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Coronavirus

Coronavirus Update, 18 Mar

Does the old malaria drug, chloroquine, work for COVID-19?

It has recently been proposed that an old, already approved drug typically used for malaria, could be used to treat COVID-19. It has even been suggested for use by governments around the world.

I looked into the research on it and it doesn’t look promising. First, there are no tests in patients. All of the work is on cells growing in test tubes in the lab. The work is shown here in this chart. In the laboratory, high concentrations can stop the virus getting into cells by >80%, which is not bad. Unfortunately, when you compare the blood level achieved in humans when the drug is given orally to the level used in the test tube experiments, the scientists used 100-times as much drug as you can get in your body. It probably doesn’t so much are the very low doses in the body.

This is the nature of research and every bit of new data, if not directly, clinically useful, moves us forward.

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Coronavirus

Coronavirus update, 16 Mar

Coronavirus death rates by age, gender, and other diseases.

The risk of death is clearly co-morbidity related, so worse in patients with heart disease, diabetes, lung disease, or cancer..

My belief is that the age and gender relationships are ‘secondary’ and not real. They simply reflects that the older you are and if you are male, the more likely you are to already have the diseases/conditions that make the virus more severe.

Also important: the lack of/rare incidence in children does NOT mean they are not getting the virus; they are just strong and killing it rather than the other way around.

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Coronavirus

Coronavirus update, 1130 GMT 16 Mar

Diaries of 24 Viruses: How long they are asymptomatic, when & what symptoms appear first, and what can we learn.

Chart 1:

Our Chinese colleagues have published an important paper recently. The first chart shows 24 rows, each row an individual patient. The vertical brown line is the day of diagnosis. The gray boxes on the left, labelled with negative numbers along the top, are asymptomatic days before the diagnosis. They end backwards in time on the day of the probable infection.

This can never be known for sure of course, but this is a standard way to do this research. The beige color are the days in the hospital. Symbols are various tests done along the way. Their meaning is on the bottom.

Learnings:

1. It took 7 to 21 days from exposure to a clinical diagnosis of the virus.

2. Two patients, C5 and C6, had NEGATIVE DNA tests during that time, the one everyone wants to take. So in these patients the test was done too early (24 to 72 hours after exposure) and came back negative. They could have gone out and partied, thinking they could not transmit the disease.

3. I love patient C8! She’s a 95 year old woman who has symptoms, tests positive for 5 days, tests negative for two days, and is discharged on day 7! So there, virus; Girl Power!

3. Patient C4 and C9: A 5 year old boy and a 10 year old girl. So this DOES infect kids. School closings noted. Also, the 10 year old spent 21 days (and still there at time of publication) in the hospital, so, not a walk in the park for her.

4. The arrow at the right end is a patient cured, going home. Only 9 of 24 were discharged at the time of the paper and some are in the hospital for three weeks and beyond. This slow recovery impacts resources of course.

Chart 2:

This is a kind of worse case scenario, all in one family. Case 13 from the above table. The husband spent 48 hours in Hubei, where he picked up the disease. He then returned to his family, a wife, son, and daughter-in-law.

Learnings:

1. The husband, 67 years old, NEVER had any symptoms. He was admitted because of what happened to his family. And the DNA test, the ‘Gold Standard’ was positive four times in a row over six days, and then was NEGATIVE twice and positive twice. Why the variability? When you have no symptoms you have very little virus so you don’t test positive for it but you sure can pass it on.

SO YOU CAN TRANSMIT THIS DISEASE WITH SO FEW VIRUS COPIES THE DNA TEST IS NEGATIVE.

2. The wife, age 64, had a fever and cough three days before admission, tested positive on admission, and rapidly deteriorated and went into the Intensive Care Unit. She remained in serious condition at the time of publication.

3. The 35 y son had a fever and cough eight and five days, respectively, before the DNA test was positive. His DNA test was negative within five days of hospitalization and he was discharged after 16 days. So focus; a GOOD outcome for a patient who gets in the hospital is a 16 day stay. A resource problem.

4. His wife, age 36, had a fever and cough eight days before a positive DNA test, spent six days in the hospital and. went home healthy.

FINAL LEARNING:

A screening test should be quick, easy, cheap, give fast answers, and be highly sensitive.

