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Cardiovascular Disease

Angiotensin and the Coronavirus

There’s quite a bit of confusion around the ACE proteins and coronavirus infection, and I can see why. The names in this area are pretty confusing, for one thing, and if you’re not familiar with the tangled feedback loops that you get in human biology, it all starts to look like a tangle of wires pretty quickly. So let’s have a look at the outlines of the system.

At right is a (pretty darn simplified) scheme. Angiotensinogen is a 452-amino-acid protein that’s secreted by the liver (and has several functions all by itself). Its first ten amino acids are cleaved off by the enzyme renin to give you Angiotensin-I (also known as proangiotensin). That small peptide is then made even smaller by angiotensin-converting enzyme 1 (ACE-1), and interestingly, no one’s ever found a function for angiotensin-1 other than to sit around and get cleaved in this way. This extra regulatory step has presumably come in handy over the eons.

ACE-1 takes off two more amino acids to give you the octapeptide known as angiotensin-II, and that one has profound effects on raising blood pressure (it has many other functions as well). It does this by binding to cell-surface proteins called angiotensin receptors (there’s more than one type of these and they have a whole list of other downstream functions, but that takes us further afield). So you can see how an ACE-1 inhibitor could be good for high blood pressure, by blocking any formation of angiotensin II, and a renin inhibitor would be as well, by blocking the whole process a bit further upstream, and something that blocked that last binding step (an antagonist of the angiotensin receptor) would also probably work. All three of those are in fact classes of hypertension drugs – the ACE-1 inhibitors came first (captopril in 1980, a famous triumph of 1970s med-chem and led to a whole slew of improved -opril drugs). The angiotensin receptor blockers came next (drugs with the -sartan suffix), and there are several of them. Renin inhibitors were far more painful to discover and develop, for a lot of reasons, and there’s still only one on the market (from 2007).

Now to the coronavirus connection. You’ll note that ACE-2 enzyme in the chart, and that one (formerly rather obscure) is having its moment in the the spotlight. It’s expressed near the surface of various epithelial cells – blood vessels, for sure, but also lung, intestine, and others. As shown, it is capable of clipping both angiotensin-I and angiotensin-II down further, to even small peptides (angiotensin 1-9 and 1-7) that have activities of their own. So it has its cardiovascular roles to play, but it’s become known for being a protein recognized by various coronaviruses to gain cell entry. There are others, naturally, and their relative importance can differ from virus to virus, but ACE-2 was shown to be important for the earlier SARS virus, and this current SARS-CoV-2 is quite similar. A cryo-EM structure of full-length ACE-2 with a coronovirus spike protein has recently appeared.

So something that binds to ACE2 and interferes with that viral hijacking would probably be quite interesting. Problem is, we don’t have much of anything like that. ACE-1 inhibitors, as fate would have it, are not inhibitors of ACE-2 – the enzymes are cousins, but not similar enough for the activity to cross over. It’s not completely clear to me if a small molecule inhibitor in the active site would interfere with the viral interaction anyway, and it would be nice to have a few to see, but I’m not aware of any such compounds. The confusion around the phrase “angiotensin receptors” has led to some people outside of the medical field wondering if the antagonist drugs (the sartans) would interfere with ACE-2, but that doesn’t happen, either (there’s another story with those, though – see below).

A recent letter to The Lancet has noted that comorbidities reported so far for severe coronavirus patients include hypertension and either type I or type II diabetes. These patients are often being treated with ACE-1 inhibitors or angiotensin-receptor antagonists. The tricky part is that both diabetes itself and treatment with either of those drug classes increases the expression of ACE-2 protein. At first thought, that would probably not be a good thing, loading up the cells with more viral target proteins. But wait: there’s another effect, as noted in this new paper. It builds on reports from China to suggest that a mechanism of lung injury during the viral infection may be through inappropriate effects of excess free angiotensin-II protein, which is floating around out there because the ACE-2 that would normally be soaking it up is occupied by coronavirus particles. If that’s the problem, then increasing the amount of ACE-2 protein might paradoxically be just what you want to do to restore some balance to the angiotensin system. In that case administering more angiotensin receptor antagonists would be an effective way to upregulate the production of ACE-2.

There are a lot of such bounce-shot three-cushion mechanisms out there, so it’s not a crazy suggestion. That second paper proposes sorting through the existing patient data to see if there are correlations between severity of infection and angiotensin receptor antagonist therapy in particular, and I believe that this is ongoing. Epithelial cells are going to have ACE-2 protein on their surfaces no matter what, so the virus is going to be attacking those as a route of entry. If that second paper is right, then it could be that throwing more ACE-2 onto those membrane doesn’t make the viral infection much worse, but does lessen the associated lung injury. If we’re going to have a lot more coronavirus patients, this would be a very good thing to know.

 

241 comments on “Angiotensin and the Coronavirus”

  1. Angiotensinogen_pedant says:

    Really interesting write-up of a complex area. There is a very, very, minor issue in the text though, Angiotensinogen is actually 452 amino acids long, the precursor Pro-angiotensinogen is 485, with the extra part removed during secretion.

    1. Derek Lowe says:

      Right you are! I missed that step – corrected the number.

      1. Bruce Maryanoff says:

        First let me state that I am a chemist, not a geneticist. The following comment is meant to stimulate thought on the severity of COVID-19 relative to ACE-2. Not all ACE-2 proteins would have the exactly the same structure. There are polymorphisms in the genome, such as insertion-deletion modifications. Levels of ACE-2 across humans will vary according to inherent genomic expression. Taken together, a hypothesis could be posited that a spectrum of severity of response to COVID-19 coronavirus infection correlates to factors involving ACE-2 gene expression levels and/or gene polymorphisms. Perhaps, certain Italian familial lines, such as those of the Fuscos, are predisposed to more severe reactions, with a genetic underpinning. Might this issue account for the exaggerated severity of COVID-19 in Italy?

        1. Scott Flick says:

          excelent point.
          Closer examination of the correlations between the different genotypes and their affects on gene expression will surely be fruitfull. Hopefully we can learn quickly, to help these wonderful folks who are dieing out so quickly.

          Thank you for sharing…. information is so important, on this subject.

          Wish us All, Good Luck. Fight the good fight. 🙂

          1. Mary Hamilton says:

            I read most of the suppositions and have an idea not mentioned. Ace inhibitors are indeed derived from venom. So are most of the heart medications. I have an allergy to insect venoms of many types. Nitro lowers my BP immediately but I take the venom meds daily anyway for non-stress diastolic hypertension & heart disease. I also have Graves Disease. The one link I see in Diabetes, Heart, auto-immune & Covid is venom. Could it be an auto-immune reaction killing people because they have acquired an auto-immune condition due to venom medications? Genetics play a part in familial high BP, maybe diabetes.

        2. Angela says:

          I’m on lisinopril 40 mg I’m a 42 yr old female.. is this med…one of the ones they was talking covid-19

          1. Becky says:

            Yep. Lisinopril is one of those.

          2. Kirk says:

            Yeah , it is. I’ve been type 1 55 years. age 3 now 58. They wanted me on lisinopril back in 1990. I complied for a month. I coughed so bad I said forget it. Even on the lowest dose. I looked up ace inhibitors then and found out they were modeled after pit viper venom ( a rattlesnake is an example). That’s all I needed to know. I have no complications and I never catch cold or flu either. NO BUENO!

        3. Wendy says:

          I’m not scientific techie and have no idea what I just read. I am also on lisinopril as well as metropolol and hydrochlorithyazide. What does this mean in yearns if the Coronavirus?
          My son is T1d and on insulin and Lantus.
          Can someone explain in non-scientific terms the general population can understand.

          1. Sue says:

            Sir I am type 1 diabetic,been on ace inhibitors enalapril for approx. 24yrs.Diabetic for 49yrs.Over time I have had swine flu,sars men’s etc,3 different types and each time was given flu vaccine,and each time I was floored by these infections for 6 weeks,surely there must be a link,and in your considered opinion,would you have a covid19vaccine or,would you ask for blood pressure meds to change first? Appreciate your views.Sheilding in isolation and fear.Regards

          2. Landon says:

            There is no information that suggests anyone on ACE inhibitors like lisinopril or captopril or ARBs like losartan should stop their medications even if they are positive for COVID. Some even suggest it is beneficial to be on these medications. The current recommendation is for people to continue their current blood pressure medications because we know that stopping them can actually cause harm because of the high blood pressures. Studies are still ongoing, but for now, please do not stop your blood pressure medications. I am currently a medical student in a course focused on COVID and pandemics.

            Here are links to the current studies.
            https://doi.org/10.1002/ddr.21656
            https://www.nejm.org/doi/full/10.1056/NEJMsr2005760
            https://jamanetwork.com/journals/jama/fullarticle/2763803

        4. Ajoz says:

          Yumiko Imai and co. https://www.jstage.jst.go.jp/article/circj/advpub/0/advpub_CJ-10-0045/_pdf
          found already in 2010 the dependence on polymorphism

          ”The human ACE gene (dcp1) is located on chromosome 17q23 and contains a restriction fragment length polymorphism within the coding sequence of intron 16 defined by the presence (insertion, I) or absence (deletion, D) of a 287-bp repeat. This polymorphism determines the function of ACE and the human ACE D allele confers increased ACE activity. Importantly, recent cohort studies of ARDS patients showed a marked correlation between ACE I/D polymorphism and the susceptibility and mortality of ARDS.The D/D genotype was significantly increased in patients with ARDS compared with control patients without ARDS respiratory failure being ventilated in the intensive care unit. In addition, the ACE D/D allele correlated with mortality in the ARDS group, and patients carrying the ACE I/I genotype have shown a significantly increased survival rate.These findings implicate genetic factors of the RAS in the susceptibility, progression, and lethality of ARDS in human patients.”

        5. Judith Julyan says:

          That’s a point I have pondered in recent weeks. Surely it must be to do with different genomes.

        6. Jim Roof says:

          Another thing to consider then thinking in terms of familial genetic predispositions that may lead to a more sever COVID-19 infection… New York and New Jersey are about 40% Italian descent.

        7. Bruce Thompson MD says:

          There are several agents that may help to prevent or reduce severity that came from investigations about the SARS-CoV-1 in 2003 and published in 2013. SARS-CoV-2 entry into the cell could be blocked both by S-protein neutralizing antibodies and TMPRSS2 inhibitors (camostat mesylate).

          1. Jim Glasgow says:

            Bruce I read these studies most notably
            “Inhibition of the interaction between the SARS-CoV Spike protein and its cellular receptor by anti-histo-blood group antibodies.” (September 2008).
            Strikingly similar to what they said in the China January study in China on Blood Type O and its interaction with this S protein. I have heard that Covid 19 is similar in design and cell entry. Curious on your thoughts.

          2. Bruce Thompson MD says:

            Sorry, Jim for the late reply. Busy with a new job opportunity. What a great question about blood types and viral protection. After reviewing “Inhibition of the interaction between the SARS-CoV Spike protein and its cellular receptor by anti-histo-blood group antibodies,” I suspect a lot would depend on to what degree ABH antigen is synthesized by the COVID-19 infected cells. A previous study cited in this article indicated that pneumocytes, enterocytes, and epithelium of the distal tubules could synthesize the ABH antigen. The type II pneumocytes host the ACE2 receptor. As you know, this is the receptor site for this virus. Synthesis of ABH antigen by an infected type II pneumocyte should be protective. I wonder if there is any current data on COVID-19 and blood types or the synthesis of the blood group antigen by these specific pneumocytes. Let me know if something like this is emerging.

          3. Bruce Thompson MD says:

            Quick follow-up, a non-peer review article DOI 3/2020, “Relationship between the ABO Blood Group and the COVID-19 Susceptibility” may demonstrate risk and benefit by blood groups. Group A and AB more susceptible while O significantly less. This may indicate the need for heightened protection of persons with these A or AB.

          4. Bruce says:

            I am speculating in a broad sense, that persons who are at high risk for COVID-19 related mortality have an underlying endothelial dysfunction. As you are probably aware that such dysfunction is characterized by the attenuation of vasodilation and disrupting vascular homeostasis. This results in proinflammatory and prothrombotic properties. COVID-19 affects the ACE2, Ang 1-7 which mitigates the vasoconstrictive properties of AII. Some younger patients may have unrecognized dysfunction in whom strokes have been reported. Perhaps early markers of this type of dysfunction such as microalbumin could alert us to patients at high risk.

        8. Karen says:

          Spot on reasonable hypothetical observation, maybe tip of such iceberg?

          1. mike says:

            re bloodgroups the paper noted 25% vs 38% – so, good, but not huge…

        9. Srdstm says:

          Additionally, ace2 gene is expressed on the X chromosome. As with other sex-linked genes a female then has two chances of having at least one copy with a mutation that for whatever reason is more protective toward sars-cov2 infection, but a male only has one the one copy. This could account for the observed increased levels of more severe covid-19 illness in men.

      2. Chandra Gupta3 says:

        Derek – would this be right ?

        “Just to be clear – its not Diabetes alone that is the problem – its people with type II diabetes, who are treated with ACE-1 inhibitors ; this is where I align with Dr Lehrer – overuse of antibiotics, of drugs and relaxing without thinking about what the drugs may open the patient up to.”

