Low Interest Rates Versus Helicopter Money

This NYT piece catalogues the implosion of corporate debt that CEO's could not resist because the Federal Reserve kept interest rates so low.  Had stimulus been in the form of simply giving people at the bottom money to spend, we would not have this junk debt hangover.  

Who's Profiting from the Coronavirus Crisis?

Air Travel and Aerosols

WaPo piece on the issue.  

For my wife to get back she will have to do 10 hours in the air between Moscow and DC plus a connecting flight to get to Moscow.  Probably 15 hours total including time on the ground.  I was thinking she might be able to come in July.  But the more I think about it, the risk is probably too high.  

Aerosols

Airborne Coronavirus Detected in Wuhan Hospitals

This is not really surprising.  The very efficient spread on ships suggested that the infection was spreading through ventilation systems.  In hospitals, air handing is an important issue with concentrations of infected patients shedding virus particles through their exhalations and fluids.  

The hospital standard is 6 air changes per hour (ACH), meaning that all of the air in a patient's room must be replaced six times an hour.  This standard appears to have been adopted in 2001 when it was increased from 4 to 6 ACH.  This 2014 engineering article suggests that the standard is a consensus guess rather than a research-based conclusion.  

Especially if Covid-19 patients are concentrated on a single floor, which is necessary to reduce the risk to other hospital patients and staff, the concentration of particles is almost certainly quite high.   This NYT opinion piece raised the issue of dose-response and the question of whether the severity of the illness increases with the amount of virus particles inhaled.  

These Coronavirus Exposures Might be the Most Dangerous

As with any other poison, viruses are usually deadlier in larger amounts.   

Smokers fare better?  Really?

Why are Smokers Being Hospitalized Less Often?

Yet Another Odd Effect

Covid-10 mimics Kawasaki disease in young children.

Italy, UK explore possible COVID-19 link to child inflammatory disease

Epidemic of Political Malpractice

An Epidemic of Political Malpractice

Eventually, someone is going to write a history of the 2020 pandemic.  The central theme will be that it was as much a political as a medical problem.  It will be a story of how people with political power made choices in their personal self-interest that facilitated the spread of the infection and greatly amplified its effects.   

It began with the local communist party officials in Wuhan.  This New York Times piece describes how, after the close call with SARS, a sophisticated reporting system was put in place to identify similar outbreaks and reduce the opportunity for political interference.  To the world's great loss, that system fell victim to the instinct to suppress bad news it was designed to overcome. 

China Created a Fail-Safe System to Track Contagions.  It Failed.

It continues today with politicians who try to gain or maintain political power by opposing the only available tools of control when there is no cure and no vaccine.  Reducing the opportunity for people to infect each other is the only method we've got.  It is very disruptive.  No one likes it.  So it is easy to gain a following by criticizing it.  

The virus cannot reproduce on its own.  It requires the machinery of the human body to make copies of itself.  So human beings are the factories that make the virus.  

Humans not only make copies of the virus, they also help it to propagate.  The copies populate bodily fluids and ride them out into the world.  Some of them will make their way into another human host who is added to the virus-making productive capacity.  

The process of infection is so efficient that the growth in virus-producing capacity is geometric.  It can cause the number of virus factories to double every few days.  The power of doubling is humbling because the numbers get very big, very fast.  Half a million becomes 4 million in just three cycles.  

The opponents of the bitter medicine prescribed by epidemiology can legitimately argue that the economic consequences of lock-downs will produce bad health effects of their own.  It is undeniable that people having less money and losing health insurance will limit access to healthcare and lead to a different set of problems.   The question comes down to which set of problems is worse.  

Despite the human cost, perhaps it would be best for everyone if the "let 'er rip" approach were tested in a few places so we would have evidence of which path costs more in human suffering.  It appears likely that the US may provide some experiments of this type as officials in red states avoid adopting measures or dial back measures that are in place.  The citizens of those states will be the nation's guinea pigs, some willing and others not.  

Thrombotic Stroke

The platelet activation by free hemoglobin was attractive as a building block for an argument that cell-free hemoglobin was behind the Covid toes and livedo reticularis that some people with Covid-19 seem to get.  The thought was that vasoconstriction caused the former and blood clots caused the latter.  That idea seems to be grinding to a halt. 

But something is going on with blood clots.  

Young and middle-aged people, barely sick 

with Covid-19, are dying of strokes

What I can't Find

I have been unable to find anything that says whether Covid-19 patients have normal levels of nitric oxide (NO).  I have, in contrast, found multiple references to inhaled NO therapies being trialed.  

I have been looking for something to support or refute the idea that the coronavirus depresses NO levels by causing hemoglobin to leak out of red blood cells and into the blood plasma.  It was the idea that low NO levels might be causing the Covid toes phenomenon that started me down this path.  

It's not a direct refutation, but I found the reason why there is no blood test for NO.  

"Direct NO detection in blood is very challenging due to its high reactivity with cell-free hemoglobin that limits NO half-life to the millisecond range." 

So if NO in the blood is always zapped within milliseconds by cell-free hemoglobin, it's hard to see how a little more spilled hemoglobin could alter the normal picture if NO is "scavenged" out of the blood in milliseconds in healthy people.  

