Coronavirus Pandemic Update 37: The ACE-2 Receptor – The Doorway to COVID-19 (ACE Inhibitors & ARBs)
En décembre 2019, un coronavirus (CoV) distinct a été déterminé comme étant responsable d’une épidémie de pneumonie atypique potentiellement mortelle, définie comme la maladie du coronavirus 19 (COVID-19), à Wuhan, dans la province du Hubei, en Chine. Ce nouveau CoV, appelé Syndrome respiratoire sévère aigu (SRAS) -CoV-2, s’est révélé similaire au CoV responsable de la pandémie de SRAS en 2002.
Qu’est-ce que le coronavirus?
Les CoV sont une grande famille de virus à ARN monocaténaire à brin positif qui infectent une grande variété de vertébrés. Ils sont nombreux chez les chauves-souris, mais peuvent être trouvés chez de nombreux autres oiseaux et mammifères, y compris les humains. Le CoV peut provoquer une variété de maladies telles que l’entérite chez les porcs et les vaches et les maladies des voies respiratoires supérieures chez les poulets. 1 Chez l’homme, le CoV a tendance à provoquer des infections légères à modérées des voies respiratoires supérieures, comme le rhume. 2.3 Cependant, au cours des deux dernières décennies, il y a eu des flambées de maladies respiratoires graves et parfois mortelles, qui se sont ensuite révélées être causées par de nouvelles PAC pathogènes pour l’homme. Ces souches de CoV, dont on a déterminé qu’elles étaient phylogénétiquement distinctes du CoV humain ordinaire, provenaient de chauves-souris et ont été transmises à l’homme, généralement par l’intermédiaire d’un hôte intermédiaire. 1,4,5 Ces souches ont montré une virulence plus forte et sont passées rapidement d’un homme à l’autre. Bien que l’infection par ces CoV produise généralement des symptômes bénins, pour certaines personnes, les réponses ont été plus graves. Dans les cas extrêmes, le décès est survenu en raison d’une insuffisance respiratoire progressive due à une altération alvéolaire. 3,4,6
| Figure 1 L’ACE-2 est le récepteur de la cellule hôte responsable de la médiation de l’infection par le SRAS-CoV-2, le nouveau coronavirus responsable de la maladie à coronavirus 2019 (COVID-19). Le traitement avec des anticorps anti-ACE-2 perturbe l’interaction entre le virus et le récepteur. |
Comparaison des pandémies de SRAS et de COVID-19
La pandémie de SRAS de 2002 a commencé dans la province du Guangdong, dans le sud de la Chine. Selon l’Organisation mondiale de la santé (OMS), le CoV responsable de cette maladie, le SRAS-CoV, s’est rapidement propagé à 29 pays d’Asie du Sud-Est, entraînant 8096 cas confirmés de SRAS, dont 774 sont décédés. 7.8 La pandémie d’aujourd’hui a dépassé ces chiffres. L’OMS estime qu’à ce jour, plus de 110 000 personnes dans plus de 100 pays ont reçu un diagnostic de COVID-19, dont plus de 4 000 sont décédées. 9 La propagation rapide de cette maladie respiratoire a conduit à un effort international coordonné pour caractériser rapidement l’agent d’étiologie afin de développer des vaccins et / ou des agents thérapeutiques potentiels qui ciblent spécifiquement le virus ou les composants des cellules hôtes nécessaires à la réplication. viral
Identification et caractérisation du SRAS-CoV-2
L’identification et le séquençage du virus responsable de COVID-19 (voir la séquence de la protéine SARS-CoV-2) ont déterminé qu’il s’agissait d’un nouveau CoV qui partageait 88% de l’identité de la séquence avec deux COV du SRAS dérivés de chauves-souris, qui suggère qu’il provient de chauves-souris.. 10 De plus, il a été démontré que ce CoV, connu sous le nom de 2019-nCoV ou SARS-CoV-2, présente une identité de séquence de 79,5% avec SARS-CoV. 5.10 Le génome coronaviral code quatre protéines structurales majeures: la protéine de pointe (S), la protéine centrale (N), la protéine de membrane (M) et la protéine d’enveloppe (E). 6 La protéine S est chargée de faciliter l’entrée du CoV dans la cellule cible. Il se compose d’une courte queue intracellulaire, d’une ancre transmembranaire et d’un grand ectodomaine composé d’une sous-unité de liaison au récepteur S1 et d’une sous-unité S2 qui fusionne la membrane. 11 L’analyse de la séquence du génome de la protéine SARS-CoV-2 S a montré qu’elle n’est identique qu’à 75% au SARS-CoV S. 5.10 Cependant, l’analyse du motif de liaison aux récepteurs (RBM) dans la protéine S a montré que la plupart des résidus d’acides aminés. essentielles pour la liaison aux récepteurs ont été conservées entre SARS-CoV et SARS-CoV-2, ce qui suggère que les deux souches de CoV utilisent le même récepteur hôte pour l’entrée dans les cellules. Le récepteur d’entrée utilisé par le SRAS-CoV est l’enzyme de conversion de l’angiotensine 2 (ACE-2). 13
