WHO launches global megatrial of the four most promising coronavirus treatments

Kai Kupferschmidt and Jon Cohen in Science:

Drugs that slow or kill the novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), could save the lives of severely ill patients, but might also be given prophylactically to protect health care workers and others at high risk of infection. Treatments may also reduce the time patients spend in intensive care units, freeing critical hospital beds. Scientists have suggested dozens of existing compounds for testing, but WHO is focusing on what it says are the four most promising therapies: an experimental antiviral compound called remdesivir; the malaria medications chloroquine and hydroxychloroquine; a combination of two HIV drugs, lopinavir and ritonavir; and that same combination plus interferon-beta, an immune system messenger that can help cripple viruses. Some data on their use in COVID-19 patients have already emerged—the HIV combo failed in a small study in China—but WHO believes a large trial with a greater variety of patients is warranted.

Enrolling subjects in SOLIDARITY will be easy. When a person with a confirmed case of COVID-19 is deemed eligible, the physician can enter the patient’s data into a WHO website, including any underlying condition that could change the course of the disease, such as diabetes or HIV infection. The participant has to sign an informed consent form that is scanned and sent to WHO electronically. After the physician states which drugs are available at his or her hospital, the website will randomize the patient to one of the drugs available or to the local standard care for COVID-19. “After that, no more measurements or documentation are required,” says Ana Maria Henao Restrepo, a medical officer at WHO’s Department of Immunization Vaccines and Biologicals. Physicians will record the day the patient left the hospital or died, the duration of the hospital stay, and whether the patient required oxygen or ventilation, she says. “That’s all.”

More here.

Thursday Poem

Osmosis: in which molecules of a solvent pass through
a membrane to achieve equilibrium.

Osmosis

Example: I place my hand in a pool of salt.
Some stays. Some seeps into my skin.
Everything goes exactly where it’s supposed to.

Example: Prudencia Martín Gómez leaves Guatemala at 18
to surprise her husband in California.
Like most beings, most of Prudencia’s body is water.

When Prudencia is found
60 miles from the US-Mexico border,
a pile of clothes, limbs, and a puddle of wet sand,
is she the corpse?
or was she
the water?

If Prudencia is water,
and the desert is
a ground, then Prudencia went
exactly where she was supposed to.

If migration is a pipe
and employment is a sponge,
then Prudencia went
exactly where she was supposed to.

Some would like to build a wall,
and water always seeps through,
but much does not.

Most days, water dries in the bed of a pick-up truck
clutching a seven-year-old daughter.

Read more »

It’s All Just Beginning

Justin E. H. Smith in The Point:

Though mild, I have what I am fairly sure are the symptoms of coronavirus. Three weeks ago I was in extended and close contact with someone who has since tested positive. When I learned this, I spent some time trying to figure out how to get tested myself, but now the last thing I want to do is to go stand in a line in front of a Brooklyn hospital along with others who also have symptoms. My wife and I have not been outside our apartment since March 10th. We have opened the door just three times since then, to receive groceries that had been left for us by an unseen deliveryman, as per our instructions, on the other side. We read of others going on walks, but that seems like a selfish extravagance when you have a dry cough and a sore throat. This is the smallest apartment I’ve ever lived in. I am noticing features of it, and of the trees, the sky and the light outside our windows, that escaped my attention—shamefully, it now seems—over the first several months since we arrived here in August. I know when we finally get out I will be like the protagonist of Halldór Laxness’s stunning novel, World Light, who, after years of bedridden illness, weeps when he bids farewell to all the knots and grooves in the wood beams of his attic ceiling.

More here.

I had no immune system for months and avoided viral illness, and you can too

A. M. Carter in Medium:

I had a bone marrow transplant in 2017. Most people don’t really know what that is. In the simplest possible terms, it means that my doctors gave me a new immune system, by replacing my sick bone marrow with healthy bone marrow from my sister.

The transplant process is basically a blood transfusion, but instead of blood cells, I received new immune cells from the bone marrow, which then took over my body and made it their new home, thus giving me a new immune system that worked normally.

