It may lead to positive results, but it takes a long time to confirm its effectiveness

I agree with you that ACEI/ARB's are valuable in preventing COVID 19 & also in the management of patients . This should be useful in the high risk elderly patients with hypertension & DM .

In lungs RNAs for both of the proteins used by SARS-CoV-2 mainly in cells called type II pneumocytes.

ACE2 does help in the entry of SARS-CoV-2 into human cells. And previous animal studies show that ACE inhibitors and ARBs upregulates ACE2 expression. This effect could increase risk for or severity of COVID-19. Meanwhile, some researchers hypothesize that ACE inhibitors and ARBs could benefit patients with COVID-19 through various mechanisms. E.g ACE2 converts angiotensin 2 to angiotensin 1–7, that has beneficial anti inflammatory properties, by upregulating ACE2 either ACE inhibitors or ARBs, could enhance this process.

Check out it,

"ACE Inhibitors and ARBs During the COVID-19 Pandemic Allan S. Brett et al."

Thank you Sana for your contribution.

In a retrospective study in Hubei province in China, COVID 19 patients, admitted to 9 hospitals in a multi-centre study, between December 31st and February 29th 2020. 1128 hospitalised adult patients with hypertension and diagnosed with COVID 19 were included in the study. There were 188 patients taking ACEI/ARB and 940 not taking ACEI/ARB with a median age of 64 years.

ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users (ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%; P = 0.01)).

Another factor in this discussion is that the marked increase of non-Caucasian ethnicities has been observed of healthcare workers who have succumbed fatally to the COVID 19 virus could be related to hypertensive drug treatment regimens, as there is a difference, according to the treatment British Hypertension Society recommendations, for combining blood pressure lowering drugs for different ages and ethnicity, where black patients and older patients tend to be treated with diuretics and calcium channel blockers whereas the younger or non-black patients receive ACEI/ARB and Beta blockers.

Azra Mahmud, John Feely, Choice of First Antihypertensive: Simple as ABCD? , American Journal of Hypertension, Volume 20, Issue 8, August 2007, Pages 923–927.

Demographic factors rather than use of ACEI or ARBS explain high COVID mortality in males and old age

Increased mortality in patients with COVID-19 is related to of demographic characteristics associated with increased ACE2 expression, such as older age and male sex.

Therefore, use of ACEI or ARBs in such patients can not be blamed for increased mortality.

Fernández-Atucha A, Izagirre A, Fraile-Bermúdez AB et al. Sex differences in the aging pattern of renin-angiotensin system serum peptidases. Biol Sex Differ. 2017;8:5. 18.

Walters TE, Kalman JM, Patel SK et al. Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling. Europace. 2017;19:1280–1287. 19.

Chappel MC, Ferrario CM. ACE and ACE2: their role to balance the expression of angiotensin II and angiotensin-(1-7). Kidney Int. 2006;70:8–10

Thank you so much for sharing this Muhammad. However, the discussion so far does not suggest that ACE1 or ARB increases the fatalities, in fact, quite the opposite, according to the Hubei study.

Chappel MC, Ferrario CM. ACE and ACE2: their role to balance the expression of angiotensin II and angiotensin-(1-7). Kidney Int. 2006;70:8–10.

Yes, ACE2 inhibitirs are having incremental benefits in some cases.

I agree ACE2 looks best

The Rise of New Coronavirus Infection (COVID-19): A Recent Update

• DOI: 10.14744/ejmo.2020.22222

Article On Facing the SARS-CoV-2 (COVID-19) with Combination of Nano...

Recentemente, escrevemos um artigo, que será publicado no International Journal Science Cardiovascular, mostrando a interação entre a SARS-CoV-2 e o Sistema Renina Angiotensina (SRA). Baseado, nessa interação, que explica os sintomas mais prevalentes e a forma de contaminação por COVID-19, podemos inferir que os inibidores dos receptores AT1 ou inibidores da ECA1 seriam fármacos eficientes. No entanto, não foi isso que os estudos que investigaram essa hipótese, observaram até o momento. Novos estudos estão sendo realizados com o objetivo de investigar melhor essa hipótese.