L’ACE-2 est une métallocarboxypeptidase transmembranaire de type I présentant une homologie avec l’ACE, une enzyme connue depuis longtemps comme un participant important du système Rénine-Angiotensine (SAR) et une cible pour le traitement de l’hypertension. 14 Elle est principalement exprimée dans les cellules endothéliales vasculaires, l’épithélium tubulaire rénal et les cellules de Leydig dans les testicules. L’analyse par PCR 15.16 a montré que l’ECA-2 est également exprimé dans les poumons, les reins et le tractus gastro-intestinal, tissus qui abritent le SRAS-CoV. 17-19 Le principal substrat de l’ECA-2 est l’angiotensine II. L’ACE-2 dégrade l’angiotensine II pour générer de l’angiotensine 1-7, abaissant le SAR. De plus, 15,20 ECR-2 ont démontré une fonction protectrice dans le système cardiovasculaire et d’autres organes. 15
ACE-2 est un récepteur d’entrée pour SARS-CoV-2
En se basant sur les similitudes de la séquence RBM entre SARS-CoV-2 et SARS-CoV, plusieurs groupes de recherche indépendants ont cherché à savoir si SARS-CoV-2 utilise également ACE-2 comme récepteur d’entrée cellulaire. Zhou et al. ont montré que le SRAS-CoV-2 peut utiliser l’ACE-2 d’humains, de fers à cheval chinois, de civettes et de porcs pour pénétrer dans les cellules HeLa exprimant ACE-2. 5 Hoffmann et al. Des résultats similaires ont été rapportés pour les humains et les chauves-souris ACE-2. 21 Plus, Hoffmann et al. ont montré que le traitement des cellules Vero-E6, une lignée cellulaire de rein de singe connue pour permettre la réplication du SRAS-CoV, avec un anticorps anti-ACE-2 (R&D Systems, n ° AF933 au catalogue), bloquait l’entrée de pseudotypes VSV exprimant la protéine. SARS-CoV-2 art. 21
Il inhibe l’entrée des blocs d’activité TMPRSS2 SARS-CoV-2
Pour que le SRAS-CoV pénètre dans une cellule hôte, sa protéine S doit être clivée par des protéases cellulaires sur 2 sites, appelés protéines d’amorçage S, afin que les cellules et les membranes virales fusionnent. Plus précisément, l’initiation de la protéine S par la sérine protéase TMPRSS2 est cruciale pour l’infection par le SRAS-CoV des cellules cibles et se propage dans tout l’hôte. 23.24 Hoffmann et al. étudié si l’entrée du SRAS-CoV-2 dépend également de l’initiation de la protéine S par TMPRSS2. Le traitement de la lignée cellulaire pulmonaire humaine Calu-3 avec du mésylate de camostat inhibé par la sérine a partiellement bloqué l’entrée de pseudotypes VSV exprimant la protéine S. du SRAS-CoV-2.21 Des effets similaires ont été observés lors du traitement avec le mésylate de camostat. avec des cellules pulmonaires humaines primaires et avec des cellules Calu-3 incubées avec du véritable SARS-CoV-2. 21
Avens pour les thérapies COVID-19
Ces nouvelles découvertes pourraient avoir un impact considérable sur le développement de thérapies efficaces pour COVID-19. Par exemple, des anticorps anti-ACE-2 peuvent être utilisés pour bloquer la liaison du SARS-CoV-2 au récepteur. De plus, les inhibiteurs de TMPRSS2 peuvent être utilisés pour empêcher l’entrée du SRAS-CoV-2 dans les cellules hôtes. Camostat a été utilisé pour traiter la pancréatite chronique au Japon et est actuellement testé en phase 1/2 aux États-Unis. 26 S’il est considéré comme sûr, le camostat peut être une option de traitement potentielle pour les infections à CoV. 27 Il est également possible que les anticorps développés pendant l’infection par le SRAS-CoV puissent aider à prévenir ou à traiter le COVID-19. Hoffmann et al. ont montré que les sérums des patients guéris du SRAS réduisaient l’entrée de la protéine S SARS-CoV-2 dans les cellules Vero-E6. 21 Cependant, d’autres études sont nécessaires pour déterminer si l’une de ces options est efficace pour perturber l’interaction entre le virus et le récepteur. in vivo
98 commentaire
Great… I’m 35 and currently take 10mg amlodipine and 20mg lisinopril. My blood pressure was around 145/80ish before the meds. Never went over and sometimes lower. Now if I stop the meds it goes up to 189/105 in that ballpark. Sucks to suck I guess.
What if the virus is bound to or has destroyed all the ACE 2 receptors…would the resulting free serum AT 2 result in the aldosterone cascade described in severely ill COVID-19 cases?
In lecture 61 you also also said ace-2 receptors exist inside cell walls of veins, arteries. COV-2 binds with these receptors and causes a cascade of symptoms leading to blood clots. Watch the lecture. My question is where are all the ace-2 receptors in the body and can each receptor in every organ they inhabit be affected by the virus binding to it, if those receptors can be exposed to it as it travels through the body ?
Is this the area of work, Dr. Josef Penninger from UBC in Vancouver is engaged in? I saw a YouTube video about trials of medication that uses the ACE2 approach as you described.
I’m not real bright. Can someone please tell me if I should completely self isolate if I’m on ACE hypertension medication.