        1. Joan Tendler says:

          The serious side effect of ACE-inhibitors exactly matches the symptoms of the virus-dry cough, leading to swollen airways, or angioedema-so I think there must be a very close connection. Also, the virus is thought to have begun in a venomous snake, and ACE-inhibitors are derived from snake venom. ACE-inhibitors, the virus, as well as snake venom, all increase bradykinin, which causes swelling, as a histamine reaction, which can lead to death. There may therefore be a clear pathway to at least alleviating this problem.

          1. Kirk says:

            Modeled after pit viper venom. Hmmmm…

          2. Lee says:

            I started taking enalapril about 15 years ago and had dry cough. Read somewhere that the MFR of the drug has something to do with this cough and sure enough I asked my PCP to switch me from Ranbaxy to a different mfr I did not have that dry cough any more. I do not use enalapril any more but switched to losartan since it does not aggravate my gout as much.

      3. Chandra Gupta says:

        Derek :

        “I can’t parse this – I don’t understand what they’re saying, I have to reread from top ”

        But wait: there’s another effect, as noted in this new paper. It builds on reports from China to suggest that a mechanism of lung injury during the viral infection may be through inappropriate effects of excess free angiotensin-II protein, which is floating around out there because the ACE-2 that would normally be soaking it up is occupied by coronavirus particles:”

      4. Chandra Gupta says:

        Derek

        Also remember – the virus is an icosahedron – a dreamed up Plato solid structure – mathematical. The Entire Surface is made up of 20 equilateral triangles.

      5. Bruce Thompson MD says:

        ON HERD IMMUNITY, the next catchphrase on the horizon!!!
        How long will his pandemic last depends on the time it takes to achieve “herd immunity” or “social immunity.” This occurs when a virus hits a population but is destroyed by the immune system of the protected members whom it is likely to encounter first. It’s like a pinball bouncing around and hitting immune members then drops out before encountering a non-protected member. Estimates are around 90% plus immunity of the herd before this effect reaches maturity. Herd immunity can occur naturally and through vaccinations. Question: How is social distancing going to affect this process? Will this herd immunity happen in time to prevent the resurgence of a second wave as in 1918? Any ideas?

      6. Eva says:

        using angiotensin II receptor agonist may cause excessive accumulation of the ACE-2 and sometimes excessive production of a protein doesn’t allow for proper folding and distortion of its receptor structure, which may preclude viral binding. Just thinking of why Angiotensin II receptor agonist might have lead to improvement in outcomes.
        Testing for excessive cytokine storm at the same time could help in blocking excessive immune activation in cases where accummulation of ACE-2 induces immune activation especially in HLA susceptible populations.

      7. Bernardo Fuentealba says:

        I think… it is necessary to separate the function of ACE2 into two stages: 1. BEFORE INFECTION (which is favored with high levels of ACE2)
        2. INFECTED with SARS.CoV-2 where it would contribute to counteract the inflammatory process.
        Ibuprofen increase too the ACE2 level:
        GW25-e4430
        Ibuprofen Attenuates Cardiac Fibrosis via Restoring the Imbalance of ACE and
        ACE2 in Diabetic Rat
        Qiao Weili1, Wang Cheng2, Zhang Fan1, Liu Yaowu1, Yan Changdong1, Sun Hong1,
        Yin Xiaoxing1 1Xuzhou Medical College, 2the Affiliated Hospital of Xuzhou Medical College
        Conclusions: The results suggested that treatment with ibuprofen could ameliorate the
        cardiac fibrosis in diabetic rats. The anti-fibrotic effects of ibuprofen were realized by
        reduction of ACE/AngII/AT1-R axis and enhancement of ACE2/Ang (1-7) /Mas-R
        axis, leading to the decrease of TGF-b1 and mTOR expression.

      8. Bruce Thompson MD says:

        Patients with endothelial dysfunction and associated diseases such as hypertension, CAD, HF, PVD, DM, and CRF are likely at the highest risk for COVID disease severity in addition to immunodeficiencies. Microalbuminuria is an early marker of endothelial dysfunction and could potentially detect patients at the highest risk for disease progression to ARDS.

        Apparently, the SARS-coV damages the ACE2 receptors by endocytosis. This attenuates some of the counter-regulatory effects of ACE2 by Ang 1-7 expression. The unopposed effects of A-II make persons with pre-existing endothelial dysfunction more vulnerable. If A-II also stimulates the expression of Ang 1-7, then ARBs may also have a protective effect by competitive inhibition of the A-II receptor.

    2. Ken says:

      After the 10 amino acids are cut off to become proangiotensin, what happens to the other 400+?

    3. Paula A. C. Andrade says:

      Did anyone found anything on Coronavirus infections on patients with Sarcoidosis? Since one aspect of Sarcoidosis disease is the increased production of ACE it would be interesting to know the outcomes in this particular host (would the disease work as a protect factor or would it make it a more severe viral infection? )

      An add:
      It’s interesting to note that ground-glass opacities it’s also found on the pulmonary impacts of sarcoidosis.

      1. Marc Z says:

        Paula, I was thinking the exact same thing and began researching this the moment it crossed my mind. Google led me to your comment. My thoughts would be that an increase in ACE would reduce sensitivity and downregulate the receptors for it, thereby reducing the amount of possible entry points and hopefully reducing severity. Not really sure how or if it would work but I’d be more than interested in finding out

        1. Angela Fleming says:

          I am not a medical student or scientist or Dr. I’m looking for info.
          I had a dissecting thoracic aortic aneurysm in 2017. I lived through emergency surgery. I’m on losartin and beta blocker and amlodipine. I’m terrified in these times. Is losartin a good thing right now? Am I more at risk?

          1. Derek Lowe says:

            It actually looks like losartan, the other ARBs, and the ACE inhibitors as well all have a *protective* effect for people who come down with the coronavirus. You shouldn’t worry!

    4. George Pierson, Md,PhD says:

      There is an angiotensin 2 antagonist C21. Do you know if it has been investigated?

      1. Christian Kle says:

        C21 is an AT2 agonist. It would be really interesting to see its effects on Covid-19 patients.
        Apparently they are planning a study after some preclinical studies. Plans revealed yesterday:
        https://news.cision.com/vicore-pharma-holding-ab/r/vicore-pharma-submits-letter-of-intent-for-a-clinical-trial-application-for-a-phase-ii-study-in-pati,c3077316
        Unfortunately we’ll have to wait, as the study hasn’t even started yet.

        1. Barry says:

          but it’s not clear that agonism at the ACE2 active site is relevant to Coronavirus binding

    5. Chandra Gupta says:

      When Does the Liver Secrete Angiotensinogen ? Under what conditions ?

    6. I am taking losartan which is an angiotensin receptor blocker. I read that there is a clinical trial in Minnesota about this drug for improving CONV patient health condition.

    7. Benjamin Fox says:

      Can someone please extend your research to maritime pine bark, Pycnogenol as a possible solution to block binding to the cell in question thus hindering the lung cell type 2 access, so replication process is avoided, in security of networks we use two step authentication protocols, so I believe blocking this group of virus, can possibly be handled the same way, and over a hot cup of TEA

      1. Jan says:

        So are you thinking Maritime Bark can help prevent Covid-19?

    8. Bruce Thompson Md says:

      “Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs. Moreover, there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans. Indeed, animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects. In summary, based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection.”

    9. Kathy Cradler says:

      Can anyone please tell me if blood group A negative rh factor has ace 2 receptors? Does not having the antigen D help out in perhaps not getting Sars-Cov2?

  2. MTK says:

    For some more detail especially with respect to the question “Should I continue to use my sartan or pril?” see this link.

    http://www.nephjc.com/news/covidace2

    1. Macclesfield says:

      Thanks Derek and MTK for the summary and links…much appreciated!

    2. Chris Phoenix says:

      Read that with a grain of salt. Among many other observations, they say, “Patients who survived SARS-CoV have altered lipid metabolism even 12 years later and thus may have worse long-term outcomes including cardiovascular disease.”

      But the paper they got this from linked the metabolic effects to high-dose treatment with methylprednisolone – not to SARS infection itself.

      Multiple typos are another clue that this page was written in a hurry – as is appropriate – but don’t assume the links say what the page claims they say.

  3. cynical1 says:

    Thanks for the write up. I saw a decent write up on some of this which wasn’t behind a paywall: Return of the Coronavirus: 2019-nCoV, Viruses 2020, 12, 135; doi:10.3390/v12020135 and references contained therein.

    And they do know where the SARS virus binds to ACE-2 and given the homology with Covid-19 they are guessing binding at the same place. If it is the active site, seriously how hard would it be to do a high throughput screen for an enzyme inhibitor. Even it is not the active site, it’s not like we don’t have technology to look at fragments of the Spike proteins that bind and set up screens to see if a small molecule can interfere with that binding. And from what I saw, it also appears as if they can grow up these coronaviruses in Vero cells which seems like a relatively easy way to measure direct antiviral effects. And unlike HIV, you may not need a nM antiviral effect to keep people from dying. Perhaps if all the large Pharma companies with millions of compounds in their collection hadn’t shuttered their antiviral groups years ago they might be working on something like this instead of everybody waiting around for a vaccine. It’s up to you Gilead!

    Your last part about whether a sartan or ace inhibitor would be a good thing or a bad thing is disturbing and one that I’d rather like to know sooner rather than later since I take a sartan everyday and live in the state with the most cases in the US. The other comorbidity is age which sort of goes hand in hand with hypertension. It also doesn’t seem like it would take very long to answer this question of whether severity was correlated with use of sartans or ace inhibitors. Check with the hospitals and see what drugs these people are taking. Call Italy, they would know. But that would imply that our federal government could get their sh*t together and do something and that’s not likely to happen any time soon. Maybe I’ll call Governor Cuomo. At least he’s not as dumb as the clowns in the federal government.

    1. Keith Jantz, MD says:

      Like you I am on a sartan but also over 70 and infected. After 4 days of rhinorhea, fever, and cough, I took myself off the sartan and switched to a calcium channel blocker. Became asymptomatic in 24 hours. Anecdotal? Yes, but wasn’t waiting for the FDA to save me. We must think outside the box for solutions in times like these.

      1. Dr.Ravikumar says:

        Thanks (ace2 blockers but pt go to hypertension)

      2. Joseph Taylor says:

        Do you think the ACE2 downregulated in that short period of time? Which ARB were you taking

        1. Michael Segal says:

          The Gurwitz paper “Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics” hyperlinked in the text notes that “The AT1R antagonists losartan and olmesartan, commonly applied for reducing blood pressure in hypertensive patients, were shown to increase cardiac ACE2 expression about three-fold following chronic treatment (28 days)”.

          I would not be surprised if the effect is a lot faster, but hours seems faster than expected.

      3. Kathleen Mazanec says:

        My husband is in his second or third week of having the COViD 19 with severe spikes and fevers chills shaking. We have been advised to use Tylenol and discontinue ibuprofen. He is taking the max of 4000 mg of liquid Tylenol daily. We have had the EMTs to the house twice but he is not in respiratory distress. He is currently taking Micardis. Spoke to our internist and my husband’s cardiologist and while they are not sure if there is a direct connection with adverse reactions in taking an ARB and Covid19 we are switching my husband to a calcium channel blocker today. My concern is that is that mocardos helping protect him from respiratory problems and should we just be waiting this out! So confused about what to do for him. Could anyone weigh in? Also he is 65 and is on cholesterol medicine as well.

        1. Julia Pam says:

          Hi, Hope all is well. How is your husband doing now? Hope he is better. Stay strong!

        2. Denise says:

          Hoping your husband is better! Was there improvement after him getting off his heart medication?

        3. David Cruz, ND says:

          Hope your husband is better.
          Apart from the changes your husband has made in changing his meds.
          Some studies have shown that Vit D is important for Renin-Angiotensin system regulation (hormonal pathway for blood pressure regulation). Resulting in less Renin and downregulation of Ace receptors. So it would be at least good to take a multivitamin that has Daily requirements of Vit D3. And now more than ever that we don’t go outside and take some sun.
          Good Luck

      4. jimmy says:

        Hello Dr. Jantz, would appreciate finding out how you are doing and how things turn out. I take Losartan every day and wondering whether I should discontinue that in the case I also come down with Covid-19.

        1. David Cruz, ND says:

          Hi,
          There is still not enough evidence to say for certain but using my logic.
          Losartan is and Angiotensin II inhibitor. When you block something in your body, your body tends to think its not producing enough so it tries to up-regulate is production. AKA. Make more angiotensin II. One of things needed to make more angiotensin II would be to make more ACE2 receptors. And with more ACE2 receptors there could be more “room” for Coronavirus to enter the body.
          If it was me, just to be safe I would try to find other ways to regulate blood pressure.

      5. Mildred says:

        Just wondering. Would we see the same effect if someone was on the more natural ‘anti-ACE peptides’ as opposed to the conventional pril or sartan? Would it make any difference?

      6. Ragune Neeb, MD says:

        Yep, same happened to me (over 60). I take 8mg Candesartan only occasionaly, but every time, I took it, I felt the next day, some flu symptoms were back (4-5 times). It says in the side-effects 1-10 patients have flu-like symptoms. I never understood, why. But since now we are Corona-aware, this side-effect seems relevant to be.

