Tag Archives: coronavirus

Asthma, Inhaled Steroids and Covid-19

If you, like the skeptical cardiologist, suffer from asthma you may be wondering if you are at a higher risk of contracting Covid-19 or developing more severe respiratory complications from the disease once infected.

There are 25 million asthma sufferers in the United States, about 8% of the population and many of us are using as primary treatment a combination of inhaled beta-agonists (for immediate relief) and inhaled corticosteroids (ICS) (for long-term conditioning of the lung).

How are these treatments influencing our risks during the Covid-19 pandemic?

A commentary published online in Lancet Respiratory medicine suggested that there is a lower prevalence of asthma in patients with Covid-19. However, the sum of evidence from this commentary and elsewhere is insufficient to say asthma is protective.

When there is an absence of evidence, as we saw with hypertension as a risk factor and hydroxychloroquine as a treatment, the tendency of journalists is to obtain a quote from a physician who has treated patients with Covid-19 to buttress a particular argument. Quotes which say something like “we don’t know” or “there is not enough evidence right now” are highly unlikely to be published whereas anecdotal speculation is always intriguing (but often misleading.). The New York Times published this quote on the topic:

“We’re not seeing a lot of patients with asthma,” said Dr. Bushra Mina, a pulmonary and critical care physician at Lenox Hill Hospital in New York City, which has treated more than 800 Covid cases. The more common risk factors, he added, are “morbid obesity, diabetes and chronic heart disease.”

A major problem in sorting out asthma as an independent risk factor is that many papers are lumping all “chronic respiratory diseases” together which puts asthma in a bucket with chronic obstructive pulmonary disease (COPD) and interstitial lung disease like pulmonary fibrosis. There are striking differences in the demographics and prognosis of these diseases. For example, patients with COPD are older and much more likely to have smoked cigarettes, two factors clearly associated with Covid-19 risk.

In addition, asthma in older adults is highly associated with obesity, a well-recognized independent risk factor Covid-19 complications.

Among adults aged 60 and over, there was a significant trend of increasing asthma prevalence with weight status: 7.0% among normal weight adults; 9.1% among overweight adults; 11.6% among adults with obesity.

In addition, almost no data is available on asthma stratified by severity and treatment. The severe asthma patient who requires oral corticosteroids is markedly different from the mild asthmatic whose only treatment is intermittent inhaled beta-agonists.

These data, like the data on hypertension, should be taken with a grain of salt, but at a minimum, we can say there is no signal that asthma by itself increases the risk of Covid-19 infection.

Inhaled Corticosteroids and Covid-19

The authors* of the commentary in Lancet which implied asthma (and chronic respiratory disease) was protective against Covid-19 infection also concluded that

“the possibility that inhaled corticosteroids might prevent (at least partly) the development of symptomatic infection or severe presentation of COVID-19 cannot be ignored”

They cited some very preliminary data to support this contention:

in in-vitro models, inhaled corticosteroids alone or in combination with bronchodilators have been shown to suppress coronavirus replication and cytokine production. Low- quality evidence also exists from a case series in Japan, in which improvement was seen in three patients with COVID-19 requiring oxygen, but not ventilatory support,

Personally, I have always worried that my use of ICS put me at a higher risk of respiratory infections because corticosteroids are potent immunosuppressives, potentially lowering my immune response to bacterial, viral, or fungal infections. This 2019 meta-analysis in Infection found a 24% higher rate of upper respiratory tract infection in patients using ICS.

Due to these concerns, when the pandemic began I purposely cut back on my Advair usage. Fortunately, my asthma has been very mild since I started taking Dupixent for eczema 3 years ago. Since then, Dupixent has been approved for treatment of asthma. (By the way, although dupilumab is a targeted biologic therapy that inhibits signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), two key proteins that may play a central role in type 2 inflammation that underlies atopic dermatitis and several other allergic diseases we have no idea if it increases or decreases Covid-19 risks or complications.)

Does ICS usage increase or lower our risk of Covid-19 outcomes?

This figure from a review of the topic shows where in the process ICS could influence Covid-19, either increasing or decreasing risk of 1) initial infection 2) progression to pneumonia or 3) progression to ARDS and death once pneumonia is established.

