TWiV 632 Recap: The Miasma of Anti-Think

TWiV 632 once again contains nuggets of great value. It remains the best source about SARS COV-2 and the disease it causes: COVID19, but it takes 2 hours to listen to, which has discouraged even many physicians from cleaving to it.

Apologies to the TWiV crew, but so many of my friends demanded a summary, I felt compelled. 
Here's the link to the actual show, which I highly recommend:

https://www.virology.ws/2020/06/29/twiv-632-countering-a-miasma-of-anti-think/

Daniel Griffin reviewed the dexamethasone study out of Britain which is likely an advance: As he has said previously, it looks as if COVID 19 typically has a one week phase during which, if you are going to be really sick with this disease, you feel ill then, with cough, fever, malaise, achy. It is during this time the virus is replicating full tilt.

Nuggets:
1. Many people, from 40-70%, especially younger folks, have few or no symptoms but shed virus prodigiously during this first week.
During this week is when antiviral drugs like Tosi and remdesivir may help by thwarting viral replication.
2. During the 2nd phase, the 2nd week, is when all Hell breaks loose and the immune system, in some patients, fires off like an ammunition dump hit by a rocket and "cytokine storm" explodes. 
During this phase glucocorticoids (cortisol, dexamethasone, hydrocortisone, prednisone) likely can make a significant difference in survival--the Brits showed a 30% reduction in deaths using dexamethasone. 
He is likely correct to say if dexamethasone helps likely all the members of this class will.

He does not explain sufficiently why this class of drugs had not been used more widely before this study: the fear was using a drug which dampens immune response in the face of an infective agent (i.e. the virus) you'd be stripping the body of its only defense against the virus, namely a fully functioning immue system (B cells and T cells, innate and adaptive immune systems.)
This diminishing of the anti infection firepower turns out to be offset by the benefit of protecting the body against the police called out to defend the body, because at this phase, it's the police, who start shooting good guys and bad guys alike, who cause most of the trouble.

Griffin repeats one thing which sets the Phantom's hair on fire: He once again recounts stories of a time when he was in training when medicine was practiced on the basis of pronouncements from pompous older physicians about how to practice based on the experience of these doctors rather than on controlled, prospective studies. Griffin trained in NYC (the Phantom estimates in the 1980's-1990's) and the Phantom can say with great authority the great majority of physicians at the teaching hospitals in NYC during those years made great efforts to support their recommendations by reference to the medical literature of controlled studies. Apparently, Dr. Griffin had some run ins with some officious, supercilious docs who thought their own experience was better than prospective, controlled, randomized studies and he has never quite recovered. 
But as Siddhartha Murkhurjee has pointed out, there are simply not enough studies for every question to be able to use studies to guide clinical practice in every question.
Another quibble, the Phantom has it on good authority that as far back as February all patients admitted to the Mt. Sinai hospital system with COVID 19 got glucocorticoids on admission but since there was no placebo arm and since the patients were given glucocorticoids in some cases while they were in the viral replication phase, the results were not encouraging. 

3. After patients get past the 1st two to three weeks, they are set ups for coagulation events: strokes, clots to the legs or feet cutting off arterial blood flow and requiring amputation and anticoagulation can save patients from this fate.

So treatment of patients infected has improved substantially and has been guided, increasingly, by better controlled studies.

Racaniello ruminated on how this siege is likely to end, along with Rich Condit: They think it will become like other coronoviruses before, a sort of ever present virus, which children will get, get over and be immune to, never really getting all that sick. There will then be no need for a vaccine because it will be controlled by herd immunity, but it will always be with us, like the other coronoviruses which give us the "common cold."
A vaccine sometime in the next 18 months would help save older members of our population, say people born between 1940 and 1970, who might not survive an encounter with this virus and will be long dead before SARS COV-2 becomes just another coronavirus. 

Brianne Barker noted that antibodies, which are made by B cells (and might be thought of as the small arms fire of the immune system) likely do not last long and even if they do, might not be very important in protecting against illness from the virus. It's the T cells, the heavy artillery, which may kill off the virus or at least protect against its worse ravages and there are no readily available, widespread tests currently being used to study or track T cell response. During a discussion of the emails she mentioned a $2000 machine which could be used to measure T cell function and could be used in studies of how the population is responding to SARS COVd-2.  But the big point is, even if we could readily measure antibodies, it may not be the antibodies which confer protection.