In order for the transplant to work, I had intensive chemotherapy to kill off my original defective immune cells. For a month before and for many months after my transplant (until the new immune cells fully took over), I did not have a functioning immune system. This means I was vulnerable to EVERYTHING.

Many transplant patients get weird infections that most people have never heard of. Many common viruses, that healthy people easily clear without a single symptom, become deadly in a person with no immune system to fight them.

More here.

Bill Gates says we can’t restart the economy soon and simply “ignore that pile of bodies over in the corner”

Theodore Schleifer in Vox:

Bill Gates rebuked proposals, floated over the last two days by leaders like Donald Trump, to reopen the global economy despite the Covid-19 coronavirus outbreak, saying that this approach would be “very irresponsible.”

Gates did not mention Trump by name, but the American president has said that he may decide to relax some of the country’s “social distancing” in order to jumpstart the country’s shut-down economy. Gates, the country’s leading philanthropist, has been among the most active tech leaders in using his resources to try and contain the virus.

“There really is no middle ground, and it’s very tough to say to people, ‘Hey, keep going to restaurants, go buy new houses, ignore that pile of bodies over in the corner. We want you to keep spending because there’s maybe a politician who thinks GDP growth is all that counts,’” Gates said in an interview with TED Tuesday. “It’s very irresponsible for somebody to suggest that we can have the best of both worlds.”

More here.

The Coronavirus Crisis Reveals New York at Its Best and Worst

Adam Gopnik in The New Yorker:

It happened slowly and then suddenly. On Monday, March 9th, the spectre of a pandemic in New York was still off on the puzzling horizon. By Friday, it was the dominant fact of life. New Yorkers began to adopt a grim new dance of “social distancing.” On a sparsely peopled 5 train, heading down to Grand Central Terminal on Saturday morning, passengers warily tried to achieve an even, strategic spacing, like chess pieces during an endgame: the rook all the way down here, but threatening the king from the back row. Then, when the doors opened, they got off the train one by one, in single, hesitant file, unlearning in a minute New York habits ingrained over lifetimes, the elbowed rush for the door. In the relatively empty subway cars, one can focus on the human details of the riders. A. J. Liebling, in a piece published in these pages some sixty years ago, recounted the tale of a once famous New York murder, in which the headless torso of a man was found wrapped in oilcloth, floating in the East River. The hero of the tale, as Liebling chose to tell it, was a young reporter for the great New York World, who identified the body by type before anyone else did: he saw that the corpse’s fingertips were wrinkled in a way that characterized “rubbers”—masseurs—in Turkish baths. Only someone whose hands were wet that often would have those fingertips. On the subway, in the street, nearly everyone has rubbers’ hands now, with skin shrivelled from excessive washing.

At the other end of the day, in Central Park late at night, the only people out were the ones walking their dogs. Dogs are still allowed to have proximity, if only to other dogs. They can’t be kept from it. The negotiations of proximity—the dogs demanding it, the owners trying to resist it without being actively rude—are newly arrived in the city. Walking home down the almost empty avenues, you could see the same silhouette, repeated: dogs straining toward dogs on long-stretched leashes, held by watchful owners keeping their distance, a nightly choreography of animal need and human caution.

More here.

Wednesday Poem

“A war footing is a matter of standing on one leg on a ledge of the Grand Canyon
in a ruthless wind imagining wings and immortality being superseded by wisdom.”
…………………………………………………………………………………………
—Adrian Barbarino

As I lay with my head in your lap, Camerado

As I lay with my head in your lap, Camerado,
The confession I made I resume,
what I said to you
…….. in the open air I resume:
I know I am restless, and make others so;
I know my words are weapons, full of danger, full of death;
For I confront peace, security, and all the settled laws,
…….. to unsettle them;
I am more resolute because all have denied me, than I could
…….. ever have been had all accepted me;
I heed not, and have never heeded, either experience, cautions,
…….. majorities, nor ridicule;
And the threat of what is call’d hell is little or nothing to me;
And the lure of what is call’d heaven is little or nothing to me;
Dear camerado! I confess I have urged you onward with me,
…….. and still urge you, without the least idea what is our
…….. destination,
Or whether we shall be victorious, or utterly
…….. quell’d and defeated.