F1.medium.gif

There are theoretical arguments to suggest the use of ICS could either improve or worsen all 3 stages.

The review of 59 publications on Covid-19 concluded:

Following examination of the full texts including translations of those in Chinese, no publications were identified as having data on prior ICS use in patients with SARS, MERS or COVID-19 infection. No data were available for either a qualitative or narrative answer to the review question.

The bottom line right now is that we don’t know if ICS use is an important risk factor in Covid-19 outcomes.

Should ICS Stay or Go

The recommendations of the CDC, and all pulmonary/asthma societies at this point is to stick to your current asthma action plan. If that includes taking an ICS, keep on taking it at current levels.

In fact, the AAAAI  and other major asthma or pulmonary organization emphasize that patients should remain on their current medications because experiencing an exacerbation event and the need for hospitalization, in those who become poorly controlled, could actually increase patient exposure and the risk of infection.

I’ve gone back to taking my ICS at pre-pandemic levels and I don’t consider that my asthma puts me at any higher risk during the pandemic.

Skeptically Yours,

-ACP

N.B. Common inhaled corticosteroids include:

  • Beclomethasone (QvarTM)
  • Budesonide (Pulmicort FlexhalerTM)
  • Ciclesonide (AlvescoTM)
  • Flunisolide (AerospanTM)
  • Fluticasone (Flovent Diskus TM, Flovent HFATM, Arnuity ElliptaTM)
  • Mometasone (AsmanexTM)

ICS are commonly combined with long-acting beta agonists.  The “purple circle” Advair is one such combination.

N.B. The authors of the Lancet commentary seem to have heavy ties to companies that stand to profit from sales of ICS

DMGH has received personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, and Sanofi, and non-financial support from Boehringer Ingelheim and Novartis, outside of the submitted work. RF has received grants from GlaxoSmithKline and Menarini, outside of the submitted work. AA has received grants from AstraZeneca, GlaxoSmithKline, and Menarini, and personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, and Menarini, outside of the submitted work. OS and JRB declare no competing interests

Here are the references they cited suggested ICS might be beneficial against coronavirus.

  1. Yamaya M, Nishimura H, Deng X, et al. Inhibitory effects of glycopyrronium, formoterol, and budesonide on coronavirus HCoV-229E replication and cytokine production by primary cultures of human nasal and tracheal epithelial cells. Respir Investig 2020; published online Feb 21. DOI:10.1016/j.resinv.2019.12.005.
  2. Matsuyama S, Kawase M, Nao N, et al. The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15. bioRxiv 2020; published online March 12. DOI:10.1101/2020.03.11.987016 (preprint).
  3. Iwabuchi K, Yoshie K, Kurakami Y, Takahashi K, Kato Y. Morishima T. COVID-19. Three cases improved with inhaled ciclesonide in the early to middle stages of pneumonia. 2020. http://www.kansensho.or.jp/uploads/ files/topics/2019ncov/covid19_casereport_200310.pdf (accessed March 27, 2020; in Japanese).

 

Does Hypertension Put You at a Higher Risk for Infection or Death From Covid-19?

Early news reports of fatalities in China from coronavirus strongly implied that hypertension was an independent risk factor for severe disease and death.

Bloomberg and many other seemingly reliable news sources relied on one Chinese doctor’s anecdotal statements along with a Lancet article to make this claim:

“A top Chinese intensive care doctor told Bloomberg that of 170 patients who died in January in Wuhan, nearly half had hypertension, and anecdotally he said that he and other doctors have noticed hypertension is prevalent in those who die.”

However the actual Lancet report on 191 patients published March 11, 2020 , entitled Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study did not find hypertension or heart disease to be an independent risk factor for severe respiratory disease or death.

Of the 191 patients, 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).

Although patients with hypertension were more likely to die than those without hypertension this does not prove hypertension is an independent risk factor

Age was by far the most significant risk  factor and the older patients also had more hypertension. When all variables were factored into an analysis, hypertension and heart disease were not significantly related to death:

Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission

Heart disease and hypertension were not significant factors after accounting for age.

Nephrology Journal Club (NephJC) has an excellent discussion (frequently updated and well-reference)  on this topic here. After looking at all current publications in this area they agree with me that the current data do not support the idea that hypertension is an independent risk factor for either getting SARS-CoV2 or having a more serious illness from it.

