Guess which Chinese city was epicenter of chemical supplies for fentanyl manufacture

The plot continues to thicken:

... Though some clandestine labs that make fentanyl from scratch have popped up sporadically in Mexico, cartels are still very much reliant upon Chinese companies to get the precursor drugs.

Huge amounts of these mail-order components can be traced to a single, state-subsidized company in Wuhan that shut down after the outbreak earlier this year, said Louise Shelley, director of the Terrorism, Transnational Crime and Corruption Center at George Mason University, which monitors Chinese websites selling fentanyl.

“The quarantine of Wuhan and all the chaos there definitely affected the fentanyl trade, particularly between China and Mexico,” said Ben Westhoff, author of "Fentanyl, Inc."

“The main reason China has been the main supplier is the main reason China is the supplier of everything — it does it so cheaply,” Westhoff said.

“There was really no cost incentive for the cartels to develop this themselves.” ...

The above passages are from an April 19 Associated Press investigative report headlined 'Cartels are scrambling': Virus snarls global drug trade published via AOL News.  

The entire AP report, put together by a team of journalists scattered around the world, is very interesting, very informative. But it was the mention of Wuhan that caused me to do a double-take. Despite all reasonable arguments to the contrary, claims persist that China's government did engage in a cover-up in the early days of the viral outbreak in Wuhan, or at the least delayed sharing vital data on the outbreak with other governments.  If the claim is correct surely the massive amounts of money from the fentanyl trade would have been a factor in any shoot-yourself-in-the foot decisions. 

At any rate, given that the supplier in question was state-owned, Beijing doesn't have the fig leaf of claiming a 'criminal element' was covertly running the enterprise.

But from the rest of the report, what goes around comes around; as with many other globalized industries, Mexico's drug trade is now looking to make what they'd previously imported from China. As to how long the self-reliance would last -- another truism is that when money talks nobody walks. However, if China's government is smart they'll forego the profits from fentanyl given the mind-boggling amounts of money they've lost from the pandemic-fueled slowdown in global trade.

By the way, that Wuhan was the epicenter of the fentanyl manufacturing trade could explain how that city became a huge global transport hub.  

******** 

They were always guessing about basic facts related to the Covid outbreak

Now researchers are starting to get a little more clarity.

Wuhan’s Coronavirus Death Toll Surges by 50% After China Revision; The Wall Street Journal, 4/17.

The revisions are perfectly reasonable, I should add.  There was no cover-up in China, any more than than there was one in the United States about American death tallies. Even under the best of circumstances, the number of deaths from the Covid infections will still end up being educated guesses.  These were the worst of circumstances. It's the same with trying to pinpoint the timing and locus of the initial outbreak.  

Cambridge Study: COVID-19 May Have Started in September 2019 South of Wuhan; Sputnik, 4/17

*******

New Yorkers take the masked life in stride

Charming study of a young woman and her regal dog basking in the sun in Central Park West.

Photo by Stephen Yang for The New York Post's April 14 photoessay of New Yorkers wearing face masks. 

********
  

Diabetic patients with Covid at great risk. New research helps explain why.

Discovered: Metabolic Mechanism of Cytokine Storms

By Ruth Williams
April 15, 2020
The Scientist

By studying influenza in mice and cells, researchers identify a glucose metabolism pathway critical to the dysregulated immune response that kills many infectious disease patients, including those with COVID-19.

A study of influenza infection shows that glucose metabolism is a driving force underlying the development of the often deadly inflammatory response known as a cytokine storm, according to a report in Science Advances today (April 15). The results, which identify potential drug targets for future treatments, may partly explain why patients with diabetes are at an increased risk of serious complications and death from influenza and other infections. Preliminary data indicate this appears to be the case for COVID-19 as well.

“It’s a nice piece of work building on previous observations from influenza and other viral systems,” says immunologist Paul Thomas of St. Jude Children's Research Hospital who was not a member of the research team. “It really drills down to the molecular mechanism of . . . this metabolic regulation of inflammation and viral replication.”

During an infection, the body’s immune system ramps up the release of molecules called cytokines, which circulate in the blood stream like messengers calling upon immune cells to come and join the fight. In some patients, for largely inexplicable reasons, this battle cry continues even after the invading pathogen begins to retreat.

“The initial point of this inflammatory response is to counteract infection,” says Haitao Wen, who is an infection and immunity researcher at the Ohio State University College of Medicine and was not involved in the study, “but if it is not well controlled, then at the later stage it will cause collateral damage to tissues, especially lung tissue.” Such a sustained excessive cytokine release, or storm, is the cause of death in a variety of infectious diseases including the flu, COVID-19, Ebola, and sepsis.

Little is known about what instigates the uncontrolled surge in cytokine secretion, but there are clues. The transcription factor interferon regulatory factor 5 (IRF5) is critical for pro-inflammatory cytokine production and, if it is genetically deleted in mice, the animals are protected against influenza-induced cytokine storms. The inflammatory response to influenza infections is also known to drive up glucose metabolism, in part so that immune cells have the necessary energy to mount a strong response, and also because the virus needs the sugar to replicate, explains Thomas.

Shi Liu of the State Key Laboratory of Virology at Wuhan University and colleagues now link these threads, identifying a specific glucose metabolism pathway that is required for activating IRF5-induced cytokine production in cells and mice. This so-called hexosamine biosynthesis pathway, a well-known metabolic process, is also required for viral replication, they show.