I’ve been wondering if increased ACE as seen in sarcoidosis would be protective or detrimental. From this great presentation, it looks like it could most definite be detrimental. Any thoughts?
does vaping increase chance that the covid 19 virus enters the lungs cells « i read that the nicotine increases the ACE2 «
I didn’t understand why ARBs and ACEI can be harmful. I concluded that actually those meds can be some kinda treatment for covid_19 you see: indwells catalytic site of ACE & prevents edema and therefore lung infection ��
Sombody please lighten me up!
Have you looked into how nicotine can upregulate ACE-receptor and downregulate ACE2? Smoking seem to upregulate ACE2, but the use of nicotine without smoking seem to downregulate the receptors.
So.
Take ace inhibitors, get more infection.
Don’t take ace inhibitors, get less infection, but be more susceptible to other health issues
Perfectly engineered virus.
The real problem is why are so many people obese unhealthy not taking care of their health and with first twinge of pain go rushing to get prescribed drugs.. Why can’t people look after their health.? They think I’ll eat what I want get overweight drink too much alcohol because there’s a drug for everything. I have perfect good health and I put it down to fact I eat a healthy diet maintain a normal weight don’t drink alcohol eat very little meat and never eat red meat. I believe in taking care of my health if everyone around me has a cold I don’t catch or maybe once in 5 or 6 years. I also believe in positive thinking. Its people who say « stay I’ll catch you’re cold » who have negative attitude that do in fact catch cold. Its been shown that you can overcome your genetic inheritance ie if your father dies in his 40s from a heart attack you can avoid that fate by lifestyle changes.My health is really too important for me not to take care of it.
I’m not sure if this is some kind of pharmaco industry lobby or what, but it certainly gets pretty confusing after 8:55. First of all it’s strange to say that there are two types of states in body – high and low of angiotensin II. That may be the case if we are considering usage of ACE inhibitors, but normally there is a Renin–angiotensin system in a body which regulates angiotensin II. Angiotensin II is causing vasoconstriction by activating angiotensin receptor AT1R. Then there is a counter mechanism in which ACE2 (angiotensin converting enzyme 2) is processing angiotensin II and creating angiotensin (1-7) which has a vasodilatory property. It is also known, that angiotensin || is one of mediator of ACE2 decrease. So, by blocking creation of angiotensin || (ACE inhibitors) or blocking angiotensin || receptor AT1R (ARBs), there is increase in ACE2 expression. Question is how such a interference with normal body mechanisms influences infection by virus SARS-Cov2, when it is known that ACE2 serves as entry point into cell for this virus. I think it is not correct and misleading to say, that only in case of high level of angiotensin II there is vasoconstriction because « AT1R receptor comes off ACE2 and furthermore opening in ACE2 allows for coronavirus to bind ». Nowhere I have found that AT1R receptor is somehow related or dependent on ACE2. AT1R receptor simply reacts to angiotensin II, no matter how much of angiotensin II there is, because it is one-to-one relationship. Also ACE2 reacts to virus independently of AT1R receptor and it seems logical that if ACE2 expression is increased, it is more probable that virus gets into cell. If there is interference with normal body mechanisms which are not fully understood, how can you say how much impact there is, possibly also regarding to behaviour of cells during virus infection.
Delta9THC has a remarkable effect on blood pressure. Could this be replaced these meds by a natural protector who also benefits the receptors CB1 and CB2
Or aliskirnen?!? Please tell me we are trying this as well. Already FDA approved(albeit not for really impaired) but atleast a treatment option.
Hi Dr. Seheult. I am fascinated by the ACE2. Thank you for explaining that people should not stop taking their blood pressure medications, like myself. Further, I have been taking Losartan for many years now and I have had bronchitis (not pneumonia) even while taking the Losartan. In the past, I had taken Linsipril but I developed a dry cough, which is one of the side effects of the medication. I am happy with the Losartan because it keeps my blood pressure low. After watching this video on ACE2, I understand how my blood pressure medication Losartan works on my body. I hope that the University of Minnesota is able to start their study on Losartan and the effects on Covid-19 patients because after watching this video, sounds promising.
Nice research analysis on a most current medical development. The epidemiology and the fact older ppl tend to be over »managed » by pharmacos is only aggravating a sad morbidity of pneumopathy….
Why is it that ATR-1 dissociates from ACE2 in the presence of high AT-II? Is it because ATR-1 has a higher affinity for AT-II than ACE2?
Also, why are ARBs depicted on the left side of this diagram at 10:25? In a simplistic sense, ARBs lower BP. By drawing it on the left side of the diagram “covering” the ATR-1/ACE2 complex, it makes it seem that ARBs prevent AT-II conversion into AT1,7. Shouldn’t ARBs be drawn on the right side of the diagram, directly on the lone ATR-1 receptor?
Btw, great video. These questions aren’t supposed to be any kind of criticism – I’m just trying to get a better understanding since I don’t entirely understand some of these mechanisms. Thank you!
