Category Archives: COVID-19

An Update On ACE2, RAAS and Covid-19: Still No Reason To Stop Or Change Your Blood Pressure Medication

Previously, I wrote a detailed post on concerns that have been raised about certain blood pressure medications potentially  increasing the risk of contracting SARS-CoV-2 or increasing the likelihood of death and serious disease related to the virus.

Millions of patients worldwide with heart failure and hypertension are taking drugs that inhibit pathways in the renal angiotensin aldosterone system termed angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs.)

Lisinopril and ramipril are common ACE inhibitors whereas valsartan, losartan, and irbesartan are common ARBs.

Speculation that these drugs might be contributing to mortality associated with COVID-19 was initiated by a “Rapid Response” published online March 3 by the British Medical Journal in response to an editorial on “preventing a COVID-19 pandemic.” and “Correspondence” to the Lancet published March 7.

Since then I’ve been following this topic closely but nothing has emerged from any new data or new expert analysis to suggest that patients should stop taking ACE inhibitors or ARBs.

Yesterday, an excellent summary of the topic from some of the world’s leading authorities was published in the New England Journal of Medicine entitled “Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19″

It begins with this wonderful sentence: “The renin–angiotensin–aldosterone system (RAAS) is an elegant cascade of vasoactive peptides that orchestrate key processes in human physiology.”

The authors outline in detail the possible interactions between ACE2 receptors and SARS CoV-2.

For those not interested in the scientific details in the paper, the Cliff’s Notes version of this article is below. Basically, we have insufficient data to know if patients taking RAAS inhibitors are at higher or lower risk for serious SARS-CoV-2 infection.


KEY POINTS RELATED TO THE INTERPLAY BETWEEN COVID-19 AND THE RENIN–ANGIOTENSIN–ALDOSTERONE SYSTEM

  • • ACE2, an enzyme that physiologically counters RAAS activation, is the functional receptor to SARS-CoV-2, the virus responsible for the Covid-19 pandemic
  • • Select preclinical studies have suggested that RAAS inhibitors may increase ACE2 expression, raising concerns regarding their safety in patients with Covid-19
  • • Insufficient data are available to determine whether these observations readily translate to humans, and no studies have evaluated the effects of RAAS inhibitors in Covid-19
  • • Clinical trials are under way to test the safety and efficacy of RAAS modulators, including recombinant human ACE2 and the ARB losartan in Covid-19
  • • Abrupt withdrawal of RAAS inhibitors in high-risk patients, including those who have heart failure or have had myocardial infarction, may result in clinical instability and adverse health outcomes
  • • Until further data are available, we think that RAAS inhibitors should be continued in patients in otherwise stable condition who are at risk for, being evaluated for, or with Covid-19

So my recommendations (and more importantly the recommendations of every major society or organization which has weighted in on this topic) to patients remain the same: don’t stop your ACE inhibitor or ARB due to concerns about coronavirus.

Skeptically Yours,

-ACP

Another Coronavirus Quiz

Al Lewis, at Quizzify continues to provide the public brief quizzes with well-researched answers that help even the well-informed better understand SARS-CoV-2 and COVID-19. Today a fourth quiz was released available here (along with the first three 10 -question quizzes.)

Take a few minutes and see if you can beat my score of 875/1000.

Al’s teaser:

Examples of questions from the quiz:
  • Does UV light destroy the virus?
  • How long does food need to be refrigerated at 36 degrees to be safe?
  • What’s the right way to shield yourself when passing near someone else?
  • How much tonic (quinine) water do you need to drink to equal a dose of chloroquine? [SPOILER ALERT: Don’t even think about it.

Skeptically Yours,

-ACP

How Coronavirus Turns Walking Into Awking

Today a guest post from the  wife of the Skeptical Cardiologist who has invented a new word for these difficult times.