Hexosamine biosynthesis starts with glucose and results in an end product called uridine diphosphate N-acetylglucosamine (UDP-GlcNAc)—pronounced UDP-GlickNack. This nucleotide sugar is sometimes added to proteins—a process called O-GlcNAcylation—to modify their activity. Liu’s team now shows that O-GlcNAcylation of IRF5 is necessary for the transcription factor’s cytokine-producing activity.

Genetically deleting the enzyme that performs O-GlcNAcylation, called OGT, or IRF5 itself inhibited inflammatory cytokine production as well as viral replication in mice and cells. The knockouts also improved the animals’ survival of infection, suggesting the two factors may be targets for future therapies.

The team also showed that patients infected with influenza have higher blood glucose levels and more O-GlcNacylation of IRF5 than healthy controls. Furthermore, blood glucose levels correlated tightly with levels of inflammatory cytokines.

[GRAPHIC - Pathway from influenza infection of a cell to production of cytokines]

The results show that “there is a connection [between] influenza virus infection, enhanced glucose metabolism and cytokine storm, all linked through O-GlcNAcylation of IFR-5,” Mengji Lu, a virologist at the University Hospital Essen and a coauthor of the study, writes in an email to The Scientist.

Although the study focused on influenza, cytokine storms are also a common cause of death in COVID-19, and patients with metabolic disorders including diabetes seem to be more at risk of such severe complications. In a Science Advances press release, Liu says, “We believe that glucose metabolism contributes to various COVID-19 outcomes since both influenza and COVID-19 can induce a cytokine storm, and since COVID-19 patients with diabetes have shown higher mortality.”

For influenza and COVID-19, “mortality rate is definitely higher in patients with diabetes” says Wen. But, he adds, the explanation for this may be more complicated than simply an abundance of glucose providing fuel to the inflammatory fire. It’s more likely to do with how glucose metabolism is dysregulated in such people, he says.

Even without diabetes or other apparent underlying conditions, a patient can succumb to a cytokine storm. So the work is “broadly relevant,” says John Teijaro, an immunologist and microbiologist at the Scripps Research Institute who was not involved in the study. It also “opens up a couple of different potential drug targets for cytokine storms,” he says, such as OGT and IRF5. And because inhibiting these factors prevented both cytokine production and viral replication, drugs against these molecules may suppress inflammation “without compromising host immunity and viral control,” Teijaro says, “which is really the holy grail.”

Q. Wang et al., “O-GlcNAc transferase promotes influenza A virus–induced cytokine storm by targeting interferon regulatory factor–5,” Sci Adv, 6:eaaz7086, 2020.

[END REPORT]

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Covid: "We started to think, 'Why bats?'"

Why Bats Make Such Good Viral Hosts
By Katarina Zimmer
May 31. 2020
The Scientist

The bat version of the STING protein helps dampen the mammals' immune response to infection, researchers have found. ... Despite STING’s role in viral responses, Zhou believes that the mutation may be conserved in bats for a different reason, one related to another aspect of bats’ livelihood. Fragments of the bats’ own DNA can also be released into their cells’ cytoplasm as a byproduct of the strenuous effort bats make during flight, Zhou says. This has led him to the [working] hypothesis that the mutation originally provided an evolutionary advantage to bats by preventing their immune systems from boiling over every time the animals fly.

Bats carry and transmit some of the world’s deadliest zoonotic viruses: Ebola, Marburg, Nipah, and the pathogen behind severe acute respiratory syndrome, SARS coronavirus, to name a few. What has puzzled researchers for a long time is why bats don’t appear to get sick from their unusually high microbial loads. 

The question has been nagging Peng Zhou, a virologist at China’s Wuhan Institute of Virology, for more than a decade, ever since he took part in a survey of bat populations in southern China. Zhou and his colleagues were looking for the strain of the SARS coronavirus responsible for the 2003 outbreak that sickened more than 8,000 people worldwide and killed nearly 800. 

“We started to think, why bats?” he says.

[...]

And with that, Zhou and his colleagues were off and running. Fascinating story, great science. 

********

Covid: A return to the issue of cytokine storms

But many doctors are unfamiliar with this niche concept or how to treat it, experts said. "Everyone’s talking about cytokine storm as if it were a well-recognized phenomenon, but you could have asked medics two weeks ago and they wouldn’t have heard of it,” said Dr. Jessica Manson, an immunologist at University College London Hospital.
-- See April 1 NYT report below.

From Boston University School of Public Health discussion website: Defense Mechanisms; Deficient Immunity; Cytokine Storm section (emphasis mine):
[BEGIN QUOTES]
However, under some circumstances that are not well understood, the immune response does not subside normally. Instead, there is unbridled inflammation within tissues and key organs. Certain types of infection seem to carry a higher risk of cytokine storm, e.g., systemic infection and septic shock, SARS, bird flu, Hanta virus infection, and Ebola.

During the 1918 flu pandemic there was an unusually high death rate among healthy young people between the ages of 20-40. These appeared to be due to respiratory failure as a result of excess accumulation of edema fluid in the lungs as a result of an excessive inflammatory response. A similar phenomenon was noted during the H1N1 influenza pandemic in 2009.

[END QUOTES]

The New York Times, April 1, 2020

The Coronavirus Patients Betrayed by Their Own Immune Systems

By Apoorva Mandavilli

[emphasis mine]

A “cytokine storm” becomes an all-too-frequent phenomenon, particularly among the young. But treatments are being tested.

The 42-year-old man arrived at a hospital in Paris on March 17 with a fever, cough and the “ground glass opacities” in both lungs that are a trademark of infection with the new coronavirus.