That is, if I ask God to be my lab assistant (in medical jargon, absolute truth against which a test is going to be compared) and to give me 100 known coronavirus patients one week from being sick enough to go to the hospital, how many of that 100 can I pick up with my test? Combining other studies here tells me that 90 of these patients, one week before hospitalization, had either a fever or could not hold a big breath for 10 seconds without coughing.

So turning it upside down, if you pass both tests, you have only a 10% chance of being sick next week. It might be that the 10% are going to be like Case 13, who never had a symptom, but who are silent carriers. In this case only God knows they are sick.

So checking breath hold and temp, with 90% sensitivity, is not bad for two tests that are free and take less than 2 minutes!

Reference for above: https://link.springer.com/artic…/10.1007%2Fs11427-020-1661-4

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Coronavirus

Coronavirus update, 0020 GMT, 16 Mar

A tour inside the virus: Observations from sequencing all 30,000 letters in the virus from 512 patients

I last talked about this chart over a week ago. As you know, a lot changes in a week. The chart has almost doubled in complexity, thanks to the hard work, 24/7, of scientists from all over the world. Two things jump out at me, one a ‘fact,’ you can take to the bank, and one a ‘theory’ worth keeping our eyes on.

Before getting into the weeds here let’s review how to look at this chart.

First, if you are color blind you are going to need a color-reading friend to help you. Start with the map of the world. The colors are assigned as the location a patient was when the swab in the throat was taken and the virus was found. I wish they had stuck with the eight-crayon set I had in kindergarten instead of these beige tones but they have their reasons, I suspect. The bigger the circle, the more samples from that region.

Now the left side. Here is the genealogy, the family history of the coronavirus. While it reproduces without a mate, it still has new ‘generations’ going to the right in time, from Dec 2019 to Mar 2020. Every branch is a change in one letter in the 30,000 letters of the booklet entitled, ‘Instruction Manual for a Human Cell to Make a Coronavirus.’

By the way, since the typical book has about 1500 characters per page, this little horror story would be only 20 pages long! Not even Edgar Allen Poe could be so dark in so few pages! 🙂

The vast majority of these spelling errors don’t change the protein lego piece of the virus, which is where it interacts with the cell. Proteins are the action figures of life. The DNA/RNA are the instructions, which you follow, building your lego figures, until you have built your warrior, king, etc. and then you set the instructions aside. They truly are no fun!

If the DNA spelling error doesn’t change a lego piece in the protein, which is most of the time, it CANNOT, by the laws of biology, have a clinical impact on either the host or the virus. A few change the protein lego piece from one to another but, again, they are mostly, likely to have no clinical impact. They are just like those unique family ear, nose, toe, etc. (lego) shapes we all recognize at summer family reunions and picnics!

But now for two observations:

Observation One: Start at the first branch, what I have marked with a red and green arrow. The green arrow leads to 374 ‘children viruses,’ the red arrow leads to 138 ‘children viruses.’ So the ‘green virus’ has caused 73% of all of the cases anywhere in the world that have been sequenced. That’s a big difference.

When you follow the red arrow to the right and see where it’s children migrated to, you see the big, red cluster on the US. The second map shows the US up close with the bright red and ‘off red’ cases identified; here you see the Seattle epicenter as a big red dot.

When you search the top branch you see the occasional red dot, meaning in the US. But my estimate is that about three-fourths of all US cases can be traced to our ‘Patient Zero’ index case, a student who returned in mid-Jan from vacation in Wuhan to Seattle. One case in San Francisco is traced to him but it mostly stayed in WA state.

What does this mean? At this point the US cases are largely limited to the index case from China, and not from its largest concentration of active cases, Europe.

Second observation: this is raw speculation but it is important enough to keep in mind. Another cool feature of this chart on the website is that it tells you the exact page, line, and position of every letter change in the full 30,000 letter set. So you can see that, again an estimate, 80% of the cases make a change in the RNA which does not make a change in the lego piece in the protein it is the blueprint for. So by the rules of biology, these changes can NOT have a clinical significance. But the other 20% do change a single lego in the protein. While single lego piece protein changes are rare clinical events, two examples, sickle cell anemia and cystic fibrosis, involve a single lego piece change in the six billion letter human Book of Life which shows up a serious, life threatening diseases.