Dear MedCram, is there any update on the ARB usage research? I’ve been using ACE inhibitor for about 8 years, and the issue of having this medication may worsen the covid made me worried as hell
Awesome Video. Even though it left me with more uncertainty, I feel that I have a better understanding of the relationship between the ACE-2 receptor and COVID-19. Thank You -Joe
I just wanted to say thank you.. I found your site and instantly knew you were one of the few that will help us survive. I watch all of your videos, learn a ton and have helped many become aware of your site. I think the president and his cabinet watches as well, some of the news briefings have said many things you have in your videos, thus I know you are helping many. Thank you again for your amazing work and brain!!!
Thank you for your excellent videos on the Covid 19. It seems that from your explanation that the ARBs such as Losartan might be beneficial against the ARDS. Especially out of the case report from Dr. Reza Nejat from Iran of seeing benefit with the Losartan. I wonder if it might be worthwhile to consider trying to solubilize the Losartan as an aerosol to spray directly into the lungs to gain maximal local treatment to optimize the ant inflammatory efficacy while potentially mitigating some undesired effects of the drug more generally if the patient blood pressure is low or variable?
Thank you for all of the work that you do with these videos! I’m a clinical scientist, and watching your material really inspires me to continue on with my plans to attend medical school.
Excellent review, congratulations
Didi you see some difference between Losartan and the other ARBs
Maybe something related to the Exp3174 metabolite
Thanks
Wouldn’t the increase in ACE2 receptor sites in patients treated with ACE2 increasing drugs help create a better chance of getting chloroquine to the cell to let more zinc in to stop the replication of the virus? They should study that.
So can you please answer that question. Why does the Ace-i and ARBs treatment cause ACE-2 expression? It should decrease the ACE-2 expression.
Very interesting though I’m having a little difficulty understanding how ARBs would reduce AT-II and therefore take us down the low AT-II scenario. I read somewhere in the past that Vitamin D3 has an inhibiting action of Renin synthesis so maybe can’t hurt to ensure your vitamin D3 is up to par. This will especially be significant while isolating ourselves inside for long periods.
I truly love these vids. Does anyone know any resources describing the low vs high ATII states and the associated engaging/disengaging of ATR1 in the catalytic site of ACE2 ( 9:00) ? I would like to read more about the ATR1/ACE2 complex. Thanks.
Is it true that Rh negative blood lacks these ACE2 receptors that the virus can enter?….thus possibly making people with Rh Negative blood incapable of contracting Covid-19? At least by airborne transmission?
What do you think about Giapreza (Angiotensin 2) as a first line vasopressor?
Also, if ACE 2 dissociated levels are increased in the high Angiotensin 2 diagram, I wonder if the ACE2-Receptors downregulate because of the abundance of ACE2.
If so, then could this be protective against contracting the virus but bad when one actually contracts it, @medcram?
Correction: I see now. ACE 2 IS the receptor. High Angiotensin 2 states can increase ACE 2 levels.
The statement from the European hypertension council is so predictable and depressing — just keep taking your medicine and stop asking questions. Maybe it’s unfair to point out that the statement is from an Italian doctor — whose country is experiencing by far the world’s worst death rate from this disease.
In fact, as this video shows, there is a very plausible reason why ACE inhibitors might greatly increase the risk of severe disease from this kind of a virus. And there is strong circumstantial evidence that people taking ACE inhibitors are dying at much higher rates. And there simply isn’t time to do double-blind studies. The time to save lives is now.
can you please show us how our cells in our body / blood can fight COVID-19? Or how our cells change and adapt to this new virus?
Perhaps chronic use of these drugs can cause up regulation of ACE receptors worsening a Covid19 infection but new short term use can have a protective effect?
Thanks so much for all these videos, I’m not a medical professional but it’s so nice to get a scientific well-grounded view of all this instead of the crazy panic and hype the media does.
I now see how hard you work
have been working
everything with a hint of hope
you shared
…
and dear friend
i now see your desperation
everything anything to help
how can we not value you
thank you and the team
gerard a fan
I believe research ha since been done in Italy and in NY where most deaths have hypertension as a comorbidity factor median age about 62…it didn’t matter if it was controlled hypertension or not and just slightly more risk for those on Ace or ARB’s. So if you have hypertension and are over 50..you/we need better protection!
When, in a situation like this, I feel that Tripoli is being bombed in Libya, Iran asks for help but there is an American veto and ordinary people die, the US and the UK have bombed Iranian emplacements in Iraq, but that cracks the being human everything, W Covid19, annihilate the human being, fill the morgues, make them cremate, who suffer, who despair, go covid let them pass to men what they let animals pass…..
Can you please tell your opinion about Vitamin D use? I’m a total dummy here and I don’t know what to do: some say Vit D is good for the immune system and some say Vitamin D is bad with CoVid-19 as it increases ACE-2 expression. I’m very confused:(
I’m very confused. I’m currently taking 20mg of Lisinopril. I questioned this medication with COVID 19 and my doctor switched me to Valsartan 40mg. She said to switch cold turkey. I need a second opinion. Please help.
Ok, so its ben a month since this was posted. Is there any update to this ? Are patient’s taking ACE 2 inhibitors at a greater risk of mortality from COVID 19?