Ainda, nessa direção levanto a ideia do quão importante é o exercício físico já que é um dos recursos mais potentes para regulação do SRA. E isso, pouco ainda tem sido comentado e nada nesse sentido tem sido investigado. Não sabemos, por exemplo, qual a prevalência de indivíduos ativos recuperados da SARS-CoV-2 e como está essa prevalência entre os mortos e se ele conferiu proteção adicional a população de risco.

Jefferson Petto.

Thank you so much for this, I have included a translation, Jefferson, in case other interested parties in this discussion and don't speak Portuguese.

Myokines are also important cytokines as an infection control released by muscle cells and expressed during exercise and participate in immunomodulation and tissue repair and maintenance. Aerobic exercise provoke a systemic cytokine response, interesting......

Jefferson's contribution in English

We recently wrote an article, which will be published in the International Journal Science Cardiovascular, showing the interaction between SARS-CoV-2 and the Renin Angiotensin System (SARS). Based on this interaction, which explains the most prevalent symptoms and the form of contamination by COVID-19, we can infer that AT1 receptor inhibitors or ACE1 inhibitors would be efficient drugs. However, this is not what the studies that investigated this hypothesis have observed so far. New studies are being carried out in order to better investigate this hypothesis. Still, in this direction I raise the idea of ​​how important physical exercise is since it is one of the most powerful resources for regulating the SARS. And that, little has yet been commented on and nothing in this regard has been investigated. We do not know, for example, what the prevalence of active individuals recovered from SARS-CoV-2 is and how that prevalence is among the dead and whether it has given additional protection to the population at risk. Jefferson Petto.

I agree with the author that Maybe Angiotensin Receptors Blockers can bring a protection against COVID 19 instead of pills which act on Angiotensin Enzyme Convertor

And not on its receptor

Dear Dr. have a nice Sunday.

In my RG open question about the dramatic situation of Lombardia (N.Italy)

I propose the test of the natural compounds from Artemisia, according to previous extensive bibliographical reviews about toxic effect in potential biocontrol.

I hope this is useful.

RG open question and Artemisia review references: https://www.researchgate.net/post/The_novel_Coronavirus_in_N_Italy_Lombardia_COVID19_2019nCoV_SARSCoV2_shows_a_fatality_rate_compatible_with_SARS-MERS_Why#view=5eabf2ae32592944281a872b

______________________________________

https://www.researchgate.net/figure/ResGa-FxFac-post_fig102_339781431

|n.2|....The following 12 virus species have been recognized, both DNA-virus and RNAvirus, both phyto-virus and zoo-virus: BVDV bovine viral diarrhea virus; COPV, canine papilloma virus; DEN/2, dengue virus 1; FIV, feline immunodeficiency virus; HBV, human hepatitis B virus; HCMV, human cito-megalo virus; HFLUV, human influentia virus; HIV, human immunodeficiency virus; HSV/1, human herpes virus 1; HSV/2, human herpes virus 2; JUNV, junin virus; TMV, tobacco mosaic virus. ....

.. ... FROM Artemisia: absinthium, afra, annua, anomala, arborescens, capillaris, caruifolia, douglassiana, herbaalba,verlotorum, vulgaris.....

.. ... Natural compounds: aesculetina, arcapillina, artemisinina, artesunate, beta-arteannuina, beta-sitosterolo, deidro-artemisinina, deossi-artemisinina, isorhamnetina, N-N-N-3p-coumaroil-spermidina, stigmasterolo.

Taking a completely different tack to address hyperinflammation, in a recent communication from Dr Stephane Arminjon who piloted a COVID 19 therapy using antihistamine to dampen the hyper inflammation in patients with COVID 19 infections, it is reported that this therapy approach to be promising but requires larger cohorts to confirm the implied significance. I have attached his report.