Because my job can be pretty sedentary sometimes, I try to walk at least two to three miles every day (in addition to my regular cardio). I love Europe – you have to walk everywhere, and so I try to continue that behavior when we are here in the States.

Normally going for walks in my neighborhood, I will encounter occasional dog walkers, or baby walkers, or runners… but not many.

Lately, because of the coronavirus pandemic, it seems that everyone is out walking, even in terrible, dreary, cold weather. I think it’s encouraging that people are so committed to daily exercise now, because it really is so important to stay healthy and positive.

But I’ve noticed a funny phenomenon. Because of the 6 feet distancing in effect, it’s getting more challenging for me to go on walks. I am constantly having to move to the other side of the street or the middle of the road to avoid people.

It’s incredibly awkward because I don’t want to offend anyone and make them feel like I think they are infected. But at the same time, I’m trying to follow the rules and protect myself.

While out walking the other day, I was laughing to myself about this behavior and thinking that someone should invent a term for it. The new word would perfectly describe  “awkwardly & suddenly moving to the other side of the street when you realize you’re sharing a sidewalk with someone coming towards you” (behavior necessitated by a desire for keeping a six foot distance during the COVID-19 pandemic)

I thought of 2 words – awkward and walking, and came up with “Awking“. Then I started to wonder if I could get this on Urban Dictionary (or if somebody had already come up with it.) I looked it up, and there were a couple of definitions for my word, but not the one that I was thinking of. So I looked up how to submit on Urban Dictionary, followed the instructions, and submitted it. Within five minutes they responded and said that my word had been approved!! It’s silly how happy this made me. Me, a humble Gen Xer who is not well-versed in “kids today” language.

My immortal contribution to slang!  🤣  (turns out its not so hard to get a word approved on Urban Dictionary, but hey whatever, ha!)

Now you must excuse me…
I need to cross to the other side of the street to keep 6 feet away from my neighbor.


Speaking of neologisms, a few months ago while scanning the blurb on the wrapper of a keto-friendly snack  I created by accident the portmanteau word, farb. Thus far, I have not submitted it to Urban Dictionary.

Neologically Yours,

-ACP

N.B. The featured image comes from @BDStanley on Twitter. Beatleish lyrics of relevance on that tweet include “We were talking about the space between us all.”

 

In The Time of Coronavirus What Should Be Considered A Normal Temperature And What Is A Fever?

As a medical student, I was taught that the normal temperature of humans is 37.0°C (98.6°F) and that the upper limit of normal temperature is 38.0°C (100.4°F). The criterion for fever during this current SARS-CoV-2 epidemic is still considered to be a temperature over 38.0°C (100.4°F) despite strong evidence supporting a lower temperature cut-point.

Multiple studies in the last 30 years have clearly established that the average human temperature has dropped progressively in the last 150 years and is more accurately considered to be 36.8°C (98.2°F).

Moreover, normal temperature varies between individuals and multiple other variables including according to what time of day it is taken.

For example, when I take my temperature first thing in the morning it is 96.4°F. Later in the day, it rises to 97.4°F. After exercise, it reaches 98.0°F. My overall average is 97.0, significantly lower than the canonical average.

This change in the average normal temperature and the upper limits of normal has significant implications for temperature screening for the determination of fever and consequently who may or may not have a coronavirus infection.

Origins Of 98.6 As Normal

The concept of 98.6 as normal can be traced back 150 years to work from the German scientist Carl Reinhold August Wunderlich who made multiple measurements of axillary temperature in 25000 subjects. Wunderlich reported a range of 36.2°C (97.2°F) to 37.5°C (99.5°F). Although he also noted a significant diurnal variation in temperature, with a nadir in early AM and peak in later afternoon,  he would have considered me hypothermic.

Wunderlich also felt that temperatures >100.4 were “probably febrile.”

Change in Temperature Over Time

Studies since Wunderlich have shown a progressive decline in the average human temperature. Mackowiak, et al, (PDF available here) published  data showing a substantially lower normal human temperature such that  that 98.6 “should be abandoned as a concept relevant to clinical thermometry.”

