Coronavirus updates December 2022

[missy]

"

Analysis: How Accurate Are China's COVID-19 Death Numbers?​

By David Stanway and Nancy Lapid
December 23, 2022




(Reuters) - China's narrow criteria for identifying deaths caused by COVID-19 will underestimate the true toll of the pandemic's current wave there and could make it harder to communicate the best ways for people to protect themselves, foreign health experts warn.
Only deaths caused by pneumonia and respiratory failure after contracting COVID will be classified as having been caused by the coronavirus, a leading Chinese medical expert said on Tuesday.
Deaths from complications at other sites in the body, including underlying conditions made worse by the virus, would be excluded from the official toll, said Wang Guiqiang, head of the infectious disease department at Peking University First Hospital.
Experts familiar with hospital protocols in China told Reuters that such cases were not always excluded previously, though sometimes COVID would be ruled out as a cause of death if a formerly positive patient had tested negative a day or two before dying.

Wang said the criteria had changed because the Omicron variant is less likely to cause other life-threatening symptoms, though China's hospitals are still required to judge each case to ascertain precisely whether or not COVID was the ultimate cause.




The methods for counting COVID deaths have varied across countries in the nearly three years since the pandemic began.
Yet disease experts outside of China say this specific approach would miss several other widely recognised types of potentially fatal COVID complications, from blood clots to heart attacks as well as sepsis and kidney failure.
Some of these complications can increase the chances of death at home, particularly for people who are not aware that they should seek care for these symptoms.

The new definition "clearly won't capture all deaths from COVID," said Dr. Aaron Glatt, an infectious diseases expert at Mount Sinai South Nassau Hospital in New York and a spokesperson for the Infectious Diseases Society of America. "To say you're going to ignore anything else going on in the body makes no sense and is scientifically inaccurate."
Last month, Korean researchers reported that 33% of Omicron-related deaths between July 2021 and March 2022 at one large hospital were due to causes other than pneumonia.
CAN CHINA'S COVID DATA BE TRUSTED?

With one of the lowest COVID death tolls in the world, China has been routinely accused of downplaying infections and deaths for political reasons.

A June 2020 study of the country's initial outbreak in Wuhan starting in late 2019 estimated 36,000 could have died at the time, or 10 times the official figure.

A study published by the Lancet in April, which looked at COVID-related mortality in 74 countries and territories over 2020-2021, estimated there were 17,900 excess deaths in China over the period, compared to an official death toll of 4,820.

Globally, the study estimated 18.2 million excess deaths in 2021-2022, compared with reported COVID deaths of 5.94 million.

The new announcement from China raised concerns the government was seeking to disguise the true impact of relaxing its draconian "zero-COVID" controls after nearly three years of disruptive lockdowns and mandatory mass testing.




Despite widespread reports that funeral homes and crematoriums are struggling to cope with a surge in demand, China's official death numbers have not spiked, with no new fatalities reported for Dec. 21 and only seven deaths reported since the government announced on Dec. 8 that "zero-COVID" restrictions would be removed.

China actually cut its accumulated death toll by one on Dec. 20, bringing the total to 5,241.

China's National Health Commission did not immediately respond to requests for comment about the country's COVID statistics and excess mortality.

Even if China were to continue defining COVID deaths more broadly, the official data is still unlikely to reflect the situation on the ground, given how quickly infections are now spreading, said Chen Jiming, a medical researcher at China's Foshan University.

"The reported counts of cases and deaths are only a very small portion of the true values," he said.

Ben Cowling, an epidemiologist at the University of Hong Kong's School of Public Health, said the official death tally would be very low even if a broader definition were in use, "because so little testing is being done" now that China has discontinued mass surveillance.

On the other hand, Cowling said, labeling every person who died while positive for COVID as having died from the disease could lead to an over-count. Such an approach "can also be criticised because it can, and has, included coincidental deaths such as in people hit by a bus while having mild COVID."

Dr. Mai He, a pathologist at Washington University in St. Louis who was involved in the Wuhan study published in 2020, said there was still a lack of faith in the integrity of China's numbers.

"The persistent critical issue is a lack of transparency; people cannot use their data to do research and analysis, (or) provide guidance for the next step," he told Reuters.

The lack of trust in China's statistics is also causing panic among members of the public, said Victoria Fan, senior fellow in global health at the Center for Global Development.

"It's in the best interest of the government to be more transparent, because a lot of the behaviors that the public is exhibiting is because they don't have information," she said.

(Reporting by David Stanway in Shanghai, Nancy Lapid in New York, and Julie Steenhuysen in Chicago; editing by Michele Gershberg, Sandra Maler and Lincoln Feast.)


"

 

[missy]

"

Merck's COVID Pill Does Not Cut Hospitalization, Death Rates in Many Vaccinated Adults: Study​

By Natalie Grover
December 23, 2022




LONDON (Reuters) - Merck & Co Inc's COVID antiviral molnupiravir speeds up recovery but does not reduce the hospitalisation or death rate in higher-risk vaccinated adults, detailed data from a large study showed on Thursday.
The drug, which prevents the virus from replicating, generated nearly $5 billion in sales for the U.S. drugmaker in the first three quarters of 2022.
Preliminary data from the study, carried out in the winter of 2021-2022 when the Omicron variant was dominant, was unveiled in October. As a result, doctors are already considering limiting molnupiravir's use, for instance, in Australia.
The latest results offer more detail and have been peer-reviewed.

The study, called PANORAMIC, compared the oral pill against standard treatment alone in people over 50 or those aged 18 and older with underlying conditions. They had been unwell with confirmed COVID for five days or fewer in the community setting.




When Merck originally tested molnupiravir, it was found 30% effective in reducing hospitalisations, but that was in unvaccinated patients.
In the latest study, led by University of Oxford researchers, nearly all of the more than 25,000 patients in the study had received at least three vaccine doses.
These results demonstrate that vaccine protection is so strong that there is no obvious benefit from the drug in terms of further reducing hospitalisation and deaths, said study co-author Jonathan Van-Tam from the University of Nottingham.

The drug was, however, effective in reducing viral load and can help hasten patient recovery by roughly four days, researchers estimated based on study data.
There might be circumstances in which molnupiravir could be useful, for instance, in under-pressure health systems where it could be used to help key workers back to work quicker, said co-chief study investigator Chris Butler from the University of Oxford.
But ultimately, those benefits need to be weighed against the drug's cost, added co-chief study investigator Paul Little from the University of Southampton. The drug, which was developed with Ridgeback Biotherapeutics, is estimated to cost several hundred pounds for a five-day course.
"For the moment, I think you have to say that don't use this drug in the general population, including those at slightly higher-risk," said Little.

Extremely clinically vulnerable patients, although eligible to enroll in PANORAMIC, were encouraged to access COVID treatment directly from Britain's National Health Service, so the molnupiravir findings are less applicable to highest-risk patients, authors wrote in the medical journal Lancet.

Last month, Britain's National Institute for Health and Care Excellence (NICE) recommended against the use of molnupiravir at current prices because the cost-effectiveness estimates are higher than what it considered an acceptable use of the national health system's resources.

(Reporting by Natalie Grover in London; Editing by Richard Chang)

"

 

[missy]

MashupMD

Up-to-date medical news aggregated from trusted medical associations, journals, physicians and news outlets from around the world.

mashupmd.com

"

COVID-19 vaccines and the Nuremberg Code​

It has been a while since I’ve written about this particular topic, which is why I think it a good time to revisit it, particularly given that over the last month there seems to have been a large uptick in antivaccine rhetoric centered around portraying COVID-19 vaccines as a new Holocaust and the concomitant desire for Nuremberg-style trials—complete with hashtags on Twitter like #Nuremberg2, #NurembergTribunal, the ominous-sounding #Nuremberg2TickTock, and related hashtags targeting Anthony Fauci, Bill Gates, and other perceived “enemies”—for public health officials, with punishment meted out afterwards for their “crimes.” In these calls for “Nuremberg 2.0,” the proposed punishment can range from imprisonment—”lock them up!”—to truly bloodthirsty calls for the gallows or even the guillotine. While I have written about this particular narrative far more extensively at my not-so-super-secret other blog, here I have mostly just alluded to it; so I thought it would be useful to discuss how the Nuremberg Code and Holocaust have been misused by antivaxxers for a long time. What we are seeing is nothing new in terms of content. What is new is the volume and broad reach of the narrative. Basically, calls for retribution disguised as “justice” against public health and vaccine advocates have reached places that I never would have predicted before when I first started writing about them over a decade ago.

First, however, let’s provide a taste of what I mean from antivax websites and social media. I will list quite a few examples, just to give readers an idea of what I’m talking about. First, attorney and long-time antivaccine advocate Mary Holland published an article on Robert F. Kennedy Jr.’s website titled “Those Who Violated Nuremberg Code Must Be Prosecuted for Crimes Against Humanity” that was the “inspiration” (if you will) for me to write this post, which is a transcript of her speech given for a conference titled “75 Years of the Nuremberg Code — Never Again Forced Medical Procedures“, a public conference held on August 20 in Nuremberg to commemorate the 75th anniversary of the Nuremberg Code. Unsurprisingly, it was hosted by Action Alliance, which appears to be a group of German antivaccine activists. Her speech was amplified by Mike Adams on Natural News, and one of the highlights that you might have seen being shared was a speech by a Holocaust survivor named Vera Sherav, in which she likened the COVID-19 response to the Final Solution and deemed it “the New Eugenics” in which this time “instead of Zyklon B gas, the weapons of mass destruction are genetically engineered injectable bioweapons masquerading as vaccines.” Meanwhile, antivaxxers are promoting narratives that COVID-19 vaccines are killing millions of people, an example being Steve Kirsch (whom I’ve written about before here) claiming that as many as 12 million have been killed by them worldwide, and that “they” are “killing people worldwide at a rate at least 6X faster than the Germans did”. (I kid you not; if you don’t believe me, click on the link.) Unsurprisingly, Mike Adams is amplifying this claim as well, with headlines like “10,000 people A DAY being killed by covid vaccines; worldwide fatalities likely larger than the HOLOCAUST” and “The mass culling of the HUMAN HERD is now under way… here’s exactly how it’s being accomplished to achieve mass extermination“.