      7. Scott Groehler says:

        I’m glad your doing better. Because of your post I asked my Physician to change my ARB to a CCB. I have the luxury of time to transition to a CCB. Because of the upregulation of AT-2 receptors, I devised a tapering schedule, to avoid any spike in my BP. It’s been difficult to find any information on the time it takes to down regulate these receptors and any data on how fast that happens.

    2. Susan Nasus says:

      This is in reply to Dr. Keith Jantz on March 22, 2020.
      see his post below as reference.
      I am a 72yr old female, healthy lifestyle, runner, mostly raw greens and salmon diet but, I have a mitral valve prolapse which requires antibiotic premedication. A few moments of the chills and momentary sharp little chest pains, maybe a tiny cold sweat and some tiredness are my alarm that something is passing through my system. I stop running or skiing or whatever I’m doing and wait them out. then proceed to grab 2 motrin, and 2-4 500mg from my stash of Amoxicillin and hold off on anything too strenuous for a day or two. I too, cannot wait for FDA or Dr. F. to collect their checks from pharma. I need what works and should be over the counter, which could be the very successful quinine combinations that have been used for many years, many of which include both alkaloids to avoid palpitations. These drugs exist and refusing to use them and letting people die while Dr. F and FDA fat cats, who I’m sure have stashes of prophylactic HChloroquine, is criminal. Those drugs are essential global health medications, are over the counter in most countries and have been used and studied for well over a 100yrs as prophylactics for the military, missionaries and travelers around the world. Those of you who put people first, not personal profit, are in a position to go public with this in a big way. Collectively let the president know the efficacy and speed with which these known cures work. I believe he will stop the obfuscation of those at the NIH, FDA and other profit motivated bureaucrats. I had force my doctor to give me Hydroychloroquine, Z-pack, and now Tamaflu to keep in case I come down with that virus. I, like Dr. Jantz, can’t wait around for these brittle, corrupt officials to save my life. Please use your influence to give a voice to those who needlessly lose loved ones or suffer from ravages of this virus. Thank you. Susan

      Keith Jantz, MD says:
      22 March, 2020 at 8:01 am
      Like you I am on a sartan but also over 70 and infected. After 4 days of rhinorhea, fever, and cough, I took myself off the sartan and switched to a calcium channel blocker. Became asymptomatic in 24 hours. Anecdotal? Yes, but wasn’t waiting for the FDA to save me. We must think outside the box for solutions in times like these.

      1. Yuki Hadeishi says:

        I appreciate your general approach. If I were you, though, I’d be careful proceeding treating yourself without medical advice. As you probably know, there is at least one report of an American who died self-medicating with hydroquinolone (can’t remember with or without Z pack) to treat what he thought was coronavirus (don’t know whether it, in fact, was). Wish I could find the news report for you. Stay healthy!

    3. Lori Armstrong says:

      I would just like a straight answer, is there ANY evidence that taking an Ace or ARB puts you at a higher risk for death if you contract Covid-19? Simple question so please answer in layman’s terms as I am not a biologist.

      1. HFM says:

        Straight answer: with the data we have, we could barely prove that water is wet.

        There is evidence that, if you have existing metabolic syndrome (particularly hypertension and / or Type II diabetes), you REALLY do not want this virus. Which makes sense. It’s taking a system that’s already breaking down and shoving it even harder in that direction.

        It’s also true that people with metabolic syndrome are often taking drugs of the class that we’re talking about. One interpretation: these drugs are dangerous, because people taking them die of COVID-19 more often. Another interpretation: these drugs are actually helpful, as they block the pathological changes caused by both metabolic syndrome and COVID-19. They aren’t doing enough to get an otherwise older and less robust person back to the death rate of a healthy 20-year-old, but the situation would be even worse without those drugs.

        I am a computational biologist whose first job was working on SARS. I believe that the second option is true. If I found myself in a hospital with a nasty case of COVID-19, I’d be using my last self-powered breaths to try to convince them to slip me some losartan. That said, let’s be very clear – this is speculation. We’re about a half-step above reading the tea leaves right now. We simply don’t know.

        The current advice is to refrain from changing your blood pressure treatment if you’re stable and wouldn’t have fiddled with it otherwise. That’s probably the only sensible position to take right now. Watch this one, though; the science is moving fast.

        1. Joe says:

          Thanks for the above opinion. My question is would Enalapril (which I am on) make matters worse or better in your opinion? Everyone is talking about Losartan. Not the other ACE inhibitors.

          1. Derek Lowe says:

            No, there is no evidence that the ACE inhibitors make things worse. The “sartans” are another class of drugs targeting the angiotensin system, and there’s as yet no evidence that they make things worse, either.

  4. Urukai says:

    Hi Derek,

    long time fan. I have dedicated some time to this topic. 2 notes:

    – Take a look at MLN-4760 as an inhibitor of ACE2.
    – Take a look at this paper that seems to indicate that Ibuprofen increases ACE2 in rats and could be one of the reasons why ibuprofen is contraindicated in COVID-19

    Thanks

    1. Zinc says:

      Do we know that “ibuprofen is contraindicated in Covid-19” based on correlative data, or because someone concluded an ACE2 increase is bad and ibuprofen is known to increase it? There’s some controversy as to whether an increase of ACE2 is a bad thing with Covid-19, as it also has protective effects and it may be the lack of ACE2 for the protective effect is a bigger danger than the baseline growth of the virus. There are studies designed to determine which is the case, but they haven’t gotten to the point where it’s known if ACE2 produces good or bad results in Covid-19 infections and whether the answer to that would apply to all patients or just certain ones.

      1. MonkeyFactor says:

        No there is no evidence for that.

        Ibuprofene has some side effects like all drugs but not linked to ACE2 or COVID-19.

        It was an “uneducated” guess, WHO has alsp retracted their warning now due to lack of scientific rational and evidence.

        Such bombastic claims that leak into MSM only help scare people/patients already scared and confused.

        1. Joe says:

          Could it simply be that it was an antipyretic? A fever speeds up the immune response. Sort of surprised they didn’t list Tylenol as well.

    2. John Lee says:

      Great points and interesting take on inhibition vs activation of ACE2. The old Millennium compound MLN-4760 is an ACE2 inhibitor but as I recall there were some concerns over renal and cardiovascular issues associated with its use. Effectiveness, Risk-Benefit Dose and Length of Treatment / Exposure … all come to mind but nonetheless it was a highly effective ACE2 inhibitor.

      1. Anon says:

        MLN-4760 recently resurfaced in an Alzheimer’s study, link in my handle, and probably not in a way that improves the likelihood of it being a viable option for treatment unfortunately.

  5. Urukai says:

    Here is the paper with Ibuprofen and ACE2:

    https://www.karger.com/?DOI=10.1159/000375362

  6. Crni says:

    Any reason Tolicizumab would be effective?

    Link to article in my handle

    1. John Wayne says:

      It could make sense, especially if the deaths are related to a cytokine storm. Clinical data trumps what everybody thinks.

  7. Andre Brandli says:

    Derek, these two news reports of a human monoclonal antibody known as 47D11 that was found to bind to SARS-CoV-2 and SARS-CoV and potently inhibit the virus’ infection of Vero cells, might be of further interest in the context of today’s blog post:

    First Report of Human Monoclonal Antibody That Blocks SARS-CoV-2

    https://www.technologynetworks.com/biopharma/news/first-report-of-human-monoclonal-antibody-that-blocks-sars-cov-2-332110?utm_campaign=NEWSLETTER_TN_Breaking%20Science%20News&utm_source=hs_email&utm_medium=email&utm_content=84836003&_hsenc=p2ANqtz–L_EdmhwTX2e6_W_5US47pcdHtXk2Sra_vTLOIoXJc77_VJYFNPhF_IKzNRKSItm6QsM0KpHjO6Bm43RZ8wBG-6MP1GQ&_hsmi=84836003

    Unique discovery in Erasmus MC: antibody against corona

    A world premiere from Erasmus MC and Utrecht University: they found an antibody against COVID-19. The scientific publication of the group of ten scientists is ready for assessment by the leading journal Nature.

    https://www.erasmusmagazine.nl/en/2020/03/14/unique-discovery-in-erasmus-mc-antibody-against-corona/

    Reference:
    Wang et al. (2020). A human monoclonal antibody blocking SARS-CoV-2 infection. bioRxiv. https://doi.org/10.1101/2020.03.11.987958

  8. CharlieMock says:

    How about looking into Bovine Colostrum for it’s effects on Ace2 Inhibition in Humans?

    Cured me of Clostridium Difficile whereas three rounds of Vancomyacin and Dificid failed. Believe it to have strong respiratory immune components as well.

    No vested interest, just a layman trying to help.

    https://www.frontiersin.org/articles/10.3389/fnut.2018.00052/full

    https://scialert.net/abstract/?doi=jpt.2014.37.45

    https://link.springer.com/article/10.1007/s13594-013-0154-1

    https://www.researchgate.net/publication/334742929_Colostrum-derived_bioactive_peptides_obtained_by_fermentation_with_kefir_grains_enriched_with_selected_yeasts

    1. Simon Auclair the Great and Terrible says:

      Colustrum is full of secretory immunoglobulin iga

  9. CHA says:

    Is this related in some news that recommend to take paracetamol instead of ibuprofen?

    1. loupgarous says:

      That’s a different issue and pertains to enhanced risk of complications during or after pneumonia.

      “Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients”,
      Guillaume Voiriot et al is a review of the medical literature discussing rish of complication/lung damage with or without prior exposure to various NSAIDS
      . It doesn’t address Covid-10 directly, but since pneumonia appears during Covid-19 in the elderly and is associated with increased death rates, it’s probably worth reading.

      1. Chris Phoenix says:

        The Lancet article states, “ACE2 can also be increased by thiazolidinediones and ibuprofen.”

        1. Milos Svircev says:

          Yes, but they do it in offhand manner and without any references.

      2. Paul says:

        There are several issues here that are getting mixed up I think. It would be useful if someone with more knowledge of the area could provide some wider context:
        All NSAIDs seem to interfere with the immune system, at least in vitro (Bancos et al 2009, PMID: 19345936)
        All NSAIDs seem to increase the risk of epyema (eg Voiriot et al 2019 PMID: 31163625)
        Increased ACE2 might be a risk factor in getting SARS-CoV2. It looks like a good working hypothesis but we need better studies. Evidence for the thiazolidinediones doing this looks fairly strong with several studies. However, the evidence that Ibuprofen may increase ACE2 looks much weaker (I can only find this slightly tangential evidence: Qiao et al 2015, PMID 25896805). Does anyone know of stronger evidence for this? Have any studies been done on other NSAIDs?
        There seem to be a lot of false rumours doing the rounds on this (eg https://www.bbc.com/news/51929628) but is the rush to use paracetemol instead of ibuprofen backed up by hard data rather than supposition and hypothesis?

        1. MonkeyFactor says:

          Good thesis how? Basically every cardiology association around the world has debunked as thesis without any evidence. They have not bothered to read articles about SARS, MERS, flu and so on.
          No reference to current or previous epidemics. The mention ACE2 in rat testis for some reason. There is quite a few (thousands) publications from about 2000-2020. The whole RAS system is interlinked and very complicated with many feed back loops and influence on immuneresponse. It seems the speculation happend just because on of at least one receptors have the name ACE, and that it would make sense to attack the “ACE2” receptor and implicate it as a pathogenic. While the spikes on the virus acts like “velcro” and has strong affinity for ACE2, but ACE2 is not the problem, it can perhaps be part of the solution.

          Another potential harm with is that og stop ACE inhbitor or ARB/sartan (you risk higher blood pressure (and in worst case stroke/heart attack, esp people with heart failure) and switch to a calcium channel blocker it can be more difficult to get treatment as hydroxycholorquine seems to be doing best so far (19.3.2020). And together calcium channel blockers and hydroxycholorquine you can slow down the electric impulse in your heart to much as both slows down the electric impulse that control our vital heart beats.

          1. DDunne says:

            As a layperson, just curious – could one switch to a beta blocker instead of ACE or calcium channel drug? Or are they not really in the same “league” for lowering blood pressure?

          2. loupgarous says:

            @DDunne: Talk to your doctor before changing meds. None of us here are going to accept responsibility for horrible outcomes based on anything we say. And for God’s sake don’t eat anything sold to clean aquariums.

            That said, beta-blockers’ mechanism of action is not connected to the renin-angiotensin system. They’re not front-line therapy for high blood pressure because the newer medications work better and don’t have the long list of contraindications (reasons not to take beta blockers) and adverse side effects that beta-blockers do.

            Your doctor’s read your chart and knows which drugs work best for yoi. Your doctor is also better-informed than any of us about other drugs you’re taking that might interact badly with beta-blockers. Some drugs talked about for Covid-19 might affect the heart in ways that beta blockers might make worse. Again, your doctor knows best if you shouldn’t have beta-blockers. Ask your doctor before changing your meds. Good luck and God bless.

  10. loupgarous says:

    Thanks for clearing up the confusion (to the extent that’s possible), Derek!
    This guide summarizes several medical professional groups’ take on whether or not to discontinue/modify antihypertensive therapy while at risk of contracting Covid-19.