So that's the quick and dirty on TWiV #632.
Apologies to TWiV, but we need a brief summary.
NB: THIS IS NOT A SUMMARY AUTHORIZED BY TWiV OR ANY MEMBERS OF THE ESTIMABLE TWiV TEAM, WHO ARE STALWARTS, ONE AND ALL.

My Friend the Mulberry Tree

When I first moved to New Hampshire, to a new home built as a model for a new street there was an old tree in the front yard which I considered cutting down. 
I'm loathe to cut down any tree, which makes me a poor landscaper, but I respect things which have potential for longevity.

Van Gogh, The Mulberry Tree

This particular tree had, stuck in its lower limbs, a wooden barrel painted white which I asked the builder to remove but he referred me to his job foreman who told me the neighbors liked that barrel right where it was. Of course, there were only two other houses on the street and neither set of neighbors seemed to know the barrel was even there; that foreman knew the house was sold and made himself scarce never completing a single item on the list of final stipulations.

I climbed up and disassembled the barrel, no mean feat, and was left with the tree, which over the next 12 years shed branches and dared me to trim many others, which looked dried and unhealthy, but somehow bloomed each Spring.

It also sheds some sort of fruit, berries, which attracted one year a most stubborn skunk, who arrived around dusk and fed on the berries covering the ground. I flashed lights at this black and white marauder, banged pans, threw stuff but all that ever accomplished was the dousing of my dog with skunk perfume, a devilish stink to try to remove from a dog. I threatened the skunk with death by  bow and arrow, which made no impression whatsoever on the skunk, but horrified my good friend, a coyote aficionado and birder, who told me that skunk was only doing what any skunk would do when presented with a bounty of berries. For whatever reason, although the tree has every year shed bountiful berries all around its base, the skunk has not yet returned. 

Finally, this year, I googled the fruit and the leaves and discovered what I have growing in my front yard is a white mulberry tree. 

Mulberry trees can be male or female or both and some of the fruits can change from one "sex"--such as trees or flowers have sex--to the other. The berries on this tree clearly are both "male" and "female" side by side.

The tree is really too close to my front porch but it does shade a third of the lawn and under its branches the grass thrives, while the grass  beyond the reach of the branches, has burned to a crisp, exposed to full blazing sunlight most of the day.

This tree is host to squirrels, of course, but also to shifts of birds, a veritable bird hotel, with three large black birds, raucous as drunken sailors yesterday. You could only catch glimpses of them through the leaves. They might have been ravens, but more likely just big crows.  Some other song bird arrived today and it sounded like it had a bull horn. Never could see it, the leaves being too thick, but it just about rattled my windows with its voice. Through all this, sparrows, magpies, robins flitted around on the other floors of the tree, and it sounded like somebody had set up a roof top bar in the upper levels with lots of flapping wings. It's like having a disreputable hotel next door, with wild parties, loud scenes going on inside rooms you cannot see into but only hear through porous walls.  Today, a bouncer apparently threw a squirrel out of the joint: I saw him crash to the ground stagger to his feet, and scamper away. 

Red mulberries are native to New England but white mulberries are more Asian trees, where they are used to grow silkworms.

I have never seen a silk worm on this tree.

It had a hole in it, about six feet up the trunk which bleed some sappy fluid, but this sealed over about 2 years ago. Every spring, before it leafs up, I trim away branches which look dead to me, but what looks dead in a branch is not always telling: Some of the deadest looking branches beyond the reach of my trimmer tool have leafed up lushly now in summer. 

The first couple of years, I thought this an ugly tree, one of several ugly trees on my yard. I planted some river birches and I tended the paper birches planted along the lot line by the builder but the birches got borer beetle and have just about died out. They also bend over in heavy snows and they are beautiful but fragile and likely will have to be cut down and replaced with something more hardy. The Mulberry tree, however, shrugs off the ice and snow of New Hampshire winters and blooms again, fruits up in summer. It's earned my respect. 

Obadiah Youngblood White Mulberry 

To replace my failing birch trees, I'd consider Sycamores (London plain trees)  which I've admired in Central Park and elsewhere in New York City. These are beautiful, stately trees, with gorgeous, variegated bark and spreading limbs. 

But I think I'll let this Mulberry live out its life. We've come to tolerate each other, although I don't always like the crowd it attracts.

 Now, however, after 12 years, I sort of think of it as a friend. 

A Ride Along the New Hampshire Seacoast

When the Phantom decamped from inside the Beltway of Washington, D.C. his friends and neighbors were puzzled.  The DC suburbs have been a transient's place since just after World War II. People arrive for jobs with the federal government; administrations change; people move. 