Feel free to scroll past if you are one of those readers who so objects to embedded Tweets.

[NOTE to PSers: I couldn't copy the tweets and if you want to see them click onto the link I provided above]

In particular, this narrative has resurfaced since COVID-19 vaccines were approved for children:


It is, of course, not limited to that at all:


I’ll discuss these principles in a moment, in particular how they do not apply to COVID-19 vaccines and vaccine mandates. In the meantime, here are a few more examples:







Such calls are not limited to just vaccine advocates. Unfortunately, COVID-19 conspiracy theorists of all stripes have taken up the call, including those who think that COVID-19 originated in a “lab leak”. This particular example also shows how the narrative of a “Nuremberg 2.0” has reached beyond the antivaccine fringe and been taken up by a number of politicians:


Anecdotally, more and more vaccine advocates, myself included, are reporting to me that they are being targeted with threats, and here are some receipts:



And my favorite, here are threats that everything I Tweet is being “saved” to use as evidence against me:




I note that, even though I now have over 72K followers on Twitter, the threats and abuse that I receive are nothing compared to what a number of other vaccine advocates receive, particularly as a result of the “Nuremberg 2” narrative. So let’s compare what the antivax narrative about the Nuremberg Code, which was promulgated as a result of the Nuremberg Medical Trials in 1947, with reality and discuss why antivaxxers have long abused them, to the point where I once coined the term “Nuremberg Code gambit,” much as I coined the term “pharma shill gambit,” to describe a common false narrative by antivaxxers and medical science deniers. If you understand what the Nuremberg Code actually says, its role in the history of bioethics and evolving protections for human subjects in medical research, and how it has now been largely supplanted by the Helsinki Declaration, you will be better equipped to understand why the antivax narrative is so harmful.

Vera Sharav and Mary Holland
Vera Sharav and Mary Holland appearing at an antivaccine, anti-public health event disguised as a 75th anniversary of the Nuremberg Code.
Mary Holland and Vera Sharav invoke the Nuremberg Code

If you look at the lineup of the event commemorating the 75th anniversary of the conclusion of the Nuremberg Trials, you’ll probably recognize a few names other than Mary Holland. For example, Tess Lawrie, one of the foremost promoters of ivermectin as a highly effective treatment for COVID-19, was a prominent figure at the event, as was Rolf Kron, an antivax homeopath (but I repeat myself) from a COVID-19 “resistance” group called Doctors Stand Up. There were also groups of Holocaust survivors included, which was particularly distressing to me given my online history of combatting Holocaust denial dating back to the 1990s. I didn’t watch the entire event, which is archived at RFK Jr.’s website, but I watched enough and read enough transcripts to get the gist of the overall theme, which was, predictably, that COVID-19 public health responses, particularly the “experimental” vaccines, violate the Nuremberg Code.

I note with some amusement how Mary Holland includes in her talk an expression of disappointment that representatives from the governments of the Allies (the United States, the United Kingdom, and Russia) declined to take part:

I am especially honored to be here because the authors of the Nuremberg Code were doctors and lawyers from the United States who sought to prevent future horrors. And they built on medical and legal ethics established here in Germany before the Nazi regime.

I deeply wish that U.S., British, Russian and German government representatives were here to stand with us, as well as representatives of the global mainstream media.

It is a sad commentary that they are absent.

I wonder why these nations didn’t send representatives. Could it be that they recognized this farce for what it was?

Let’s see what Holland’s narrative is, though. It’s pretty predictable if you know anything about the antivaccine movement:

Tragically, in the last two-and-a-half years, we have witnessed a global assault on the Nuremberg Code.

Governments, medical establishments, universities and the media have violated the very first principle and every other principle of the code’s 10 points.

They have coerced people into being human guinea pigs.

They have forced people on penalty of their livelihoods, their identities, their health, their friendships — and even their family relationships — to take inadequately tested, experimental, gene-altering injections as well as experimental tests and medical devices.

Those who have intentionally, knowingly and maliciously violated the principles of the Nuremberg Code must be punished.

They must be called out, prosecuted and punished for crimes against humanity. This is one of our key tasks.

We must stop this. And we must ensure this does not happen again.

See the narrative? Vaccine advocates have committed “crimes against humanity” in supporting vaccination against COVID-19 and vaccine mandates for certain jobs and activities. You can watch the whole thing at RFK Jr.’s website, but there’s no real need given that a complete transcript was published.

Throughout the rest of the talk, Holland portrayed the vaccines as “experimental” and deadly, stating at one point, “In the U.S. and here in Europe, no vaccine has ever remotely compared to these injections — the risk and death profile of these injections is unprecedented.” They are not experimental, and, contrary to the claims of mass death due to vaccines, they are not deadly; indeed, they are amazingly safe.

As I’ve said many times before, even when they were authorized under emergency use authorization (EUA) in the US, they had still undergone large phase 3 randomized clinical trials involving tens of thousands of subjects demonstrating safety and efficacy. Any pharmaceutical or vaccine that has cleared such a hurdle is, scientifically speaking, not “experimental” anymore. The term “investigational” is a legal term specific to the FDA and its mandate; all it means is that the drug or vaccine has not yet gone through the entire regulatory process in order to achieve full FDA approval. The mechanism of an EUA was designed to allow the FDA to act faster in the case of an urgent situation. If a global pandemic killing (then) hundreds of thousands of people didn’t qualify, I don’t know what does. Oddly enough, even after the mRNA-based vaccines achieved full FDA approval, antivaxxers continued to portray them as “experimental”.

Moving on, I’ve been meaning to write about Vera Sharav for a long time. Indeed, she warrants her own post, and what I write about her here will be far briefer than is warranted. Before I go into her background as a Holocaust survivor and founder of a group ostensibly devoted to patient rights, informed consent, and, above all, the protection of human research subjects in medical research, let’s take a look at a bit of what she said in her speech, which can be viewed in its entirety, again, on RFK Jr.’s website, although the antivaccine blog Age of Autism helpfully provided a transcript.

To start out her speech, Sharav recounted her history:

In 1941, I was 31⁄2 when my family was forced from our home in Romania & deported to Ukraine.

We were herded into a concentration camp – essentially left to starve. Death was ever-present. My father died of typhus when I was five.

In 1944, as the Final Solution was being aggressively implemented, Romania retreated from its alliance with Nazi Germany. The government permitted several hundred Jewish orphans under the age of 12 to return to Romania. I was not an orphan; my mother lied to save my life.

I boarded a cattle car train – the same train that continued to transport Jews to the death camps – even as Germany was losing the war.

Four years elapsed before I was reunited with my mother.

Sharav (born Vera Roll) had fallen victim to a move by the fascist government that ruled Romania and was allied with Hitler at the time, in which some 145,000 Romanian and Hungarian Jews were moved to an area known as Transnistria along the Ukraine border, which became one of the most notorious killing fields of the war, with as many as 250,000 Jews were killed or allowed to die of disease and starvation. The Rolls were sent to a town called Mogilev, which had been turned into a concentration camp by the Romanians and Nazis. Her father died there of typhus within weeks of their arrival.

In her speech, Sharav made an explicit parallel between the Final Solution and COVID-19 and more or less correctly blamed eugenics for the Holocaust. I say “more or less” because there was more to it than just eugenics, the belief that Jews were subhuman, and that German Aryans were the “master race”. Hitler also believed that the Jews were working to destroy Germany and had decided that he had to destroy them before they could succeed. In any event, she was correct that the Holocaust didn’t happen all at once, observing that it “did not begin in the gas chambers of Auschwitz and Treblinka”, had been “preceded by nine years of incremental restrictions on personal freedom, and the suspension of legal rights and civil rights”, and that the stage had been “set by fear-mongering and hate-mongering propaganda”. While this description was correct, unfortunately Sharav then pivoted to liken the current climate to the escalating restrictions and persecutions of the Jews during the Holocaust:

By declaring a state of emergency—in 1933 and in 2020, constitutionally protected personal freedom, legal rights, and civil rights were swept aside. Repressive, discriminatory decrees followed. In 1933, the primary target for discrimination were Jews; today, the target is people who refuse to be injected with experimental, genetically engineered vaccines. Then and now, government dictates were crafted to eliminate segments of the population. In 2020, government dictates forbade hospitals from treating the elderly in nursing homes. The result was mass murder. Government decrees continue to forbid doctors to prescribe life-saving, FDA approved medicines; government-dictated protocols continue to kill.

The media is silent – as it was then. The media broadcasts a single, government-dictated narrative – just as it had under the Nazis. Strict censorship silences opposing views.
In Nazi Germany few individuals objected; those who did were imprisoned in concentration camps. Today, doctors & scientists who challenge the approved narrative are maligned; their reputations trashed. They risk losing their license to practice as well as having their homes and workplace raided by SWAT teams.