Mackowiak, et al found in 148 individuals the average temperate was 98.2 (36.8). These individuals were monitored over a 48 hour period and the average and range varied considerably

Screen Shot 2020-03-28 at 9.29.19 AM

The average temperature varied according to time of day.

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In the graph above if we look at 6 AM temperature measurement, we see the average is actually 97.5°F. My 6 AM recordings of 96.4°F puts me in the bottom fifth percentile. More importantly, 99% of subjects had a temperature of <98.9°F.

If one is recording a temperature on a patient at 6 AM and it is >98.9 that should probable be considered abnormal. On the other hand, if the temperature is being measured between noon and 6 PM, >99.8 should be considered abnormal.

A publication from earlier this year in eLife confirmed that the average temperature in humans is progressively dropping.

The researchers used measurements from the Union Army Veterans of the Civil War (N = 23,710; measurement years 1860–1940), the National Health and Nutrition Examination Survey I (N = 15,301; 1971–1975), and the Stanford Translational Research Integrated Database Environment (N = 150,280; 2007–2017)

They found:

mean body temperature in men and women, after adjusting for age, height, weight and, in some models date and time of day, has decreased monotonically by 0.03°C per birth decade..

Screen Shot 2020-03-28 at 8.12.20 AM

As you can see from the graph above, the average temperature has dropped from the 1970s to the 2000s. The most recent temperatures from 2007 to 2017 in orange lie consistently below the green temperatures from 1971 to 1975. This is irrespective of gender (men in top two graphs, women in bottom two) and race (white in left boxes, black in right boxes.)

Additionally, in all categories (except perhaps civil war men) average temperature declines significantly with age.

Choosing A Cut-point Temperature To Decide Fever

All of this temperature variation data would be simply of academic interest but given the COVID-19 pandemic, the definition of fever has become incredibly important.

If we choose a cut-point that is too high we risk missing cases. If we choose one too low we risk overwhelming the limited testing resources and unnecessarily alarming patients.

What I have decided to do is to establish a norm for myself based on time of day. If I record a temperature >1.8 °F over my norm I will consider myself as having a fever.

Clearly, this doesn’t work for widespread screening of the public which is occurring now at multiple sites as most individuals have not established what is their normal average temperature, let alone their average temperature by time of day.

At a minimum, though, it seems to me that public health authorities should recognize the lower normal average temperature and the corresponding lower cut-point fever that has been known since 1997.

Adjusting the cut-point to >99.8°F for abnormal would align more closely with what is currently known about the range of normal human temperatures.

Thermoregulatorily Yours,

-ACP

Food and The Coronavirus

Marion Nestle at her blog Food Politics has put together an updated and tremendous compendium of information about food during these troubled times.

I’ve quoted it in detail below.

Key points to keep in mind.

 

To Date There Is No Evidence Of Coronavirus Transmission By Food

 

See her detailed post on this here.

For produce her recommendation is

To be 100 percent safe while eating fresh produce

Do what you would do in countries without safe water supplies—follow the P rules and only eat foods that are:

  • Piping hot (hot temperatures destroy viruses and other microorganisms)
  • Peeled (wash hands before and after)
  • Purified (cooked and not recontaminated)
  • Packaged (industrially packed, frozen, or dried)

As always, wash hands.

If you have fresh produce, wash it.  When in doubt, cook it.

Avoid Dubious Schemes For Immune Boosting.

I have noticed that the snake oil salesmen are doubling down on their products and promoting all kinds of useless immune supplements  Let the buyer beware-these untested products are as likely to lower your immunity as raise it. 

Grocers Have A  Viable Supply Chain And Are Not Shutting Down

Don’t hoard food and supplies that other people may need


From Marion Nestle:

Does food transmit Coronavirus?  