Two days later, his condition suddenly worsened and his oxygen levels dropped. His body, doctors suspected, was in the grip of a cytokine storm, a dangerous overreaction of the immune system. The phenomenon has become all too common in the coronavirus pandemic, but it is also pointing to potentially helpful drug treatments.

When the body first encounters a virus or a bacterium, the immune system ramps up and begins to fight the invader. The foot soldiers in this fight are molecules called cytokines that set off a cascade of signals to cells to marshal a response. Usually, the stronger this immune response, the stronger the chance of vanquishing the infection, which is partly why children and younger people are less vulnerable overall to coronavirus. And once the enemy is defeated, the immune system is hard-wired to shut itself off.

“For most people and most infections, that’s what happens,” said Dr. Randy Cron, an expert on cytokine storms at the University of Alabama at Birmingham. But in some cases — as much as 15 percent of people battling any serious infection, according to Dr. Cron’s team — the immune system keeps raging long after the virus is no longer a threat. It continues to release cytokines that keep the body on an exhausting full alert. In their misguided bid to keep the body safe, these cytokines attack multiple organs including the lungs and liver, and may eventually lead to death.

In these people, it’s their body’s response, rather than the virus, that ultimately causes harm.

Cytokine storms can overtake people of any age, but some scientists believe that they may explain why healthy young people died during the 1918 pandemic and more recently during the SARS, MERS and H1N1 epidemics. They are also a complication of various autoimmune diseases like lupus and Still’s disease, a form of arthritis. And they may offer clues as to why otherwise healthy young people with coronavirus infection are succumbing to acute respiratory distress syndrome, a common consequence of a cytokine storm.

Reports from China and Italy have described young patients with clinical outcomes that seem consistent with this phenomenon. It’s very likely that some of these patients developed a cytokine storm, Dr. Cron said.

In the case of the 42-year-old patient, the suspected cytokine storm led his doctors to eventually try tocilizumab, a drug they have sometimes used to soothe an immune system in distress.

After just two doses of the drug, spaced eight hours apart, the patient’s fever rapidly disappeared, his oxygen levels rose and a chest scan showed his lungs clearing. The case report, described in an upcoming paper in Annals of Oncology, joins dozens of accounts from Italy and China, all indicating that tocilizumab might be an effective antidote to the coronavirus in some people.

On March 5, China approved the drug to treat serious cases of Covid-19, the disease caused by the coronavirus, and authorized clinical trials. On March 23, the U.S. Food and Drug Administration granted approval to the pharmaceutical company Roche to test the drug in hundreds of people with coronavirus infection.

Tocilizumab is approved to quieten the chatter of immune molecules in rheumatoid arthritis and in some types of cancer. It mutes the activity of a specific cytokine called interleukin-6 that is associated with an over-exuberant immune response.

“That’s the rationale for using the drug,” said Dr. Laurence Albiges, who cared for the patient at the Gustave Roussy Cancer Center in Paris.

Even as researchers look for treatments, they are trying to learn more about why some people’s immune systems go into this dangerous overdrive. Genetic factors explain the risk, at least in some kinds of cytokine storms.

There are many variations on the phenomenon, and they go by many names: systemic inflammatory response syndrome, cytokine release syndrome, macrophage activation syndrome, hemophagocytic lymphohistiocytosis.

Broadly speaking, they are all marked by an unbridled surge in immune molecules, and may all result in the fatal shutdown of multiple organs.

But many doctors are unfamiliar with this niche concept or how to treat it, experts said.

“Everyone’s talking about cytokine storm as if it were a well-recognized phenomenon, but you could have asked medics two weeks ago and they wouldn’t have heard of it,” said Dr. Jessica Manson, an immunologist at University College London Hospital.

A patient battling a cytokine storm may have an abnormally fast heart rate, fever and a drop in blood pressure. Apart from a surge in interleukin-6, the body may also show high swirling levels of molecules called interleukin-1, interferon-gamma, C-reactive protein and tumor necrosis factor-alpha.

This storm, if it develops, becomes obvious a few days into the infection. But the sooner doctors catch on to it and treat it, the more likely the patient is to survive. Too late, and the storm may be beyond control, or may already have caused too much damage.

There is a relatively simple, rapid and easily available test that can detect whether a patient’s body has been taken over by a cytokine storm. It looks for high levels of a protein called ferritin.

But if the test does suggest a cytokine storm is underway, what then?

The seemingly obvious solution is to quell the storm, Dr. Cron said: “If it’s the body’s response to the infection that’s killing you, you need to treat that.”

The reality is trickier, especially given the lack of reliable data for Covid-19. But noting that drugs like tocilizumab are taken regularly by people with arthritis, Dr. Cron said the benefit would probably outweigh potential harm if someone is facing death.

“We need evidence-based data, but in a pandemic, where we’re flying by the seat of our pants, we always have to treat the patient in front of us,” he said.

Other drugs might also be useful against cytokine storms. For example, a drug called anakinra mutes interleukin-1, another of the wayward proteins. Clinical trials of anakinra for Covid-19 are also underway. A report published this week suggested that hydroxychloroquine, a much-spotlighted malaria drug that also calms an overactive immune response, might also be effective as a treatment for those who are mildly ill from coronavirus.

Doctors could also turn to corticosteroids, which broadly turn down the entire immune response. That poses its own danger, by exposing the patient to other opportunistic infections, especially in a hospital. “It’s about getting the balance right between suppression of the over-exuberant immune response and still allowing the immune response to fight the virus,” Dr. Manson said.

A group of experts convened two weeks ago to discuss the best ways to collect more data and to treat patients who appear to have cytokine storm. It’s already clear that the complexities of the immune system and the course of coronavirus mean there is no single best treatment.