I do not understand why more ICE-2 receptors would increase the chance of getting Covid 19 since only one virus has to enter the cell right? So why should ICE-2 densitiy make much difference? The virusses will find an ICE2 anyway and enter the cell. Also I read elsewhere on the interwebs that another effect of this ‘tan’ medications is that in practise it somehow prevents a complication in the covid 19 patients that is a major cause of death: creation of fluid in the longs from which they sufficate. Apart from that: very nice presentation. Thank you for your work.
you are really smart I am going to watch this more than once the fact they have underlying health conditions in itself speaks to how COVID attacks someone
15:15 to 15:20 « …may be on the high side » You did not say why the levels are actually on the high side with ace inhibitor.
I wonder if an ACE 2 activator would help in this situation. It would decrease the concentration of angiotensin 2 and increase the concentration of angiotensin 1,7 plus the body might respond to these changes by decreasing the amount of ace 2. Not sure though if there are any drugs that are activators of ace 2.
I do not see that the two theories are mutually exclusive. The upregulation of ACE2 by ARBs and ACEi’s is at the level of gene expression and thus a longer-term response. Long-term administration of ARBs and ACEis will lead to a lung, where the cells are studded with more ACE2 and thus with more doorways for the virus to enter – thus being in line with the theory of the Lancet-paper.
The explanation by MedCram and the European Society is at the level of enzyme function and is thus looking at the short term effects of ARBs and ACEis. Thus the drugs can have opposing effects on susceptibility for the virus on the one hand and on the short-term treatment of infected patients with ARDS on the other.
In other words, the drugs will help to alleviate the problems of a patient who is already infected and in a critical state – because in such a patient the spike protein of the many viruses down in the lung reduces local ACE2-function, thus leading to vasoconstriction and hypertension – which can then be countered with short term administration of ARBs and ACEis.
But on the the other hand the current long-term treatment of hypertonic patients with ARBs and ACEis would lead to an initially higher concentration of ACE2 in the lung tissue, thus making them more prone to get a severe infection in the first place.
Thus, there might be some truth to the Lancet-theory, which would be bad news for patients on ARBs and ACEis. And at the same time truth to what MedCram says. It’s a matter of timing!
Is it not an opportunity to revisit our Understanding of hypertension. Do we need to treat essential hypertension with ACE INHIBITORS? CAN WE NOT LOOK at alternative lifestyles. No red lights. No coffee. No rush rush rush without any real reason. Why don’t we not all go to work from 7 to 5. And so on.
I got lost on low AT2 combining with receptor and high AT2 not combining with receptor. Is that because of excess? No mention of the synthesis of Aldosterone or how it feeds back onto Angiotensinogen to regulate blood pressure.
The respiratory system does not carry out its physiological function (of gas exchange) until after birth. The respiratory tract, diaphragm and lungs do form early in embryonic development. The respiratory tract is divided anatomically into 2 main parts:
upper respiratory tract, consisting of the nose, nasal cavity and the pharynx
lower respiratory tract consisting of the larynx, trachea, bronchi and the lungs.
In the head/neck region, the pharynx forms a major arched cavity within the phrayngeal arches. The lungs go through 4 distinct histological phases of development and in late fetal development thyroid hormone, respiratory motions and amniotic fliud are thought to have a role in lung maturation. Branching is a key mechanism/process in lung development leading to alveolar saccules after about 23 branching generations (range of 18–30).
The two main respiratory cell types, squamous alveolar type 1 and alveolar type 2 (surfactant secreting), both arise from the same bi-potetial progenitor cell.[1] The third main cell type are macrophages (dust cells) that arise from blood monocyte cells.
Development of this system is not completed until the last weeks of Fetal development, just before birth. Therefore premature babies have difficulties associated with insufficient surfactant (end month 6 alveolar cells type 2 appear and begin to secrete surfactant).
Respiratory Links: respiratory | Science Lecture | Lecture Movie | Med Lecture | Stage 13
American College of Cardiology, the American Heart Association, the Heart Failure Society of America, and the European Society of Cardiology—have issued guidelines saying patients should not stop taking the antihypertensive drugs because there’s no evidence to support the claim that they cause more-severe SARS-CoV-2 infections.
In support of that recommendation, Ankit Patel, a clinical and research fellow focusing on the kidneys at Brigham and Women’s Hospital in Boston, and his Brigham colleague Ashish Verma dug into the literature to address the confusion and reported March 24 in JAMA that there’s no definitive evidence to suggest ACE inhibitors and ARBs increase the severity of COVID-19. Another team of doctors, writing in the March 30 issue of the New England Journal of Medicine, came to the same conclusion.
Instead of making COVID-19 symptoms worse, some antihypertensive drugs may actually reduce the severity of infections, and could therefore be used to treat the disease, both sets of doctors say. A closer look at the underlying mechanisms of the medications has also buoyed another idea for how to treat COVID-19—give patients the enzyme ACE2 as a decoy to direct SARS-CoV-2 away from their cells. A biotech company developing such an approach using recombinant ACE2 received regulatory approval today (April 2) to start clinical trials on COVID-19 patients.
Many sperm + 1 egg increases chances for pregnancy.
Why wouldn’t many corona viruses + one cell increase chances for infection?