Walt Whitman
from
Leaves of Grass

How blood from coronavirus survivors might save lives

Amy Maxmen in Nature:

Hospitals in New York City are gearing up to use the blood of people who have recovered from COVID-19 as a possible antidote for the disease. Researchers hope that the century-old approach of infusing patients with the antibody-laden blood of those who have survived an infection will help the metropolis — now the US epicentre of the outbreak — to avoid the fate of Italy, where intensive-care units (ICUs) are so crowded that doctors have turned away patients who need ventilators to breathe. The efforts follow studies in China that attempted the measure with plasma — the fraction of blood that contains antibodies, but not red blood cells — from people who had recovered from COVID-19. But these studies have reported only preliminary results so far. The convalescent plasma approach has also seen modest success during past severe acute respiratory syndrome (SARS) and Ebola outbreaks — but US researchers are hoping to increase the value of the treatment by selecting donor blood that is packed with antibodies and giving it to the patients who are most likely to benefit.

A key advantage to convalescent plasma is that it’s available immediately, whereas drugs and vaccines take months or years to develop. Infusing blood in this way seems to be relatively safe, provided that it is screened for viruses and other components that could cause an infection. Scientists who have led the charge to use plasma want to deploy it now as a stopgap measure, to keep serious infections at bay and hospitals afloat as a tsunami of cases comes crashing their way. “Every patient that we can keep out of the ICU is a huge logistical victory because there are traffic jams in hospitals,” says Michael Joyner, an anaesthesiologist and physiologist at the Mayo Clinic in Rochester, Minnesota. “We need to get this on board as soon as possible, and pray that a surge doesn’t overwhelm places like New York and the west coast.” On 23 March, New York governor Andrew Cuomo announced the plan to use convalescent plasma to aid the response in the state, which has more than 25,000 infections, with 210 deaths. “We think it shows promise,” he said. Thanks to the researchers’ efforts, the US Food and Drug Administration (FDA) today announced that it will permit the emergency use of plasma for patients in need.

More here.

The Tip of the Iceberg: Virologist David Ho Speaks About COVID-19

From Caltech Magazine:

Are you optimistic that these measures combined with research will be enough to combat the coronavirus?

I personally believe we will blunt this epidemic, but I think we wasted a good four to six weeks largely because of lack of testing and lack of a certain preparedness. But I think we could still make a difference and bring it under control with very harsh measures.

But again, are these measures sustainable? We’ve got to expect that businesses must reopen and schools must teach again. Whether it’s travel or sports or live entertainment, we’re going to have to return to some semblance of normalcy. But what are the measures that are effective and sustainable? That’s a question we as a society have to deal with. We need to buy time so that gradually the population will have a degree of immunity.

Most importantly, we need to buy time to allow science to deliver solutions. We’re going to have to develop drugs, antibodies, and vaccines. I think the mobilization by the scientific community, from my perspective, is amazing. So many people have mobilized and jumped on this and are contributing, from discovering small-molecule drugs that could block various enzymes of this virus to coming up with antibodies that could neutralize the virus.

More here.

Recalling Djuna Barnes, A Modernist Mover and Shaker

Jade French at the TLS:

As the subtitle of this collection of essays plainly implies, Barnes did modernism her way. She might have been ambivalent about the movement, resulting in what Daniela Caselli calls her “aesthetics of uncertainty”. But there is no doubting her credentials as a modernist mover and shaker: as a Left Bank journalist, an interviewer of James Joyce, the author of that late modernist masterpiece Nightwood (1936) and the beneficiary of Peggy Guggenheim’s largesse. Yet Barnes also slips away from easy chronology and canonization, not least because of her longevity. Born in 1892, she died in 1982, at the age of ninety, having outlived many of her peers by decades. On its dust jacket and between chapters, Shattered Objects acknowledges that longevity by featuring photographs of her in later life. The visual representation matters. Barnes’s reputation has long been framed as a story of decline – as that of a once dazzling author turned (by the mid-century) recluse.

more here.