Keeping up with Coronavirus  

How to survive working at home (watch out for junk food) 

How to take action

Advice for the food industry

  • US lays out new COVID-19 guidelines for food industry  The Trump Administration released a set of coronavirus guidelines for all Americans, with special provisions for critical infrastructure industries like food and beverage. Brands have been adapting this week to the new reality, while keeping employee safety a top priority…. Read more

What’s happening with supermarkets and supply chains?

What to avoid: dubious schemes for immune boosting

Who profits from this?

What else?


Still Socially Distanced,

-ACP

Best Practices For Social Distancing To Mitigate COVID-19

To flatten the curve and mitigate the impact of coronavirus we should be practicing social distancing.

It is not obvious to most how this should be accomplished but there is a great article on this at The New Yorker which discusses an information sheet on the topic provided by Dr. Asaf Bitton,

The New Yorker piece goes into more detail on topics such as what to do when you go outside, how often to shower, the importance of walks, how to respond if someone you are sheltering with gets sick, and the whether it is best to order take-out food or cook your own.

I’ve reproduced the nuts and bolts of Dr. Bitton’s information sheet below the line.


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1. We need to push our local, state, and national leaders to close ALL schools and public spaces and cancel all events and public gatherings now.

A local, town by town response won’t have the adequate needed effect. We need a statewide, nationwide approach in these trying times. Contact your representative and your governor to urge them to enact statewide closures. As of today, six states have already done so. Your state should be one of them. Also urge leaders to increase funds for emergency preparedness and make widening coronavirus testing capacity an immediate and top priority. We also need legislators to enact better paid sick leave and unemployment benefits to help nudge people to make the right call to stay at home right now.

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2. No kid play dates, parties, sleepovers, or families/friends visiting each other’s houses and apartments.

This sounds extreme because it is. We are trying to create distance between family units and between individuals. It may be

particularly uncomfortable for families with small children, kids with differential abilities or challenges, and for kids who simply love to play with their friends. But even if you choose only one friend to have over, you are creating new links and possibilities for the type of transmission that all of our school/work/public event closures are trying to prevent. The symptoms of coronavirus take four to five days to manifest themselves. Someone who comes over looking well can transmit the virus. Sharing food is particularly risky—I definitely do not recommend that people do so outside of their family.

We have already taken extreme social measures to address this serious disease—let’s not actively co-opt our efforts by having high levels of social interaction at people’s houses instead of at schools or workplaces. Again—the wisdom of early and aggressive social distancing is that it can flatten the curve above, give our health system a chance to not be overwhelmed, and eventually may reduce the length and need for longer periods of extreme social distancing later (see what has transpired in Italy and Wuhan). We need to all do our part during these times, even if it means some discomfort for a while.

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3. Take care of yourself and your family, but maintain social distance.

Exercise, take walks/runs outside, and stay connected through phone, video, and other social media. But when you go outside, do your best to maintain at least six feet between you and non-family members. If you have kids, try not to use public facilities like playground structures, as coronavirus can live on plastic and metal for two to three days, and these structures aren’t getting regularly cleaned.

Going outside will be important during these strange times, and the weather is improving. Go outside every day if you are able, but stay physically away from people outside your family or roommates. If you have kids, try playing a family soccer game instead of having your kids play with other kids, since sports often mean direct physical contact with others. And though we may wish to visit elders in our community in person, I would not visit nursing homes or other areas where large numbers of the elderly reside, as they are at highest risk for complications and mortality from coronavirus.

Social distancing can take a toll (after all, most of us are social creatures). The CDC offers tips and resources to reduce this burden, and other resources offer strategies to cope with the added stress during this time.page3image3897750480

We need to find alternate ways to reduce social isolation within our communities through virtual means instead of in-person visits.

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4. Reduce the frequency of going to stores, restaurants, and coffee shops for the time being.

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Of course trips to the grocery store will be necessary, but try to limit them and go at times when they are less busy.