    1. Chris Phoenix says:

      See my comment above – that page seems to make at least one misinterpretation of a paper they reference – it asserts that lipid metabolism is altered following SARS, but the paper’s authors clearly think it was methylprednisolone that caused it.

  11. Cook says:

    It’s simply a matter for research funding….I know plenty of guys that could make ACE2 inhibitors quicklike but live in a lab somewhere hoping for the day when then get funding. The crisis just shows that pharma is dumb.

    1. Charles H. says:

      But after you make them you still need to show both that they are effective, and also that the cure isn’t worse than the disease. There are reasons it’s not a quick process.

  12. Bill says:

    Excellent writeup, Mr. Lowe; I loved how it tied in pharmacology with all of the fuss regarding the SARS-CoV-2.

    Just one point of curiosity…what is your opinion on the potential anti-viral properties of NSAIDs? There was one animal study from 2006 that seemed to suggest that indomethacin may lower titres of the SARS-CoV and some even say that naproxen might be useful for the 2019 CoV.

    Any idea what the mechanisms might be or if there is any substance to this notion at all?

    Link to study here: https://www.ncbi.nlm.nih.gov/pubmed/17302372

    As a health care professional, I appreciate your efforts at keeping us informed!

  13. Paul says:

    Isn’t TMPRSS2 a better target than ACE2 for drug therapy in SARS-Cov-2? Any news on trials with the inhibitor camostat? Is anybody running virtual screens of existing drugs against such targets?
    On a related topic there is increasing evidence that chloroquine might be effective and Sanofi are apparently making 300k doses of hydroxychloroquine available for treatment of patients. Any ideas on mechanism of its antiviral activity against Covid-19?

    1. Yuki Hadeishi says:

      I would venture the mechanism of action of chloroquine and hydrochloroquine in COVID-19 are as zinc ionophores. Not sure how Zn acts but could modulate immune response somehow— I’m not an immunologist. Sorry I could not be more helpful…

      1. Snyr says:

        Zinc metalloproteases?

  14. Simon Auclair the Great and Terrible says:

    https://asiatimes.com/2020/03/australia-lab-to-human-test-reputed-covid-19-cure/j

    The remdesivir mechanism is likely clear but the chloroquine as above

    1. loupgarous says:

      “https://asiatimes.com/2020/03/australia-lab-to-human-test-reputed-covid-19-cure/j
      The remdesivir mechanism is likely clear but the chloroquine as above”

      All I’m seeing is a bitmap of a nice lady with a dot on her forehead.

      1. Simon Auclair the Great and Terrible says:

        Sorry! Posted it again.

  15. David Ye says:

    Has anyone thought of blocking transmembrane ACE 2 to reduce virus binding area while flooding the system with free floating PEGylated ACE 2 enzyme, which would do the job of inhibited embedded ACE 2 while also inactivating viral spikes?

    1. George says:

      How do you make Pegylated ACE2? On what site do you attach PEG and what MW of the PEG chain do you use?

  16. cb says:

    Why is the death rate in Germany (85M people) so low. Today March 18th reported cases 11302 and 27 death. Compare a neighbor: Netherlands (17M people) reported 2051 and 58 death. Other hypertension drugs in Germany…..other…..??

    1. steve says:

      I think the answer to your question is Pilsner. There is a clear dose-response in terms of protective effects.

    2. Barry says:

      The reported mortality rate is sensitive to the efficiency of diagnosing mild or asymptomatic infections. In the U.S., the rate looks very high because we have missed most of them. In countries where testing is more thorough, the denominator is bigger and the ratio is smaller.

      1. cb says:

        My question is directed to the clear endpoint: death. Concerning the population size of Germany (85M death 27) and the fact that the virus is spreading there for at least a month the number of death is remarkably low relative to neighboring countries with open borders such as the Netherlands (17M death 58). Relative to the population size this is about 10-fold more death in the Netherlands, whereas the infection started somewhat later. I feel there is a hidden factor in Germany which is worthwhile to identify……one of the suggestions regarding Pilsner is a nice one, but Heineken beer from the Netherlands should work similarly.

    3. Erica Hyatt says:

      I believe one major difference may be that Germany is testing a much higher proportion of the population and thus also counting people with mild illness and asymptomatic people. In the Netherlands we can perform 2000 tests per day and by next week will be increasing the capacity by an additional 1200 tests.

      Germany has been testing a much larger proportion of the population- and early on- which has helped them contain the spread of the disease.

      Also most of the German cases were younger folks who were infected on ski holidays. They tend to get less sick, recover more quickly and pass the virus to others of the same age.

      As the virus spreads to people over the age of 60, I think we’ll see the death rate increase.

      1. Again, I believe the poster’s question had to do with the low death number, given Germany’s population, since SARS-CoV-2 has been circulating for now a month-and-a-half, at least, not so much the death rate per se, which is clearly affected by the aggressive testing in place. In a news article I read recently, it mentioned testing, but also the “Coronavirus taxis” or some such that directly transported those who are symptomatic to the many, many ICU’s they have– so many they are providing care for COVID-19 patients from other nearby European countries, such as Italy. They were prepared, tested, tested, tested, and had a coherent, rational, and society-wide response.

  17. Michael Ginsberg, M.D., M.S. says:

    Hi, Derek! I’ve been reading your blog since I was a freshman taking Organic Chemistry in college. Today, 24(!) years after I discovered your blog on Corante, I’m a physician and a former molecular virologist with a graduate degree in molecular biology, so you can imagine that I am watching all of this unfold in that mood of horrified fascination so familiar to my profession.

    As time goes on, I’m convinced that the hypertension/diabetes link first described is actually a marker for the metabolic syndrome. The Chinese doctors described hypertension, and cardiovascular diseases as risk factors. Italian intensivists described the same, but added OBESITY as the most common comorbidity that they were seeing in critical patients. They also described severe glycemic alterations in critically ill patients. As the metabolic syndrome is a pro-inflammatory state, it stands to reason that THIS is the link to increased risk of a cytokine storm. I am going to guess that our Chinese colleagues did not mention obesity because obesity is so much less common in China.

    The trouble with the “increased ACE2” hypothesis is that it presumed that surface ACE2 concentration is THE rate-limiting factor in the infection. Viral infections and the immune response are way more complex that such a simplistic model. Indeed, coronaviruses (including this one) can induce cells to fuse (syncytia), allowing viral components to pass directly from one cell to the next, completely bypassing any surface receptor.

    There will, of course, in any large-scale epidemic, be fit young people who get very sick and even die. You will hear a lot about them because it’s tragic and scary when that happens. But a risk factor is merely a probability.

    Moreover, most physicians suspect that disease severity may also correlate with the size of the initial viral innoculum. If you get infected by a few hundred virus particles, the infection ramps up slowly and your immune system can get ahead of it. If you get infected by 10^9 particles, the infection will get ahead of the immune system and involve a larger immune response. I think that’s why only ~20-30% of infections on the cruise ships were asymptomatic, while more recent estimates put as many as 75% of infections as asymptomatic.

    1. DTX says:

      Michael – Thank you for your very lucid response. The idea that the initial viral innoculum is correlated with severity is fascinating & makes biologic sense.

    2. ScientistSailor says:

      regarding inoculum, that is an interesting hypothesis. Is there any data to support it? I’m skeptical, because I would suppose (I’m a chemist) that viral replication rates are so fast that initial inoculum would be irrelevant…

      1. The Scary Viroid says:

        Microbiologist here. There is usually a minimum effective dose of any pathogen

    3. Thomas McEntee says:

      To an aging process chemist, this is a very interesting thought…but immunology makes my head spin. Does the recent report ‘Obesity Exacerbates the Cytokine Storm Elicited by Francisella tularensis Infection of Females and Is Associated with Increased Mortality’ (Pubmed 30046592) add anything to what you are suggesting?

    4. mark vanderwater says:

      Purely based on anecdotal reports, I have gotten the impression that health care providers in the 20s-50s have higher rates of severe illness than the same age group in the general population. I wonder if this could be due to the high concentration of viruses the may be exposed to during intubation of patients and other treatment scenarios.

    5. Karin says:

      The initial viral load inoculation makes so much sense. That would explain why when the healthcare providers get it, they get very sick. They are likely getting multiple dosings in a short time frame.

    6. Layman Here says:

      So, are there any known ways to innoculate someone with a few 100s of virus particles rather than 10^9? Could this be scaled to many young healthy adults?

    7. Bias for action says:

      Very detailed and good response, I second that.

      I doubt too many of the intial patients where on too much medications so also it was not mentioned in the publication. (The WHO also do not collect information about medications in the surveillance/report form, smoking neither, CDC the same not questions about current meds that would be very useful to data mine now to see what puts people risk or may be beneficial)

      Also more relevant risk than ACEi/ARB is smoking, COPD, air pollution if you take a look at satelitte photos of Whuan before and after it looks like the air quality is similar to at least 20 cigaretts pr day (not evidence based but thick smoge)

      And smoking (and poor air quality can be suspected to do the same) is known to affect ACE2 as well as age, hypertension, meta-bolic syndrom and DM 2 (and 1?). And it seems in this hypothesis it seems like it is almost better to be untreated, and of the main authors are PhD with no training in making diagnosis and treatment recommendation and not familiar with clinical use of ARB/ACEI or history.

      1. Tying together two lines of thought. One related to viral inoculum -> if you think about how respiratory virus airborne particles successfully infect their target cells , you see that mucosal defense is not just anti body or cell mediated, but also facilitated thru the presence of a well functioning healthy mucosa. Most NSAIDs result in rapid and measurable changes to that mucosal barrier. This is most evident in the GI tract but could also be true for other.mucosa. In this model, access to ACE2 receptors could be further altered by mucosal factors. Dry cracked mucous membranes found in winter weather oropharyngeal mucosa may make infectivity even higher.

    8. Heather says:

      I’ve been reading this thread for an hour and my head is spinning! It is so interesting but so beyond me.
      I take Losartan and Metoprolol. I stopped taking amlodipine because it made my ankles swell.
      I’m very physically active ( was. Now am in the house all day every day ) but I am also overweight and 49 yrs old.
      I get pneumonia or bronchitis almost every time I catch a cold ever since I had swine flu & subsequent pneumonia10 yrs ago.
      I am so scared.
      I am hoping I already had it. I wonder if any of you think it’s possible?
      I went to Vegas Feb 8 – 10. On Feb 14 I started to get sick. I ended up with pneumonia. Zpac did nothing. It was very different than any other cold or flu I’ve ever had. I had a fever for like 7 days. I ached so bad it was like being stabbed with ice picks.
      I could not get up my stairs without being totally winded. I finally got better.
      I’m hoping so much that was it because I don’t know what to do to keep myself from dying if I get sick.

      1. Heather says:

        I put my comment in the wrong place.
        I continued to read this thread and may have alleviated some of my anxiety.
        If I did have it maybe my Losartan is why I got better.
        I forgot to say the whole thing started with diarrhea and body aches. Both of which went on longer than the pneumonia did.
        I wish I could get an antibody test.
        This thread ( the parts I can actually understand) has been fascinating, ..and terrifying.
        Thank you to every doctor, scientist, chemist, virologist, and any other with a title ending in “ist” that contributes to this discussion.
        I am so impressed by this thread and so thankful you all exist. You all are going to save the world, literally.

  18. Simon Auclair the Great and Terrible says:

    Here is Wikipedia stab @ chloroquine mechanism

    Antiviral Edit
    Chloroquine has antiviral effects,[31] which works by increasing endosomal pH required for the virus/cell fusion process[32][33]

    Chloroquine also seems to act as a zinc ionophore, thereby allowing extra cellular zinc to enter inside the cell and inhibit viral RNA dependant RNA polymerase. This could be the potential mechanism of action of chloroquine against COVID-19.[34][35]

    1. Lj says:

      Thanks for the information about zinc.

    2. Yuki Hadeishi says:

      Bingo! Sounds very likely. Should have read below before commenting above!

      1. Robert Verkerk says:

        Zn becomes defficient in case of inflammation

  19. Simon Auclair the Great and Terrible says:

    Here is the chloroquine/remdesivir link

    https://asiatimes.com/?s=Australian+covid+cure

  20. Simon Auclair the Great and Terrible says:

    Derek do you mind deleting the one wayback with the Hindu lady? Sorry about that.

    Your math captchas are insultingly easy! Give us @ least algebra:)

    1. loupgarous says:

      You say that, but when CAPTCHA asks you to supply the proof to Fermat’s theorem, you’ll see!

  21. Alicia Woodson says:

    A little bit random but myself not being a medical doctor this leads me to a question. My son and daughter both had primary aldosterone and cortisol disorder. They are both salt wasters and my daughter before being diagnosed at 3 weeks was FTT sodium 109 potassium 9.6(very sick obviously). Has there been any reports on how SARS-CoV-2 affects those on hormone replacement of this type then others who produce their own hormones(aldosterone and cortisol)?