At the Gustave Roussy Cancer Center, doctors treated another coronavirus patient with tocilizumab. That individual did not show any improvement with the drug.

“The response to the pathogen, the virus, is totally different in different individuals,” said Dr. Fabrice André, an oncologist at the center. “The trials will determine in which patients it works.”

[END REPORT]

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Are Americans getting too fat?

Covid-19 can also affect the brain

The following is a very important report today from The Wall Street Journal. The biggest takeaway is that people must start looking beyond the standard list of symptoms to spot whether they've been infected by the virus.  Are the neurological symptoms found in a significant number of  cases caused by the virus itself, or touched off by the body's response to the virus?  Not known at this point.  

"When this virus first came out, the general feeling was that there wasn’t much in the way of neurological manifestations. This was a pulmonary process.” 

Coronavirus Ravages the Lungs. It Also Affects the Brain.
By Daniela Hernandez
April 14, 2020 4:28 pm ET
The Wall Street Journal

As Covid-19 cases mount, doctors are seeing patients who are experiencing symptoms like seizures, hallucinations and loss of smell and taste.

A patient in Japan had seizures. An airline worker ended up in a Detroit hospital, where doctors diagnosed her with a rare form of brain damage. Others reported auditory and visual hallucinations or losing their sense of smell and taste.

What they share: presumed or confirmed coronavirus infections.

As the number of confirmed Covid-19 cases worldwide reaches 2 million, clinicians are realizing the disease doesn’t just ravage the lungs and hurt the heart. It also can, in a significant proportion of cases, affect the nervous system in myriad little-understood ways.

Through a growing number of papers, doctors around the globe are chronicling Covid-19’s lesser-known neurological manifestations including brain inflammation, hallucinations, seizures, cognitive deficits and loss of smell and taste. It is unknown whether these are caused directly by the virus infiltrating the nervous system, or by the body’s immune response to infection.

The hope is these reports could speed up diagnosis. Some patients say they were going out in public, potentially exposing others, due to lack of awareness of these symptoms. The reports could also open avenues of research that elucidate whether the virus gets into the brain, how long neurological symptoms might persist, and whether a full recovery can be expected.

In late March, while keeping quarantine, Dwantrina Russell noticed she couldn’t smell the bleach she was using to sanitize her Houston bathroom. Since then, most of the 47-year-old business owner’s symptoms of Covid-19, including fever and a violent cough, have receded. But she said she can only smell things like cleaning products or food if they are close by.

The range of effects could take decades to play out. Some epidemiological studies and lab experiments with other viruses suggest severe infections could set in motion molecular events that might increase the risk of developing neurodegenerative disorders, like Alzheimer’s or Parkinson’s, many years later. The links are a matter of debate among neurologists and neuroscientists.

Last Friday, Chinese doctors published a study of 214 hospitalized patients in Wuhan showing that more than a third had neurologic symptoms. The most common included dizziness, headaches, impaired consciousness, skeletal-muscle injury and loss of smell and taste. The paper—published in the Journal of the American Medical Association and the largest to date on the disease’s impact on normal nervous-system function—also documented rare, but more serious, effects including seizures and stroke, which occurs when a blood clot hits the brain.

“When this virus first came out, the general feeling was that there wasn’t much in the way of neurological manifestations. This was a pulmonary process,” said S. Andrew Josephson, chair of neurology at the University of California, San Francisco. “This article should open up everyone’s eyes that this disorder affects the brain as well.”

The novel coronavirus, called SARS-CoV-2, isn’t the only virus known to affect the nervous system. Research in humans and animals has shown that non-coronaviruses such as HIV, measles and certain influenza strains can infect the brain or affect its function through inflammatory responses elsewhere in the body. Laboratory studies have shown that other coronaviruses can infect nerve cells.

Some neurologists hypothesize, based on results from animal studies, that the sometimes fatal breathing problems seen in severe Covid-19 cases might be in part due to direct infection and subsequent malfunction of the brainstem, which is involved in coordinating breathing.

“We are certainly on a learning curve in terms of understanding what the neurological manifestations would be” of SARS-CoV-2 infection, said Florian Thomas, chair of neurology at Hackensack University Medical Center in New Jersey.

On April 4, Cobain Schofield, a 25-year-old lighting technician based in Liverpool, said he realized that he couldn’t smell a pungent brand of garlic bread he likes. He consulted government-run health sites, but these didn’t list anosmia, the medical term for the condition, as a Covid-19 symptom, so he figured he was coronavirus-free.

Days later, he developed in his nose a “burning sensation while breathing,” he said, and a nurse at a nearby clinic told him several patients with confirmed Covid-19 diagnoses also had anosmia. He has been in quarantine since.

“Knowing now that I could have been spreading it, it’s quite a horrible feeling,” he said, adding that he had probably been experiencing anosmia for days before he noticed.

Whether a coronavirus infection affects the ability of receptors in the nasal cavity to detect odorants or the nerves that shuttle the odor-containing signals to the brain is unknown. Loss of smell and taste are common during other respiratory infections. (Much of what humans perceive as taste is related to smell.)

n the U.S. and elsewhere, policy makers and public-health officials have asked patients to avoid going to the hospital unless suspected Covid-19 symptoms like fever and cough don’t improve, or if they have trouble breathing. Critical-care neurologists said the messaging should expand to make patients more aware of brain-related symptoms.