What if the higher rate of disease in Europe than in America and Australia is tied to a lego piece change in the proteins of this virus?

Only time will tell.

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Coronavirus

Coronavirus update, 1315 GMT, 15 Mar

Why is 75,932 an amazing number?

Because it is the number of people around the world who were infected with the coronavirus, got sick, got better, and are now completely recovered, moving their life back to normal.

They are 75,932 testaments we can get through this!

So let’s stop and give the Human Race a high five…

well no, a high wave…

ah, maybe from about three feet apart! 

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Coronavirus

Coronavirus update 1430 GMT

How to win? Taiwan’s response is best practice

This post is to compare confirmed cases in various countries and learn what works.

I constructed this simple chart. It ranks countries by the number of cases per million population.

Three points.

1. South Korea, China, and Taiwan are the only countries that have won the battle; cases peaked and have been diminishing for over a week. But their results are very different. South Korea has 80 cases for each one in Taiwan; China has 28 cases for each case in Taiwan. So this is a qualitative as well as quantitative difference.

More on the remarkable results for Taiwan below.

2. ALL other countries on this chart have many more cases than Taiwan AND are experiencing exponential growth, albeit at slightly different rates, but exponential none the same. The time it takes for a “one log growth” is six days to 10 days, depending on which country you are talking about. Translation: in a week, plus or minus a couple days, the case load as of today will be ten-times more. So Italy goes from 18,000 to 180,000; UK from 1140 to 11,400; Germany from 3953, to 40,000; US from 2340 to 20,000+. Remember previous posts on severity, etc. but for the next two weeks the absolute case number will be the story, the headlines. As of this writing 46% of cases are outside China; in next 72 hours you will see headlines “more cases outside of China than inside.”

3. I understand it is hard to teach a drowning man to swim. But at least in Germany, UK, and USA, there is still some time (a few days) to study what Taiwan did and slow the virus down.

This chart is completely self explanatory. You have to read it slowly, from top to bottom, and understand how they thought about the “triage” of three situations. The success here was not better doctors, nurses, technology, etc. These helped but the true success factor was people, one by one, over and over again, taking PERSONAL responsibility for staying in their house 24/7 for the 14 days if they found themselves in one of the situations on this chart. I have not seen a number but my estimate is well above 95% of people did their job.

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Coronavirus

Coronavirus update, 0900 GMT Friday the 13th

The Actuary’s Perspective: understanding risk

We humans are not very good at understanding risk; being struck by lightening, having a heart attack or getting cancer, or dying of the coronavirus, officially a “pandemic” as of this week.

We are told a group of people of a certain age, or preexisting condition, has an X% chance of dying from the coronavirus. But without being able to compare it to something we know as a background comparison, something in our pre-coronavirus real world, it is hard to understand.

Luckily, places like the CDC have stats galore. Table after table of the number of deaths per 100,000 of every age group. So let’s compare getting the coronavirus and recovering to just living, day after day, at certain points in life.

First thought experiment:

Which is safer, less likely to kill you? A: Being under 60 years old and getting the coronavirus, or B: Being any age, 15 years or older, and simply staying alive for 365 days, living from one birthday to the next.

If you picked A you are right! In Wuhan, about 28 people under age 60 out of every 100,000 died of the coronavirus. For comparison, according to the CDC, folks age 15-24 have a one year death rate of 80 per 100,000. So you are about three-times more likely to die just living for a year than you are of dying of the coronavirus. It goes up from there. So living one year, at any age after 15, is riskier than dying of the coronavirus! Skydivers excluded from this discussion! ?

Second thought experiment:

Let’s stack the deck against you.

In this experiment I will make you 75 years old, give you coronavirus and put you in the hospital. Are you on death’s door? No way. It’s still a pretty good risk. You have a 92% chance of leaving the hospital and returning to your life.

The other choice I will give you is being 75 years old and just living your life. We all know that if you are 75 years old, and even though you are active and having fun playing golf, taking long walks with friends, going to church, etc. you are at a higher risk of dying than you were when you were younger, say 30 years.