  22. Duane says:

    This is a disease that is more severe and deadly in the aged, hypertensive, and diabetic. Two consistent findings in these three groups are decreased expression of ACE2, and increased expression of AT-1 receptors compared to the young. If young people have higher ACE2, and that was the factor allowing faster viral innoculation, then it would be worse in the young, but it is not. Aging, diabetes, hypertension, COPD are all conditions that are associated with higher levels of the AT-1 receptor, with greater age or severity related to higher levels. Tissues also react to hypoxia by upregulating AT-1 receptors, and there are more AT-1 receptors on activated lymphocytes. Note the pattern consistent with this disease. Immune competence is less of a factor in this disease as evidenced by the fact that it spares the young almost completely.

    In patients with predisposed ACE2/ACE1 imbalance, the viral attachment and internalization of ACE2 increases stimulation of the larger population of AT-1 receptors within the local tissue eliciting further edema, leading to hypoxia, increase AT-1 receptors, etc. I will be interested in the results of the Losartan study. As for me, I will continue to take my sartan feeling much better to have more ACE2 than less.

    1. Johannes Rasmussen says:

      I completely agree.
      The mechanism of ARDS in SARS 1 and 2 is likely in big part mediated by Angiotensin II action on AT1 receptor which is unregulated in the most comorbid disorders. SARS CoV2 down regulates ACE2 upon infection and thereby send Angiotensin II through the roof. (Also note in a new study from washington state that Obstructive Sleep Apnea is indeed very prevalent among the severe cases. This disorder also have upregulation of AT1. )
      Losartan will likely be beneficial in reducing severity of ARDS in Covid-19

      1. Janet Masleid says:

        Thank you for your opinion on that.

  23. charlesj says:

    There is a preprint on MedRxiv from a group in Sichuan, highlighted in a video commentary by Harlan Krumholz of Yale (see link), noting that the viral sequence is evolving, and raising the possibility that selection on the ACE2 binding site may be driving its spread:

    https://www.medpagetoday.com/infectiousdisease/covid19/85500

    From the preprint:

    “Virus genome data from France indicate that SARS-CoV-2 strains carrying
    ORF3a:c.752gGt>gTt often have a S:c.1099Gtc>Ttc mutation in their S gene, which
    interacts with ACE2 to mediate viral entry into its host cells3 , and is regarded as a
    critical factor for viral transmission and virulence4, 5 . It is not clear if this mutation
    enhances host cell entry but this information would be of great importance in
    assessing the potential for increased virulence of Group 4 SARS-CoV-2 strains
    carrying this mutation.”

  24. KK says:

    Covid-19 Receptor ACE2 is entering into the body by the response of mammalian cell Receptor ACE2.
    Can we use genetically engineered bacterial/ plant drugs to decrease the level of ACE-2 Enzyme?
    After a decreased level of ACE2 enzyme, Bacterial (Mutant), Anti SARS-Covid-2 Receptor ACE-2 can be used to stop the virulence of the virus.?

  25. SLR says:

    I know it’s a bit of a taboo subject, but I don’t understand why no one seems to have even tried increasing IGF-1 in a set of critically ill patients to see if it might improve their survival rates.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757506/#S5title

  26. Gary Smith says:

    You might like “Angiotensin and Systems Thinking – wrapping you mind around the big picture”.
    Once you realise that the ACE2 pathway is prohealing and anti-inflammatory, and that chronic inflammation is immune suppressive (yes really), then the fact that virus’s latch on and block the ACE2 pathway then this all starts to make sense.

    PMID: 23533336

  27. Susan says:

    OK… I’m reading teacher so I can read the words, but I do not understand the content because I do not have, as we in the reading world call “background knowledge.” I heard one doctor on ABC News talk about ace in inhibitors and how they may connect to the coronavirus, so I have a question…
    I take Enalapril should I stop taking it? I understand it’s an ace inhibitor.
    I appreciate your informative article, but as I said,I can’t understand it!

    1. Derek Lowe says:

      Yeah, it’s a lot to take in! But no, you should not stop taking enalapril.

    2. Edwin Harris says:

      Hi, Of course you should consult your doctor before altering any medicinal regimens, but you might point out to your physician that ACE inhibitors stimulate an increase in the expression of ACE2 receptors. These are distinct receptors, so a medication like Losartan that binds to the ACE2 molecule has no direct effect on the ACE molecule. If you are taking you medication for high blood pressure, he/she may approve switching to Losartan which may also decrease the severity of a novel Coronavirus infection since it also binds to the ACE2 receptor and Losartan would block some of this action.

    3. Ed Harris says:

      Hi Susan,
      Of course you should consult your doctor before altering any medicinal regimens, but you might point out to your physician that ACE inhibitors stimulate an increase in the expression of ACE2 receptors (bad for the current outbreak). These are distinct receptors, so a medication like Losartan that binds to the ACE2 molecule has no direct effect on the ACE molecule. If you are taking your medication for high blood pressure, he/she may approve switching to Losartan which may also decrease the severity of a novel Coronavirus infection since it binds to the ACE2 receptor and would In turn block some Coronavirus binding.

      1. none says:

        Losartan binds to the Angiotensin-II receptor, blocking binding of Angiotensin-II therefore likely leading to an increase in circulating Angiotensin-II. That is not ACE-2, that is the enzyme that chops off part of angiotensin-II.

    4. loupgarous says:

      I live just down the road from my state’s only Covid-19 fatality. I’ve been taking 10mg lisinopril/12.5 mg HCTZ for years. I’m convinced by the medical advice out there to not change a blood pressure treatment that’s worked (this one has).

      There are theories that this class of ACE inhibitor may actually give the virus which causes Covid-19 something to tatch on to beside ACE2 receptors in cell walls. It sounds just as plausible as any other theory, but more importantly, it’s a comforting thing to think while obeying doctor’s orders.

      Praying for you and your loved ones.

  28. BigPhaseMasc says:

    ACE in the hole.

    ACEhole.

    There, I said it, it’s ou there, you can stop thinking it.

  29. K says:

    So if you were on losartan for moderate high BP (140/90 unmanaged – 125/85 managed), would you wish to change to a calcium channel blocker? Mid 30s otherwise healthy.

    1. K says:

      The challenge of course is there is a boatload of stuff out there theorizing it’s both good and bad so as a non-medical person it’s hard not to be frightened of either choice.

    2. Derek Lowe says:

      I’m not the place to come to for personal medical advice, but neither the CDC and WHO are recommending that people on hypertension medication change their routines.

      1. Kandomere says:

        CDC also advice not to wear mask. But a 2003 study show that mask is 68% more effective against SARS than handwashing.

  30. Akin says:

    I came across a link regarding a link between hypertension drugs and covid19 severity. I’m not in the medical field, so a lot of this is going over my head. I’m on Valsartan. How concerned should I be? Should I stop taking it?

    1. Derek Lowe says:

      I’m not the place to come to for personal medical advice, but neither the CDC and WHO are recommending that people on hypertension medication change their routines.

  31. MJN says:

    AT-1 is on the Angiotensin II receptor, ACE (angiotensin converting enzyme) II is a co-enzyme, not the receptor. ARB’s “sartans” are a class of drugs for hypertension, a Doctor might use them if a person is on an ACE inhibitor, but develops side effects, with cough being the biggest one. ARB stands for angiotensin II receptor blocker. Semantics.

  32. Amine Marref says:

    It has been suggested recently that one of the potential ways to go forward to tackle CoViD-19 with respect to ACE2 is to inject some soluble ACE2 so that the virus gets busy with the injected ACE2 and leaves the normal ACE2 on the epethelial cells.

    In this respect, how does Ibuprofen which reportedly increase ACE2 work? Does it increase ACE2 attached to cells, or does it trigger creation of ACE2 that would float around in plasma?

  33. I wonder if the increased susceptibility to severe COVID-19 disease might have a more simplistic explanation: Those with increased numbers of ACE2 receptors in the lung bases and/or in the gut, whether due to genetic or environmental factors, are predisposed to severe disease. ACE2 expression is increased in differentiated (ciliated) cells in the lung. Those who smoke or live in polluted areas would, therefore, be at increased risk. (More receptors) Those with high-carb diets (think pasta and bread) are prone to dysbiosis which leads to increased ACE2expression in the gut, and may explain why patients who present with diarrhea and COVID-19 are more likely to have severe disease. As for the controlled hypertension-severe disease connection: Those who genetically have more ACE2 receptors in the first place respond better to ACE inhibitors. I doubt stopping their med will change the outcome for COVID-19 but might simply represent a genetic risk. Long story short: don’t smoke and lay off the empty carbs! If you responded well to an ACE inhibitor: wash your hands and work from home.

  34. Drug developer says:

    FYI, clinical trial just begun in Minnesota using losartan: https://clinicaltrials.gov/ct2/show/NCT04312009

    100 patients per arm, RDBPC, etc.

    1. Robert Verkerk says:

      ACE2 has been (or still is) a therapeutic target for hypertension treatment. There have been been (still are?) attempts to develop allosteric activators of the enzyme. I agree with you that it is doubtful that an inhibitor would prevent virus binding to ACE2. An allosteric activator causes a more pronounced modification of the spacial conformation enhancing the chance that the binding affinity of the virus-ACE2 interaction diminishes. As an additional advantage small vessel hypertension will lower.

  35. Robert Verkerk says:

    ACE2 has been (still is?) a therapeutic target for treating hypertension by developing allosteric activators. In contrast to small inhibitor molecules, actuators induce more profound changes in tertiary conformation. This hopefully reduces the affinity of the virus for ACE2. An additional advantage is reducing ANGII and small vessel hypertension.

  36. Mike C says:

    As someone not involved in the medical field, I found this video very informative.

    Coronavirus Pandemic Update 37: The ACE-2 Receptor – The Doorway to COVI…

    https://youtu.be/1vZDVbqRhyM.

    1. Jean-Marc Mienville says:

      Very good video indeed! But it left me a bit confused: the AT1 receptor that binds to ACE-2, is that just a kind of auxiliary protein (the substrate’s “binding site”?) needed for conversion?

  37. DrB.Venkata rao. says:

    In my openion it is better to use ACE inhibitors on COVID -19 patients and high risk people to reduce Mortality ,and prevention of infection by monitoring,Blood pressure because side effects of hypo tension

  38. Atrica says:

    Interesting also that zinc supplementation may affect the apo/holo ratio of ACE2.

  39. PeerT says:

    I have looked into the Germany vs. Italy paradoxon to see if there might be a possible correlation to administration of RAS drugs. Here are the DDD of ACEi and ARB pulled from http://www.agenziafarmaco.gov.it/sites/default/files/rapporto_osmed_primi_9_mesi_2011.pdf and https://link.springer.com/chapter/10.1007/978-3-662-54630-7_8 respectively. (2011 figures were avaiable for both regions).

    Italy vs Germany (mono plus combined with diuretics) DDD per 1000
    ACEi: 116,5 vs 69
    ARB: 93,4 vs. 24
    Total: 210 vs. 93
    It seems that Italy has a generally much higher DDD, partially to be explained by the difference in old age population. Especially striking is the huge difference in Sartane application of 3.9 : 1 (IT:DE). Of course no one knows if this has any relevance to mortality. So please do not take this as a suggestion to alter medication to e.g. Renin-Blockers etc.

  40. Norbert Nwankwo says:

    Viral particles are mainly proteins (amino acids in linear formation). ACE2 enzymes are also proteins. We have extensively analyzed proteins (over 1000) using digital signal processing techniques such as Resonant Recognition Method (RMM) and Informational Spectrum Method (ISM). I invented some biomedical devices including Computer-Aided Drug Resistance Calculator (US20150370964A1) using ISM. Investigating the proteins associated with the COVID-19 using ISM and appropriate Amino Acid Scales will be of help in the discovery of both anti-COVID 19 agents and vaccines. I look forward to this- Norbert Nwankwo.

  41. Sciencemagreader says:

    Two hunches to contribute to the discussion.

    “Mounting evidence indicates that vitamin D regulates the renin-angiotensin system. … These results suggested that decreased plasma 25(OH)D levels were associated with increased activity of the renin angiotensin system.”. This is why Vitamin D affects blood pressure, diabetes, and a slew of other maladies related to the renin-angiotensin system. Simply, taking Vitamin D to sufficiency (over 30ng/ml 25(OH)D serum level) has proven positive effects on human health. I believe that many of the patients who are severely affected have severe vitamin D deficiency as a co-morbidity.

    Second, the experience of children and the Coronavirus is a puzzle. Has anyone related the mild impact on the virus to children’s HIGHER renin and angiotensin II levels, which decline at around age ten?

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1627246/

  42. Sciencemagreader says:

    Two hunches to contribute to the discussion.

    “Mounting evidence indicates that vitamin D regulates the renin-angiotensin system. … These results suggested that decreased plasma 25(OH)D levels were associated with increased activity of the renin angiotensin system.”. This is why Vitamin D affects blood pressure, diabetes, and a slew of other maladies related to the renin-angiotensin system. Simply, taking Vitamin D to sufficiency (over 30ng/ml 25(OH)D serum level) has proven positive effects on human health. I believe that many of the patients who are severely affected have severe vitamin D deficiency as a co-morbidity, thus a disregulated renin angiotensin system.

    Second, the experience of children and the Coronavirus is a puzzle. Has anyone related the mild impact on the virus to children’s HIGHER renin and angiotensin II levels, which decline at around age ten?