Symptoms like confusion, trouble speaking or numbness on one side of the body should also be red flags. Those symptoms can signal an impending stroke, which, if not treated within a certain time window, can lead to permanent brain damage, they said. Covid-19 patients are at higher risk of stroke due to the virus’s impact on blood clotting.

For already hospitalized patients, doctors are running standard neurological exams that include low-tech tests like asking patients to follow simple commands, in conjunction with more high-tech diagnostics like brain imaging as needed, neurologists said.

Northwell Health, a health-care system in New York, plans to soon start using portable MRIs to monitor the brains of very sick patients, some of whom are sedated and on ventilators, according to Richard Temes, Northwell’s director of neurocritical care.

The hospital system is also using another type of brain-monitoring test, known as an electroencephalogram, to ensure patients aren’t having silent seizures, he said. Catching problems early increases the chances that patients’ brains can fully recover.

“As we fight this illness, we’re saving the lungs. We’re saving the heart and we’re saving the kidneys. But the brain is who we are,” said Dr. Temes.

[END REPORT]

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"How much of the coronavirus does it take to make you sick? The science, explained"

By Alex Hogan
April 14, 2020
STAT

Infectious respiratory diseases spread when a healthy person comes in contact with virus particles expelled by someone who is sick — usually through a cough or sneeze. The amount of particles a person is exposed to can affect how likely they are to become infected and, once infected, how severe the symptoms become.

The amount of virus necessary to make a person sick is called the infectious dose. Viruses with low infectious doses are especially contagious in populations without significant immunity.

The minimum infectious dose of SARS-CoV-2, the virus that causes Covid-19, is unknown so far, but researchers suspect it is low. “The virus is spread through very, very casual interpersonal contact,” W. David Hardy, a professor of infectious disease at Johns Hopkins University School of Medicine, told STAT.

A high infectious dose may lead to a higher viral load, which can impact the severity of Covid-19 symptoms.

Viral load is a measure of virus particles. It is the amount of virus present once a person has been infected and the virus has had time to replicate in their cells. With most viruses, higher viral loads are associated with worse outcomes.

“The more viral particles that get into the lungs, the more damage to the lungs that is probably happening,” said Hardy.

One study of Covid-19 patients in China found that those with more severe symptoms tended to have higher viral loads.

“It’s not proven, but it would make sense that higher inoculating doses will lead to higher viral loads, and higher viral loads would translate into more pathogenic clinical courses,” said Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center.

People with higher viral loads may also shed more whole viruses, which makes them more contagious, compounding the danger of spreading disease more widely.

If exposure to higher doses, or even frequent low doses, of SARS-CoV-2 does lead to worse health outcomes, there are significant implications for health care workers who are routinely exposed to Covid-19 patients.

“Someone caring for large numbers of patients on the wards, if they’re not wearing PPE [personal protective equipment], there might be a high frequency of exposure as well as a high dose of exposure,” Barouch said.

In Italy, a country particularly hard-hit by the virus, about 9% of reported cases were health care workers. Here in the U.S., 10% of Covid-19 cases in California were health care workers, according to the California Department of Public Health.

[END REPORT]

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Italians should have done for Easter what the Mormon Tabernacle Choir did

Pundita, can we please not fight on Easter Sunday? Well it's too late now. I got so depressed seeing Andrea Bocelli singing all alone on Easter in that vast empty cathedral, I couldn't finish watching. 

Okay, there was an organist to keep him company. But why couldn't Milan's city fathers have taken inspiration from the Italians who sung from their balconies during the Covid lockdown and the Mormon Tabernacle Choir's great use of the 'virtual' choir?

Now here's the way to sing in celebration of Easter! A three hundred-strong choir joined by two thousand people from all over the world singing their parts individually into their computers, and it all gets joined together by tech wizards for the most incredible rendition of Handel's Alleluia! Chorus I've ever witnessed. When the screens start lighting up behind the in-house choir -- I have no words.  

Virus be darned, lockdowns be darned! The Italians who sang from their balconies showed we can't be stopped from singing! 

Happy Easter, everyone!
  

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Easter Dance and Singalong

Bravo Jerome Adams!

U.S. Surgeon General Jerome Adams is under fire from America's speech police for his use of slang they consider offensive to the 'black community' while he warned blacks and other minorities to quit smoking, drinking alcohol, and taking drugs.  

I think the real reason they jumped on Adams is that he's a Trump pick for surgeon general post. And the booze, cigarette, and dope lobbies are surely outraged that such a high-visibility black is encouraging other blacks to cut loose those substances. I remember what it took to get alcohol and cigarette advertising billboards out of America's inner cities. Those ads were fiendishly clever. Designed to convey the idea to the poorest blacks that with Johnnie Walker Black scotch and Newport cigarettes they could still be part of mainstream America. 

But let the  speech police rant. Hat's off to Adams for his strong message, and his showing of the inhaler he always carries in case he gets an asthma attack. 

The Daily Mail report on the kerfuffle has video of his speech. Worth watching.  

********

Top of page headline links Drudge Report 4/10, 11:50 PM ET

Most of the links on the Drudge page relate to the pandemic; below are just the top-featured ones, at the left-hand side of the page.  The large headlines at the top middle page read:

FEAR OF SECOND WAVE IN SUMMER
CITIES BEGIN CANCELING FOURTH OF JULY EVENTS
FEDS COVER-UP NURSING HOME DEATHS
TESTING BOTCHED

You do have to look at the report attached to a link if the headline grabs you because the wording can be misleading; for example, the headlined quote from a former FDA Commissioner is actually that Covid would've been more deadly than the Spanish Flu given the state of medicine in 1918. 