What Sharav meant when she mentioned “FDA-approved medicines” was clearly the repurposed and unproven drugs hydroxychloroquine and ivermectin, neither of which are actually effective in treating COVID-19. As for the rest, you can see the same narrative that many antivaxxers have promoted that likens pandemic restrictions to another Holocaust at worst or, at minimum, to incipient fascism. I do have to wonder: Who are these physicians arguing against COVID-19 vaccines and for alternative treatments like ivermectin who have had “their homes and workplace raided by SWAT teams”? I like to think that I’m up on all the latest COVID-19 news, particularly about “contrarian” doctors, and I don’t recall ever having encountered a news story in which any of these doctors had their home or office raided by a SWAT team. Is she referring to Dr. Simone Gold, who was sentenced to 60 days in prison for trespassing in the US Capitol Building during the January 6 insurrection? Help me out here.

Of course, Sharav concluded her speech by bringing it back to the Nuremberg Code, warning:

Those who declare that Holocaust analogies are “off limits”—are betraying the victims of the Holocaust by denying the relevance of the Holocaust.

The Nuremberg Code has served as the foundation for ethical clinical research since its publication 75 years ago.

The Covid pandemic is being exploited as an opportunity to overturn the moral and legal parameters laid down by the Nuremberg Code.

The Nuremberg Code is our defense against abusive experimentation.

While it is not incorrect to state that the Nuremberg Code is important as a foundation for ethical human subjects research and that it is a defense against abusive experimentation, it is not complete to say that either, as I will discuss in the next section. In the meantime, I’ll simply quote from near the end of Sharav’s speech:

Transhumanists despise human values, & deny the existence of a human soul. Harari declares that there are too many “useless people.” The Nazi term was “worthless eaters”

This is the New Eugenics.

It is embraced by the most powerful global billionaire technocrats who gather at Davos: Big Tech, Big Pharma, the financial oligarchs, academics, government leaders & the military industrial complex. These megalomaniacs have paved the road to another Holocaust.

This time, the threat of genocide is Global in scale.

This time instead of Zyklon B gas, the weapons of mass destruction are genetically engineered injectable bioweapons masquerading as vaccines.

This time, there will be no rescuers. Unless All of Us Resist, Never Again is Now.

That’s right. Vera Sharav directly compared COVID-19 vaccines to the Zyklon-B gas that Nazis used as one of their main tools of mass extermination of the Jews. She also repeated an old antivaccine claim, namely the portrayal of vaccines as a form of “transhumanism“.

I started this section by mentioning that I had long been meaning to write about Vera Sharav. The reason is that she had aligned herself with antivaxxers years before the pandemic. For example, in this STAT News story from 2016, she expressed her belief that Andrew Wakefield had been railroaded:

But her distrust of the drug industry and medical research institutions has also led her to embrace some dubious heroes, including discredited British physician Andrew Wakefield, who falsified data to imply a link between vaccines and autism.

Wakefield’s medical license was revoked for a series of ethics violations, and most in the mainstream medical community blame him for raising unjustified doubts about the safety of vaccines. Yet Sharav puts him on her “honor roll” of “exemplary professionals,” along with Florence Nightingale.

“My research and my gut tell me that Wakefield has been wronged,” she said. “One thing I’ve learned from early in my life is that if I don’t stay true to my gut feeling, then I’m lost. I don’t have any control.”

That same news story also described her better history, how she had been a force for protecting human subjects in medical experiments, founding the Alliance for Human Research Protection after the death of her son, who had suffered from schizophrenia, from neuroleptic malignant syndrome, an uncommon but frequently deadly side effect of antipsychotic drugs that causes muscle rigidity and fever and can ultimately lead to organ failure and death. I’ve perused that the AHRP website before, but let’s take a look at one of the two articles that greet visitors to its homepage:

AHRP website on 8/28/2022
That illustration by David Dees on the right is a classic antivax conspiracy image that I’ve seen on quack websites going back at least a decade, if not longer.
Let’s just put it this way. If you use an image by David Dees to illustrate your article, you have gone far down the antivaccine road. Worse, the image is blatantly antisemitic. Notice how the “vaccine enforcement” officer has a badge of the Star of David with the word “Zion” in it. As for the article itself, it’s a typical antivaccine-style screed in which adverse events recorded in the Vaccine Adverse Events Reporting System (VAERS) database are represented as definitely having been caused by vaccines when, in fact, anyone who understands VAERS knows that you can’t do that. Seriously, both articles are nothing but standard antivax propaganda, and not even antivax propaganda chock full of conspiracy theories about COVID-19 vaccines that could plausibly be portrayed as “human subjects protection”. The same is true of the other article, in which vaccination is described in typical antivax language as a “medical assault”. Throughout the website, vaccines are frequently referred to as “child sacrifice” in articles dating back more than a decade. This “pivot” is not a pivot, and the antivax lean of AHRP is not new, nor is her demonization of COVID-19 vaccines new. She was doing it in 2020, an example of which comes from an interview from October 2020, as COVID-19 vaccines were making their way through the regulatory process. In the interview, titled “Nazism, COVID-19 and the destruction of modern medicine: An interview with Vera Sharav“, Sharav characterized the push for a vaccine as being all about the profit, saying at one point:

You don’t read about it in the media because the media is very much part of the business empire that’s ruling that.

Vaccines are an empire, and now they really want to do a vaccine globally.

Do you know what kind of a market that is? More than 7 billion people for a vaccine. Can you even count the kind of profits, no matter what they charge for it?

That’s what their goal is. That’s the whole allure of this COVID 19 vaccine. It’s that market.

You get the idea. What Vera Sharav was saying nearly two years ago was indistinguishable from the rhetoric I was seeing on hard core antivaccine sites, such as Natural News and, yes, RFK Jr.’s website, where the interview was published. Her antivax rhetoric remains indistinguishable from that of RFK Jr., Mike Adams, Del Bigtree, Andrew Wakefield, and basically all the major antivax “thought leaders” (if you can call it thought). Whatever her achievements in raising awareness of shoddy human subjects research practices, the dangers of certain pharmaceuticals, the frequency of nontherapeutic research, and the increasingly cozy relationship between medical academia and big pharma, Vera Sharav has clearly followed others down the road from skepticism of psychiatric drugs to extreme distrust of pharma to outright antivax.

But what about the Nuremberg Code?

Nuremberg Doctors' Trial
Nazi doctors facing justice in Nuremberg in 1947
COVID-19 vaccines and the Nuremberg Code

With the just completed discussion in mind, let’s circle back again to the Nuremberg Code, a set of principles for human subjects research that published in 1947 as part of USA vs. Brandt et al. (also often called the Doctors’ Trial) as one result of the Nuremberg Trials. The trial involved doctors who had been involved in Nazi human experimentation and mass murder disguised as euthanasia. Of the 23 defendants, seven were acquitted, while seven were sentenced to death. The rest received prison sentences ranging from 10 years to life imprisonment.

There are ten points to the code, which was published in the section of the verdict entitled “Permissible medical experiments”:

The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, overreaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs, or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.
The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.
The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.
The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.
No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.
The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.
Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.
The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.
During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible.
During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.
It is true that the Nuremberg Code remains one of the foundations of medical ethics governing human subjects research. It is, however, old and has been largely supplanted, for all practical purposes, by newer statements of human research ethics. While it is certainly true that these newer statements (which I’ll discuss in a moment) echo many of the points of the Nuremberg Code, it’s also true they go beyond them.

Before I do that, though, here’s the key deficiency in the arguments that antivaxxers have been using that invoke the Nuremberg Code is actually quite simple, as I once wrote over a year ago on Twitter:

To reiterate, the Nuremberg Code only applies to human experimentation. Notice how each of the ten points of the Nuremberg Code mentions “the experiment” or “experimental” treatments. The Code is not about medical treatment, only medical experimentation involving human subjects. I don’t know how it can be made much simpler than that. Of course, the desire to appeal to the Nuremberg Code is why antivaxxers try so desperately to misrepresent COVID-19 vaccines as being “experimental”. It’s also why I like to retort that no one was forced, coerced, or otherwise mandated to sign up to be a subject in any of the clinical trials of the Pfizer or Moderna vaccines (or any of the other currently approved vaccines) that led to their authorization under an EUA and ultimately to their full FDA approval. Again, vaccines that have passed phase 3 clinical trials and been shown to be safe and effective are not, from a scientific viewpoint, “experimental” anymore. They might still be considered “investigational” from a legal standpoint because all that means is that they haven’t gone through the full FDA process yet, but that’s it. Even while they were still being distributed under an EUA and before they were granted full FDA approval, from a scientific and medical standpoint COVID-19 vaccines being used have been legitimate medical preventative treatments, even when they did not yet have full FDA approval.

The second part of the Nuremberg Code gambit most commonly used is the deceptive appeal to “informed consent”. Of course, as I like to point out, while antivaxxers like to think they are really advocating for informed consent (and probably actually do think that), in practice, what they are advocating for is something that I like to refer to as “misinformed refusal”. (I used to call it “misinformed consent” before I realized that this term didn’t quite catch the essence of what antivaxxers do.) It’s an antivaccine trope that I’ve been dealing with at least 17 years, if not longer.

Here’s the idea. Antivaxxers vastly exaggerate the risks of vaccines and even attribute nonexistent risks to them (e.g., autism, autoimmune disease, sudden infant death syndrome) that are not at all supported by science. At the same time, they deny or downplay the benefits of vaccines, portraying them as largely ineffective and claiming that “natural” immunity from the disease is far superior to vaccine-induced immunity. Thus, if parents listen to the antivaccine narrative about the risk-benefit profile of vaccines, they will believe that the risks of vaccines outweigh the benefits. They might even believe that vaccines are not only ineffective, but dangerous, deadly even. That’s where my term “misinformed refusal” comes in. It’s the refusal of vaccines based on misinformation that portrays a falsely unfavorable (and even terrifying) risk-benefit ratio.