Among the patients with COVID-19, it seems the prevalence of prior h/o HT is higher in those who develop severe disease than those who do not. Same applies for development of ARDS or death – but mostly in unadjusted analysis. See table below for more. The last two rows are the best quality data so far, and suggest the association between COVID-19 severity and hypertension is attenuated after adjustment.

updated HT table.JPG

Sources: Guan et al, NEJM; Huang et al, Lancet; Wang et al, JAMA; Zhang et al, Allergy; Zhou et al, Lancet; Wu et al, JAMA IM; Italian report (PDF); Chen et al, BMJ; Shi et al, JAMA Cardiol; McMichael et al, NEJM; Guo et al, JAMA Cardiol; Bean et al, MedRxiv 2020; Petrilli et al, MedRXiv 2020

As can be seen, most of the studies except the last two, did not adjust for age. Even age-stratified association of hypertension would have been a more useful way to see these data to understand this issue a bit better. We hope more data in coming days will clarify this relationship. Unlike what we stated earlier, the Zhou et al study did not adjust for hypertension.

Source: AHA website , using NHANES data

Source: AHA website, using NHANES data

As can be seen above, hypertension in the general population closely associates with increasing age, hence any association with hypertension may merely represent confounding due to age, and should be interpreted after careful analysis.

The Question Is Definitively Answered

The speed at which data and studies are being published on Covid-19 is so rapid that a study has been published since I began writing this post which I feel definitively answers my title question.
Using observational data on 8910 hospitalized patients in 169 hospitals in Asia, Europe, and North America, investigators examined cardiovascular factors that were associated with in-hospital death.
Surprisingly, in this database, although the average age of the 515 nonsurvivors was 56 years versus 49 years for the 8195 survivors, there was no difference in the prevalence of hypertension. In fact survivors had a slightly higher prevalence of hypertension (26.4% versus 25.2%) despite being younger than the nonsurvivors.
A multivariable logistic-regression model identified age>65 years, coronary artery disease, heart failure, arrhythmia, COPD and current smoking as independently associated with in-hospital death.
nejmoa2007621_f1
Hypertension was not independently associated with in-hospital death.
Interestingly, patients receiving ACE inhibitors and statins were substantially less likely to die.
In Summary
  1. Hypertension does not put you at a higher risk of serious illness or death due to Covid-19.
  2. As discussed in previous posts (see here and here), there is no reason to stop taking your ACE inhibitor or angiotensin receptor blocker (ARB) blood pressure medication during this pandemic. (Also don’t start demanding you be put on an ACE inhibitor-the protective association seen in one study does not prove causality, we need randomized trials to show drugs safety and effectiveness!)
  3. Be very skeptical of early anecdotal reports and small trials rushed to publication (especially “preprints” which have not been peer-reviewed) during Covid-19. The poorly substantiated claims that hypertension was a major risk factor for death and that ACE inhibitors increased patient’s risk during Covid-19 have proven false. As better data emerges regarding hydroxychloroquine, despite enthusiastic anecdotal reports from some physicians, this drug has not been proven safe and/or effective for Covid-19 treatment.

Skeptically Yours,

-ACP

 

A Reliable Source for Reliable Sources During Covid-19

It is a daunting task tracking down reliable information during Covid-19. Misinformation tends to spread like …the coronavirus. The Baker institute Blog is providing excellent succinct summaries of reliable information and sources as the pandemic evolves.

The post below  originally appeared on the Baker Institute Blog April 20, 2020  and was  coauthored by Vivian Ho, Ph.D. (@healthecontx), James A. Baker III Institute Chair in Health Economics, Kirstin Matthews, Ph.D. (@stpolicy), Baker Institute  Fellow in Science and Technology Policy and Heidi Russell, M.D., Ph.D., Associate Professor, Department of Pediatrics, Baylor College of Medicine and Associate Director, Center for Medical Ethics and Health Policy, Baylor College of Medicine.


Having finished our fifth week in isolation, we are encouraged that the nation may have passed its peak date for the number of new cases and new deaths. We update you on efforts to identify treatments for the coronavirus, as well as policymakers’ discussions on when to reopen the economy, what that might look like, and where government funding should be directed. Previous issues are posted here.