Coronavirus found in air samples up to 13 feet from patients...
CDC: Cases Double In Week...
Former FDA Commissioner: 'Far More Deadly than Spanish Flu'...
Traces found in wastewater at high levels...
Antibody test in German town shows 15% infection rate...
Here's Where Coronavirus Hides in Your Body...
Patients report strange new symptom: Fizzing...
Half have neurological problems...
Michigan bans travel between residences...
Boston suburb threatens $100 fines to anyone walking in wrong direction...
Congress Debates Using Smartphone Data...
Record Bankruptcies Predicted as Unemployment Soars...
DEBT TOPS $24 TRILLION...
Feds promised small businesses up to $2 million in loans. Now it's maxing out at $15,000....
FAUCI: Americans could eventually carry certificates of immunity...
MAG: Pandemic Will Cleave Nation in Two...
Los Angeles shut through May 15...
New York won't reopen without massive testing...
Italy extends lockdown despite business pressure...
IT CAN'T GO ON FOREVER!
SICK MAP... . 

Drudge top of page headline links 5:40 pm ET April 9

Drudge Report

New York daily death toll reaches third-straight record at 799...
Inside the Epicenter...
Outbreak Aboard Second Navy Carrier...
Virus traces found in wastewater at high levels...
DC mayor: All shoppers at grocery stores must wear masks...
Major Meat Processors Shutting Down Plants Nationwide As Employees Get Sick...
After Violent Night, Chicago Mayor Puts Curfew On Liquor Sales...
Prison riot in Washington state...
UK lockdown indefinitely...
Trump Rips WALL STREET JOURNAL as 'Fake News' For Criticizing Press Briefings...
White House to require coronavirus tests for journalists...
How single cough spreads across supermarket...
Video shows particles from runners can infect you...
Immune system gone haywire doing more damage than covid itself?
More and more testing positive AGAIN...
Most New York Cases Came From Europe, Genomes Show...
Federal stocks of protective equipment nearly depleted...
Mnuchin says could be 'open for business' in May...
16.8 million Americans thrown out of work as toll rises...
Fed Chair Powell says U.S. economy deteriorating with alarming speed...
Pumps Another $2.3 Trillion... Why relief to small businesses has lagged...
Crisis Legacy: Mountains of Debt...

********

More from the physician re severe immune system reactions to COVID-19

My email exchanges with a physician I've known for a quarter century were touched off when I asked for her opinion about my 4/7 post titled The worst COVID-19 symptoms remind me of severe allergic reaction. My remarks did not go over well with her as you can see from an update to the post. 

Today, after digesting the physician's comments, I conceded on this blog that I had made a couple gaffes, but after politely eating crow I posted a 4/9 Wall Street Journal report "Haywire Immune Response Eyed In Coronavirus Deaths, Treatment," which I thought tended to shore my argument, and sent it to the physician. Below is her response, prefaced by additional remarks she'd sent on April 8 in response to my first post.  

"People with severe allergic reactions tend to have cardiovascular collapse rather than the kind of respiratory issues seen in Covid. They may both need to be on a ventilator, but if that is the case in the short term it doesn't matter why specifically they need a ventilator. Prior to getting on a ventilator you need to be unable to oxygenate your lungs on your own with all medical interventions failing."

[In response to the WSJ report]

"Yes but it is the virus that causes the hyperactive immune response. On death certificates they never want doctors to put respiratory arrest because everyone who dies has a respiratory arrest. If the person did not get infected by Covid, they would not find themselves eating dinner and suddenly have a "hyperactive immune response" and drop dead. They die of ARDS (adult respiratory distress syndrome) cause multi-organ system failure, but basically they die of Covid. This is ridiculous hair-splitting in my humble opinion."

All right. First, I think a little more crow-eating is in order given that cardiovascular collapse is not the same as respiratory failure. So while the symptoms of a severe allergic reaction and a severe reaction to Covid are on the face of it strikingly similar (see my 4/7 post for comparisons), it would be stretching the definition of an allergic reaction out of shape to consider it the same as a reaction to Covid or even similar.

This doesn't mean the medical description of a severe allergic reaction couldn't be revised to include the kind of respiratory issues found in extreme immune responses to Covid. But right now the point is useless; it would be a long march for scientists before they could prove or disprove it.  

So at the moment, it looks as if my argument is in tatters; however, I see a way to salvage a few scraps. But now I have to get ready to go grocery shopping, a task in Covid Lockdown Washington, DC that is now as close to living in Stalinist Russia as I'd ever want to get.

So, tomorrow or late tonight will be the next post. Until then, stay safe Pundita this is not the time for sarcasm.  

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"Haywire Immune Response Eyed In Coronavirus Deaths, Treatment": WSJ UPDATED 5:30 PM

UPDATE
I've had to eat more crow. Please see this Pundita post, just published: More from the physician re severe immune system reactions to COVID-19
END UPDATE

" ... an increasing number of experts believe a hyperactive immune response, rather than the virus, is what ultimately kills many Covid-19 patients."
-- The Wall Street Journal, Haywire Immune Response Eyed In Coronavirus Deaths, Treatment; April 9

"But I think most suggestive of all is that for some who are infected with COVID-19, their immune system goes crazy fighting the virus, which is exactly what happens with the most severe allergic reactions, both of which are life-threatening. It looks to me as if it could be the same situation, only that physicians do not associate the symptoms of COVID-19 infection with an allergic reaction."
-- Pundita, The worst COVID-19 symptoms remind me of severe allergic reaction; April 7 

For those who asked why I didn't initially defend the argument I made in the April 7 post, because there was no defense for what I did.  I lost my temper over a remark made to the press by a physician about COVID-19. Loss of temper is okay, but it's not okay for me to write for a public platform before I've calmed down. If I'd been thinking straight, I would've asked the physician I knew to review the post before I published it. Instead, I asked for help as an afterthought.  So I was left to eat crow in public, which serves me right.  (See the physician's remarks in the update to the April 7 post).