SEEMS TO ME THAT this vlog and that study are a bit backwards… HOW is it that an ARB… ACE-2 Receptor BLOCKER causes MORE ACE-2 receptor cells to form, rather thanbeing BLOCKED.?. Thus, also blocking SARS-CoV-2………………
perhaps. now. in respite time. reflect on: 1. climate change. 2. contribution to emergence of new species. ( viruses. current epidemic) 3. resources. exhausted. so. what now. 4. the next round. of new viruses. new fires (Australia.whole continent on fire. ) 5. what really needs to be done on global scale. 6. United Nations. so far ineffective. how to make Nations stop. 7. stop the mistaken priorities. ( economy. growth.. ) more factories. more cattle. more cars. planes. whether this happens or not. (Adley Huxley: things out of mind. are still out there. progression still goes on. and just ignore problem. problem does not go away. Not least is the MINING BOOM ( BLOOMBERG) ! BARBARA STREISAND: HE HAD THE NErVE TO TELL ME.. that mining shares are up up..
CHEESE CHEESE CHEESE….higher incidence of severe infection in ITALY, SPAIN, UK, FRANCE and SWITZERAND !!! they all eat lots of cheese containing Lactobacillus helveticus as do yogurt drinks…..ACE inhibitors…
Got little confused. You said ACE-Inhibitors and ARBs increases the level of ACE2. Is it right or wrong? Because, later you said, ACE-Inhibitors stops ACE enzyme which results in decreased level of AT-II. And, less chance of ATR-I docking out from ACE2 and lesser amount of ACE2. This would mean, ACE-Inhibitors causes less amount of ACE2 (being docked out from ATR-I)
Silly question, however, I am an engineer not a biologist… So with a low AT-II the ATR-1 receptor occupies the ACE-2 receptor? So we have the the cell receptors binding with each other? @ 9:17
I am a clinical pharmacist and the RAAS system brings back some pharmacy school trauma. I recall drawing out this mechanism countless times. I recall that when a person is on an ACE-I, after time their angiotensin II levels go back to baseline and that the potential mechanism for BP lowering is inhibiting the breakdown of bradykinin (which is metabolized by ACE). Side note, bradykinin is a vasodilator and also responsible for dry cough.
Because of angiotensin II levels going back to baseline levels even while on an ACE-I, I would suspect patients on ARBs to have a better outcome when infected with COVID-19. Someone mentioned on here that Korea utilizes ARBs and someone else mentioned Italy uses primarily ACE-Is. German death rates seem very low, anyone know if they use ACE-Is or ARBs?
Here’s another video that’s going way off track. When you get symptoms take vitamun c 4000 mg every 15 minutes for an hour your symptoms should go away. And then take the vitamin C as needed
I switched to a beta blocker, could not take the chance as I am a Perfusionist providing VV ECMO in the ICU setting. Using PPE but exposed every day so I thought it best to switch until this is over.
Have you heard about the Pepcid study, small study but supposed to reduce viral replication?
Dr tony Fauci was on a recent jama utube presentation saying they noted a larger amount if deaths due to covid 19 in those taking ace inhibitors. I hope he is wrong.
74% of the deceased people in Italy had hypertension and 52% of the deceased had ACE-inhibitors or ARB. Why didn’t this medication then helped them? 98% of the dead had ARDS, so this medication didn’t prevent them from having ARDS. Hypertension is by far the most important risk factor, why should it be important in a virus desease at all? If I stop the ACE-I/ARB medication and take Ca-antagonists, I have the normal risk, so if we dont know, which effect is more important, why take that risk?
How long on average does it take for the ACE 2 (doors) to return to a normal closed state after stopping an ACE Inhibitor?
How does ACEI increase the expression of the ACE receptor? If ACEI blocks ACE receptor then AT II is not produced. If AT II is not produced in high amount then how is the expression of ACE 2 increased. Please educate
Do the ACE2 receptor and virus spike proteins tangle together like velcro loops and hooks, or are there chemical bonds? What causes the spike binding site to fold out, lower pH?
Persistent dry *cough* is a very common side effect of ACE inhibitors, as well as a Covid-19 symptom. Is there a physiological parallel?
I think the explanation for ACE cough is elevated bradykinin…? It’s much more rare with ARBs (indeed used as an alternative for these cases), but controversially said by some to also cause cough, potentially. My mother’s on Losartan, which I suspect of causing her persistent cough for the last year. So I’m worried about her potential additional susceptibility to coronavirus infection. Frustrating that there’s no clear answers, obviously…
I stopped taking Lisinopril 40mg daily a week ago when I heard it could worsen the infection. I guess now I should get back on the medication?
I’m slowly getting to the point of the same embriological origin of lung and GIT TISSUE ( SO CALLED Endodermal embriological cells )
A brilliant and articulate lecture. One thing that is very curious and bothers me: the epidemiology data that I am aware of from other countries are simply stating, and keep saying, that « hypertension is an apparent risk factor for severe COVID-19 ». I have never seen any epidemiology data that say that « UNCONTROLLED hypertension is a risk factor » or any data that say « patients who were taking Losartan were at higher risk », etc. Please keep us informed here (I am on Losartan). James T. Lee MD PhD
Dear colleagues, if the patient started to get fever, stopping ACEi and ARBs and beginning CCBs is the best choice now, as » less is more » meaning decreasing the drugs taken by patients is good « esp. The drugs that have controversy » till the viral infection end, we ve got to remember that more than 75% of mortalities has either HF, HTN, Dx or combinations of them, it may be confounding.. but better to be safe than sorry
Another interesting aspect about ACE2 is that it is encoded on the X-chromosome. This might be part of the explanation why men – who have only one X-chromosome – are more at risk from COVID-19 than women with their two X-chromosomes.