Epidemiology and Treatment

Health experts warn us not to expect a single peak day in terms of new cases, deaths, or otherwise. Daily reports of new cases and deaths can fluctuate depending upon the availability of tests and delays in reporting. The New York Times’ juxtaposes a bar graph of the number of new cases by day with a line calculating the 7-day average of these numbers, indicating that the number of new cases has fallen to less than 30,000 per day. The 7-day average of new deaths also has begun to fall, to roughly 2,000 per day.

On Friday Worldometers estimated that 58,000 people in the U.S. have recovered from the coronavirus. Mark Lipsitch, an epidemiologist at Harvard University, provides a compelling case that most individuals who contracted the virus will have an immune response, some better than others. He suggests that the immune response will offer some protection over the medium term — at least a year — and then its effectiveness might decline. This view that contracting the virus yields only temporary immunity, is shared by other experts. Thus, treatments and a vaccine for COVID-19 are crucial in ultimately conquering this pandemic.

To date, researchers and drug companies have launched over 100 human experiments to identify treatments for the coronavirus. However, an article in the Washington Post warns that the lack of coordination across investigations could generate numerous small-scale trials with conflicting answers. For example, there are more than two dozen separate U.S. trials listed for the anti-malarial drug hydroxychloroquine. Some use the drug as a preventive, others as a treatment; some in combination with other drugs, and some with no comparison group. Information from multiple investigations is often better, but coordination across these studies could have yielded larger sample sizes and cleaner study designs, so that results could be used to prioritize treatments. Francis Collins, director of the National Institutes of Health has been working behind the scenes to launch an unprecedented public-private partnership to achieve better coordination.

In the scientific journal Immunity, researchers review the COVID-19/SARS-CoV-2 vaccine development and its challenges  In addition, the WHO cataloged a long list of potential candidates, and an article from “The Scientist” describes frontrunners that hoped to be tested this year, providing details on each vaccine’s approach to target the virus as well as preliminary evidence. Meanwhile, fake news regarding causes of and treatment for coronavirus are circulating through social media. The World Health Organization (WHO) has posted a series mythbuster infographics to dispel rumors such as one that 5G mobile networks spread COVID-19.

Policy Response

Public health experts continue to emphasize that passing the peak number of cases or deaths does not mean that the pandemic is over, and that we will need to maintain social distancing in one form or the other for months to come. More than a dozen states have extended stay-home orders past the White House deadline of April 30th. In the meantime, governors on the east and west coasts were reported last Monday to have formed pacts to decide when they would reopen their economies. Governors of Midwest states followed suit soon afterwards. These pacts will draw on facts and science to create plans to re-open each state in a way that limits new outbreaks of coronavirus. Among the steps are contact tracing, treatment and social distancing measures.

For example, last week we highlighted the recommendation for A National COVID-19 Surveillance System which included capacity to conduct 750,000 coronavirus tests per week. Unfortunately, most parts of the country report test supply shortages that remain “crippling.” Experts emphasize the need for contact tracers, to identify those who could have contracted the virus by coming into contact with someone who has tested positive for the virus. Policy makers are acting on that recommendation, with the C.D.C. planning to hire hundreds of contacts tracers and, it is in discussions to divert 25,000 Census Bureau workers to do contact tracing in the coming weeks and months. Experts suggest that employers can do their part to reduce the spread of coronavirus by offering screening at their place of business. Employers can help workers to safely self-isolate at home and work with local health authorities to improve contact tracing.

As TIME magazine stated, “Public health experts have savaged President Donald Trump’s decision to cut U.S. funding to the WHO.” Critics include U.N. Secretary General António Guterres and the editor-in-chief of the Lancet medical journal, who called the decision “a crime against humanity.” The administration is reportedly withholding funds, because the WHO failed to adequately investigate early information about the virus’s ability to spread between humans and for not criticizing China for its lack of transparency over the virus. This view is echoed in an article in The Atlantic, which points to structural problems at the WHO that make the organization vulnerable to misinformation and political influence, in this case by China. Nevertheless, the U.S. pays for about 22% of the WHO’s budget. Cutting funding for international public health initiatives in the midst of a crisis could have dire consequences for Americans in the future.