It may lead to positive results, but it takes a long time to confirm its effectiveness

Until now there is no evidence about influence of the renin–angiotensin–aldosterone system (RAAS) inhibitors and the prevalence or evolution of patients with Covid-19. ACE inibitors or ARBs are not indicated to avoid this disease according to NHI and other important international societies of Cardiology but if patients are taking this drugs before as treatment for high blood pressure or congestive heart faillure, it must be continued.

In a retrospective study in Hubei province in China, COVID 19 patients, admitted to 9 hospitals in a multi centre study, between December 31st and February 29th 2020. 1128 hospitalised adult patients with hypertension and diagnosed with COVID 19 were included in the study. There were 188 patients taking ACEI/ARB and 940 not taking ACEI/ARB with a median age of 64 years.

ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users (ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%; P = 0.01)).

• Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19 [published online ahead of print, 2020 Apr 17]. Circ Res. 2020;10.1161/CIRCRESAHA.120.317134. doi:10.1161/CIRCRESAHA.120.317134

In another study, among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, a lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group,

• Yang G, Tan Z, Zhou L, et al. Effects Of ARBs And ACEIs On Virus Infection, Inflammatory Status And Clinical Outcomes In COVID-19 Patients With Hypertension: A Single Center Retrospective Study [published online ahead of print, 2020 Apr 29].Hypertension. 2020;10.1161/HYPERTENSIONAHA.120.15143. doi:10.1161/HYPERTENSIONAHA.120.15143

Attachment of diag COVID19 and ACE-2

Rico-Mesa JS, White A, Anderson AS. Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB. Curr Cardiol Rep. 2020;22(5):31. Published 2020 Apr 14. doi:10.1007/s11886-020-01291-

lopinavir-ritonavir

A recent publication in The Lancet, ‘Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. ' Ivan Fan-Ngai Hung, et al, May 8th 2020, found alleviation of symptoms and shorter duration of viral shedding but only in 199 patients with mild disease to moderate disease and no patients died.

A New England Journal of Medicine published a paper on a therapy of Lopinavir–Ritonavir but did not find any significant improvement compared to the previous standard treatment. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19’ Bin Cao, M.D., Yeming Wang, M.D., Danning Wen, M.D., Wen Liu, M.S., Jingli Wang, M.D. May 7th 2020

Lopinavir–Ritonavir is, of course, the antiretroviral therapy used to treat patients who are HIV positive.

There has been a lot of speculation about the role of the renin-angiotensin-aldosterone system and medications that target it on the severity of COVID-19, since angiotensin-converting enzyme 2 (ACE2) is used by SARS-CoV-2 as a functional receptor to enter into cells (including type II pneumocytes and kidney tubular epithelial cells). Data is limited so far but there is no current evidence that use of ACE inhibitors or angiotensin-receptor blockers (ARBs) is associated with worse outcomes in patients with COVID-19 (Mancia et al, NEJM, 2020, Reynolds et al, NEJM, 2020).

Thank you Mehmet for contributing and I would like to add to your suggestion by highlighting a previous post for this discussion where I quoted a paper claiming that ACE/ARB drugs, in patients with pre-existing hypertension compared to those patients with hypertension taking a non ACE/ARB drug regimen had significantly lower CRP and lower procalcitonin, a lower proportion of critical patients and a lower death rate. Granted this was not a clinical trial and retrospective, if we were to be pedantic, but it certainly contributes some significant evidence to support the concept.

• Yang G, Tan Z, Zhou L, et al. Effects Of ARBs And ACEIs On Virus Infection, Inflammatory Status And Clinical Outcomes In COVID-19 Patients With Hypertension: A Single Center Retrospective Study [published online ahead of print, 2020 Apr 29].Hypertension. 2020;10.1161/HYPERTENSIONAHA.120.15143. doi:10.1161/HYPERTENSIONAHA.120.15143

hello dr

follow

Please go through the attached article.

Many thanks, Talha. Hoping that all these suggested proposals for anti-COVID 19 prove successful. Wishing you every success with your research.

Patients suffering from COVID-19 and taking ACE Inhibitors and ARBs did not have an increased risk of poor outcome or any beneficial effect.