Schlock Sculpture

Morgan Meis in The Easel:

When you look at the work of an artist like Richard Serra, or better yet, stand next to a classic Serra piece, you begin to understand how important the physical problem of balance and uprightness is for contemporary sculpture. Take one such classic work, Fulcrum (1987). The work consists of five fifty-five-foot tall slabs of COR-TEN steel. It dominates one of the entrances to the Liverpool Street station in London. Standing next to Fulcrum can be genuinely scary, all the more so when (and if) you realize that the huge slabs of steel are balanced one against the other simply by weight and angle. So, these slabs of steel can, theoretically, kill you. In fact, Serra’s sculptures have killed before and might do so again. Serra’s Sculpture No. 3 famously ended the life of a rigger named Raymond Johnson, who was crushed by it during installation at the Walker Art Center in 1977.

Hearing Serra talk about sculpture, it’s hard not to come away with the feeling that, while he has no desire directly to harm anyone with his art, he endorses a kind of aggressive and confrontational attitude toward artmaking. “Art, for the most part,” he has said, “is about concentration, solitude and determination.” The quietness of the steel versus the implied sense of power and violence-it is all part of the Richard Serra act.

More here.

Azra Raza talks about her book “The First Cell” with EconTalk host Russ Roberts

From the EconTalk podcast of The Library of Economics and Liberty:

Raza argues that we have made little progress in fighting cancer over the last 50 years. The tools available to oncologists haven’t changed much–the bulk of the progress that has been made has been through earlier and earlier detection rather than more effective or compassionate treatment options. Raza wants to see a different approach from the current strategy of marginal improvements on narrowly defined problems at the cellular level. Instead, she suggests an alternative approach that might better take account of the complexity of human beings and the way that cancer morphs and spreads differently across people and even within individuals. The conversation includes the challenges of dealing with dying patients, the importance of listening, and the bittersweet nature of our mortality.

More, including the podcast and a transcript, here.

Watch the Films of Éric Rohmer on His Centenary

Richard Brody at The New Yorker:

Those young movie nuts would launch the French New Wave, along with Rohmer, who was its virtual godfather; yet it took him two decades to put his ideas into practice. What made the difference for this group’s movies was a new mode of production—scant budget, small crew, rapid shooting. For Rohmer, these methods helped him fuse his way of filming with his way of living—and he lived a very strange life. (There’s a remarkable biography of him by Antoine de Baecque and Noël Herpe.) His practices—blending documentary and aestheticism, subjectivity and classicism—also made his characters’ romantic doings seem deceptively frivolous, their intellectual disputations ironically austere. The overarching subject of his films is avoiding the temptations of a false love (often but not always in the form of lust) while pursuing, awaiting, anticipating, or hardly even hoping for a true one. In a handful of films, such as the deeply disturbing “The Marquise of O” and his final film, “The Romance of Astrée and Céladon,” he tips his hand with the abstract extremes of his ideas—including the nearly impossible radicality of Christian love (which, in his view, is also romantic).

more here.

The Age of Surveillance Capitalism

Tim Wu at the NYRB:

To most people, the assertion that we are living in Skinner boxes might sound alarming, but The Age of Surveillance Capitalism goes darker still. Skinner, at least, saw himself as a do-gooder who would save humanity from its own delusions. His behavioral engineering was meant to build a happier humanity, one finally at peace with our lack of agency. “What is love,” Skinner wrote, “except another name for the use of positive reinforcement?”

Zuboff, in contrast, sees Silicon Valley’s project of behavioral observation in the service of behavior control as lacking an interest in human happiness (other than as a means); its goal is profit. That’s why Zuboff calls it “surveillance capitalism.”

more here.

the greatest threat isn’t the loss of human life but the loss of what makes us human

Jill Lepore in The New Yorker:

When the plague came to London in 1665, Londoners lost their wits. They consulted astrologers, quacks, the Bible. They searched their bodies for signs, tokens of the disease: lumps, blisters, black spots. They begged for prophecies; they paid for predictions; they prayed; they yowled. They closed their eyes; they covered their ears. They wept in the street. They read alarming almanacs: “Certain it is, books frighted them terribly.” The government, keen to contain the panic, attempted “to suppress the Printing of such Books as terrify’d the People,” according to Daniel Defoe, in “A Journal of the Plague Year,” a history that he wrote in tandem with an advice manual called “Due Preparations for the Plague,” in 1722, a year when people feared that the disease might leap across the English Channel again, after having journeyed from the Middle East to Marseille and points north on a merchant ship. Defoe hoped that his books would be useful “both to us and to posterity, though we should be spared from that portion of this bitter cup.” That bitter cup has come out of its cupboard.