The Nuremberg Code, as important as it has been in the history and development of human subjects protections during medical research, has largely been supplanted by the Belmont Report (published in 1976) and the Declaration of Helsinki. The Belmont Report, for instance, goes beyond the Nuremberg Code by delineating the boundaries between medical practice and research. It also rests on basic ethical principles of respect for persons, beneficence, and justice, while emphasizing the importance of voluntariness (as the Nuremberg Code), a detailed discussion of benefits and risks (informed consent), and the selection of subjects. The Declaration of Helsinki, last updated in 2013, is similar, but goes into much more detail about informed consent. It also addresses the ethics of the use of placebos, post-trial provisions, and the dissemination of results. It even addresses the use of unproven interventions in clinical practice outside of clinical trials.

Finally, in the US, the federal regulations governing human subjects research are enshrined under the Common Rule, which was originally instituted in 1981 and was last significantly revised in 2018. Basically, the Common Rule is the operationalization of the principles of the Belmont Report and the Declaration of Helsinki into regulations governing human subjects research carried out by the federal government, institutions that receive federal funding, and pharmaceutical and device companies seeking FDA approval for their products. It requires Institutional Review Board (IRB) approval and oversight of human subjects research, among other requirements for ethical human research and lays out the requirements for informed consent, as well as for research compliance by institutions. In effect, the Common Rule lays out the standard of ethics that govern not just human subjects research funded by the federal government or subject to FDA regulation for FDA approval, but in essence nearly all human subjects research. Almost all US academic institutions require their researchers to adhere to the Common Rule regardless of funding sources.

So why do antivaxxers always mention the Nuremberg Code and almost never the Belmont Report, Declaration of Helsinki, or the Common Rule when claiming that vaccine mandates somehow violate human subjects research protections and/or informed consent? The reason is simple. Neither the Belmont Report, the Declaration of Helsinki, nor the Common Rule were written or promulgated in response to Nazi war crimes. The Nuremberg Code, on the other hand, was written as part of the verdict of the Doctors Trial at Nuremberg as a first attempt to codify what principles that should govern ethical human subjects research.

In other words, the simple reason that antivaxxers point to “informed consent” for (or, as I like to call it, misinformed refusal of) vaccines along with the Nuremberg Code is because it’s a Godwin. It not-so-subtly compares physicians, public health officials, and vaccine advocates to Nazis. That’s the one and only purpose of the Nuremberg gambit. If it weren’t, in order to try to portray vaccines as “experimental” or “unproven,” antivaxxers would instead refer to the Helsinki Declaration, which is the most recent and most applicable set of ethical principals governing human subjects research. They don’t. That should tell you all you need to know about the Nuremberg gambit other than that COVID-19 vaccine mandates do not violate the Nuremberg Code anyway.

The Nuremberg gambit: Beyond antivaxxers

Unfortunately, the Nuremberg Code gambit is a Godwin that has permeated not just hard core antivaccine messaging. Indeed, it’s spread to pretty much every corner of COVID-19 contrarianism, minimization, and resistance to any sort of pandemic-related mandate, be it “lockdowns”, vaccines, or masks. (Nuremberg has even infiltrated “gender critical” narrative about gender-affirming care for transgender youths, with one group likening doctors practicing gender-affirming care to Josef Mengele, the infamously cruel Nazi doctor at Auschwitz.) I’ll start by invoking a Tweet that has been cited on this blog before, mainly by Jonathan Howard:


It’s interesting to note that Jeffery Tucker of the Brownstone Institute could have chosen pretty much any other image for his article, but he chose that of a guillotine, the symbol of the Reign of Terror, a series of executions and massacres after the French Revolution, with the guillotine being the favored method of individual executions. In the article, shared by Martin Kulldorff, one of the three writers of the Great Barrington Declaration, that propaganda piece of anti-lockdown hysteria that basically advocated letting COVID-19 rip through the young and healthy population, the better to achieve “natural herd immunity” as fast as possible, while somehow—it’s never really specified how—using “focused protection” to keep safe the elderly and those with chronic health conditions at high risk for serious disease and death due to COVID-19.

The first time that I first saw this image, I couldn’t help but ask: If Tucker wasn’t calling for executions, why did he and the Brownstone Institute choose a very menacing image of a guillotine? They could have chosen literally any other image, but they didn’t. They chose a view of a guillotine that emphasizes the blade ready to fall, a very ominous and threatening image. (It very much looks like the view of a guillotine that someone near the front of the crowd baying for blood during the Reign of Terror might have had—or the view that someone walking up the steps to be executed might have had.) If Tucker and the Brownstone Institute were really interested in portraying justice, instead of retribution, wouldn’t an image of a courtroom or a jury—or of virtually anything other than a guillotine—have been more appropriate? Did Dr. Kulldorff not even see the not-so-subtle message that such an image paired with an article like Tucker’s broadcasts? As an aside, I’ll also ask this question: Does anyone know who else used the guillotine as a method of execution besides le tribunal révolutionnaire during the Reign of Terror? The Nazi regime in Germany! No, seriously, look it up if you don’t believe me. Members of the White Rose resistance, for example, were executed by guillotine after show trials.

Reign of Terror or Nuremberg 2? Does it matter? The idea is vengeance against enemies of antivaxxers disguised as “justice”. This fantasy of retribution is not new, either, as I pointed out, referencing a 2017 post by an antivaxxer named Kent Heckenlively:


Note the same sort of imagery from a man who has in the past demanded the “complete surrender” of vaccine advocates, promising them—maybe—mercy if they recant and confess their “crimes”. These “crimes”? Given that at the time the predominant misinformation believed by antivaxxers was that vaccines cause autism, the “crimes” were advocating policies that make children autistic.

As I often say (admittedly sometimes ad nauseam) in the age of the pandemic, everything old is new again, and the same thing applies to the Nuremberg Code gambit. The difference is not the antivax fantasy of retribution against their perceived enemies, but rather that the language and rhetoric that was, until relatively recently, only associated with the hardest of hardcore antivaxxers, has started to wend its way into the mainstream, with right wing pundits like Tucker Carlson taking up the narrative, likening COVID-19 vaccine mandates to the cruel and grossly unethical experiments that Nazis and Japanese carried out using prisoners during World War II, while mangling what Nuremberg is about by describing such mandates as “forced treatment” rather than abuse of human experimentation. Misunderstanding aside, this gave his interviewee, Robert “inventor of mRNA vaccines” Malone, the opportunity to thank Carlson for bringing up the Nuremberg Code:


Perhaps the most frightening thing about the pandemic is how antivaccine narratives once viewed as fringe even among most antivaxxers, the province of only the hardest of the hardcore, are now being amplified by mainstream pundits with millions of viewers and used by “think tanks” like the Brownstone Institute to stoke fear of vaccines and potential violence against vaccine advocates. That’s always been the purpose of the Nuremberg Code gambit. Unfortunately, today the chance of the Nuremberg Code gambit resulting in actual violence is higher than it’s ever been.


"

 

[Gloria27]

MashupMD

Up-to-date medical news aggregated from trusted medical associations, journals, physicians and news outlets from around the world.

mashupmd.com

"

COVID-19 vaccines and the Nuremberg Code​

It has been a while since I’ve written about this particular topic, which is why I think it a good time to revisit it, particularly given that over the last month there seems to have been a large uptick in antivaccine rhetoric centered around portraying COVID-19 vaccines as a new Holocaust and the concomitant desire for Nuremberg-style trials—complete with hashtags on Twitter like #Nuremberg2, #NurembergTribunal, the ominous-sounding #Nuremberg2TickTock, and related hashtags targeting Anthony Fauci, Bill Gates, and other perceived “enemies”—for public health officials, with punishment meted out afterwards for their “crimes.” In these calls for “Nuremberg 2.0,” the proposed punishment can range from imprisonment—”lock them up!”—to truly bloodthirsty calls for the gallows or even the guillotine. While I have written about this particular narrative far more extensively at my not-so-super-secret other blog, here I have mostly just alluded to it; so I thought it would be useful to discuss how the Nuremberg Code and Holocaust have been misused by antivaxxers for a long time. What we are seeing is nothing new in terms of content. What is new is the volume and broad reach of the narrative. Basically, calls for retribution disguised as “justice” against public health and vaccine advocates have reached places that I never would have predicted before when I first started writing about them over a decade ago.

First, however, let’s provide a taste of what I mean from antivax websites and social media. I will list quite a few examples, just to give readers an idea of what I’m talking about. First, attorney and long-time antivaccine advocate Mary Holland published an article on Robert F. Kennedy Jr.’s website titled “Those Who Violated Nuremberg Code Must Be Prosecuted for Crimes Against Humanity” that was the “inspiration” (if you will) for me to write this post, which is a transcript of her speech given for a conference titled “75 Years of the Nuremberg Code — Never Again Forced Medical Procedures“, a public conference held on August 20 in Nuremberg to commemorate the 75th anniversary of the Nuremberg Code. Unsurprisingly, it was hosted by Action Alliance, which appears to be a group of German antivaccine activists. Her speech was amplified by Mike Adams on Natural News, and one of the highlights that you might have seen being shared was a speech by a Holocaust survivor named Vera Sherav, in which she likened the COVID-19 response to the Final Solution and deemed it “the New Eugenics” in which this time “instead of Zyklon B gas, the weapons of mass destruction are genetically engineered injectable bioweapons masquerading as vaccines.” Meanwhile, antivaxxers are promoting narratives that COVID-19 vaccines are killing millions of people, an example being Steve Kirsch (whom I’ve written about before here) claiming that as many as 12 million have been killed by them worldwide, and that “they” are “killing people worldwide at a rate at least 6X faster than the Germans did”. (I kid you not; if you don’t believe me, click on the link.) Unsurprisingly, Mike Adams is amplifying this claim as well, with headlines like “10,000 people A DAY being killed by covid vaccines; worldwide fatalities likely larger than the HOLOCAUST” and “The mass culling of the HUMAN HERD is now under way… here’s exactly how it’s being accomplished to achieve mass extermination“.