But people also grow up in those suburbs and some return, reconnect with their childhood friends, and those folks tend to stay. 

And to go to New Hampshire! 

A rural state with only 4 electoral votes?  Purple on good years, but red mostly.

But then Phantom would explain about summer vacations at Lake Winnipesaukie and they'd say, "Well, I guess I can see that. But you're not living on the lake."

No, on the Seacoast. 

Obadiah Youngblood, Beach Plum

New Hampshire actually does have a seacoast, 18 miles of it and the biggest town, the most working class town, is Hampton, where the Phantom lives. As you progress north along the coast the towns get more and more upscale, North Hampton, Rye and finally Portsmouth. 

Portsmouth has two iconic churches--the Old North Church with its 165 foot steeple where everyone who was anyone after 1638 visited, Washington, John Paul Jones, and later Daniel Webster was a deacon there. And South Church, home to the U-U, a Unitarian church with a poster near the door which says: "Don't Believe in God? That's all right. Come on in!"

Portsmouth has an ornate theater, the Music Hall which books famous performers who do not fill stadiums but who do fill large theaters in cities--Lilly Tomlin, Aaron Neville, Lyle Lovett, Art Garfunkel. And it has the Leftist Marching Band. 

On his bike ride today, the Phantom passed the new sand sculpture, which appears every year just up Rte 27 from the Old Salt restaurant, welcoming visitors, who have been late in arriving owing to COVID19. He was cheered to discover the bra-less mermaid is back. Several years ago she so shocked local residents the sculptor was cajoled into providing her with a bra, which ruined the whole thing. This year she has no bra, but no nipples, so a compromise has apparently been reached.

Tough birds to photo: Woodland Road

The tree shaded route takes the Phantom past homes which rival and surpass anything in Potomac, Maryland, and the money behind these can only be imagined. In Washington, the money was sort of expected, but where does it come from in New Hampshire? There are also trailer parks in parts of town, and other parts with very modest homes. 

Route 1A, which hugs the shoreline, is ocean on one side and gargantuan mansions along the shore, most of which are visited by their wealthy owners only a few weeks a year. An ex Mrs. Koch of Koch brothers fame owns one, and she flew a big Obama banner in 2008, much to the delight of local Democrats. She hasn't been heard from since.

Along the road back from the shore is the Runnymeade Farm where Dancer's Image was raised before he won the 1968 Kentucky Derby and there's a billboard out front to commemorate that. The billboard does not mention the most interesting part of that story: That after Martin Luther King was murdered, less than a month after the Derby, Dancer's Image owner donated the winning purse to King's Southern Christian Leadership Conference and the Kentucky Derby brass was so appalled they declared that somehow a urine from the horse showed up with a banned drug and they rescinded the win and declared another horse the winner--presumably a horse owned by someone who would not give the money to Martin Luther King's people.

1968--a year so like the present it makes one remember there are certain years where everything seems to happen intermixed with years where nothing much seems to change.

Obadiah Youngblood Rte 1 A Rocky Shore

But along that same road now are Trump signs and those Trump signs are sprinkled along many wooded roads from North Hampton to Hampton.

The folks in the Washington suburbs always said those suburbs were "not the real America" by which they meant, people living there were more sophisticated and more highly educated, not to mention wealthier than small town America.  Seacoast New Hampshire might be more "real America," but if it is, then America is a hard place to figure, a place of great contrasts, extreme income and wealth inequality and impenetrable political thinking. 

On a clear, crisp June day, however New Hampshire comes as close to a Hobbit shire as any place the Phantom has known, one of those places you leave when you have to go on a quest, but you always hanker to get back home. 

TWiV : A Reliable source on COVID

TWiV Episode 631 is one of their more important episodes.
Brianne Barker (immunology), Rich Condit and Vincent Raccaniello discuss papers which actually, this week, are very relevant to what our thinking and behavior should be, at least this week.
As always, they could use an editor, but if you have time walking the dog or on the bicycle, it's rewarding.

Key points:

1/ There is a saliva test from Rutgers available at some CVS's for the virus PCR, i.e. you can tell if you are shedding virus particles, which would suggest you are actively infected. On previous episodes they cautioned that the PCR picks up only parts of the virus, and some people shed long after they are clearly recovered, as if what they have in their saliva and throats are just wreckage, debris of the virus.

2/ An Italian study of 20,000 people suggest that in people below 30 years old as many as 70% infected with SARS CoV-2 (Covid19) are asymptomatic, i.e., could be silent spreaders--although previous episodes note more than 80% of infections were spread by 10% of infected people, "super spreaders."