In passing, I found this odd thread of research that says humming increases the level of NO in the nose and sinuses.   Who would have ever guessed that.   But the original research seems to have been replicated.  

So at this point, it seems there is a lot of interest in NO supplementation as a therapy.  As to the secondary question of how it helps, the answer seems to be the inhibitory effect on viral replication.  I cannot find any answer to my question about whether NO supplementation brings other bodily processes that are regulated by NO back to their normal range.  

Nitric Oxide and Coronavirus

The next search for "nitric oxide and coronavirus" led me to this paper that was published in the Journal of Virology in 2005.  It is useful to remember that the world dodged a bullet in 2003-2004 when the first SARS outbreak.  That was a classic case of a close call that was wasted.  

The Wikipedia article about it is well worth reading. 

Close calls are extremely valuable.  They alert us to a problem without our having to suffer the dire consequences the problem could cause if not corrected.  There should be a scientific discipline dedicated to the study of close calls.  Every organization should have a close call policy that requires the near-miss to be studied in detail, the causes identified, corrective measures implemented, and periodic testing done to confirm the measures have succeeded.  

Of course, we do not do this.  People hide close calls because they don't want to be criticized for whatever failing was responsible for them.  The 2003-04 SARS story foretold, in detail, what we have experienced with Covid-19.  The current narrative closely tracks what happened back then.  

It started in November, in China.  "Early in the epidemic, the Chinese Government discouraged its press from reporting on SARS, delayed reporting to WHO, and initially did not provide information to Chinese outside Guangdong province, where the disease is believed to have originated. Also, a WHO team that traveled to Beijing was not allowed to visit Guangdong province for several weeks."  [Wikipedia]  

Sound familiar?  The virus appears to have begun with bats and from spread to civets offered for sale in a Chinese wild animal market.  Bats, Civets and the Emergence of SARS  PubMed abstract only    A Chinese paper published in 2017 reinforced this conclusion.

Here is the link to the 2005 paper.  It concludes that nitric oxide (NO) impeded the SARS virus from replicating.   

Nitric Oxide Inhibits the Replication Cycle of Severe Acute Respiratory Syndrome Coronavirus.

I found a 2009 paper that cites it and proposes two mechanisms for how NO gets in the way of replication.  The chemistry is way above my head.  

Dual effect of nitric oxide on SARS-CoV replication.

This 2018 paper features chemistry that is even farther out of reach for me.  I think my weakness is in spatial reasoning, which seems useful in understanding organic chemistry. 

Post-translational modifications of coronavirus proteins: roles and function

Hemoglobin and Nitric Oxide (NO)

Continuing down the chain of associations, I tried searching on "hemoglobin and nitric oxide" and it turns out that hemoglobin, which is normally locked up inside the red blood cells aka erythrocites, can cause mischief when it escapes into the blood plasma. Once it is loose, free hemoglobin "scavenges" nitric oxide (NO), which is a very important regulatory chemical.  This reduces the available NO, messes with the regulation, and can lead to "vasoconstriction, decreased blood flow, platelet activation, increased endothelin-1 expression (ET-1), and end-organ injury...." 

As noted in a previous post, vasoconstriction is what reduces the blood flow to your toes in the cold. Platelet activation as used in this technical article, can be loosely translated as clotting. So maybe the Massachusetts investigators are on to something, but perhaps not for the reasons the reporter suggested.  It looks more likely that inhaling NO could be helpful by restoring this chemical to its normal level by replacing what was deactivated by the renegade hemoglobin.  It is not spelled out but it seems clear the authors of this technical article use the word scavenge to mean that some sort of chemical reaction happens between the free hemoglobin and NO that takes the NO out of circulation.  

The biochemistry of nitric oxide, nitrite, and hemoglobin, role in blood flow regulation 

Covid Toes to Nitric Oxide

The toes story talked about two symptoms.  One symptom was problems with the feet that resembled frostbite and the other was a condition called livedo reticularis.  The frostbite angle led me to search on "vasoconstriction and coronavirus."  

Vasoconstriction and vasodilation are two opposite states that our blood vessels assume, depending on the conditions.  If you break these words down, the meaning is easy to guess if you don't know them already.  Our blood vessels can either constrict or dilate.  

The more constricted the vessel is, the smaller the volume of blood that can flow through it.  Conversely, the more dilated the vessel is, the larger the volume the vessel can move.  When we are out in the cold, the vessels in our fingers and toes constrict to preserve heat.  On a hot day, they dilate so that our fingers and toes can radiate some of that heat back out into the air.  

I had never heard of livedo reticularis.  When you look it up, you see it is caused by blood clots.  So now we know that Covid-19 seems to be associated with both vasoconstriction and blood clots.  

My search turned up this story about Massachusetts General Hospital testing inhaled nitric oxide (NO) to see if it protects their staff from Covid-19.  Nitric oxide is a very interesting and important chemical the human body depends on for many different functions. 

Can Inhaling Nitric Oxide Treat - Or Prevent - Covid-19?

As the coronavirus story has unfolded, I have found scattered references to hemoglobin, including comments by a medical resident with direct experience treating Covid19 patients who speculated that it was somehow important to the disease process. 

I started watching for stories with a blood angle.  This one started me off on a chain of connections that seem to be hints about what could be going on at the molecular level.  

COVID Toes