It would also be interesting to learn from the very sad deaths of four family members in New Jersey – a 70 year old lady, two of her sons and one of her daughters – whether there’s something special with that family’s ACE2-sequence or -expression pattern.
That response from the American Heart Association and others sounds a awful lot like « nothing to see here folks »..
I don’t trust the integrity of any study that is essentially protecting Big Pharma and their 200 million customer base worldwide that are taking ace inhibitors.
Excellent.
But what is the relationship of ATR-1 to angiotensin (AT), AT-I and AT-II?
Does ATR-1 bind better or worse to ACE2 if ATR-1’s (presumed) AT, AT-I
and/or AT-II site(s) is/are occupied?
Also, presumed beneficial ARB, as diagrammed, seems to suggest inhibition of the
ATR-1+ACE2 complex proceeding to the desired AT 1,7.
If you have a copper/zinc imbalance you may be more susceptible.
If you consume too many copper-rich foods you could become « Copper-Toxic »
Foods with a High-Copper Content or « Phytates » may be creating some underlying sensitivities.
NSAIDs like ibuprofen can add to « Salicylate Intolerance » that interferes with absorption of certain vitamins and minerals. These things can add to your body aches/gut issues and lower your immune system as well.
holy moly…..How come my doctor NEVER told me any of this? So when my doctor just quit me on my ‘tan’ HB medicine abruptly like that the doctor was REALLY attacking me! NOW I UNDERSTAND! That whole medical system AURORA in Wis is CABAL CORRUPT BIG TIME!
If ACE-2 polymorphism may be responsible for increased affinity of the virus to the receptor and cause more severe disease, is it possible that chronic use of ACE-i’s and ARB may be causing receptors to mutate? As opposed to the diseases causing polymorphism? ACE’s/ARBS are used to treat all these conditions – HTN, DM, CAD, CHF and all these conditions are associated with worse outcomes. Makes me think the chronic use of the drugs may cause receptor to increase affinity for the virus.
That’s scary since I take 10mg of Lisinopril. ��������
Not to mention I’m a truck driver so I have exposure from a lot of areas. I was in the Seattle a area last week, went throughout the Midwest now going to PA while having to stop in Chicago where the governor Lockdown the state. Ugh.
Just make a ACE2 inhibitor !!! Also S protein inhibition would be helpful for Coronavirus. I would combine it into this cocktail of (ACEi + Serine Protease Inhibitor + HCQ + Erythromycin + Remdesivir ) this shotgun approach has to work in my opinion !!!
You make some of the best level headed content on this crisis I have found so far.
The testing regime between counties varies wildly, based on availability of resources. So the number of sick, death rate and such seems to be uncertain at best. I hope the once this crisis is over they will collect data to learn. Perhaps a mandatory blood test taken at the first doctor appointment or something along those lines.
Does this mean to avoid quercetin which is an ace inhibitor but also acts as a zinc transport? Anyone? What about Vitamin D?
Great presentation. Excellent information. Godspeed to both public and private institutions in their research and conclusions; ultimately leading to solutions. Thank you.
So, what are some hypothetical reasons or scenerios that would explain the increase in expression of ace 2 receptors? And also, I do not quite understand the physiology between low and high amounts of angiotension 2 concentrations. you said that with low concentrations, ACE1 receptors sit on top of the ACE2 catalytic site, however with increase concentration of angio2, while it may interact with atr-1, wouldn’t angio2 also interact with ace 2 receptors as well? does this mean that the sarscov2 have more affinity than the preexisting angio2 on these receptors? finally, to sum it all up, youre saying that the complications of sarcov2 are due to the activation of atr1 from surplus angio2, as it causes consequent vasocontriction, APE, ARDS. and since the virus attaches itself to the ACE 2, the benfits of vasodilation and decrease in inflammation does not occur? is that correct? can someone help me with this?
If it comes out that the Euro Council is wrong, them and all other experts who have made such conclusive statements should be held responsible for their dangerously hubristic and overconfident statements.
About the KO mice who have “better outcomes” when given AT-11, are you saying better than with none at all? If so I don’t understand how that relates to the difference between having a normal amount vs having an extra amount. Shouldn’t it be possible even likely that have none AND having extra are both harmful?
A lifelong (70) kidney patient with ‘essential hypertension, uncontrolled until a few years ago, when atenolol+lisinopril+hctz proved relatively effective, I am finding this information both worrying and puzzling. As my teacher once said: « It seems the more we learn, the less we know. »
Guys, the treatment is already developed! Have a look at aperion biotech / apn01 — originally developed for sars cov – 1.