Health and Human Services is distributing the first $30 billion in emergency grants to hospitals and doctors from the CARES Act according to their historical share of revenue from the Medicare program for seniors — not according to their coronavirus burden. States lightly hit by the coronavirus, such as Minnesota, are getting more than $300,000 per COVID-19 case, while New York is receiving $12,000 per case. The HHS decision raises the prospects that hospitals in hard-hit areas will be weighing their financial health more heavily than patient well-being for each additional COVID-19 case that comes through their doors.

On the Medical Frontlines

Evidence of strain on the healthcare workforce continues to mount.  The Centers for Disease Control (CDC) published a report estimating at least 9,282 United States health care workers have been sickened by COVID-19, and at least 27 died.  This is likely an underestimate because of how local or state authorities report cases. The CDC concluded that approximately half of these providers were exposed in their workplace.  The worse outcomes were in the over 65 workforce, although death and critical illness occurred at all ages. The first installment of a bi-weekly survey of medical staff across the country was performed by MedPage Today.  The responses suggest that regional variation in the share of the healthcare workforce that is temporarily out, critically ill or dead because of COVID-19 lies between 1% and 20%.  The proportions are much higher in concentrated areas like New York.  For an in-depth account of healthcare workers who died from COVID-19, we applaud the stories found in Lost on the Frontline.

Healthcare workers are particularly at risk when performing nasal swabbing to test for the coronavirus, which requires the provider to stand directly in front of the person being tested. The swabbing generates a natural reflex to cough or sneeze, sending droplets into the air. To that end the first COVID-19 test of saliva was approved by the FDA this week.  This new test will allow patients to spit into a vial and hand it back to the health care worker. The test is not yet available in most health care organizations, and questions remain about its accuracy. But as these hurdles are overcome, this safer, simpler testing would also circumvent the shortage of nasal swabs that is hindering test availability across the country.

In the coming we week, hopefully new cases of the coronavirus and daily death toll continue to decline. We are most concerned about the continuing short supply of coronavirus tests. We hope that federal, state, and local governments aggressively pursue efforts to hire and train contact tracers throughout the country. Debate has begun on what role smartphone apps by Apple and Google could play in contact tracing, and we will follow that discussion closely. We also look forward to reviewing state governors’ developing plans to reopen their economies.


Still socially distanced but ever skeptically Yours,

-ACP

Aaron Carroll Answers Forty Coronavirus Questions In Twenty-Two Minutes

In these times of great uncertainty, the public has lots of questions about the coronavirus. Finding good answers can be exhausting.

Aaron Carroll, at The Incidental Economist, is providing lots of high quality, easily digestible answers to his followers through a series of videos he has created.

I’ve been following his writing for some time and enthusiastically reviewed his book about diet and diets, The Bad Food Bible, in 2018:

I recently discovered a food/diet/nutrition book which with I almost completely agree. The author is Aaron Carroll,  a pediatrician, blogger on health care research (The incidental Economist) and a Professor of Pediatrics and Associate Dean for Research Mentoring at Indiana University School of Medicine.

He writes a regular column for the New York Times and covers various topics in health care. His articles are interesting,  very well written and researched and he often challenges accepted dogma.

Like the skeptical cardiologist, he approaches his topics from an unbiased perspective and utilizes a good understanding of the scientific technique along with a research background to bring fresh perspective to health-related topics.

Yesterday, he posted an updated video addressing 40 COVID-19 questions which may answer one of your many questions. Total duration is around 20 minutes.

More COVID-19 Questions & Answers

Skeptically Yours,

-ACP

Should You Be Wearing a Mask in Public During Covid-19?

President Trump announced yesterday that the CDC is advising “the use of nonmedical cloth face covering as a voluntary health measure.”

The CDC website today states:

CDC recommends wearing cloth face coverings in public settings where other social distancing measures are difficult to maintain (e.g., grocery stores and pharmacies), especially in areas of significant community-based transmission.

CDC also advises the use of simple cloth face coverings to slow the spread of the virus and help people who may have the virus and do not know it from transmitting it to others.  Cloth face coverings fashioned from household items or made at home from common materials at low cost can be used as an additional, voluntary public health measure.

For a detailed and well-referenced article on the argument for wearing a mask in public I recommend this article ( Should You Wear a Mask in Public for Coronavirus? — Diet Doctor). 