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1627246/

    1. Leonard says:

      I agree about Vitamin D but at the same time Vitamin D also increases the expression of ACE2. But its possible that could be a good thing? Really need to get this ACE2 thing figured out.

    2. GetCarter says:

      This new study seems to imply that increased ACE2 expression gives a better outcome:

      https://www.medrxiv.org/content/10.1101/2020.03.31.20038935v1

      At least in patients with hypertension.

      Whether it increases the chance of contracting it in the first place is another matter.

  43. Sharon says:

    Layperson
    I have read and re read numerous articles and find myself very confused.
    I take 50mg of Losartan daily, should I be asking my doctor to change my meds to chlorithalidone or hydrochlorothiazide.
    Does Losartan make Coronavirus more aggressive.
    Please someone answer me in simple terms.
    Thank you and stay safe

    1. Derek Lowe says:

      No one knows. It might make for more of a problem, or it might protect you. No one knows yet. Not an MD myself, but in these circumstances it would seem prudent to stick with what’s working for you until we know more.

  44. philippe renaudin says:

    Hi,

    Can you comment this one : https://www.bmj.com/content/368/bmj.m406/rr-11

  45. Elizabeth Groninger says:

    So I’ve been doing some research on AERD (Asprin -or other NSAID, Exacerbated Respiratory Disease) and I think it is much more common than people realize. It involves a reaction to NSAIDs in the respiratory system which includes nasal polyps, loss of smell and asthma. I am wondering if it is not just coincidence that NSAIDs make corona worse in some? Someone smarter than me should investigate as I only have superficial knowledge of these things.

  46. Jean-Marc Mienville says:

    Did anyone try to inject the virus to a set of mice and the virus + angiotensin I to another set?
    https://www.sigmaaldrich.com/catalog/product/sigma/a9650?lang=en&region=US

    1. Jean-Marc Mienville says:

      Just heard that mice do not express ACE2, and there seems to be a shortage of ACE2 expressing transgenic mice (those that were used to study SRAS in 2002-2003)
      🙁

  47. AKK says:

    I hope its OK to ask this. I’ve been reading about ACE2 and found some references to certain herbs which it is claimed can upregulate ACE2 and inhibit ACE. I realise most people here are probably very skeptical of using herbs, but I just thought it worth sharing: https://tinyurl.com/v8ourgm

  48. Breda Holland says:

    When an ACE inhibitor is stopped how does ACE2 respond and in what timeframe? What is the relationship with prior dosage and duration?

  49. SKN says:

    ACE2 is not the bad guy. But downregulation may take a few weeks. People stopping on their own risk, and if you get sick now (in heart failure that can happen i a few days), this is bad time to end up in hospital.

    1. Breda Holland says:

      Thanks, SKN, I’m in my 40’s with hypertension due to life circumstances and lifestyle factors, both of which I changed months back, BP has come under control along with low dose meds and a thorough cardio check shows no damage and a perfect heart so I’m in a good situation to monitor bp as I go and have already come off.

  50. Roger Tyrelle says:

    I’m on Lisinopril and just stopped taking it. I’m still young and haven’t had any side affects from high blood pressure. yet. I will ask my doctor to switch to a calcium channel blocker. Here is another article stating that lisinopril increases ACE2 expression 4.7 fold.

    https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.104.510461

  51. Martin Tufteland says:

    Covid-19 -> decreased ace2 activity -> Increased angiotenson II -> increased AT1-receptor activation -> amplified proinflamatory response & and activation of fibroblasts -> worsening ARDS & increased mortality.
    AT1-r blocker like losartan could be a potential lifesaver in COVID-19..

    https://drive.google.com/file/d/1KzD1EsyHdNJ-X2nVGPV1TbAlO1XrLqHr/view?usp=drivesdk

    https://drive.google.com/folderview?id=1H2aubA36e3qrBBQ54huIeF2BLdm6GADb

    1. PC says:

      Right on Martin

      https://link.springer.com/article/10.1007/s11427-020-1643-8, not included in the Gurwitz article.

      Don’t care what the UoMinn studies show, my Losartan stands at the ready (along with lots of Vits C and D

      Thanks for all the pertinent articles.

  52. Amanda Jones says:

    Take a look at this article, it nicely explain why ARBs could be beneficial in COVID-19:

    https://www.karger.com/Article/FullText/507305

  53. Adrian says:

    Im not a scientist in any way shape or form, but I have read alot of the articles that have been linked here and I have a question about blood type and what antigens each type has. There was a paper published in 2008 stating that people with that were exposed to the virus during the Hong Kong hospital outbreak that had O blood type were less suseptible to contracting SARS-CoV1. Is it because that blood group lacks the antigens to interact with the virus spike? And with the recent study out of China that hasn’t been confirmed or peer reviewed, also States the same findings. Is there any correlation between blood group and likelihood to contract the virus? Forgive my ignorance on the matter but there seem to be alot of smart people on this thread and I thought I’d ask you. Thanks

    1. Allison says:

      Curious here as well

    2. Jim Glasgow says:

      I read alot as well Adrian, . Papers related to SARS from 2008 and the Blood Type O and A , and the similarities with Covid 19. wondering if any answered you. I didnt see anything but maybe I missed it?

  54. There is a difference between lisinopril and Losartan mechanism. Please discuss.

  55. Erin says:

    Hi,

    Does anyone know where I can find information on whether angiotensin receptors increase in number after giving ARBs or ACE inhibitors? Thank you

    1. Derek Lowe says:

      Angiotensin receptors are upregulated by a larger supply of angiotensin, so ACE inhibitors would be expected to have the opposite effect: less angiotensin, fewer receptors (or at least no upregulation). As for the angiotensin receptor antagonists, at least in rodents blockade of one of the AT receptors can increase the amount of the other, but the situation is complicated (https://www.ncbi.nlm.nih.gov/pubmed/14506547). Haven’t found a direct answer for humans.

  56. Rhonda orchard says:

    I am so confused by all of this..I take curcumin and am concerned about its effects on ACE2 what exactly it does and if its dangerous with covid19.
    I’m getting perplexed with everything I’m reading on
    this. ty in advance.

  57. Hello,
    Samuel F. Yanuck was on your webinar Thursday, March 25 and stated Vitamin D was immune-supporting in the protection against the corona virus. I’ve noticed in some documents and videos that it’s actually the opposite? Claiming Vitamin A and Vitamin D normally would support colds and flues yet the uniques viruses of SARS and H1N1, increase levels of the docking ACE protein 2 hence increasing the chances of the coronavirus.

    Please see this video, it may peak your interest.
    https://www.youtube.com/watch?v=AZSbaVt6TLw

  58. christine shuaibu says:

    Chemist here- Very interesting article and replies. May be too much focus has been placed on blocking or increasing ACE2 receptors. Their role is vital but it must be balanced. Rather the focus should be on preventing the Spike protein from cleaving and binding to the host cell membrane and hence preventing viral entry. Someone mentioned another mode of entry which did not utilize the ACE2 receptors. This is very important too. Also Vitamin D should not be increased it will probably give a worse outcome.

  59. Sasan says:

    Does angiotensin ii upregulate or downregulate ace2r. As you may know angiotensin ii has recently been approved as a vasopressor (giapreza), so the question is if it’s use would be beneficial or detrimental in these pts.

  60. Galina Goldshleger says:

    “Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor”
    https://doi.org/10.1016/j.bbrc.2004.05.114
    Biochemical and Biophysical Research Communications
    Volume 319, Issue 4, 9 July 2004, Pages 1216-1221

  61. Viktoria says:

    I am homozygous
    on ACE2 what
    to take or do?

  62. Lee Leatham says:

    Has anyone considered if the availability of ACE 2s could possibly be a rate limiting step in the ability of the virus to infect cells? I somehow doubt it.

  63. Ok, here is my experience which is quite recent. I’ve had plenty of opportunity for exposure in FL and I believe I just went through a case of COVID 19, but never met the requirements for a test. I read this article at the peak of my problems and now want to relate exactly what I think I have just gone through. 46 y/o male, fit, 6′ 180, former marathon runner, turned weight lifter and biker. I have a healthy diet, no medical problems except high BP. Currently on Hydrochlorothiazide(25)/Lisinopril(40). Noticed my BP was increasing over the course of the week. By Friday it was high, I had a cough and runny nose. I vomited in the morning. If I coughed deep enough, I felt every so slight lung pain. NO other symptoms ever. Blood pressure continued to rise over the weekend, lung pain faded. By the end of the weekend, I was seriously considering the ER. BP was up to 165/98 or so, with spikes higher. Called my Doc office first thing Monday in a panic. Bag packed to go to the office or ER. While the nurse was trying to get to the Doc (maybe a 2 1/2 hour period), I suddenly felt a wave of peacefulness. I can only describe it as the feeling the first day I ever took BP meds. I knew something was up. By evening, back to normal, with no lung pain if I coughed and a very shallow clearing cough remains through the day after. Again, my lung pain and coughing were present, but very, very subtle. Nausea was present for 4 hours max. No fever, chills, fatigue, anything else. It was like my body stopped absorbing my meds for a week, peaking for about 3 1/2 days. The principles outlined in the article could be the cause for this. Obviously I did not change my dosage for fear of what I have been reading. I can give very detailed specifics to those interested. This is top-level.

  64. Garrett Taravella says:

    What are your thoughts on Thyomsin Alpha?

  65. Julian TF says:

    Nebulise directly with angiotensin 1-7.

    Like SARS-CoV, SARS-CoV-2 induces shedding of ACE2’s extracellular domain during the infection process. (Side note: mass spectrometric analysis should demonstrate unusually high levels of ACE2 peptides in the urine of infected patients and could be used as a cheap diagnostic method).

    Although shed ACE2 extracellular domains still show some catalytic activity in the bloodstream (converting ang II to ang 1-9 and ang 1-7), the critical problem is that loss of function is localised to the site of infection. This skews the ang II : ang 1-7 ratio firmly in favour of ang II, creating the potential for a cytokine storm and extensive tissue damage as ACE2 cannot serve its function of preventing excessive neutrophil accumulation and promoting an optimal immune response

    Patients with pre-existing hypertension are at particularly high risk because loss of function of ACE2 will trigger system-wide vasoconstriction as ang II levels are elevated relative to ang 1-7. When sustained, this will signal up-regulation of Ace2 gene expression, feeding through to higher protein expression of ACE2. The virus triggers a feedback loop, creating more binding targets for virions and promoting broader infection.

    Nitric oxide has proven to be effective in COVID-19 patients who have progressed to requiring ventilation. Note that ACE2 activity promotes endogenous NO production, hence addition of NO is partially substituting for the loss of function of ACE2. Early intervention with ang 1-7 should have a similar vasodilatory outcome with additional benefits as it better compensates for ACE2 loss of function.

    Furthermore, sufficient addition of ang 1-7 should trigger native down-regulation of ACE2 activity as the RAAS regulates ACE : ACE2 activity. (ADAM17 has been identified as a key regulator of ACE2 shedding). Artificial compensation with ang 1-7 should then not only recover loss of function of ACE2, but also promote down regulation of Ace2 and / or lower protein expression of ACE2, thereby starving SARS-CoV-2 of binding targets and slowing the rate of infection.

    Ang 1-7 has passed phase 1 clinical trials and has been used in various phase 2 trials safely. It is an endogenous human peptide that can be synthesised and delivered in powder form then suspended for delivery via nebuliser (it can also be delivered orally or via injection).

    Is anyone trying it?

    1. Bruce Thompson MD says:

      Great idea! Loss of ACE2 counter-regulatory effects possibly mitigated by the administration of Ang 1-7. I think patients with pre-existing endothelial dysfunction are likely among the highest risk factors for this virus to do the most damage. This includes hypertension, coronary artery disease, chronic heart failure, peripheral artery disease, diabetes, and chronic renal failure. There is a reduced vasodilatory response with endothelial dysfunction. Reduced NO, oxidative excess, and reduced EDHF. Vasoactive A-II, endothelin-1, endogenous NO inhibitors (hypercholesterolemia, altered insulin signaling, hyperglycemia) are among the mechanisms involved in endothelial dysfunction. A therapeutic approach to endothelial dysfunction is to look at the components of the disease process that trigger the dysfunction. Blockade of RAS may improve endothelial function with reduce oxidative excess and inflammation. Microalbuminuria has been correlated to markers of endothelial dysfunction and readily available test. Early evaluation of microalbumin may stratify patients who deteriorate to ARDS.

      1. JulianTF says:

        Hi Bruce,

        My original response to you seems to have disappeared into the internet abyss…

        In short, a trial has now been filed (NCT04332666). It will involve injection of ang 1-7 (have to start somewhere).

        Ideally, investigation will expand to multiple modes of delivery as ACE2 protein expression* is:

        – highest in the epithelium of the lung (nebuliser delivery) and small intestine (capsule delivery)

        – high in mucosa-associated lymphatic tissue, particularly in the nasal & oral cavities (in fact, the highest density of ACE2 receptors that I’ve seen in the literature was in the oral mucosa of a smoker. Prime site for initial infection). Nasal / oral spray delivery suitable here.