3/ Some people who were infected no longer have the antibodies to the virus, made by B cells, but may retain immunity through their T cells.
Tests for T cell immunity are not clinically available.
Trying to figure out if a vaccine will effectively protect against the disease COVID19 may not be a simple matter of testing post vaccine antibodies, since even in their absence, T cells may have been programmed to protect.

4/ Vaccines now being rushed to production overwhelmingly are designed to attack the protein spike of the virus. But other components may be more important.  In fact, in order to be well protected vaccines might have to use more parts of the virus to achieve really adequate protection against the virus.

This is really worth listening to.

https://www.microbe.tv/twiv/twiv-631/

An Almost Real Story: Truman Capote, Non Fiction Fiction

Sitting on my front porch, looking out over the sprinklers refreshing the lawn, reading "Music for Chameleons" I could almost feel the presence of my mother.

It was not the emerald green lawn which prompted the memory of my mother, but the book I was reading. I wished she were there to talk about it.  The scene was not suburban at all:The Pierre Hotel, across from the Plaza, where the publisher of my first book took me for an early lunch. It was not quite 11:30 in the morning and the dining room had only two or three other diners, but the room was flooded with sunlight and beautiful as only some New York public spaces can be, elegant, understated, clubby and exquisite.

We had just sat down and the waiter had taken our drink orders but had not yet returned when a short, lurching cherub of a man flounced down the aisle between the tables, nearly fell flat, but caught himself on a table, righted himself and made his way to our table to say hello to the publisher, who introduced me.

It was Truman Capote, of course, and despite his bleary eyed haze he managed to methodically examine my face and his eyes lingered on mine for long enough to make any heterosexual man to feel uncomfortable, and I am one of those, but something about his detachment and helplessness put me at ease. He was what he was and I was what I was, and we would get past that.

"You were one of my mother's favorites," I told him truthfully.
"One," he said archly, "Of her favorites. Not the favorite?"
"You had some stiff competition."
Now he was interested and he swung onto a chair between me and my publisher, pulling up one leg under him so he sat on it at an angle which excluded the publisher, as if he were not even there, and he focused entirely on me."Now," he said, "You have my full attention." Somehow, that seemed like an accomplishment. "Who was my competition?"
"Katherine Anne Porter, " I said. "Among others, but mostly her."
"Well," he said. "I suppose I might forgive her a dalliance with another, of that quality."
"She had the advantage of proximity."
"Proximity?"
"We lived in Maryland, and Miss Porter taught at the University of Maryland, and she visited our house for a book club. All the teachers at my mother's school were in it,and they managed to get Miss Porter to visit."
"I might have liked that book club."
"They would have loved you."
"I'm sure."
"My mother loved watching you on T.V., being interviewed," I said. "She would stay up late to watch you on Johnny Carson if she read you were going to be on. And she had to be up early to go to work."
"T.V sells books," Capote said and looked over to the publisher in a conspiratorial way. "What we must do to sell ourselves."

With that he floated off the chair and off down the aisle toward the door to the bar.

"I published Katherine Anne Porter, you know," the publisher told me.
"I know."
"You never mentioned you knew her. You never mentioned her at all and you've been in my office, seen the books."
"It's not like I knew the lady," I said. "She just visited once, for a book club and left."

A crash exploded behind the publisher, several yards away. Capote had collapsed, taking a four foot  waiter's tray loaded with a water pitcher and glasses with him.
The staff helped him to his feet and he staggered out of the room.

"How pathetic," the publisher said. "Not even noon and he's falling down drunk."

"Wasted," I said. "Simply wasted."

Three years later, Truman Capote was dead. The publisher died three years after that.
Somehow, I managed to survive them. 
But today, we were all back together for a few minutes, my mother, too, on my porch, looking out over sprinklers, streams of water playing across the lawn. 
Music for Chameleons did that. 

Pearls from TWiV: Where We are for the moment

Listening to the last episode of This Week in Virology (#622) with a Dutch lady who does her virology at the NIH's Rocky Mountain Laboratory (RML), which is a level 3 facility where they don space suits to work with dangerous viruses, I realized how the information keeps changing but these scientists are fine with this.

TWiV remains, by far, the best source of information--I do not say "news"--about COVID19.  News organizations want to give you news, which is exactly what you do not want-- because news is only the first witness's testimony. You want to hear the whole story and you want to hear the witnesses cross examined-- and that's what TWiV gives you. 