Doesn't matter that I believed my key point still held value. I was flagrantly wrong in certain respects. I take the physician's word for it that I misread the abstract I used in the attempt to shore my argument. The topper is that I didn't need the abstract to make my key point. And I shot off my sarcastic remark about the use of beta-antagonists without knowing what I was talking about; for that I certainly needed to be corrected. And yet my essay didn't need that remark.     

All right, that's enough crow-eating. I want to move on to The Wall Street Journal report. From my reading it seems the scientists studying the coronavirus have yet to zero in on the striking similarity between hyperactive immune responses to allergens and the virus. But it looks as if they could be 15 minutes away from doing so. I'll have more to say about this is the next post; for now:  

Haywire Immune Response Eyed In Coronavirus Deaths, Treatment
Researchers are looking at treatments to suppress ‘cytokine storm,’ increasingly linked to the most severe Covid-19 cases

By Joseph Walker and
Jared S. Hopkins

April 9, 2020 7:00 am ET
The Wall Street Journal

Doctors have used the term “cytokine storm” to describe an overactive immune response triggered by external pathogens such as bacterial and viral infections.

An immune system gone haywire may be doing more damage than the coronavirus itself in patients with the severest forms of Covid-19, doctors and scientists say, a growing theory that could point the way to potential treatments.

Much remains unknown about the path the virus takes in the sickest patients, but an increasing number of experts believe a hyperactive immune response, rather than the virus, is what ultimately kills many Covid-19 patients.

The out-of-control immune response eventually causes the patients’ lungs to stop delivering oxygen to the rest of organs, leading to respiratory failure and in some cases death, the experts say. The malfunctioning immune system may be driving the rapid decline in lung function experienced by some patients, including younger and relatively healthy ones, after the initial onset of symptoms, doctors say.

[Graphic] Anatomy of a Cytokine Storm

An overactive immune response is thought to play a role in the disease progression of the sickest Covid-19 patients. [See WSJ site for the graphic.]

As scientists race to better understand the [phenomenon], pharmaceutical companies including Roche Holding AG are partnering with hospitals to explore whether drugs proven to tamp down an out-of-control immune response could help the sickest Covid-19 patients.

Some doctors are already administering the drugs to patients who are unable to breathe without the support of ventilators, or to prevent deterioration of patients who appear ready to slip into respiratory failure.

“You remove one piece of the storm, and it can quiet the whole thing,” said Kevin Tracey, president of the Feinstein Institutes for Medical Research at Northwell Health, which is testing Kevzara, an anti-inflammatory drug from Regeneron Pharmaceuticals Inc.

Doctors have used the term “cytokine storm” to describe an overactive immune response triggered by external pathogens such as bacterial and viral infections.

Proteins called cytokines are part of the immune system’s arsenal for fighting disease. When too many are released into the bloodstream too quickly, however, it can have disastrous results, including organ failure and death.

As with other diseases, it is a mystery why cytokine storms are experienced by some but not all Covid-19 patients, doctors say. Genetics may be a factor.

In the most severe coronavirus patients, the disease appears to have two stages, doctors and researchers say. First the immune system fails to respond quickly or effectively enough to the virus. Then the immune response becomes too aggressive and floods the body with cytokines.

The surge of cytokines damages blood vessels and allows fluids to seep into the lungs, filling them up like water balloons, doctors say.

“The virus initiated it,” said Ya-Chi Ho, an assistant professor at the Yale School of Medicine who studies infectious diseases. “The second problem is our immune system handled it wrong, and induces this cytokine storm and clogs our lungs. That’s why patients die.”

Drugs called corticosteroids can be used to treat patients with cytokine storms, but studies are mixed on their effectiveness, with some studies indicating that Covid-19 patients may be at a higher risk of death when treated with steroids. Some doctors are reluctant to use steroids because they broadly dampen the immune response, which is risky in patients fighting infections.

Drugs targeting specific cytokines rather than the entire immune system may be more effective, doctors say.

Among the most promising targeted treatments, doctors say, is Roche’s rheumatoid-arthritis drug tocilizumab, which is marketed under the brand name Actemra. The drug was approved in 2017 to treat cytokine storms caused by cancer treatments known as CAR-T cell therapies.

On Tuesday, a federal agency that supports health research said it is committing $25 million to accelerate a late-stage study of Actemra in Covid-19 patients.

Last month, doctors from Seattle’s Swedish Health Services used Actemra to treat a 45-year-old emergency-room physician who was infected while caring for patients from a nursing home in Kirkland, Wash.

The man was transferred to Swedish and put on life support after his lungs and kidneys began to fail, said Samuel J. Youssef, a cardiothoracic surgeon at Swedish. Lab tests showed the man’s inflammation levels were 200 times greater than the normal range, indicating he might be suffering from a cytokine storm.

The doctors at Swedish decided to administer Actemra after discussing a small Chinese study that had shown that 21 Covid-19 patients with high levels of inflammation had been successfully treated with the drug.

Over the next two days, the patient’s inflammation levels began to decline and his blood-oxygen levels increased, Dr. Youssef said. After a week, he was well enough to be taken off life support on March 23, and was released from the hospital on Sunday.