I was diagnosed last week with covid-19 and at the same developed severe HTN requiring medication as I fight this flu I’m wondering if there are any other reports of patients having new onset high blood pressure? Could this be related to the RAS imbalance as the Virus uses ACE2? I started Losartan as suggested in the Minnesota trial and my symptoms have improved, but my Blood pressure, though better, is still way above normal. I am hoping that as the viral load dissipates it will normalize. If I had pre-existing HTN I could see how this possible effect would be quite damaging. I’m curious for any other reports of high blood pressure with Covid -19. Is there a relationship?
Slightly off topic, but I was surprised to learn that ACE2 can also be found in intestinal cells (« …and also in the GI tract » @ 1:45). Could those intestinal ACE2 enzymes be an infection pathway? Does this explain why some COVID-19 patients experience vomiting, nausea, and diarrhea?
Thank you! I’m a nurse around patients and on an ARB. This was making me nervous. I feel a little better after watching this.
animal studies may show a relatively speaking protective effect when ACE NON EXISTANT ACE RECEPTOR mice. are give Inhibitors. 2, in humans there is » CONSTRUCT VALIDITY » to explain how those patients who died. during the SAARS2 viral pneumonia. EPIDEMIC. were actually on ACE INHIBITORS. the hypothesis that the ACE INHIBITORS. Their treatment for high blood pressure. is indeed an important causative factor. in worsening of their condition. finally dying. the null hypothesis is that there is no correlation between the ACE inhibitors. and the death. they died with an outburst of 1 huge inappropriate inflammation. 2, malignant hypertension. heart muscle damaged.. the CONSTRUCT validity. is that ACE 2 being very high. allowed the SAARS 2 virus to latch on and separate the normally bound ACE1 AND ACE 2 COMPLEX. thereby allowing free play of ACE1: vasoconstriction. heart muscle damage. Hypertension. and big inflammatory ineffective response.
Really easy!! I have been hearing both sides of the argument and the final truth is actually not difficult it’s real simple. The high death rates in Hypertension and Diabetes can be separated by those who are taking ACE2 and ARBS and those who are not taking [email protected] and ARBS. Simple if 2000 people died with COVID19 that had high blood pressure similar age and males and the ARBS and ACE2 death rate was 1500 vs 500 who did not take the medication then you would have an actual number to go off of either way. this could be repeated in China, Italy etc etc
We also know that men are dying 30-40% more from covid than women. And we know that men have more ACE2 receptors than women.
Sounds like more than just a coincidence.
Can someone please clarify this: If ACE inhibitors contribute to low generation of AT2, and on low AT2 in general: AT Receptor will NOT undock the ACE2 receptor, leading to less ACE2 receptors active thus less docking points for the Sars-Cov-2. That means AT-i should be beneficial in a theoretical standpoint.
This may be the most useful lecture in your series, at least for those who are currently prescribed ACE or ARBs. Would you please consider discussing the differences between the various products — e.g., lisinopril, captopril, losartan, irbesartan? My limited understanding from reading various studies and monographs is that the mechanisms of action for each drug may be relevant to COVID-19 outcomes. I believe that many current hypertension sufferers would benefit greatly from being able to intelligently discuss these issues with their physicians — many of whom are (to be kind) not fully versed in the underlying pharmacology of the drugs that they prescribe.
At 15:20….. How do we see high levels of AT-II in pts with an ACE inhibitor? That doesn’t make sense. Can somebody explain please
Wait, the way you described it, blocking formation of Angiontensin 2 using ACE inhibitor will actually help with decreasing the vulnerability to SARS-Cov-2 by decreasing Angiotensin 2 levels in the blood, hence preventing dissociation of ATR1 from ACE 2 and less opportunity for the virus to enter the cell. But on the first part of the video, it was taken that ACE inhibitors will actually make COVID-19 worse. Can you please clarify this for me.
Do you (Dr. Seheult) know if they have thought about getting the zinc to hitch-hike on the COVID « off shoots » and ride into the cell membrane with the virus?
I do not think we can control the reception of the virus with healthy cells and with the amount of benefits ACE2 allows the body to compensate with the infection.
Then our priority should be creating the medication that will decrease the viral load. Should we consider antiretroviral medication as an option for the treatment of COVID-19?
Does elevated BP in the absence of drugs also upregulate the number of ACE2 receptors? Reason I ask is that research to shows that sauna use (or heated hydrotherapy) improves cardiovascular function, including lowering BP. Exercising adequately does too. immune function is improved as well.
A couple of questions. ARBs really have an effect on ACE2 ? (10.20) Did you draw AT-I (instead of AT-II) in 10.43 ? We know that ACE2 effects both AT-I and AT-2, why ACE2 becomes available in the second scenario ? According to this logic, when AT-I increases ACE2 is occupied, and when AT-II increases it becomes open Why ? Of course AT-II goes to other receptors like vascular smooth muscles as well, but also it goes to ACE2. Why should we think that AT-II does not prefer ACE2 that much ?
Ace inhibitors are derived and then synthesized from snake venom. This Covid-19 virus is believed to have been passed to humans from snakes. Then, there is a receptor in the cells of humans that is activated by Ace inhibitors and used by the snake-originated virus to enter the human cell…is it just me or do you see a crazy connection somehow…the idea keeps on bugging me and there is no way I will be taking Ace inhibitors to lower my blood pressure…I am switching to a different class of medication for now.