Consider asking grocery stores to queue people at the door in order to limit the number of people inside a store at any one time. Remember to wash your hands thoroughly before and after your trip. And leave the medical masks and gloves for the medical professionals—we need them to care for those who are sick. Maintain distance from others while shopping—and remember that hoarding supplies negatively impacts others so buy what you need and leave some for everyone else.

Take-out meals and food are riskier than making food at home given the links between the people who prepare food, transport the food, and you. It is hard to know how much that risk is, but it is certainly higher than making it at home. But you can and should continue to support your local small businesses (especially restaurants and other retailers) during this difficult time by buying gift certificates online that you can use later.

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5. If you are sick, isolate yourself, stay home, and contact a medical professional.

If you are sick, you should try to isolate yourself from the rest of your family within your residence as best as you can. If you have questions about whether you qualify or should get a coronavirus test, you can call your primary care team and/or consider calling the Massachusetts Department of Public Health at 617.983.6800 (or your state’s department of health if you are outside of Massachusetts). Don’t just walk into an ambulatory clinic—call first so that they can give you the best advice—which might be to go to a drive-through testing center or a virtual visit on video or phone. Of course, if it is an emergency call 911.

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I realize there is a lot built into these suggestions, and that they represent a real burden for many individuals, families, businesses, and communities. Social distancing is hard and may negatively impact many people, especially those who face vulnerabilities in our society. I recognize that there is structural and social inequity built in and around social distancing recommendations. We can and must take steps to bolster our community response to people who face food insecurity, domestic violence, and housing challenges, along with the many other social disadvantages.

I also realize that not everyone can do everything. But we have to try our absolute best as a community, starting today. Enhancing social distancing, even by one day, can make a large difference.page4image3858666928We have a preemptive opportunity to save lives through the actions we take right now that we will not have in a few weeks. It is a public health imperative. It is also our responsibility as a community to act while we still have a choice and while our actions can have the greatest impact.

We cannot wait.

Asaf Bitton, MD, MPH, is the executive director of Ariadne Labs in Boston, MA.


Yours in Distance,

-ACP

A Message From Italy On Coronavirus and COVID-19

Last month the skeptical cardiologist asked Nicola Triglione, a native of Southern Italy who completed his cardiology fellowship in Milan to give us his perspective on the US and Italian health care systems.

Since Italy is now at the European epicenter of the COVID-19 epidemic and second only to China in number of

Screen-Shot-2020-03-15-at-12.02.17-PM.png
From the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU)

cases and deaths, American scientists and public health officials are now closely scrutinizing Italy’s response and outcomes.

 

 

I emailed Nicola to see what his situation was and he provided this information and advice for my readers:

Hello everyone from Milan, as you already know Italy is in lockdown over the new coronavirus (Covid-19). The northern regions of Lombardy, Veneto and Emilia-Romagna have been most affected by the outbreak and what’s happening here it’s just surreal. I just wanted to reach out to you because we all have the responsibilities to prevent this. The majority of infections are mild but the pandemic is growing at an exponential speed. The infection is much more aggressive for certain groups: elderly, cancer patients and patient with cardiovascular disease are at higher risk of dying. Hospitals are severely overloaded and the real problem is that medical staff gets sick.

My only take on is: stay home for as long as possible, lots of contagions happen before there are symptoms. Virus doesn’t spread if people don’tinteract. If we can postpone cases the healthcare system will be able to handle contagions much better. I hope the US authorities will stop public gatherings and everything really not necessary. Last but not least, we need to test everybody as limited testing only postpones the problem.

Dott. Nicola Triglione
Medico Chirurgo
Specialista in Cardiologia 

For those who want to learn more about the situation in Italy, watch this video interview with Dr. Cecconi of Humanitas University in Milan discussing the region’s approach to the surge, including clinical and supply management, health care worker training and protection, and ventilation strategies, with JAMA Editor Howard Bauchner.

Antiseptically Yours,
-ACP