Feel free to scroll past if you are one of those readers who so objects to embedded Tweets.

[NOTE to PSers: I couldn't copy the tweets and if you want to see them click onto the link I provided above]

In particular, this narrative has resurfaced since COVID-19 vaccines were approved for children:


It is, of course, not limited to that at all:


I’ll discuss these principles in a moment, in particular how they do not apply to COVID-19 vaccines and vaccine mandates. In the meantime, here are a few more examples:







Such calls are not limited to just vaccine advocates. Unfortunately, COVID-19 conspiracy theorists of all stripes have taken up the call, including those who think that COVID-19 originated in a “lab leak”. This particular example also shows how the narrative of a “Nuremberg 2.0” has reached beyond the antivaccine fringe and been taken up by a number of politicians:


Anecdotally, more and more vaccine advocates, myself included, are reporting to me that they are being targeted with threats, and here are some receipts:



And my favorite, here are threats that everything I Tweet is being “saved” to use as evidence against me:




I note that, even though I now have over 72K followers on Twitter, the threats and abuse that I receive are nothing compared to what a number of other vaccine advocates receive, particularly as a result of the “Nuremberg 2” narrative. So let’s compare what the antivax narrative about the Nuremberg Code, which was promulgated as a result of the Nuremberg Medical Trials in 1947, with reality and discuss why antivaxxers have long abused them, to the point where I once coined the term “Nuremberg Code gambit,” much as I coined the term “pharma shill gambit,” to describe a common false narrative by antivaxxers and medical science deniers. If you understand what the Nuremberg Code actually says, its role in the history of bioethics and evolving protections for human subjects in medical research, and how it has now been largely supplanted by the Helsinki Declaration, you will be better equipped to understand why the antivax narrative is so harmful.

Vera Sharav and Mary Holland
Vera Sharav and Mary Holland appearing at an antivaccine, anti-public health event disguised as a 75th anniversary of the Nuremberg Code.
Mary Holland and Vera Sharav invoke the Nuremberg Code

If you look at the lineup of the event commemorating the 75th anniversary of the conclusion of the Nuremberg Trials, you’ll probably recognize a few names other than Mary Holland. For example, Tess Lawrie, one of the foremost promoters of ivermectin as a highly effective treatment for COVID-19, was a prominent figure at the event, as was Rolf Kron, an antivax homeopath (but I repeat myself) from a COVID-19 “resistance” group called Doctors Stand Up. There were also groups of Holocaust survivors included, which was particularly distressing to me given my online history of combatting Holocaust denial dating back to the 1990s. I didn’t watch the entire event, which is archived at RFK Jr.’s website, but I watched enough and read enough transcripts to get the gist of the overall theme, which was, predictably, that COVID-19 public health responses, particularly the “experimental” vaccines, violate the Nuremberg Code.

I note with some amusement how Mary Holland includes in her talk an expression of disappointment that representatives from the governments of the Allies (the United States, the United Kingdom, and Russia) declined to take part:

I am especially honored to be here because the authors of the Nuremberg Code were doctors and lawyers from the United States who sought to prevent future horrors. And they built on medical and legal ethics established here in Germany before the Nazi regime.

I deeply wish that U.S., British, Russian and German government representatives were here to stand with us, as well as representatives of the global mainstream media.

It is a sad commentary that they are absent.

I wonder why these nations didn’t send representatives. Could it be that they recognized this farce for what it was?

Let’s see what Holland’s narrative is, though. It’s pretty predictable if you know anything about the antivaccine movement:

Tragically, in the last two-and-a-half years, we have witnessed a global assault on the Nuremberg Code.

Governments, medical establishments, universities and the media have violated the very first principle and every other principle of the code’s 10 points.

They have coerced people into being human guinea pigs.

They have forced people on penalty of their livelihoods, their identities, their health, their friendships — and even their family relationships — to take inadequately tested, experimental, gene-altering injections as well as experimental tests and medical devices.

Those who have intentionally, knowingly and maliciously violated the principles of the Nuremberg Code must be punished.

They must be called out, prosecuted and punished for crimes against humanity. This is one of our key tasks.

We must stop this. And we must ensure this does not happen again.

See the narrative? Vaccine advocates have committed “crimes against humanity” in supporting vaccination against COVID-19 and vaccine mandates for certain jobs and activities. You can watch the whole thing at RFK Jr.’s website, but there’s no real need given that a complete transcript was published.

Throughout the rest of the talk, Holland portrayed the vaccines as “experimental” and deadly, stating at one point, “In the U.S. and here in Europe, no vaccine has ever remotely compared to these injections — the risk and death profile of these injections is unprecedented.” They are not experimental, and, contrary to the claims of mass death due to vaccines, they are not deadly; indeed, they are amazingly safe.

As I’ve said many times before, even when they were authorized under emergency use authorization (EUA) in the US, they had still undergone large phase 3 randomized clinical trials involving tens of thousands of subjects demonstrating safety and efficacy. Any pharmaceutical or vaccine that has cleared such a hurdle is, scientifically speaking, not “experimental” anymore. The term “investigational” is a legal term specific to the FDA and its mandate; all it means is that the drug or vaccine has not yet gone through the entire regulatory process in order to achieve full FDA approval. The mechanism of an EUA was designed to allow the FDA to act faster in the case of an urgent situation. If a global pandemic killing (then) hundreds of thousands of people didn’t qualify, I don’t know what does. Oddly enough, even after the mRNA-based vaccines achieved full FDA approval, antivaxxers continued to portray them as “experimental”.

Moving on, I’ve been meaning to write about Vera Sharav for a long time. Indeed, she warrants her own post, and what I write about her here will be far briefer than is warranted. Before I go into her background as a Holocaust survivor and founder of a group ostensibly devoted to patient rights, informed consent, and, above all, the protection of human research subjects in medical research, let’s take a look at a bit of what she said in her speech, which can be viewed in its entirety, again, on RFK Jr.’s website, although the antivaccine blog Age of Autism helpfully provided a transcript.

To start out her speech, Sharav recounted her history:

In 1941, I was 31⁄2 when my family was forced from our home in Romania & deported to Ukraine.

We were herded into a concentration camp – essentially left to starve. Death was ever-present. My father died of typhus when I was five.

In 1944, as the Final Solution was being aggressively implemented, Romania retreated from its alliance with Nazi Germany. The government permitted several hundred Jewish orphans under the age of 12 to return to Romania. I was not an orphan; my mother lied to save my life.

I boarded a cattle car train – the same train that continued to transport Jews to the death camps – even as Germany was losing the war.

Four years elapsed before I was reunited with my mother.

Sharav (born Vera Roll) had fallen victim to a move by the fascist government that ruled Romania and was allied with Hitler at the time, in which some 145,000 Romanian and Hungarian Jews were moved to an area known as Transnistria along the Ukraine border, which became one of the most notorious killing fields of the war, with as many as 250,000 Jews were killed or allowed to die of disease and starvation. The Rolls were sent to a town called Mogilev, which had been turned into a concentration camp by the Romanians and Nazis. Her father died there of typhus within weeks of their arrival.

In her speech, Sharav made an explicit parallel between the Final Solution and COVID-19 and more or less correctly blamed eugenics for the Holocaust. I say “more or less” because there was more to it than just eugenics, the belief that Jews were subhuman, and that German Aryans were the “master race”. Hitler also believed that the Jews were working to destroy Germany and had decided that he had to destroy them before they could succeed. In any event, she was correct that the Holocaust didn’t happen all at once, observing that it “did not begin in the gas chambers of Auschwitz and Treblinka”, had been “preceded by nine years of incremental restrictions on personal freedom, and the suspension of legal rights and civil rights”, and that the stage had been “set by fear-mongering and hate-mongering propaganda”. While this description was correct, unfortunately Sharav then pivoted to liken the current climate to the escalating restrictions and persecutions of the Jews during the Holocaust:

By declaring a state of emergency—in 1933 and in 2020, constitutionally protected personal freedom, legal rights, and civil rights were swept aside. Repressive, discriminatory decrees followed. In 1933, the primary target for discrimination were Jews; today, the target is people who refuse to be injected with experimental, genetically engineered vaccines. Then and now, government dictates were crafted to eliminate segments of the population. In 2020, government dictates forbade hospitals from treating the elderly in nursing homes. The result was mass murder. Government decrees continue to forbid doctors to prescribe life-saving, FDA approved medicines; government-dictated protocols continue to kill.

The media is silent – as it was then. The media broadcasts a single, government-dictated narrative – just as it had under the Nazis. Strict censorship silences opposing views.
In Nazi Germany few individuals objected; those who did were imprisoned in concentration camps. Today, doctors & scientists who challenge the approved narrative are maligned; their reputations trashed. They risk losing their license to practice as well as having their homes and workplace raided by SWAT teams.

