people that might need to have hospitalizations so enter

this article where they actually look at the immune responses to not only this

corona virus but the SARS coven and the MERS coronavirus that was there

previously so this article was published in the Asian Pacific Journal of allergy

and immunology immune responses in kovat 19 and potential vaccines lessons

learned from SARS and MERS so let's take a look and see what they found they do a

comparison in the number of cases between those three viral infections

they also break down the demographics and they show the issues here with the

SARS cuff to the current viral infection in terms of the immune players that we

were just talking about and the thing that they bring up in this article which

is very interesting is this first point here which is delayed or suppressed type

1 interferon response during the initial infection in fact in the article they

say here to mount an antiviral response innate immune cells need to recognize

the invasion of the virus often by pathogen associated molecular patterns

so remember what the innate immune response is it is those cells that do

not require a little piece of the virus to be presented to them and so these are

not T cells and B cells that are making antibodies but rather innate cells so

these would be like macrophages monocytes natural killer cells this

would be like the airforce of the Armed Services and the things

that activate them in this case are these PA MPs or these molecular patterns

that are associated with path in this case for the coronavirus it

would be viral genomic RNA they go on to say here that for SARS coven MERS Cove

the response to viral infection by type 1 interferon is suppressed both corona

viruses employ multiple strategies to interfere with the signaling leading to

a type 1 interferon production watch what else they say here with similar

changes in total neutrophils and lymphocytes during kovat 19 SARS cub 2

probably induces a delayed type 1 interferon and loss of viral control in

an early phase of the infection what they're saying here is that the virus is

able to down regulate your immune system in the early phase of the infection and

this may be the reason why most people with this infection are initially

asymptomatic until the very end when there's a storm of cytokines in addition

no severe cases were reported in young children when innate immune response is

highly effective this may explain why young children aren't getting the

disease as severely these facts strongly indicate that innate immune response is

a critical factor for disease outcome analysis of two MERS Cub infected

individuals with different severity found that the type 1 interferon

response in the poor outcome patient which died was remarkably lower than the

recovered patients so if we go back to our picture again we see here that those

patients that are ending up in the hospital are about 20% of those that

actually get the infection and the reason why we may want to say is that

there is a decrease in the innate immunity that is the specific problem

with this virus and this seems to bear out in a recent publication in nature

medicine where they looked at immune responses and cells in a patient that

had non severe kovat 19 in fact this patient never needed to go to the

hospital and he recovered quite well of course we'll link to this and the

previous article in the description below but what they did look at here was

the amount of virus the symptoms the chest x-ray and then even more

importantly for our evaluation these monocytes and natural

killer cells so here we have monocytes and natural killer cells and if you look

at this triangle here you can see where the patient's monocytes were in relation

to where they should be in a normal healthy patient the monocytes which are

part of the innate immune system were much lower than they should have been

even though this patient only had mild disease reaffirming that it's the innate

immune response that seems to be suppressed in these kovat 19 patients

and even more so it seems monocytes and natural killer cells seem to be the

target so the question is is what is it that we can do to increase the number of

monocytes and perhaps gamma-interferon to elevate that early in the course of

this disease and we've talked before about not treating a viral fever because

we know that viral fevers are involved with the immune response as well but

I've gotten some interesting comments wondering if a patient with corona virus

doesn't have a fever what inducing a fever improve the

outcome and the immune response so knowing what we know already about

what's going on in covent 19 in terms of depressed monocytes made this German

publication back in 2002 even more interesting and here are the authors

zelner at all says that thermal effect of fever has been associated with better

survival and a shorter duration of disease in cases of infection and what

they wanted to do was to understand better what happened if they subjected

12 healthy volunteers in a 39 point five degrees centigrade hot water bath to

increase their body temperature and see what would happen to the expression of

monocytes and tumor necrosis factor alpha which is a cytokine that it

releases and they looked at this both in vitro and in vivo in humans that were

actually put into a hot water bath and what he found was that the in vitro data

showed that definitely there was an increase in the Amano sites they say

here that the expression of the endotoxin receptor cd14 and the

complement receptor CD 11 be increased after hot-water bath furthermore when

they looked at the healthy subjects after they were put into the hot water

bath they said here after three hours the response of monocytes to endotoxin

was enhanced in an ex-vivo lipopolysaccharide stimulation assay

which is basically a stimulant from a bacteria that might have infected a

human body when they stimulated the immune system they noticed that there

was greater TNF alpha release which was statistically significant so they

conclude that the thermal effect of fever directly activated monocytes the

very cells interestingly that are deficient in kovat 19 and that increased

their ability to respond to in this case a bacterial challenge but I'm sure they

would be equally as responsive to a viral challenge as well but this isn't

the only study that shows this there was a interesting article that was published

