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What We Know About ACE Inhibitors, High Blood Pressure and COVID-19by Rupert Payne, University of Bristol 25 Mar 2020 HYPERLINK "" The COVID-19 pandemic has unsurprisingly been associated with a similar epidemic of social media misinformation. But there are also some genuine clinical issues of relevance to people with existing health conditions, who are known to be more vulnerable to the disease. One particular topic that has left patients and health professionals alike confused and alarmed is the suggestion that ACE inhibitor drugs may increase the dangers of COVID-19.First introduced in the early 1980s, ACE (angiotensin-converting enzyme) inhibitors were initially used for the treatment of high blood pressure, but their role has grown over the years to include the management of heart failure, heart attacks, diabetes and kidney disease. Given that roughly one-fifth of the adult population in the UK has diagnosed hypertension, and other cardiovascular conditions are widespread, these drugs are frequently prescribed. ACE inhibitors have grown to be the third most widely prescribed drug in UK primary care and, along with their close relatives – angiotensin receptor blockers, or ARBs – they accounted for 65 million prescriptions issued in the community in 2018.ACE inhibitors work by reducing the activity of the body’s major blood pressure regulatory mechanism, the renin–angiotensin–aldosterone system. When there is reduced blood pressure in the kidney, the body produces the enzyme renin, which leads to the production of a protein called angiotensin I. This protein doesn’t have any effect on the body, but when it’s converted by another enzyme – the Angiotensin Converting Enzyme, produced particularly in the lungs – into angiotensin II, this has potent vascular effects that increase blood pressure. ACE inhibitors block this enzyme and so prevent the rise in blood pressure.The renin-angiotensin-aldosterone system. Joshya/Shutterstock So why might this matter for COVID-19? To gain entry to human cells, a key trick employed by the coronavirus is to attach to a receptor on the surface of the cells which binds to an enzyme related to ACE, called ACE2. ACE2 has different functions to ACE, including inactivating angiotensin II. ACE inhibitors do not appear to directly affect the action of ACE2. Nevertheless, they may have indirect effects that could lead to an increase in the number of ACE2 receptors. This has led to concerns that ACE inhibitors may facilitate COVID-19 disease, particularly as these drugs are used in older people with other health issues who we know are at risk of more severe respiratory complications.Visualisation of the novel coronavirus. Photo by Fusion Medical Animation on Unsplash However, the situation is not necessarily that simple. Previous work with the related condition SARS showed that reduced ACE2 (and with it, increased angiotensin II) was associated with severe lung injury. Based on this, ACE inhibitors and ARBs, by reducing angiotensin II, might actually be expected to be protective against severe lung problems. In an attempt to address these opposing theories, there is currently a clinical trial which is examining whether the ARB drug Losartan may have benefits in patients with COVID-19.The balance of these risks and benefits is currently unknown. There is a lack of epidemiological evidence to support these drugs being either dangerous or therapeutically useful in the context of this coronavirus. One case study in China of more than 1,000 COVID-19 patients found higher rates of pre-existing cardiovascular disorders in those people with more severe viral disease, although their drug therapy was not examined. But even if one might expect ACE inhibitor or ARB use to be higher in those with cardiovascular disease, these patients are also likely to be at far higher risk of complications simply due to poor underlying cardiac, renal and respiratory function – disentangling the effects of disease and therapy requires far more study.Many GPs are already being asked what they should do by understandably anxious patients, and are unsure of what to do themselves. Conflicting or misleading advice on social media has not helped the decision-making process. Discontinuation risks a deterioration in existing cardiovascular conditions, leading to further complications.More research is clearly required, but in the absence of evidence to the contrary, the European Society of Cardiology put out a position statement strongly advising continuation of ACE inhibitor and ARB therapy. In the meantime, it’s essential that patients are provided with the facts as they are currently known in order for them to make the most informed decision they can about their care.ABOUT THE AUTHORRupert Payne, Consultant Senior