So how many years of just plain living at age 75, simply being alive, is the same as a hospital trip at age 75 with the coronavirus?

According to our friends at the CDC its about 19 months, about a year and a-half. I don’t want to scare you with this but as we all know, getting old is not for sissies; but the coronavirus doesn’t change your odds much one way or the other.

So everyone, have a good day! We’ll get through this!

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Coronavirus

Coronavirus update, 2335 GMT. Lessons from Wuhan

More regional lockdowns and social distancing recommended.

Regional lockdowns plus social distancing are MORE effective than a vaccine would be in stopping this virus from spreading.

Regional lockdown and social distancing measures seem to be beginning to work. Non-China growth rate approaching non-exponential but more measures will help

Evidence from China and South Korea that they are more effective than a vaccine:

Because of the lockdown of Hubei province, <10% of cases occurred in the remainder of China. Because of social distancing inside Hubei province, >99% of the total population of the province was NOT infected. A typical vaccine, by comparison, is >85% effective; this years 2019-20 influenza vaccine is about 50% effective.

However, because of the nature of this virus, there are many cases which will appear AFTER the above measures are put in place. Specifically, based on South Korea and China, the US will have up to 70 new cases for every case identified on the day those two measures are initiated. It also took 10 and 13 days, respectively, before the daily case rate peaked (growth rate of 1.0) in South Korea and China, after these measures were put in place.

True vaccines, of course, are prophylactic and so don’t suffer from this delayed action.

The true danger: given the limited quantity of US resources and the large number of potential cases, the public health reality is that patients in the US may have to experience this disease OUTSIDE of the modern medical environment, hospitals, doctors, etc. Truly draconian. 1800s style, when families would support their loved ones at home and recovery was dependent on the patient’s constitution and God. The healthcare of my Great-Great Grandparents.

Data and analysis used to reach the above conclusions:

Graph 1. This graph was prepared on Jan 27 for Wuhan, China. It shows the growth of cases in Hubei province over the previous nine days. The blue line (actual cases) and the brown line (calculated cases) are right on top of each other. ‘Perfect’ exponential growth. Hubei had 830 cases on the day of lockdown/social distancing (the red arrow).

Graph 2. This is the same graph as graph 1 but extending the trend line into the future (the future as of Jan 27). The virus is infecting 2.5 people per infected person and can be asymptomatic for five to fourteen days. This projects that on Feb 14, 100% of the people in Hubei province would be infected. It also projects 185 million infected people on Feb 21! All 7.7 billion of us on the planet at the time I am writing this post.

Pure, unchecked exponential growth is a Biblical, Book of Revelations, Apocalypse-level event.

Graph 3. Reality in China. Black arrow, the start of lockdown and social distancing. The purple, dotted line is the daily new cases, showing the continued growth for 13 days in daily cases after the lockdown. The brown is cases under the care of the health care system. Blue is recovered cases and red is deaths.

The total cases in all of China as of today, Mar 11; 80,796 cases. As you can see, exponential growth completely ‘flopped over’ as I call these kinds of graphs. As of today, >99% of the over 11 million people living in Hubei province did NOT get infected. Analysis shows 84% of all cases in China were in this province, only 16% had spread before the lock down.

But some dangers lurk in this chart. The patients identified in brown: who is taking care of those patients and where are they? ICU beds, total hospital beds, number of respirators, number of doctors/nurses, etc. couldn’t handle this level of disease in the US.

Graph 4. The growth of cases in South Korea (SK). The arrow on Feb 20 is the day after the case load jumped from 20 to 104 in 24 hours, attributed to a church gathering. From that point on it was reported the ‘streets were empty.’ By the time it leveled off there were 67 cases for each one case on Feb 20.

I don’t have an official lockdown date for SK so this may be more US-like. Look around America; are the streets empty where you live or not?

An interesting metric: how long it has taken different countries to go from 100 cases to 1000 cases? The longer, the better

China, 5 days; South Korea, 6 days; Iran, 6 days; Italy, 7 days; France, 7.5 days; Germany, 7.5 days; US, 9 days.

Graph 5. The daily growth rate for ‘the outside China’ world is at 1.04 for the last 24 hours. It has averaged 1.10 over the last seven days. Remember, a growth rate of 1.1 is a doubling of cases in a week; 1.04, a doubling in 18 days.

