Emerging Treatments for Coronavirus


ACE Blockers and Coronavirus Infections

David Bishai, MD, MPH, PhD
Johns Hopkins Bloomberg School of Public Health
March 19, 2020

After the SARS-CoV-2 virus gets into a person’s nose,  throat, or lungs it can’t make them sick unless it actually gains entry into the inside of the epithelial cells that line those tissues. There is a receptor on human respiratory epithelial cells called the Angiotensin Converting Enzyme 2 (ACE-2). Its usual job is to cleave proangiotensin into  smaller molecules like angiotensin1-7 that help repair blood vessels in the lung. (McKinney, et al. 2014)  The SARS viruses became pathogens when they mutated to have an affinity for one small spot on human ACE-2 (Figure 1).  When ACE-2 receptors are attacked there may be less angiotensin 1-7 and less ability to repair blood vessels in the lung. Gurwitz (2020)


Figure 1. Electron microgram of the ACE-2 Receptor (Purple and Blue) and SARS-CoV-2 virus (Yellow)


Source Yan et al. 2020

There is a much more well known cousin of ACE-2 called ACE-1 which plays an important role in blood pressure regulation. We have several FDA approved drugs that block ACE-1 that end in the suffix “sartan” (eg. Losartan and Valsartan).  Unfortunately the ACE-1 blocking drugs do not block ACE-2. Furthermore, when patients take an ACE-1 drug it makes them express more of the virus-magnet ACE-2 molecule on cell surfaces.

 A knee jerk reaction might be to warn doctors: “Do not give Losartan to people during a coronavirus epidemic”.  But it is not that simple.  Reports from Chinese doctors treating critically ill patients indicate that a mechanism of lung injury during COVID-19 is having too little angiontensin 1-7  and too much pro-angiotensin and byproducts of pro-angiotensin because virus has bound up the ACE-2 receptors.  Paradoxically having more ACE-2 receptors during a severe infection might help.  Each respiratory cell is going to have some ACE-2 receptors anyway and each cell will be under attack.  Having more ACE-2 receptors might not change the outcome of whether virus will invade a respiratory cell, but it might help the body prevent lung injury. (Lowe, 2020)  None of this physiology is known with certainty. Trials are underway. We need international cooperation with more centralized health systems like Italy and China to pull of urgent data-mining of COVID-19 patient records.

We don't have answers to pressing questions. Should healthy people who are taking Losartan anyway stop taking it and switch to something else? Should people who test positive for COVID-19 and only have mild illness start taking it?  What should an ICU doctor do with a critically ill COVID-19 patient?  Which of these scientific questions should be studied first?

Comments

Post a Comment

Popular posts from this blog

Final Score on Who Handled COVID-19 Best

Image
  There is no perfect way to measure which government did best in managing the COVID-19 pandemic.   But with 48 full months of data from January 20, 2020 to January 27, it is now possible to score which area did best across the whole marathon.   For example, Hong Kong was an early sprinter getting an A+ and then faltering in vaccinating seniors and withstanding Omicron variant.   Other jurisdictions fumbled the exit ramp from Zero Covid-type policies to opening their economies.     Because testing rates varied, a measure like COVID cases, hospitalizations, or deaths could cover up a lot of hidden illness and deaths in places that could not or did not test as much as others.   This post uses Cumulative Excess Mortality numbers drawn from Our World In Data   (OWID) which were drawn from The Economist .   OWID published data for all jurisdictions regardless of how good the estimates were. I advise against making distinc...
Read more

Asset-Demiology: Public Health's Best Old Idea is the Key to Rebuild Trust

Image
Asset- demiology is a neologism that does not come up in Google (yet) 1 .  Sound it out—the “ ology ” of peoples ’ assets and strengths.  It is the logical comp anion , but neglected anti-thesis of the usual approach to health.     Health care work is all about deficits .  The work of a doctor, whether human or robot, is to transform a living breathing human into a diagnosis, problem list and treatment plan. Medical s tudents and interns are socialized to walk out of the treatment room and recite to their supervisors all the deficits and problems they uncovered.  There is no place in a standard medical record to actually list a patient’s strengths and capabilities.   The AI-training sets for robot ic medical algorithms have no way to learn the clinical relevance of patients’ strengths. To a doctor , patient=problem list .   Public health has the same pessimistic vibe.     A deficit focus has rubbed off on public healt...
Read more

Watched but Not Seen

  Among the Zulu people of South Africa the traditional greeting is “Sawubona” literally “I see you”.   Contrast that to the English, “How are you?” -- literally a demand for an evaluation.  Evaluations, peer reviews, and performance reviews can be friendly or not.   Jeremy Bentham deserves partial credit for their dark side. Jeremy Bentham thought prisons should be designed around a central panopticon , a tower that would allow the guards to watch every prisoner around the clock to deter mischief.    Modern philosophers like Michel Foucault see panopticons as pervasive in modern society–we are all under the surveillance of others and we all stay on guard to conform. Performance is quantified on scales that are tied to carrots and sticks. The numbers have a hard time saying full sentences about who we are and how we matter.   Throughout the year the sense that one is constantly being watched by a corporate evaluator leads to the stress of chronic...
Read more