around 2000 titled immune changes in humans during cold exposure effects of

prior heating and exercise they took subjects and they had them sit

in a warm bath among other things and then they exposed them to cold to see

whether or not that would also improve immunity and you can see here for the

seven subjects in the white boxes sitting in a 38 degree centigrade water

bath increased their core body rectal temperature and then after they were

exposed to cold there was a drop in the core body temperature and here when we

see the data in this second set of bar graphs which are the ones where they sat

in 38 degrees centigrade water you can see here for leukocytes which are all of

the white blood cells that there was a significant increase in the number of

white blood cells here also for the granulocytes increases well for the

lymphocytes there was an increase and also for the monocytes there was an

increase remember the monocytes is the part of the innate immune system that's

deficient we're finding out in kovat 19 what they concluded in this report

despite popular beliefs that cold exposure can precipitate a viral

infection the innate component of the immune system is not adversely affected

by a brief period of cold exposure this is exactly the part of the immune system

that were talk about with kovat 19 they say indeed the

opposite seems to be the case the fall in core body temperature resulting from

cold exposure led to a consistent and statistically significant mobilization

of circulating cells an increase in NK cell activity natural killer and

elevations in circulating il-6 concentrations moreover in agreement

with one of our hypotheses prior exercise with a thermal clamp

significantly augmented the leucocyte granula site and monocyte response to

cold exposure prior passive heating and exercise without a thermal clamp also

tended to augment the effect of cold exposure alone but because of the small

sample size and inner subject variability these changes were not

statistically significant so interestingly what they're finding here

is that yes heat can improve the immune system like we've seen before but then

subjecting them to cold which goes against popular belief can actually

enhance the immune system especially the innate immune system which I find very

interesting because that's the portion that's affected in kovat 19 so all of

this talk about being hot and then cold reminded me of the Finnish saunas that

are so famous in that part of the world and actually in most of the Nordic

countries but not to the degree that we see in Finland so here's a study that

looked at a single Finnish sauna session on white blood cell profile and cortisol

levels in athletes and in non athletes and in this study they only looked at

nine people which is kind of a low number so we might not be able to see

statistical significance but let's see what they found

so for those of you who don't know what a Finnish sauna is it's quite extreme

the sauna can go upwards of two hundred degrees Fahrenheit which is very close

to the boiling point of water during the sauna session the human body is

alternatively exposed to hot and cold stimuli hot air in the sauna room

affects the skin and the respiratory system this leads to a rise in body core

temperature up to as high as thirty nine degrees centigrade while the skin

temperature might be as high as forty two degrees centigrade and then after

this is done there is a fast cool down and then they go back into the

sauna to heat up once again so what happened to the white blood cells in

this situation they found here that there was a statistical significant

increase in the number of white blood cells particularly more noticeable in

the athletes than in the non athletes some of these were statistically

significant and some of them were not possibly related to the low number of

subjects in this study they found here that a significant increase in monocyte

count was accompanied by a significant increase in the number of neutrophils

and eosinophils only in the athletes which could have

been caused by a reduced cortisol secretion compared to the untrained

subjects remember this is only after one session in the sauna so let's take some

stock about what's going on we've got the infection that occurs here at this

point in time and then we have at this point in time some of those about 20%

will end up in the hospital with pneumonia secondary to cytokine storm as

it's been often called why is it that people are asymptomatic early on and it

may be that the immune system is being suppressed well if we inflame the immune

system if we increase the immune system with thermal regulation and hyperthermia

is it possible that we could actually precipitate a storm situation and get

the patients in the hospital sooner without actually helping out the

patients well that's a good question and it's a possibility and that's why I

found this publication so interesting they talked about this interleukin il-6

which has been implicated in the cytokine storm that patients with

pneumonia gets when they had kovat 19:00 the paper is long but I found this

paragraph very enlightening although febrile temperatures initially

increase the production of pro-inflammatory cytokines by

macrophages at sites of inflammation there is also evidence that thermal

stress dampens cytokine synthesis once macrophages have become activated this

sequence of events is analogous to a natural fever which often occurs after

macrophages and other and nate's immune cells initially encounter

PMPs remember PA and peas from that first article that we looked at in this

regard human monocyte derived macrophages produce less TNF less il-6

and less il-1 beta when exposed to febrile temperatures then heat in

experienced cells heat reduces transcription of pro-inflammatory

cytokines and also lowers cytokine mRNA stability thermal treatment of LPS

activated macrophages also appears to dial down inflammation so what they're

showing here is that fever can actually reduce the cytokine storm and improve

the innate immune system now they actually have a model of this with mice

who have arthritis collagen induced arthritis when they exposed the mice to

fever range hyperthermia they had significantly less joint damage so they

say that collectively these findings suggest that strategic temperature

shifts contribute to a biochemical negative feedback loop that actually

protects the tissues against damage from excessive cytokine release following