Only two countries have seen exponential growth peak and tapper off, SK and China, and the day before they peaked they were above 1.1. Qualified good news as it is probably unfair to compare two closed systems/countries to the world, where we still have places at the beginning of the growth.

P.S. – When Taiwan closed all school for two weeks over a month ago, I recommended the same thing for the US. We have had 48 cases and 1 death, the lowest in China neighbors, as of this writing.

Caveat: all of this is subject to the ‘garbage in/garbage out’ principle. It is impossible to independently verify ANY of the data provided by these countries. Keep that in mind.

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Coronavirus

Coronavirus Update 1120 GMT Mar 12

One test determines who lives and who dies.

Other new learning: hospitalized patients shed virus for 8-37 days so isolation is ALWAYS necessary inside the hospital

Okay, it is possible some of you will end up going to the hospital with a possible infection. A study published 72 hours ago from Wuhan teaches that, of all the diagnostic tests you can do when you show up at the hospital, and there are dozens, only ONE matters. This includes all blood tests as well as even chest x-rays.

Before diving into it I want to pause and say again, even if you end up in a hospital, like the 191 patients in this study did in Wuhan, China, in the middle of a completely swamped medical system, 72% of the patients still survived!

We’re going to make it through this folks!

Okay, preparing for the worst case scenario:

Write the words “d-dimer test” on a slip of paper and put it in your wallet or purse with your driver’s license/ID.

Why? read on:

Findings: A simple blood test called “d-dimer test” looks for blood clots. Every hospital in the world can run it. In this study, patients arriving at the hospital with a value above 1.0 microgram/mL had an ‘odds ratio’ (OR) of 18.4 of dying compared to patients below 0.5, who were defined as 1.0. Between 0.5 and 1.0 it was an increased chance of dying but not significant. This means you are over 18 times more likely to die if you fail this blood test. 93% of the folks above 1.0 at entry didn’t make it.

Age: NOT a factor. Don’t let them say ‘ you’re old so you will die more easily.’ While the average age of survivors (56 y) was younger than non-survivors (69 y) the impact of this difference was only an odds ratio of 1.1, or a 10% higher risk, compared to a 1840% increased risk for d-dimer!

Other organ problems: as expected, if you show up with this virus and problems with other organs you are worse off. Surprisingly, heart disease was the worse, OR 21.4; chronic lung disease, OR 5.4; hypertension, OR 3.1; diabetes, 2.9. So heart disease alone is worse than the d-dimer test but when the whole clinical picture is looked at heart disease drops out, leaving the d-dimer test. Detail: in this study they used something called the SOFA=Sequential Organ Failure Assessment for this part of the analysis. So tell them to calculate this as well.

Let’s thank the doctors on the front lines in Wuhan, China for putting this together to benefit the rest of the world!

The figure, which contains a clinical summary of surviving and non-surviving patients, contains the reference to the article in Lancet.

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Coronavirus

Coronavirus update, 1222 GMT, 11 Mar

Two topics today:

1. A simple test you can do to know you are NOT infected.

2. I think I found the Achilles Heel of the coronavirus.

What it is and three simple things you can do to not get infected and become the warrior Paris, who killed Achilles in the Trojan War.

Coronavirus Test:

This is a respiratory virus so, very early, even before you have a fever, it is multiplying quickly in your lungs. The daily test, to do before breakfast, for example, is simple. You and your kids make a game of seeing who can hold their breath the longest. Start with a big, full breath. If you can hold your breath for longer than 10 seconds without coughing, choking, having discomfort, stuffiness or tightness, really any symptoms from your lungs, it is VERY unlikely you have the start of an infection. Make a game of it with the kids.

If you can hold your breath without coughing for >10 seconds you are NOT infected yet with the coronavirus.

Two Caveats: it is very sensitive but not very specific. So every cold, dust, etc. will test positive. So DO NOT run to the emergency room if you can’t pass this right now. If you fail it you have no idea if you have this new infection. Conversely, if you pass it you are very unlikely to be infected at that moment. If you start doing it, you have a few symptoms, can’t make it 10 seconds, etc. and it starts to get worse, be sure to write down the time you tested it and a description of how it went, etc. Your healthcare provider will appreciate the timeline of these symptoms.