        – present throughout the endothelium of the cardiovascular system (injected delivery)

        ACE2 expression tends to track inflammation, so the most effective treatment method (when delivering ang 1-7) will vary from patient to patient, according to their inflammatory condition, and will correlate strongly with pre-existing inflammatory conditions that have led to up-regulation of ACE2 (significantly CVD, diabetes and smokers).

        * note that there is a very weak correlation between Ace2 gene expression and ACE2 protein expression due to the activity of ACE2 sheddases. RNAseq studies should be taken with a grain of salt. Defer to the proteomics.

    2. Jean-Marc Mienville says:

      > Is anyone trying it?
      What about those trials you mention?
      So, down-regulating the enzyme by increasing its by-product, is that the idea? Sounds good but what about those patients with low BP? Could the substrate, ATII, also work, in this case keeping ACE-2 busy and unavailable to the virus?
      In terms of drug design, what about a covalent, high-affinity, low-efficacy ligand of ACE-2? Could that be an option to lock the door?
      (this is not at all my field of expertise, sorry if I’m goofing, just trying to understand…)

      1. JulianTF says:

        Hi Jean Marc,

        See above post responding to Bruce. A clinical trial has now been started and I hope for the best!

        > So, down-regulating the enzyme by increasing its by-product, is that the idea?
        That’s part of it, yes (and has been demonstrated in animal studies), but the primary aim is simply to compensate for loss of function of ACE2 (by providing the molecule that it usually catalyses)

        > what about those patients with low BP?
        Probably not a huge issue in this case as ACE2 loss of function leads to high blood pressure. Certainly constant BP monitoring is essential throughout treatment.

        > Could the substrate, ATII, also work, in this case keeping ACE-2 busy and unavailable to the virus?
        A variation on this is to “keep the virus busy” by injecting rhACE2, which also aims to counteract loss of function as TMPRSS2 activity causes ACE2 to shed from the cell surface. There is a clinical trial underway for this. Another clinical trial that has been withdrawn was to inject ACE2 fragments (the extracellular domain) in an attempt to bind virions.

        > In terms of drug design, what about a covalent, high-affinity, low-efficacy ligand of ACE-2?
        If you mean a ligand that looks like ACE2’s binding domain and binds the viral S1 domain, hence blocking it, then yes, that’s a great idea! If you mean a ligand that gums up ACE2, then that’s not such a great idea (unless also simultaenously dosing with ang 1-7 to counteract the loss of function of ACE2 caused by the ligand).

        > (this is not at all my field of expertise, sorry if I’m goofing, just trying to understand…)
        We need all the brains we can get on this! Don’t apologise!

        Regards, Julian

        1. Jean-Marc Mienville says:

          Thanks a lot Julian for your response!
          I do not understand why the trial with ACE2 fragments was abandoned. I understand the rhACE2 option to compensate for the loss of function, but there are many other vasodilators! And perhaps the fragments could be designed to covalently bind the virus (I insist on this “covalent” aspect for the sake of efficacy and low dosage – hence low cost? – and I seem to remember from my very old Master’s in biology that the trick is to attach an inorganic group to the peptide – any chemist in here?)…
          I’ll also take advantage of your encouragement to ask again the question I posted a little further up. It’s based on the video (which I find great in terms of both contents and container: what is that sensational software? We need it here to teach our confined students!) posted by Mike C (https://youtu.be/1vZDVbqRhyM). The question(s) bear(s) on the terminology used: perhaps my (also very old) PhD in pharmacology is outdated, but I had never heard of something (ACE2) that can be both an enzyme and a receptor. OK, maybe if an enzyme sits on a cell membrane it can also be called a receptor. But it gets worse: the ligand of that receptor is also a receptor! ATR1, the receptor for angiotensin II. Is that latter receptor the same as the physiologic receptor in vessels, adrenal cortex and brain that transduces vasoconstriction, aldosterone secretion and thirst? Or, as my initial question asked, is it just a kind of auxiliary protein (bearing the substrate’s “binding site”?) needed for catalytic conversion?
          Just semantics? Just curious…

          1. Derek Lowe says:

            The terms are indeed confusing. The ACE2 protein is certainly more commonly classified as an enzyme. But as you guessed, since the virus uses it as a binding site on the membrane, it’s been called a “receptor” for the virus. As for angiotensin, the confusion is between the angiotensin peptide and the receptor that it binds to. So ATR1 (and ATR2) are classic transmembrane receptors that have angiotensin peptide as their ligand. And angiotensin peptide is also a substrate for the ACE2 enzyme. As people who aren’t into cardiovascular pharmacology (or any kind of pharmacology) write stories and news items about all this, the language gets terribly confused, which is why you have people mixing angiotensin peptide, angiotensin converting enzymes, and angiotensin receptors all together.

    3. mary says:

      Ginger reduces Angiontensin 2
      https://www.ncbi.nlm.nih.gov/pubmed/23479389

      + increases IFN B

  66. Jimmy Flodin says:

    I´m Jimmy Flodin from Sweden. I Watch some videos regarding RAAS system, very informative. I have an follow up question regarding ACE & ARB’s RAAS system. Hence ARB drugs will block the receptor ACE1, would it not also prevent COVID-19 to enter the cell? And in contradiction if you use ACE Inhibiter drugs it will leave more space for Covid-19 to enter into the cell? What is yours thought regarding my assumptions.

    1. Julian TF says:

      Hi Jimmy,

      SARS-CoV-2 binds to ACE2, not to ACE. The two enzymes ACE and ACE2 are structurally similar (the underlying genes are homologues), but their biological functions are opposite. ACE acts in a pathway that leads to vasoconstriction (higher blood pressure), ACE2 does the opposite.

      So ARBs and ACE inhibitors have been designed to interfere with the ACE pathway but specifically not the ACE2 pathway.

      Mixed messaging in the mainstream media regarding ACE inhibitors and ARBs comes from mixed data regarding whether or not medications lead to an up-regulation of ACE2. It varies from drug to drug. The idea is that if a medication leads to higher ACE2 expression, then it may worsen COVID-19 as more ACE2 receptors are available for binding.

      The official advice coming from the AHA (and I agree with it) is that patients should not taking ACE-Is or ARBs unless under specific medical advice

      https://newsroom.heart.org/news/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician

      Given that SARS-CoV-2 destroys ACE2 function leading to worsening hypertension, it would be a very bad idea to stop taking hypertension-related medication and make it worse! In fact, as many have already suggested, strategic use of ARBs and ACE-Is may be useful as a treatment against SAR2-induced hypertension.

      Regards,

      Julian

      1. JulianTF says:

        *typo above, should read: “not stop taking”.

  67. Robert says:

    I am a person with chronic Sarcoidosis 40 years with proven pulmonary fibrosis in tissue 20 years age and I had an ARB Olmetec and Olmetec Plus that kicked off the Sarcoidosis and made worse the fibrosis.

    I believe reading an autopsy report of a COVID19 patient Published in New England Journal of Medicine that COVID19 produced fibrosis in the patient.

    Be careful because reports the Angiotensin II at the exposed AT2 receptor can make worse the fibrosis in lung tissue.

    And ACEi ARB’s and CCD can all raise the Renin and Angiotensin II levels.

    This fibrosis was induced by bleomycin.

    Angiotensin II type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409315/

  68. Roberto Bartolomeu says:

    ARBs block angiotensin -2 AT1 receptors, increasing ACE-2 and up-regulating ACE-2 receptors. As Coronavírus uses ACE-2 receptors and there are more receptors, the greater the viral infestation. This dates are comproved across cientific works. If diabetics and hypertensive patients or patients with heart failure exchange the ARBs for other vasodilators, wouldn’t there be less mortality in these groups?

  69. THIYAGARAJAN says:

    As per second news paper clause to upregulate the production of ACE 2 receptors to kill or arrest the spread of Corona virus.then why the doctors preferred some other medicines instead of potassium intake, I read one more studies via Google intake of potassium to stimulate the ACE 2 production,what is the reason behind us.pls advise

  70. Heather K says:

    My question is less about the receptors and more about the virus itself.

    Covid-19 is known as a respiratory illness. It is not coming out that this virus can also showing up as a gastrointestinal virus with little or no respiratory symptoms for patients. It takes longer for patients to recover from the gastrointestinal virus (GV), than the respiratory virus (RV). GV taking an average of 44 days and RV taking an average of 31 days to show negative.
    Also, there is more research coming out showing that a person who experiences both the RV and the GV, can recover from the RV symptoms and have negative swabs from the nasal cavity, but still show active transmittable virus in a stool sample.
    The receptors primarily responsible for regulating and maintaining blood pressure are found as you stated all through the body with hot spots being places like the lungs, kidneys, and intestines. All of which respond in sync to inflammatory and anti-inflammatory properties.
    One, very very small, study done on critical patients in China showed an impressive response to a medication used for Rheumatically conditions such as Crohns and Rheumatoid Arthritis. The medication is called Actemra. There are other anti-inflammatory medications being researched in regards to response to the current Covid-19 and possible treatment as well that seem to be having significant success, even though the trials are very limited.

    Lastly, there are a significant number of “recovered” patients that are retesting positive, even for the same strand of this virus (there is the S strand and L strand). Is it possible they were never truly recovered, but the virus was hiding in plain sight, so to speak, having been present in the intestinal tract and only testing negative for the respiratory part of this virus.

    Also would learning origin of how the virus made the jump to humans pose any possible new ideas in treatment or vaccine development.
    I ask, because I have a theory that this didn’t start as a lung disease, and then move to the intestinal tract and other highly populated areas.
    What if this started as a an intestinal virus, that was passed off as a stomach “bug”, and was the milder strand of the virus, but when the virus mutated into the L strand, it became more volatile and deadly. Also, if it started as an intestinal virus, there is a very large chance that this virus has been around for significantly longer than the end of 2019. Possibly even originating in 2018 or 2017. In that event, people who came down with it as a gastrointestinal virus, may have been more susceptible to the new strand which could explain its resilience and the rate in which this virus has spread so quickly.

    1. Brian R says:

      HeatherK thanks for the informative comment. I hadn’t been aware of the GI infection, and your speculation about whether the “reaquirers” of the virus had it all along is very much of interest, given what I am learning about the limitations of the testing. GI reservoirs of the virus almost certainly wouldn’t show positive results in pharyngeal swabs.

      I have two references to bring to your attention :
      Wölfel, R., et al. (2020). “Virological assessment of hospitalized patients with COVID-2019.” Nature.
      Published in yesterday’s Nature, indicating that they could NOT reconstitute infectious virus from stool samples of 11 subjects under study in Germany. They WERE able to detect viral mRNA in stool samples, but unlike from the sputum samples they did not recover full infectious virus. I am by no means a viral or a GI specialist, and the authors state that the patients were not in the most severe category (which they were in Germany, with it’s low rates overall, I’m thinking we should all be hiking, drinking beer, and eating sausage, but then that’s probably a stereotype!). Anyway, the GI information you mentioned made me think of this paper. I had taken some solace that maybe we don’t have to worry about fecal spread when I read the paper, but now your comment makes me rethink that solace a bit, since it was just 11 patients from Germany.

      But further, to your point of whether this virus was circulating prior to 2019, as far as I am concerned one of the best serology papers I have seen (and in this I do have some expertise, and I am scouring the literature trying to figure out the best antigen(s)/epitope(s) from the virus to use for development of assays which I will probably never be able to develop since I don’t work in a laboratory with BSL3 capability), but in this one:
      Guo, L., et al. (2020). “Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19).” Clin Infect Dis. March 21
      They did screen pre-December 2019 Wuhan patients (halleluiah, nice controls!!!) and found no responsivity to the SARS-CoV2 antigen, but did find responsivity to other endemic coronaviruses (more good controls!!!). They screened decent numbers (>100) of pre-CoVid patients with respiratory concerns and found no cross-reactivity. But no mention of GI issues in these patients that I remember, so maybe they need to screen samples from a Wuhan GI cohort from 2018 to further test your hypothesis, but on first glance, no support of prior circulation.

    2. JulianTF says:

      Hi Heather,

      I like to think of this as a disease of “wherever ACE2 expression is highest”, and it’s highest (in aggregate) in the small intestine and duodenum, then the lungs. Epithelial in both cases. It’s also broadly present throughout the vascular system (endothelial).

      So yes, I also think that this is primarily a disease of the GI, that many people experience GI disturbance and clear the virus without issue (especially children). The unlucky ones are those who contract it directly in the lungs (particularly health professionals exposed to heavily loaded, airborne droplets), and for whom it spreads to the lungs from the bowels. For those with CVD or diabetes (and, rarely, neurological inflammation), it spreads further.

      SARS1 was the same. Virion counts were just as high in stool samples as they were in droplet samples (the same is true for SARS2) yet SARS and SARS2 are primarily thought of as respiratory conditions. This is likely because few people die, or even experience severe disease, from GI disturbance. We notice the respiratory, cardiovascular and neurological cases more readily. Note that, in the first wave of COVID-19 in Wuhan, more than half of patients reported first symptoms as GI disturbance. The ones showing up in ICU were the ones in which it had spread to the lungs. How many didn’t show up at all because it had not spread?