In 1665, the skittish fled to the country, and alike the wise, and those who tarried had reason for remorse: by the time they decided to leave, “there was hardly a Horse to be bought or hired in the whole City,” Defoe recounted, and, in the event, the gates had been shut, and all were trapped. Everyone behaved badly, though the rich behaved the worst: having failed to heed warnings to provision, they sent their poor servants out for supplies. “This Necessity of going out of our Houses to buy Provisions, was in a great Measure the Ruin of the whole City,” Defoe wrote. One in five Londoners died, notwithstanding the precautions taken by merchants. The butcher refused to hand the cook a cut of meat; she had to take it off the hook herself. And he wouldn’t touch her money; she had to drop her coins into a bucket of vinegar. Bear that in mind when you run out of Purell.

“Sorrow and sadness sat upon every Face,” Defoe wrote. The government’s stricture on the publication of terrifying books proved pointless, there being plenty of terror to be read on the streets. You could read the weekly bills of mortality, or count the bodies as they piled up in the lanes. You could read the orders published by the mayor: “If any Person shall have visited any Man known to be infected of the Plague, or entered willingly into any known infected House, being not allowed: The House wherein he inhabiteth shall be shut up.” And you could read the signs on the doors of those infected houses, guarded by watchmen, each door marked by a foot-long red cross, above which was to be printed, in letters big enough to be read at a distance, “Lord, Have Mercy Upon Us.”

More here.

Can a century-old TB vaccine steel the immune system against the new coronavirus?

Jop de Vrieze in Science:

Researchers in four countries will soon start a clinical trial of an unorthodox approach to the new coronavirus. They will test whether a century-old vaccine against tuberculosis (TB), a bacterial disease, can rev up the human immune system in a broad way, allowing it to better fight the virus that causes coronavirus disease 2019 and, perhaps, prevent infection with it altogether. The studies will be done in physicians and nurses, who are at higher risk of becoming infected with the respiratory disease than the general population, and in the elderly, who are at higher risk of serious illness if they become infected. A team in the Netherlands will kick off the first of the trials this week. They will recruit 1000 health care workers in eight Dutch hospitals who will either receive the vaccine, called bacillus Calmette-Guérin (BCG), or a placebo. BCG contains a live, weakened strain of Mycobacterium bovis, a cousin of M. tuberculosis, the microbe that causes TB. (The vaccine is named after French microbiologists Albert Calmette and Camille Guérin, who developed it in the early 20th century.) The vaccine is given to children in their first year of life in most countries of the world, and is safe and cheap—but far from perfect: It prevents about 60% of TB cases in children on average, with large differences between countries.

Vaccines generally raise immune responses specific to a targeted pathogen, such as antibodies that bind and neutralize one type of virus but not others. But BCG may also increase the ability of the immune system to fight off pathogens other than the TB bacterium, according to clinical and observational studies published over several decades by Danish researchers Peter Aaby and Christine Stabell Benn, who live and work in Guinea-Bissau. They concluded the vaccine prevents about 30% of infections with any known pathogen, including viruses, in the first year after it’s given. The studies published in this field have been criticized for their methodology, however; a 2014 review ordered by the World Health Organization concluded that BCG appeared to lower overall mortality in children, but rated confidence in the findings as “very low.” A 2016 review was a bit more positive about BCG’s potential benefits but said randomized trials were needed.

More here.

Tuesday Poem

At the Un-National Monument along the Canadian Border

This is the field where the battle did not happen,
where the unknown soldier did not die.
This is the field where grass joined hands,
where no monument stands,|
and the only heroic thing is the sky.

Birds fly here without any sound,
unfolding their wings across the open.
No people killed—or were killed—on this ground
hallowed by neglect and an air so tame
|that people celebrate it by forgetting its name.

by William Stafford
from
The Way It Is: New & Selected Poems
Graywolf Press, 1998