Second caveat: if you have asthma, are a smoker, have COPD, etc. it is likely you might have failed this test last year before this virus every jumped into a human. Unfortunately for you, the test may not ‘work.’

Not to put too fine a point on it, but if you can’t pass this test before getting infected, your baseline condition is one of the reasons you are at a higher risk of serious complications if you should get infected.

Achilles Heel:

This virus is nasty and diabolical and once it gets into a cell, human medicine has little to offer at this time.

The entire value proposition of a vaccine is to ‘train’ the immune system to have proteins that stick all over the virus just before it tries to enter the cell. Vaccines work by stopping or slowing cell entry. A virus is NOT technically alive and outside the cell it is as inert as a stone. So interfering with those little knobby things in the picture below with a $1 billion US vaccine may work in 18 months or so.

My idea was simpler and quicker: are there simple ‘environmental’ changes that could destabilize those spikes and maybe slow/prevent entry into the cell, not with an antibody, but with something else.

Single, infective coronavirus at pH 6 (a) and pH 8 (b).

Searching the US National Library of Medicine I found what might be an answer: a paper from 1990 that showed that a related (obviously not this one) coronavirus, which was stable for days in acidic solutions was inactivated within MINUTES in alkaline solution. Why is this important? because the virus will spend at least some time in your nose, mouth, and throat just waiting to get into your lungs. Acid/base reactions are the fastest chemistry in biology and an alkaline solution will quickly change the shape of the virus. if your nose and mouth are continuously alkaline it is inactivated before it ever gets into the lungs.

The red arrow shows how fast the virus losses it ability to infect at pH 8, alkaline conditions. The Y-axis is a log scale, so the 0.10 level is 10% of the viruses can still infect. 0.01 is 1% can still infect, etc.

The microscope picture shows normal virus in acid solution (a) and clumpy, misshapen viruses in alkaline conditions (b). But its not just looks that changed but the ability to infect cells. The next graph is how long the virus could still infect cells when exposed to different pH values. The Y-axis is a log scale. The numbers 5, 6, and 7 are normal pH values and at these pH values >90% of the virus can still infect after two days. But the lines at 8 or 9 (my hand-drown red arrow) show >95% of the virus in GONE within minutes at alkaline pH values!

So how do you get your oral cavity at pH 8, alkaline? If you do that whenever you are in the world you are giving yourself a science-based effort to NOT get infected.

First, almost every toothpaste is baking soda, alkaline pH. Teeth dissolve is acid (think cola drinks) and cavities are bacteria using acid to dissolve your teeth. So brush regularly.

Mineral water is also alkaline pH. Sip it all day to keep your mouth moist and alkaline. Just not drying out can help because if you wash the virus into the stomach it can be destroyed by gastric juices.

Second, change up that water bottle you sip on all day. Few drinks are alkaline, most juices are acidic and you can see from the chart that acid STABILIZES this virus. But two drinks are perfect: green tea (not acidic coffee, unfortunately) and mineral spring water, with bicarbonates. So fill your water bottle with green tea or mineral water and sip away, all day.

Green tea is naturally at pH 8, ideal. Don’t add sugar or lemon, which will lower the pH and make it useless. Sip it slowly as within a little while after you stop drinking your mouth will go back to acidic pH.

Finally, the Achilles Heel has a second target. Something called sulfhydryl (SH) bonds hold the different amino acid chains together. Lots of foods have natural SH bond breakers but the absolute best is asparagus. In fact, that special ‘smell’ is its sulfur-containing compounds. It is less clear this will work because it makes the INSIDE of cells rich in SH bond breakers not necessarily the outside but, what the heck, with a little Parmesan cheese, it might just add a second attack on the virus shell and in the worse case, it makes a delicious, side dish!

That ‘hot springs’ air about asparagus is one of the many SH bond breakers this vegetable has.

Reference for above study: “Conformational change of the coronavirus peplomer glycoprotein at pH 8.0 and 37 degrees C correlates with virus aggregation and virus-induced cell fusion.” Sturman LS, Ricard CS, Holmes KV. J Virol. 1990 Jun;64(6):3042-50.