What Sharav meant when she mentioned “FDA-approved medicines” was clearly the repurposed and unproven drugs hydroxychloroquine and ivermectin, neither of which are actually effective in treating COVID-19. As for the rest, you can see the same narrative that many antivaxxers have promoted that likens pandemic restrictions to another Holocaust at worst or, at minimum, to incipient fascism. I do have to wonder: Who are these physicians arguing against COVID-19 vaccines and for alternative treatments like ivermectin who have had “their homes and workplace raided by SWAT teams”? I like to think that I’m up on all the latest COVID-19 news, particularly about “contrarian” doctors, and I don’t recall ever having encountered a news story in which any of these doctors had their home or office raided by a SWAT team. Is she referring to Dr. Simone Gold, who was sentenced to 60 days in prison for trespassing in the US Capitol Building during the January 6 insurrection? Help me out here.

Of course, Sharav concluded her speech by bringing it back to the Nuremberg Code, warning:

Those who declare that Holocaust analogies are “off limits”—are betraying the victims of the Holocaust by denying the relevance of the Holocaust.

The Nuremberg Code has served as the foundation for ethical clinical research since its publication 75 years ago.

The Covid pandemic is being exploited as an opportunity to overturn the moral and legal parameters laid down by the Nuremberg Code.

The Nuremberg Code is our defense against abusive experimentation.

While it is not incorrect to state that the Nuremberg Code is important as a foundation for ethical human subjects research and that it is a defense against abusive experimentation, it is not complete to say that either, as I will discuss in the next section. In the meantime, I’ll simply quote from near the end of Sharav’s speech:

Transhumanists despise human values, & deny the existence of a human soul. Harari declares that there are too many “useless people.” The Nazi term was “worthless eaters”

This is the New Eugenics.

It is embraced by the most powerful global billionaire technocrats who gather at Davos: Big Tech, Big Pharma, the financial oligarchs, academics, government leaders & the military industrial complex. These megalomaniacs have paved the road to another Holocaust.

This time, the threat of genocide is Global in scale.

This time instead of Zyklon B gas, the weapons of mass destruction are genetically engineered injectable bioweapons masquerading as vaccines.

This time, there will be no rescuers. Unless All of Us Resist, Never Again is Now.

That’s right. Vera Sharav directly compared COVID-19 vaccines to the Zyklon-B gas that Nazis used as one of their main tools of mass extermination of the Jews. She also repeated an old antivaccine claim, namely the portrayal of vaccines as a form of “transhumanism“.

I started this section by mentioning that I had long been meaning to write about Vera Sharav. The reason is that she had aligned herself with antivaxxers years before the pandemic. For example, in this STAT News story from 2016, she expressed her belief that Andrew Wakefield had been railroaded:

But her distrust of the drug industry and medical research institutions has also led her to embrace some dubious heroes, including discredited British physician Andrew Wakefield, who falsified data to imply a link between vaccines and autism.

Wakefield’s medical license was revoked for a series of ethics violations, and most in the mainstream medical community blame him for raising unjustified doubts about the safety of vaccines. Yet Sharav puts him on her “honor roll” of “exemplary professionals,” along with Florence Nightingale.

“My research and my gut tell me that Wakefield has been wronged,” she said. “One thing I’ve learned from early in my life is that if I don’t stay true to my gut feeling, then I’m lost. I don’t have any control.”

That same news story also described her better history, how she had been a force for protecting human subjects in medical experiments, founding the Alliance for Human Research Protection after the death of her son, who had suffered from schizophrenia, from neuroleptic malignant syndrome, an uncommon but frequently deadly side effect of antipsychotic drugs that causes muscle rigidity and fever and can ultimately lead to organ failure and death. I’ve perused that the AHRP website before, but let’s take a look at one of the two articles that greet visitors to its homepage:

AHRP website on 8/28/2022
That illustration by David Dees on the right is a classic antivax conspiracy image that I’ve seen on quack websites going back at least a decade, if not longer.
Let’s just put it this way. If you use an image by David Dees to illustrate your article, you have gone far down the antivaccine road. Worse, the image is blatantly antisemitic. Notice how the “vaccine enforcement” officer has a badge of the Star of David with the word “Zion” in it. As for the article itself, it’s a typical antivaccine-style screed in which adverse events recorded in the Vaccine Adverse Events Reporting System (VAERS) database are represented as definitely having been caused by vaccines when, in fact, anyone who understands VAERS knows that you can’t do that. Seriously, both articles are nothing but standard antivax propaganda, and not even antivax propaganda chock full of conspiracy theories about COVID-19 vaccines that could plausibly be portrayed as “human subjects protection”. The same is true of the other article, in which vaccination is described in typical antivax language as a “medical assault”. Throughout the website, vaccines are frequently referred to as “child sacrifice” in articles dating back more than a decade. This “pivot” is not a pivot, and the antivax lean of AHRP is not new, nor is her demonization of COVID-19 vaccines new. She was doing it in 2020, an example of which comes from an interview from October 2020, as COVID-19 vaccines were making their way through the regulatory process. In the interview, titled “Nazism, COVID-19 and the destruction of modern medicine: An interview with Vera Sharav“, Sharav characterized the push for a vaccine as being all about the profit, saying at one point:

You don’t read about it in the media because the media is very much part of the business empire that’s ruling that.

Vaccines are an empire, and now they really want to do a vaccine globally.

Do you know what kind of a market that is? More than 7 billion people for a vaccine. Can you even count the kind of profits, no matter what they charge for it?

That’s what their goal is. That’s the whole allure of this COVID 19 vaccine. It’s that market.

You get the idea. What Vera Sharav was saying nearly two years ago was indistinguishable from the rhetoric I was seeing on hard core antivaccine sites, such as Natural News and, yes, RFK Jr.’s website, where the interview was published. Her antivax rhetoric remains indistinguishable from that of RFK Jr., Mike Adams, Del Bigtree, Andrew Wakefield, and basically all the major antivax “thought leaders” (if you can call it thought). Whatever her achievements in raising awareness of shoddy human subjects research practices, the dangers of certain pharmaceuticals, the frequency of nontherapeutic research, and the increasingly cozy relationship between medical academia and big pharma, Vera Sharav has clearly followed others down the road from skepticism of psychiatric drugs to extreme distrust of pharma to outright antivax.

But what about the Nuremberg Code?

Nuremberg Doctors' Trial
Nazi doctors facing justice in Nuremberg in 1947
COVID-19 vaccines and the Nuremberg Code

With the just completed discussion in mind, let’s circle back again to the Nuremberg Code, a set of principles for human subjects research that published in 1947 as part of USA vs. Brandt et al. (also often called the Doctors’ Trial) as one result of the Nuremberg Trials. The trial involved doctors who had been involved in Nazi human experimentation and mass murder disguised as euthanasia. Of the 23 defendants, seven were acquitted, while seven were sentenced to death. The rest received prison sentences ranging from 10 years to life imprisonment.

There are ten points to the code, which was published in the section of the verdict entitled “Permissible medical experiments”:

The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, overreaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs, or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.
The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.
The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.
The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.
No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.
The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.
Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.
The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.
During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible.
During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.
It is true that the Nuremberg Code remains one of the foundations of medical ethics governing human subjects research. It is, however, old and has been largely supplanted, for all practical purposes, by newer statements of human research ethics. While it is certainly true that these newer statements (which I’ll discuss in a moment) echo many of the points of the Nuremberg Code, it’s also true they go beyond them.

Before I do that, though, here’s the key deficiency in the arguments that antivaxxers have been using that invoke the Nuremberg Code is actually quite simple, as I once wrote over a year ago on Twitter:

To reiterate, the Nuremberg Code only applies to human experimentation. Notice how each of the ten points of the Nuremberg Code mentions “the experiment” or “experimental” treatments. The Code is not about medical treatment, only medical experimentation involving human subjects. I don’t know how it can be made much simpler than that. Of course, the desire to appeal to the Nuremberg Code is why antivaxxers try so desperately to misrepresent COVID-19 vaccines as being “experimental”. It’s also why I like to retort that no one was forced, coerced, or otherwise mandated to sign up to be a subject in any of the clinical trials of the Pfizer or Moderna vaccines (or any of the other currently approved vaccines) that led to their authorization under an EUA and ultimately to their full FDA approval. Again, vaccines that have passed phase 3 clinical trials and been shown to be safe and effective are not, from a scientific viewpoint, “experimental” anymore. They might still be considered “investigational” from a legal standpoint because all that means is that they haven’t gone through the full FDA process yet, but that’s it. Even while they were still being distributed under an EUA and before they were granted full FDA approval, from a scientific and medical standpoint COVID-19 vaccines being used have been legitimate medical preventative treatments, even when they did not yet have full FDA approval.

The second part of the Nuremberg Code gambit most commonly used is the deceptive appeal to “informed consent”. Of course, as I like to point out, while antivaxxers like to think they are really advocating for informed consent (and probably actually do think that), in practice, what they are advocating for is something that I like to refer to as “misinformed refusal”. (I used to call it “misinformed consent” before I realized that this term didn’t quite catch the essence of what antivaxxers do.) It’s an antivaccine trope that I’ve been dealing with at least 17 years, if not longer.

Here’s the idea. Antivaxxers vastly exaggerate the risks of vaccines and even attribute nonexistent risks to them (e.g., autism, autoimmune disease, sudden infant death syndrome) that are not at all supported by science. At the same time, they deny or downplay the benefits of vaccines, portraying them as largely ineffective and claiming that “natural” immunity from the disease is far superior to vaccine-induced immunity. Thus, if parents listen to the antivaccine narrative about the risk-benefit profile of vaccines, they will believe that the risks of vaccines outweigh the benefits. They might even believe that vaccines are not only ineffective, but dangerous, deadly even. That’s where my term “misinformed refusal” comes in. It’s the refusal of vaccines based on misinformation that portrays a falsely unfavorable (and even terrifying) risk-benefit ratio.