Lecturer in Primary Health Care, University of BristolThis article is courtesy of The Conversation. Read the original article. WUSTL Researchers Investigate Transfusion of Antibodies from Recovered Patients’ as COVID-19 Treatmentby Global Biodefense 25 Mar 2020 HYPERLINK "" A laboratory worker removes plasma from a vial of blood. Researchers at Washington University School of Medicine in St. Louis and elsewhere are investigating whether transfusions of blood plasma from people who have recovered from COVID-19 can prevent or treat the disease. The approach was used with some success during the 1918 influenza pandemic. Credit: Getty ImagesWith no drugs or vaccines yet approved for COVID-19 and the number of U.S. cases increasing by the thousands every day, doctors are looking to revive a century-old therapy for infectious diseases: transfusing antibodies from the blood of recovered patients into people who are seriously ill.During the Spanish flu pandemic of 1918, doctors were faced with a deadly illness and no specific treatments. Recognizing that people who had recovered were immune to the infection, some doctors tried treating their patients with blood serum from recovered flu patients. In many cases it worked.“Giving serum from newly recovered patients is a stone-age approach, but historically it has worked,” said?Jeffrey P. Henderson, MD, PhD, an associate professor of medicine and of molecular microbiology at Washington University School of Medicine in St. Louis. “This is how we used to prevent and treat viral infections like measles, mumps, polio and influenza, but once vaccines were developed, the technique understandably fell out of favor and many people forgot about it. Until we have specific drugs and vaccines for COVID-19, this approach could save lives.”Henderson was reminded of the technique by Arturo Casadevall, MD, PhD, the chair of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. Casadevall began championing the idea of using plasma from convalescing patients to treat COVID-19 in early March. Plasma and serum are both the clear fluid portion of blood, and both contain antibodies, but plasma also contains some other proteins lacking in serum.Plasma transfusion was used experimentally to treat small numbers of people during the SARS outbreak of 2002 and 2003. SARS, which stands for severe acute respiratory syndrome, is caused by a coronavirus closely related to the one that causes COVID-19. In one study, SARS patients who received plasma transfusions recovered faster than those who did not.Henderson, Casadevall and Michael Joyner, MD, a physiologist at the Mayo Clinic in Rochester, Minn., quickly joined forces and leveraged the resources at their three institutions to test the approach. Their efforts resulted in an investigational new drug application to the Food and Drug Administration that was filed March 18. If the application is approved, they plan to move rapidly to a clinical trial.“This is something that can be done very quickly, much faster than drug development, because it basically involves donating and transfusing plasma,” Henderson said. “As soon as we have individuals who have recovered from COVID-19 walking around, we have potential donors, and we can use the blood bank system to obtain plasma and distribute it to the patients who need it.”The plan is to ask patients who recover from COVID-19 to donate their blood, from which plasma would be isolated. After screening for toxins and viruses, the plasma would be transfused into people ill with or at high risk of COVID-19. The procedure for isolating plasma is a long-established technology that can be performed using equipment normally found in blood-banking facilities, and receiving plasma from these donors is as safe as any other plasma transfusion, Henderson said.The concept is simple, but the execution is more complicated. The scientists still need to determine how much antibody is in the blood of recovered patients, and how much antibody needs to be given to effectively treat or prevent COVID-19.?Brenda Grossman, MD,?a professor of pathology and immunology at Washington University School of Medicine and director of transfusion medicine at Barnes-Jewish Hospital, was brought on board to help navigate the complex regulations surrounding blood donations and transport of blood products across state lines.The idea is catching fire.“Last week, it was the three of us on a conference call,” Henderson said. “This week, we had people from all over the country – I don’t even know how many. Everyone’s excited about this. If it works, it could provide a lifeline at this early stage of the pandemic.”Tags: Clinical TrialsConvalescent SerumCOVID-19Editor PickMagazine Edition 11 April 2020SARS-CoV-2Related Posts HYPERLINK "" ................
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