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  • welcome to another COVID-19 update us continues to top the charts in

  • 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

  • infection interesting so in this period of time between when you have infection

  • documented and hospitalization if there were to be a higher temperature it could

  • improve the immune system which seems to be high I'm strung already and it would

  • reduce the cytokine storm potentially that's leading to pneumonia requiring

  • hospitalization okay so up to this point we've looked at real people we've looked

  • at cells though as surrogates for a good immune system against viruses let's

  • actually put it to the test and here we have a article asking that very question

  • does regular sana bathing reduce the incidence of common colds

  • they took 50 people that had never been in a sauna before this was an Austrian

  • study and 25 of them stayed out of the sauna and they were used as controls the

  • other 25 had sauna bathing to see if they could reduce the incidence of

  • common colds and what they found was this in the six months time that both

  • groups were recording how many common colds they got there was

  • significantly fewer episodes of common cold in the sauna group this was found