      I also share your opinion regarding testing. It is already well established that stool and sputum tests can return positive for almost six weeks after pharyngeal swabs return negative.

      https://annals.org/aim/fullarticle/2764036/sars-cov-2-positive-sputum-feces-after-conversion-pharyngeal-samples

      People are not getting re-infected. They were never clear in the first place.

      I also strongly suspect that there are many people walking around out there with the GI infection only, passing it off as a mild case of diarrhoea. They recover without issue but run the risk of infecting more vulnerable people with chronic inflammation (hence high ACE2 expression) of the lungs or circulatory system.

      Hygiene and distancing advice has been sound, but I wouldn’t mind a little more attention being paid to infection via fecal matter. Don’t use public restrooms, flush with the lid down, clean, clean, clean the hands, don’t share utensils, etc.

  71. Liz S. says:

    Hello, one topic which hasn’t discussed yet: Air pollution /fine partuculate matter 2.5 is associated with hypertension and cardiovascular diseases. At least some research evidence support, that this is driven by imbalance of ACE1/ACE2 system (upregulation of ACE1..). Could this have an impact on Covid-19, does anybody know if is has been investigated?

    1. Derek Lowe says:

      That’s a perfectly plausible hypothesis, but as far as I know it hasn’t been investigated. We’ll see if anyone else knows. . .

      1. JulianTF says:

        This was reasonably well established during SARS1 (though with a smaller pool of patients to survey).

        Particulate irritation of the lungs triggers up-regulation of ACE2 so it follows logically that the lungs of smokers and people breathing in high amounts of airborne irritants will be at higher risk of infection from SARS-CoV-2 (more binding targets). This is a key reason why male smokers are heavily over-represented in statistics from China (a wide gender difference in smoking rates). I also suspect a link between vaping-induced lung irritation (leading to higher ACE2) and COVID-19 in younger patients. Lung tissue from individuals who vape needs to be studied for ACE2 density.

        A quick grab of some relevant references:

        https://www.preprints.org/manuscript/202002.0051/v1

        https://www.ncbi.nlm.nih.gov/pubmed/29559844

        https://ehjournal.biomedcentral.com/articles/10.1186/1476-069X-2-15

  72. Edara says:

    can high calcium down regulate the ACE2 receptors. If so, can administering recurrent calcium gluconate in ARDS help fight COVID-19 patients. Can we think about administering recombinant parathyroid hormone in these patients.

  73. Sciencemagreader says:

    This is an interesting article on how COVID affects the renin angiotensin system, it basically hijacks and downregulates part of the cascade but doesn’t do so immediately. Authors note it happens after days of infection.

    https://www.futuremedicine.com/doi/10.2217/fvl.10.4

  74. My work in metabolism that has been focused on the influences of vit D on phosphate metabolism has lead to interest in the effects of ACE2 on LPS and associations with ARDS. It is possible that some of the manifestations COVID-19 are secondary to deactivation of ACE2 much as HIV acts o its target receptors. It is possible that interventions that can modulate signals downstream of a balance between the opposing effects of ACE1/ACE2 will modify the metabolic expression of SARS-CoV-2 and prevent the manifestation of ARDS. If this is possible then the catastrophic outcome of global infection is less dependent upon eliminating the virus and more on understanding the variance in its expression as COVID-19. While I do believe there are agents that could accomplish this feat that are inexpensive and easily manufactured they are not currently available and I am reluctant to add to the panic applications of unproven agents. As I see metabolism as the organization of heat, it is possible that those at risk for ARDS need ACE2 as brake on heat and when that is compromised the predisposition to ARDS becomes manifest.

    1. Ann says:

      He and his wife ingested, “Chloroquine Phosphate”
      This form is used in FISH TANKS. Article on CNN Health 3/25/2020

      1. Derek Lowe says:

        FWIW, chlorquine phosphate is also in human trials, and it is one of the standard salts of chlorquine used for human dosing.

  75. Toni says:

    Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage
    is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19
    Patients With Hypertension:

    https://www.medrxiv.org/content/10.1101/2020.03.31.20038935v1.full.pdf

  76. Ana D. Freay says:

    Do we have any feedback from patients already on hydroxyquine or any angiotensin II blocker are they protected against covid virus? How about those on pressure medications like Losartan? Why are males more susceptible for the disease?

  77. Sab. says:

    Hi, I might have some very naive questions.

    Please correct me if I got this wrong. As far as I understood:
    1) The spikes of the SARS-CoV-2 have high affinity to ACE2, i.e. uses ACE2 to enter a cell.
    2) It is suggested that this “occupation” of the virus of ACE2 might reduce the ability of Ang II to bind to ACE2.
    3a) This results in less Ang-(1-7) (and neither Ang-(1-9)) being formed, and
    3b) accumulation of Ang II.
    4) Accumulated Ang II might result in an increased activation of AT1.
    5) Activation of AT1 results in vasoconstriction (i.e. higher blood pressure), increased pro-inflammatory response (is this what results in the cytokine storm?) etc. all of which is disadvantageous for the process of the disease.

    Questions

    1) ACE2 is a converting enzyme that sits on the membrane OUTSIDE of the cell. How does the Virus manage to get its RNA INTO the cell? Is this were TMPRSS2 comes into play, and if so how is TMPRSS2 activated?

    3a) What are the functions of Ang-(1-7) and Ang-(1-9)? Ang-(1-7) seems to bind to MAS which reduces blood pressure and inflammatory response? What I don’t understand, does AT2 need to be activated for this, and how is AT2 activated?

    3b) Shouldn’t someone taking ACE-inhibitors not have a low ratio of Ang II anyways? In other words, it is suggested that ACE-inhibitors & AT1-blockers increase the level of ACE2 and this (although it initially might enhance the virus’s ability to enter cells) might be beneficial since it enables Ang II still to bind to (virus-UNoccupied) ACE2s. I.e. if it’s not good to have accumulating Ang II floating around, more ACE2 will be good to get the Ang II out of the way. However, someone on ACE-inhibitors shouldn’t have a high level of Ang II anyways, and someone on AT1-blockers should be “save” from Ang II binding to AT1 because the medication blocks the receptor. What is it about Ang II that I’m missing? Can it use other “ports” than AT1?

    Also:

    – How might AT2 and MAS be affected by the virus or an increase in Ang II (and lack of Ang-(1-7)?

    – With ACE-inhibitors & AT1-blockers potentially increasing the level of ACE2s, does this relate to only membranous ones or also extra-cellular/soluble ones? And what would extra-cellular ACE2 do to the virus?

    You can tell, I’m a very lay person, input on this is much appreciated to help me get my head around this.
    I also just recently read Plasmin would be used as entry for the cell. How does this relate to the discussion (if there are any links).

    Thanks a lot for feedback!

  78. Liz S. says:

    I found an interesting approach regarding network-based drug repurposing for coronavirus. Irbesartan seems to be an option. Someone familiar with this type of research?

    https://www.nature.com/articles/s41421-020-0153-3

  79. Cynthia says:

    I’m struggling to understand all of this. I am on Metformin for DII. Is it our medication ACE 1that helps the virus attack us more severely? Or is it Diabetes itself? Hypothetically if you were on this drug would you stop or reduce it BEFORE infection or do that AFTER infection? Are there any other drugs for DII’s to ask about temporarily? Are there any supplements or medications out there that might slow the virus from doing as much damage? I know it’s informal and nobody wants to give medical advice. But I’d like some opinions or at least be pointed to simply written articles on drugs like Metformin. Thank you in advance.

    1. Liz S. says:

      above is a link, reporting about ACE/ARB have less severe diseases (in a first report from China). They didn’t differentiate between ACE and ARBs, therefore at the moment, stay on ACE or ARBs if that is your medication. I think / hope we will have more data in the near furture to see if both medication show the same risk reduction. One important think to me is the metabolism which should be focus for the whole population. Keaping a strict mediterean diet and being activ (walking and health-sports) will very fast decrease the inflamatory pathways and thus reducing the risk of infection.

      1. Cynthia says:

        Thank you. I keep reading conflicting information.

    2. mary says:

      I don’t think metformin is the type of drug that affects ACE2. People with severe diabetes are on drugs similar to those with high blood pressure.. often spelt with a “tan ” ending e.g losatan.
      Perhaps others could comment. I am also on metformin only.

    3. mary says:

      Metformin is a different type of medication than the drugs that many diabetics are on ending with ‘tan’ e.g. losartan.
      Does any one have any comments on metformin and Covid 19 specifically?
      I have read that it is anti inflammatory and may lower IL6 so may be beneficial… even to those without diabetes.

  80. Heather Phillips says:

    I’m a 61 year old woman, taking 100mg/day Losartan for hypertension (in addition to Amlodipine). I visited London, UK on 20-23rd February, where I think I may have had significant contacts re. Coronavirus. Two close contacts developed mild symptoms in the week or so following. I have experienced very mild upper respiratory symptoms off and on since approximately 27th February, (sore throat, occasional cough, sneezing, nasal congestion etc., but no fever or persistent cough), i.e. for more than 6 weeks now. Is it possible that I may have the virus, but that the high dose Losartan is actually having a protective effect, and masking the symptoms? I would like to get an antigen test, but this is not readily available in the UK except for frontline workers. I’m also concerned that I may be a silent carrier of the virus.

    1. Liz S. says:

      even if you had been infected within the past and being asymptomatic, you would have be infectious for a couple of days an not for weeks. Face mask, social distancing and heathy lifestyle are good options to limit the risk of transmission.

      1. Heather Phillips says:

        OK, thank you for that. I have been careful to wear mask and gloves, and practice social distancing when going shopping etc. However, it has to be said that the UK government are not recommending masks for the general population. They say that there is no evidence to suggest that they are beneficial, but it’s probably because there are not enough to go round…

        1. LizS says:

          Yes, Right way with wearing a mask. I am sure we will get used to it.

  81. TK says:

    Just spitballing here IF the virus attaches via ACE-2 receptor and is already primed to infect… how about creating a prophylactic drug that is administered via nebuliser that contains the same molecular key as the ACE-2 receptor in much higher numbers than is present in the lung tissue and is not biologically active as far as the lung tissue. The purpose being if one can fool SARS-COV-2 (think that’s the name of the covid-19 corona-virus) into trying to infect the prophylactic drug molecule external to any real living cell and this may then leave that virus unable to attach to a real ACE-2 receptor on a healthy cell and since it is external to the tissue it should not alter the internal operation of the ACE-2 receptor. Of course this may all be moot and I may have misunderstood something but seems a plausible research path to reduce viral load and therefore damage in lung and mucous tissue .

  82. COLIN FORBES says:

    Hypertension and T2DM have clearly been identified as important comorbid conditions associated with most severe Pulmonary and Renal outcomes in SARS-COV-2 . But , through what possible mechanism ?
    Without benefit of specific study data , it would be safe to assume that treatment regimens for both HPT and diabetic group is likely to include an ACE inhibitor or ARB . The poorly understood ACE-2 pathway remains unaffected by ACE inhibitors . Peptide products of angiotensin 2 cleavage are likely to build up . Providing thereby , additional binding sites for Coronavirus.
    These musings being so , surely there is a public health message here that ( until a COVID-19 vaccine is developed ) , ACE Inhibitor and ARB therapy should be urgently reconsidered in these two high-risk groups .

  83. charles d weller says:

    I’m a former physics teacher and lawyer, not a biologist, but this post and discussion using scientific method suggests to me a breakthrough in thinking for solving the Covid 19 crisis. Medicine in the United States has widely adopted statistical randomized controlled trials as the gold standard, replacing fundamental concepts of scientific method. Limiting scientific thinking to RCTs is a mistake, Dr. Thomas Frieden, a former director of the Center for Disease Control, explains in an 2017 NEJM article:
    • “RCTs have substantial limitations” that “affect the use of RCTs for urgent health issues,
    • “such as infectious disease outbreaks” and
    • “Many other data sources can provide valid evidence for clinical and public health action.”
    The post explains the mechanism of the Covid 19 infection. Is it possible to evaluate hydroxychloroquine and other treatments by focusing on the mechanism of how they work to stop the virus from invading cells or otherwise using scientific theories and explanations?

  84. SK Ware says:

    ACE-Inhibitors and ARBs – Hypertension Medications with COVID-19, May 5

    https://www.youtube.com/watch?v=OudhmwulJHY

  85. Jim says:

    “So something that binds to ACE2 and interferes with that viral hijacking would probably be quite interesting.”
    Not to be Captain Obvious, but would up-regulating ACE2 to do what it was designed for do the trick? Sufficient Vitamin D down-regulates renin and up-regulates ACE2 (cleaving Ang II).
    Viola, interference with coronavirus hijacking.
    Seems straight-forward. What am I missing here?
    Thanks,

  86. E Hyuk Jeon says:

    Vitamin D Essential to Covid 19 Defense Plans Lower Serum Vitamin D linked to poor clinical outcomes
    https://www.youtube.com/watch?feature=share&v=C-2g6a9i7ss&app=desktop

    It says, “In STDIES done with other coronaviruses such as MERS and SARS, Vitamin D has been shown to run nutritional interference between the virus and ACE2 enzymes reducing adhesion properties and its ability to stick to the ACE2 enzyme.”

    Anybody would let me know the Studies (Research Papers)!

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