1. Article COVID-19 and Angiotensin-Converting Enzyme Inhibitors and An...

2. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31131-4/fulltext

Fouad, thank you so much for this contribution to the discussion. I think a useful picture is building for COVID 19 patients.

In view of ACE 1 and 2 having different actions as discussed above, ace inhibitors are safe and possibly beneficial in COVID-19 in decreasing the RAS storm. That being said, these drugs pharmacologically cannot inhibit the virus by any mechanism yet.

Thank you Pranav for cotributing.

Just to clarify what is known, as SARScov-1 and 2 share 80% structural identity and both utilise the action of ACE-2 as expressed on cell membranes some common mechanisms may occur.

COVID 19 virion’s spike glycoprotein has two subunits, S1, which binds to the receptors on the cell and another subunit that fuses with the cell membrane called S2.

The entry of COVID 19 into cells is promoted by a host transmembrane protease, TMPRSSR by two separate mechanisms. S1 binds to the ACE-2 enzyme on the cell membrane surface where the spike is activated by TMPRSS2 and cleaves ACE-2. In addition, the transmembrane protease acts on the S2 subunit, which causes an irreversible conformational change, activating it and also facilitates viral fusion to the cell membrane. Endocytosis of the virus can then occur.

Thus when the activity of ACE-2 is reduced, this should in theory reduce the ability of SARCov-2 from entering the cells through this mechanism. ACE-2 is up regulated by ibuprofen in animals.

Diagram attached-

Jeffrey K Aronson, Robin E Ferner. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers in COVID-19. CEBM, March 23, 2020

I agree to the above pathology.

However, the SARS‑CoV‑2 virus enters the cell through ACE2 receptor on the lung membrane. After entry inside the cell, SARS‑CoV‑2 virus proliferates, replicates, and causes downregulation of ACE2. ACE and ACE2 are structural homologs with different physiological functions.ACEinhibitors act on ACE, and its effect on ACE2 remains controversial.

I would like to add to my answer the fact that ACE INHIBITORS blocking the enzyme let the receptor locksmith available for virus introduction. Moreover, treatment with Angiotensin Receptors Antagonist could block the entire receptor.

Es importante tener en cuenta que la función de los Inhibidores de la Enzima Convertidora de la Angiotensina es bloquear la conversión de angiotensina por lo que no actúan a nivel del receptor y este permanece libre con su centro de reconocimiento libre lo que le permitiria unirse a otra estructuras, como pudiera ser el virus, que ya se ha demostrado presenta afinidad por dicho receptor. Por su parte, los Antagonistas del Receptor de la Angiotensina, al bloquear el receptor no permiten la formación del complejo virus-receptor, su introducción, replicación, endoteliitis y las complicaciones.

Innocent until proven guilty, so not to be stopped if indicated.

And strict use in the trials only till proven efficacy

pathophysiology as I understand

Article Angiotensin‑converting enzyme inhibitors and angiotensin rec...

Thank you Roger. I have translated your comment into English for those who do not speak Spanish.

'It is important to note that the function of Angiotensin Converting Enzyme Inhibitors is to block the conversion of angiotensin so they do not act at the receptor level and it remains free with its free recognition center which would allow it to bind to another structures, such as the virus, that have already been shown to have an affinity for this receptor. For their part, Angiotensin Receptor Antagonists, by blocking the receptor do not allow the formation of the virus-receptor complex, its introduction, replication, endotheliitis and complications.' Roger Rodriguez Guzman

That what I have always said. Don't stop the ARBs, they are blocking the receptor ACE2 from the virus attaching, and even if they are upregulating, it doesn't matter because they will be blocked by more ARB. I have also said previously, there are a great many people with angioedema to ARBs, if the antibodies are attaching to a similar stereochemical site on the ARB and the virus, they may be blocking the virus, as well. Have any ARB allergic patients developed COVID-19 infections? Imagine if the ARB-angioedema patients already have S-spike protein antibodies circulating. Maybe someone with a massive computer database can look this one up. Thank you. Gary Ordog, MD July 24, 2020.