Yes. Research shows that any barrier — tea towel, pillow case, vacuum cleaner bag — provides some protection and is better than nothing. The layer of fabric, or even paper, across the nose and mouth creates an obstacle to respiratory droplets, helping reduce the viral load that you either exhale upon someone else or they exhale upon you.

The article features this powerful graphic:

In addition to persuasive arguments for everyone wearing a mask in public, the article gives good information on mask creation and handling.

The CDC website  gives very detailed instructions on how to create the facial barrier at home and how to clean and disinfect them.

You can create one by sewing or non sewing methods. Helpful graphics are included:

You can also use a coffee filter and bandana to create a mask

 

Turbulent Gas Clouds

 

I became a believer in universal masking during Covid-19 after reading an article entitled “Turbulent Gas Clouds and Respiratory Pathogen Emissions Potential Implications for Reducing Transmission of COVID-19″ published March 26 in JAMA insights.

Figure 1 from that paper below shows a sneeze cloud projecting up to 8 meters.

The author notes

Recent work has demonstrated that exhalations, sneezes, and coughs not only consist of mucosalivary droplets following short-range semiballistic emission trajectories but, importantly, are primarily made of a multiphase turbulent gas (a puff) cloud that entrains ambient air and traps and carries within it clusters of droplets with a continuum of droplet sizes

Owing to the forward momentum of the cloud, pathogen-bearing droplets are propelled much farther than if they were emitted in isolation without a turbulent puff cloud trapping and carrying them forward. Given various combinations of an individual patient’s physiology and environmental conditions, such as humidity and temperature, the gas cloud and its payload of pathogen-bearing droplets of all sizes can travel 23 to 27 feet (7-8 m).

I’ve included additional comments from this paper at the end of this post for those with strong stomachs.

Universal Masking In Hospitals/Clinics

An opinion piece   published April 1 in  NEJM is less enthusiastic about the benefits of universal public masking

We know that wearing a mask outside health care facilities offers little, if any, protection from infection. Public health authorities define a significant exposure to Covid-19 as face-to-face contact within 6 feet with a patient with symptomatic Covid-19 that is sustained for at least a few minutes (and some say more than 10 minutes or even 30 minutes). The chance of catching Covid-19 from a passing interaction in a public space is therefore minimal. In many cases, the desire for widespread masking is a reflexive reaction to anxiety over the pandemic.

However, these authors feel that universal masking in hospitals may be beneficial for two reasons:

The first is during the care of a patient with unrecognized Covid-19. A mask alone in this setting will reduce risk only slightly, however, since it does not provide protection from droplets that may enter the eyes or from fomites on the patient or in the environment that providers may pick up on their hands and carry to their mucous membranes (particularly given the concern that mask wearers may have an increased tendency to touch their faces).

More compelling is the possibility that wearing a mask may reduce the likelihood of transmission from asymptomatic and minimally symptomatic health care workers with Covid-19 to other providers and patients. This concern increases as Covid-19 becomes more widespread in the community. We face a constant risk that a health care worker with early infection may bring the virus into our facilities and transmit it to others. Transmission from people with asymptomatic infection has been well documented, although it is unclear to what extent such transmission contributes to the overall spread of infection

Personally, I am convinced of the benefits of mask wearing and I will be wearing one when I go to my office.

Skeptically Yours,

-ACP

N.B. More about turbulent gas clouds.

Importantly, the range of all droplets, large and small, is extended through their interaction with and trapping within the turbulent gas cloud, compared with the commonly accepted dichotomized droplet model that does not account for the possibility of a hot and moist gas cloud. Moreover, throughout the trajectory, droplets of all sizes settle out or evaporate at rates that depend not only on their size, but also on the degree of turbulence and speed of the gas cloud, coupled with the properties of the ambient environment (temperature, humidity, and airflow).

Droplets that settle along the trajectory can contaminate surfaces, while the rest remain trapped and clustered in the moving cloud. Eventually the cloud and its droplet payload lose momentum and coherence, and the remaining droplets within the cloud evaporate, producing residues or droplet nuclei that may stay suspended in the air for hours, following airflow patterns imposed by ventilation or climate-control systems

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.

Screen Shot 2020-03-28 at 9.29.35 AM

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