The Nuremberg Code, as important as it has been in the history and development of human subjects protections during medical research, has largely been supplanted by the Belmont Report (published in 1976) and the Declaration of Helsinki. The Belmont Report, for instance, goes beyond the Nuremberg Code by delineating the boundaries between medical practice and research. It also rests on basic ethical principles of respect for persons, beneficence, and justice, while emphasizing the importance of voluntariness (as the Nuremberg Code), a detailed discussion of benefits and risks (informed consent), and the selection of subjects. The Declaration of Helsinki, last updated in 2013, is similar, but goes into much more detail about informed consent. It also addresses the ethics of the use of placebos, post-trial provisions, and the dissemination of results. It even addresses the use of unproven interventions in clinical practice outside of clinical trials.

Finally, in the US, the federal regulations governing human subjects research are enshrined under the Common Rule, which was originally instituted in 1981 and was last significantly revised in 2018. Basically, the Common Rule is the operationalization of the principles of the Belmont Report and the Declaration of Helsinki into regulations governing human subjects research carried out by the federal government, institutions that receive federal funding, and pharmaceutical and device companies seeking FDA approval for their products. It requires Institutional Review Board (IRB) approval and oversight of human subjects research, among other requirements for ethical human research and lays out the requirements for informed consent, as well as for research compliance by institutions. In effect, the Common Rule lays out the standard of ethics that govern not just human subjects research funded by the federal government or subject to FDA regulation for FDA approval, but in essence nearly all human subjects research. Almost all US academic institutions require their researchers to adhere to the Common Rule regardless of funding sources.

So why do antivaxxers always mention the Nuremberg Code and almost never the Belmont Report, Declaration of Helsinki, or the Common Rule when claiming that vaccine mandates somehow violate human subjects research protections and/or informed consent? The reason is simple. Neither the Belmont Report, the Declaration of Helsinki, nor the Common Rule were written or promulgated in response to Nazi war crimes. The Nuremberg Code, on the other hand, was written as part of the verdict of the Doctors Trial at Nuremberg as a first attempt to codify what principles that should govern ethical human subjects research.

In other words, the simple reason that antivaxxers point to “informed consent” for (or, as I like to call it, misinformed refusal of) vaccines along with the Nuremberg Code is because it’s a Godwin. It not-so-subtly compares physicians, public health officials, and vaccine advocates to Nazis. That’s the one and only purpose of the Nuremberg gambit. If it weren’t, in order to try to portray vaccines as “experimental” or “unproven,” antivaxxers would instead refer to the Helsinki Declaration, which is the most recent and most applicable set of ethical principals governing human subjects research. They don’t. That should tell you all you need to know about the Nuremberg gambit other than that COVID-19 vaccine mandates do not violate the Nuremberg Code anyway.

The Nuremberg gambit: Beyond antivaxxers

Unfortunately, the Nuremberg Code gambit is a Godwin that has permeated not just hard core antivaccine messaging. Indeed, it’s spread to pretty much every corner of COVID-19 contrarianism, minimization, and resistance to any sort of pandemic-related mandate, be it “lockdowns”, vaccines, or masks. (Nuremberg has even infiltrated “gender critical” narrative about gender-affirming care for transgender youths, with one group likening doctors practicing gender-affirming care to Josef Mengele, the infamously cruel Nazi doctor at Auschwitz.) I’ll start by invoking a Tweet that has been cited on this blog before, mainly by Jonathan Howard:


It’s interesting to note that Jeffery Tucker of the Brownstone Institute could have chosen pretty much any other image for his article, but he chose that of a guillotine, the symbol of the Reign of Terror, a series of executions and massacres after the French Revolution, with the guillotine being the favored method of individual executions. In the article, shared by Martin Kulldorff, one of the three writers of the Great Barrington Declaration, that propaganda piece of anti-lockdown hysteria that basically advocated letting COVID-19 rip through the young and healthy population, the better to achieve “natural herd immunity” as fast as possible, while somehow—it’s never really specified how—using “focused protection” to keep safe the elderly and those with chronic health conditions at high risk for serious disease and death due to COVID-19.

The first time that I first saw this image, I couldn’t help but ask: If Tucker wasn’t calling for executions, why did he and the Brownstone Institute choose a very menacing image of a guillotine? They could have chosen literally any other image, but they didn’t. They chose a view of a guillotine that emphasizes the blade ready to fall, a very ominous and threatening image. (It very much looks like the view of a guillotine that someone near the front of the crowd baying for blood during the Reign of Terror might have had—or the view that someone walking up the steps to be executed might have had.) If Tucker and the Brownstone Institute were really interested in portraying justice, instead of retribution, wouldn’t an image of a courtroom or a jury—or of virtually anything other than a guillotine—have been more appropriate? Did Dr. Kulldorff not even see the not-so-subtle message that such an image paired with an article like Tucker’s broadcasts? As an aside, I’ll also ask this question: Does anyone know who else used the guillotine as a method of execution besides le tribunal révolutionnaire during the Reign of Terror? The Nazi regime in Germany! No, seriously, look it up if you don’t believe me. Members of the White Rose resistance, for example, were executed by guillotine after show trials.

Reign of Terror or Nuremberg 2? Does it matter? The idea is vengeance against enemies of antivaxxers disguised as “justice”. This fantasy of retribution is not new, either, as I pointed out, referencing a 2017 post by an antivaxxer named Kent Heckenlively:


Note the same sort of imagery from a man who has in the past demanded the “complete surrender” of vaccine advocates, promising them—maybe—mercy if they recant and confess their “crimes”. These “crimes”? Given that at the time the predominant misinformation believed by antivaxxers was that vaccines cause autism, the “crimes” were advocating policies that make children autistic.

As I often say (admittedly sometimes ad nauseam) in the age of the pandemic, everything old is new again, and the same thing applies to the Nuremberg Code gambit. The difference is not the antivax fantasy of retribution against their perceived enemies, but rather that the language and rhetoric that was, until relatively recently, only associated with the hardest of hardcore antivaxxers, has started to wend its way into the mainstream, with right wing pundits like Tucker Carlson taking up the narrative, likening COVID-19 vaccine mandates to the cruel and grossly unethical experiments that Nazis and Japanese carried out using prisoners during World War II, while mangling what Nuremberg is about by describing such mandates as “forced treatment” rather than abuse of human experimentation. Misunderstanding aside, this gave his interviewee, Robert “inventor of mRNA vaccines” Malone, the opportunity to thank Carlson for bringing up the Nuremberg Code:


Perhaps the most frightening thing about the pandemic is how antivaccine narratives once viewed as fringe even among most antivaxxers, the province of only the hardest of the hardcore, are now being amplified by mainstream pundits with millions of viewers and used by “think tanks” like the Brownstone Institute to stoke fear of vaccines and potential violence against vaccine advocates. That’s always been the purpose of the Nuremberg Code gambit. Unfortunately, today the chance of the Nuremberg Code gambit resulting in actual violence is higher than it’s ever been.


"

Oh so vilifying anyone who wants bodily autonomy (to chose to have or not to have a certain medical procedure) is ok on this site now?
So antivaxxers are people who had all the vaccines done/up to date but didn't get the covid vaccines or did get the first doses but not the boosters? Who are the antivaxxers exactly, the ones watching Tucker?

Another golden post to add to the archive, unbelievable...

 

[Ella]

Folks, stop insulting each other and reporting each other or we will close this thread.

 

[missy]

"

COVID Vaccines Made mRNA a Household Name. How Can It Help in Rare Diseases?​

— A handful of companies have mRNA therapies in human trials for rare diseases​

by Kristina Fiore, Director of Enterprise & Investigative Reporting, MedPage Today December 26, 2022

This story was supported by a grant from the National Press Foundation in partnership with Fondation de France. For MedPage Today's related story on how families support rare disease research, click hereopens in a new tab or window.
One of the hardest things about managing Jordan Franks' propionic acidemia (PA) was feeding him.
Jordan never wanted to eat. His body seemed to know that food could poison him, so like many kids with PA, he was food-averse.

"My son didn't want to eat anything by mouth," his mother, Jill Chertow, told MedPage Today. "I think the most he would ever eat was like, two pieces of mac 'n' cheese. Or he would lick the salt off of a French fry."
Kids with this rare disease can't metabolize certain amino acids. So Jordan had a regular -- and intense -- schedule of formula feedings that he took in through his gastrostomy tube, or g-tube.
"There was a lot of stress in managing his nutrition," said Chertow, who is president of the Propionic Acidemia Foundationopens in a new tab or window. "He had three different powdered formulas. One was a baby formula, like a Similac. Then there was a second formula that had protein but didn't have the amino acids that were bad for him. And there was a third formula for calories."
The formulas had to be mixed and weighed to the tenth of a gram to deliver precise amounts of nutrients. Depending on the time of day, Chertow also had to mix in medications.

Jordan had six of these g-tube feedings each day, and because fasting is dangerous in children with PA, Chertow turned on a pump every night to make sure he didn't go too long without nourishment.
"It was challenging to manage all the feeds and within a timely manner," said Chertow. "You can't be too far off schedule, or it messes up the rest of the feeds for the day. Everything needs to be done pretty close to on time."
Jordan died in 2016 when he was only 16 years old. There was no treatment for PA during his lifetime, and there still isn't one. But families and researchers are hoping that the technology honed during the COVID-19 pandemic can help change that.
PA is one of a handful of rare diseases being targeted with mRNA therapeutics.
While mRNA mostly became known during the pandemic because of its use in COVID-19 vaccines, the technology had been investigated as a therapeutic long before then -- and it was hoped to have particular potential for rare diseases.