Cast of Characters

As Rich Condit, a virologist living in Austin notes, "We don't learn as much from being right as we do when we are wrong. I've been wrong about so many things since January, but I've learned a ton."

Basic questions like whether or not the virus lives and circulates in the blood stream have been an ongoing question, and depending on which week you listen, and depending on the guest expert, you get a different answer: Daniel Griffin continues to say there is no significant viremia; today's guest,the virologist from RML, says there is no significant viremia for most respiratory viruses including influenza, but given the finding of virus in the liver of influenza patients, even viruses without much viremia, may have some. SARS COV-2 may be such a virus, with a brief but important viremic phase.  Other guests--one from NIH on episode 620, John Yewdell, have noted the renal disease and coagulopathies as suggestive of a viremia of significant magnitude. 

What is emerging consistently over time is the idea the virus enters the body through respiratory mucosa, nose, pharynx, lung and during the first week the virus enters the cells, replicates, multiplies and sheds and during this time the patient often feels pretty well, although may have symptoms of fever, fatigue, cough but it's during the second week you have "cytokine storm" when the innate immune system which is sort of the carpet bombing immune system, destroying whatever gets in its path, predominates. These are the hypoxic patients who wind up in the ICU's sometimes on respirators. 

During these first 2 weeks PCR testing for viruses is accurate and positive. Testing can be done by saliva with a Robert Wood Johnson test kit or by the "brain biopsy" deep nasal/pharynx swab but a simple nose swab or saliva tests are likely just as accurate, if you can find a place which does one but these tests do not tell you about infectivity and may be seeing only the detritus of battle, fragments of non infective virus and may be found 3-4 weeks after the infection has subsided. In stool PCR + fragments persists for over a month, again, not clearly infectious.

Obadiah Youngblood "Occohee"

A secondary wave of symptoms,recrudescent fever, cough, prostration can occur a month or 6 weeks after the first presentation. This may be a new infection with the same virus in the patient who has already had it once but is not immune or simply the virus re flaring, like a smoldering fire which suddenly explodes after the firemen have left. 

In children a widespread vasculitis involving coagulation defects with widespread organ damage from clotting occurs, rarely, but at Columbia's Children's hospital, they had 300 cases in a short few weeks. Three of 300 died, or something of that order.

Spread of the virus does not occur uniformly from all patients. There are "super spreaders" who are responsible for 80% of all cases although they are fewer than 10% of patients. This is a tricky number to pin down, but if true, what would that say about all our quarantine-ing? 

Other tidbits dropped off in discussion, but not supported with studies, are:
1/ The number of patients below age 50 who die is vanishingly low. All this quarantine-ing and shut down really is to save the elderly.

2/ The chance of getting COVID diminishes exponentially once you open the windows in a room or go outside, and yet transmission among people attending open air events like political rallies was well documented in the 1918 flu epidemic, although it's not clear if the virus was spread at the rallies or in bars and pubs afterward.

3/ Aerosolized virus particles on micron sized particles likely penetrate deep inside the bronchial tree whereas big droplets tend to get trapped by nose hair, in the anterior nose (tip) and sinuses. 

4/ Antibody testing, overall is accurate only 50% of the time, which means it's a flip of the coin whether your positive antibodies really do mean you had the disease.  
And then there's the question of whether having the antibodies means they will protect you against re infection. With other COVID viruses (the common cold viruses) the antibodies do not protect against reinfection with same virus, if if they do, only for a few months. On the other hand, measuring antibodies may miss the real protective cells--the T cells--which may protect you despite the low antibody levels. With re exposure, your T cells may protect you (as happens with some vaccines) and while they hold down the fort, the B cells ramp up antibody production to really whap the virus later. So simply measure "antibodies' may not tell us much, even if we could trust the accuracy of the antibody tests.

5/ Other Covid viruses stimulate antibodies, B cells which are reserve banks for production of antibodies on re exposure and T cells which are important memory cells. But B cell antibodies do not "sterilize" the virus, i.e. remove it, they simply "neutralize" the virus and keep it from reproducing. 

6/ Measles can "wipe the slate clean" when you get the real disease, rendering you susceptible to viruses you had developed previous antibody immunity to and oral (inactivated) polio vaccine can do just the opposite, stimulate an immune response to almost all new viral attacks, at least transiently, perhaps for a year.
Vaccines against measles do not wipe clean the slate, which is important to the discussion of anti vaxers claims that it's better to get the natural disease to be really immune to future infections. Actually, with measles, you'd far rather get the vaccine, so the rest of the cells protecting you against other viruses do not get wiped clean.