“All we did was quiet the storm and support his body—his kidneys, his lungs, his heart—to give him the time to fight the virus,” said Dr. Youssef, who attributes the recovery both to Actemra as well as other interventions like being put on life support.

CytoDyn Inc., a Vancouver, Wash.-based biotech company, said 10 severely sick Covid-19 patients showed signs of recovering three days after being infused with its experimental HIV drug leronlimab, which may block the production of inflammatory cytokines. Three of the patients were taken off ventilators, including two who have since been discharged from care, according to CytoDyn.

The company is studying its drug in a trial for patients with mild-to-moderate symptoms and expects to start one for severely sick patients.

Swedish Orphan Biovitrum AB expects results in July from a study evaluating its rheumatoid-arthritis drug Kineret in combination with an antibody called emapalumab in patients in Italy, said Milan Zdravkovic, Sobi’s head of research and development.

Novartis AG and Incyte Corp. said they plan to start clinical trials of their drug ruxolitinib in Covid-19 patients with cytokine storm. The drug, marketed as Jakafi in the U.S., is approved to treat rare blood cancers.

Write to Joseph Walker at joseph.walker@wsj.com and Jared S. Hopkins at jared.hopkins@wsj.com

[END REPORT]

Not for humans to visit the god realm. But we can imagine.

The worst COVID-19 symptoms remind me of severe allergic reaction UPDATED 3X

UPDATE 5:30 PM April 9

More from the physician re severe immune system reactions to COVID-19
UPDATE 1:05 PM April 9
See Haywire Immune Response Eyed In Coronavirus Deaths, Treatment; April 9;  The Wall Street Journal

I'll have more in my next post.   

UPDATE April 8
This comment is from a physician I asked to read my post -- after I published it: 

"You misread the essay [abstract]. That is ridiculous. Every single person in respiratory failure is getting beta-agonists both before and while on the ventilator.  That’s one of the many things we do before deciding to begin ventilator treatment." 

My reply:

Ah so. Thank you!  So -- no chance that the most severe COVID-19 symptoms in younger people without serious health issues is a severe allergic reaction.  Well, another bright idea for the circular file. 

I should have run my idea by you before I published. Now I will have to eat crow for my readers rather than simply deleting the essay because what I wrote is so misleading. 

END UPDATE (There may be more updates to this post.)

Cold or flu symptoms can mimic many symptoms of an allergy, but is it possible to be allergic to a virus? If I've correctly read the abstract from a study published in 2011, it looks as if the answer would be yes -- or so close to a yes that medical intervention to treat a severe allergy might be tried with those who exhibit severe symptoms associated with COVID-19 infection. 

See "Airway allergy and viral infection," published in 2011 by the Asian-Pacific Journal of Allergy and Immunology and available for free from the U.S. National Library of Medicine, National Institutes of Health. 

As to whether an allergic reaction can touch off fever, there is an indirect route. From Healthline's article, Is Fever a Symptom of Allergies?

But can allergies cause a fever? Generally, no. Sometimes, however, allergy symptoms can make you vulnerable to a bacterial or viral infection. And a bacterial or viral infection can lead to a fever, so you can indirectly blame the fever on your allergy.

Healthline also explains --

When an allergic reaction is so severe that your breathing is jeopardized and you lose consciousness or are at risk of losing consciousness, it’s called anaphylaxis. Anaphylaxis is a medical emergency that requires immediate medical attention.

The treatment for anaphylaxis, from Healthline's article about it:

At the hospital, people with anaphylaxis are given adrenaline, the common name for epinephrine --  medication to minimize the reaction. ... In addition, you may receive oxygen, cortisone, an antihistamine, or a fast-acting beta-agonist inhaler.

Here is Healthline's list of symptoms associated with anaphylaxis:

• mental confusion

• throat swelling

• weakness or dizziness

• blue skin

• rapid or abnormal heart rate

• facial swelling

• hives

• low blood pressure

• wheezing

Also from the article:

... in the case of anaphylaxis, the immune system overreacts in a way that causes a full-body allergic reaction. ...... Some people may go into anaphylactic shock. It’s also possible to stop breathing or experience airway blockage due to the inflammation of the airways.

Sometimes, it can cause a heart attack. 

Hives and facial/throat swelling are, I think, symptoms commonly associated with an allergic reaction to an ingested substance or a insect sting, so they wouldn't apply to any allergic reaction to the COVID-19 virus. But the rest of the symptoms listed by Healthline are suggestive of the immune system's reaction to the virus. 

Here is a list of the most severe COVID-19 symptoms from a Houston Methodist Hospital article:

Serious symptoms of COVID-19 include:

• Severe shortness of breath

• Low blood pressure

• Elevated heart rate (above 100 bpm)

• Dehydration

• Profound weakness

• High fever

Blue lips/facial skin are also signs of severe COVID-19 symptoms -- of course, if the person is having trouble breathing. And the elevated heart-rate symptom, if untreated, can lead to heart failure, stroke, or cardiac arrest -- a 'heart attack,' as the Healthline list terms it.  

But I think most suggestive of all is that for some who are infected with COVID-19, their immune system goes crazy fighting the virus, which is exactly what happens with the most severe allergic reactions, both of which are life-threatening. It looks to me as if it could be the same situation, only that physicians do not associate the symptoms of COVID-19 infection with an allergic reaction.

I'm not a physician but sometimes I follow the Quacks Like school of reasoning: If it looks like something, and it quacks like something, maybe that's what it is.

Might be worth a shot, especially when you consider that a "fast-acting beta-agonist inhaler " would be much easier on the patient than a ventilator.  

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