"I think there's great potential for treating monogenic diseases" with mRNA therapies, said P.J. Brooks, PhD, acting director of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences at the NIH. "That's what you're seeing with the propionic acidemia and methylmalonic acidemia trials."
One of the companies leading those efforts is, of course, Moderna, which became a household name during the pandemic for its mRNA COVID-19 vaccine (Spikevax). It is among a handful of companies that have advanced mRNA therapeutics for rare diseases into human clinical trials.
Moderna's PA trial is furthest along, followed by its trial for a sister condition, methylmalonic acidemia (MMA). Both conditions are considered ultra-rare, with estimates that each affect about 200 families in the U.S.
The company also just enrolled the first patients into its glycogen storage disease type IA trial, and is set to begin enrolling patients with cystic fibrosis in a clinical trial in partnership with Vertexopens in a new tab or window.

Other companies with human clinical trials of mRNA agents for rare diseases include Ultragenyx with its glycogen storage disease type III (GSD III) therapy, and Arcturus with its ornithine transcarbamylase (OTC) deficiency treatment. Several other mRNA therapies for rare diseases are in preclinical studies.
The technology has its limitations, but patients and families are watching the trials closely in hopes that they will yield a treatment.
A Step Forward
Paolo Martini, PhD, worked on rare diseases long before he became the chief scientific officer for rare diseases at Moderna. He liked the field because it felt more interconnected than working on diseases with large populations like cancer or cardiovascular disease.
"In rare genetic diseases, it's almost like a family," Martini told MedPage Today. "I set up a network of [experts] all over the world, and we know each other well. There's not much known on rare diseases, so people are very collaborative."

That collaboration includes patients, patient advocacy groups, doctors, researchers, pharmaceutical companies, and others, he said.
Moderna recruited Martini from Shire in 2015, and within 2 years, Martini and his team -- in partnership with NIH researchers -- had their first major success. Mice with MMA tolerated 5 weeks of treatment with an mRNA drug aimed at the disease.
Their findings, published in Cell Reportsopens in a new tab or window, garnered attention for being the first to show that an mRNA therapy can be given repeatedly without soliciting an immune response -- one that could be problematic in and of itself, or that eventually could render therapy ineffective. Martini and team had altered both the mRNA itself and its lipid nanoparticle coating to better evade the immune system and get the drug to the liver, where it is needed.
"With a small modification in one of the nucleosides, we were able to create an mRNA that was silent to the immune system," Martini said.

The animals didn't just tolerate the therapy; they thrived, said Charles Venditti, MD, PhD, chief of the Metabolic Medicine Branch at NIH's National Human Genome Research Institute, who was a co-author of the study.
"The mRNA therapy resulted in the expression of the enzyme in the liver of mice with MMA," Venditti told MedPage Today. "It has beneficial effects in the mice; it lowered metabolite levels and improved their clinical appearance."
It also works quickly, and the level of enzyme expression in mice can be measured in a matter of hours, he added, noting that Moderna conducted additional animal studies that were used to inform their human trials for MMA and PA.
The company was just about to enroll the first patient in its MMA trial in March 2020 when COVID-19 hit.
'They Can Get Sick So Quickly'
It would have been impossible to bring kids with MMA or PA into a hospital during the early, uncertain days of the COVID-19 pandemic.

"We could not put anyone at risk," Martini told MedPage Today. "These patients are very fragile. In some instances they are immune-compromised ... so we stopped everything."
Moderna also had to divert resources to making its COVID-19 vaccine, though Martini said his team always continued pushing ahead on their rare disease treatments in parallel.
MMA and PA fall into the category of organic acidemias. In both diseases, mutations in a single gene that produces a single enzyme prevents the body from properly metabolizing certain amino acids, which causes toxic metabolites to build up in the blood, potentially leading to a metabolic crisis that can be deadly.
The severity of the condition ranges from patient to patient, depending on their exact mutation: "There's an effect by the type of mutation and the amount of residual enzyme activity that a patient has," Venditti explained.
"There can be patients with a somewhat milder condition," he added. "That doesn't mean they don't have any symptoms or signs of the condition, but they can be not as unstable as someone who has two changes in the respective genes that totally inactivate the enzyme."

Children with more severe forms of MMA or PA usually have their first metabolic crisis early in life.
Jordan Franks, for instance, was born on a Friday. By Monday, he had to be rushed back to the hospital, his mother, Chertow, said.
"These children can't even have colostrum," Martini said. "They can have metabolic decompensation and die because they can't process it."
Some children with MMA and PA are frequently in and out of the hospital because of their metabolic challenges, Venditti said. Even a regular respiratory infection can turn into a metabolic crisis.
"Any little thing that happens to them, they can get sick so quickly," he added. "With these recurrent events happening so frequently, there comes a real chance of death and disability."
Kids with MMA and PA also can have lifelong neurological damage from these early metabolic crises, Martini said.
Jordan's early crisis and subsequent crises left him non-verbal, and he also had other behavioral issues, his mother said.

A Favorable Target
The missing or defective enzyme in MMA is methylmalonyl-CoA mutase, and in PA it's propionyl-CoA carboxylase. Both are made by the mitochondria, particularly those in liver cells. Without properly functioning enzymes, methylmalonic acid and propionic acid, respectively, build up in the blood.
Essentially, an mRNA therapy that can make it into the liver can allow the enzyme to be produced, and ultimately clear the toxic metabolites.
"mRNA goes into the liver, which is a favorable target, because most of everything that you inject into the blood goes to the liver," Brooks said. "The enzyme gets made, and metabolizes the toxic metabolite."
Martini explained how the therapy works. Once the mRNA, encased in a lipid nanoparticle, is given as an infusion, it enters the bloodstream and binds with lipid-like molecules in circulation that have an affinity for hepatocytes in the liver.
The whole molecule is then pulled into the cell, which takes it apart and releases the mRNA. The mRNA is recognized and gets taken up by the ribosomes, which translate it into a protein -- in this case, the missing enzymes in MMA and PA.

"You can imagine that the same approach can be used for a lot of other diseases where you need to correct a genetic defect in the liver," Brooks said.
Currently, there's no treatment for MMA or PA. Patients rely mainly on dietary control to restrict the amount of amino acids that can't be metabolized.
Some can also consider a liver transplant, which is usually reserved for more severe cases because, like any surgery, it has its risks, and there's a need for lifelong immunosuppression. Questions also remain as to how long a transplant can be effective, and whether it can truly curb damage to other organs over time.
Experts interviewed by MedPage Today said an mRNA therapy could be a replacement for liver transplant in MMA and PA patients, or it could be a bridge to any future treatments that might provide a permanent fix, such as gene therapy.

Martini said Moderna is seeing early signs of hope in its PA trial. At its R&D Day in Septemberopens in a new tab or window, the company reported a decrease in the number of metabolic decompensation events after treatment started, according to preliminary data.
A total of 12 patients have been enrolled in four separate cohorts, he said, and all patients who have completed the study thus far are continuing into an open-label phase, "mainly because I think they believe what's happening with mRNA and potentially they're feeling better," he said.
No patient has discontinued the trial, and some participants have taken more than 15 doses so far and it appears they are still responding to treatment, he added.
"They have some encouraging biomarker evidence that the approach is working as they think it should," Brooks noted.
Moderna made some modifications to the protocol for the MMA trial that was set to start in March 2020. Martini said the first cohort of three patients has been dosed, and additional patients have been enrolled in the second cohort, totaling about five patients treated so far.

Initial data from both trials are expected in 2023, the company said.
Chertow is positive on the news, but remains cautious. Just because families decide to stay in a trial "doesn't mean it's helping," she said.
Chertow enrolled Jordan in a study of carglumic acid (Carbaglu), a treatment developed for a different condition, when he was about 6 years old.
"I knew it cut his glutamine in half, cut his glycine in half, and his ammonia was pretty good," she said. "I didn't see side effects, so I'm like, I don't know if it's helping or not, but it doesn't seem to be hurting."
"People continuing [into the open-label phase] means, 'Yeah, I guess it's safe,'" she said. "But the question is, will it change their quality of life if you have an infusion every 2 weeks?"
Other Rare Targets
Moderna is not the only company with mRNA therapies in human clinical trials for rare diseases.

Emil Kakkis, MD, PhD, is the CEO of Ultragenyx, a biotech that's focused on rare and ultra-rare diseases. Kakkis made his name in the rare disease field by developing an enzyme replacement therapy for the rare genetic condition of mucopolysaccharidosis in the 1990s when enzyme replacement therapy was an emerging treatment strategy.
Now, along with other gene therapies and treatment strategies for other conditions, Ultragenyx has an mRNA therapy for GSD III in human trials. The company has dosed patients in its phase I/II trial, which is currently testing different doses, and plans to have early results in 2023.
They focused on GSD III because it appeared that the treatment wouldn't need to be given as frequently, Kakkis said.
"We found with some others, the [protein or enzyme] didn't last long enough, and you'd have to give the treatment weekly," he said. "For GSD III, it appeared that if you could get rid of the toxic carbohydrate that's building up, it didn't matter if you didn't have the enzyme there for a few weeks. The toxic carbohydrate would build up slowly over time and you could clear it again, so there's the possibility of treating this disease less frequently, maybe once a month."

"We've been looking primarily at situations where you can treat less frequently, so that we don't keep tickling the immune system constantly," he added.
Ultragenyx has partnered with Arcturus on that compound, and the latter company is also independently investigating an mRNA therapy for OTC deficiency. That trial is in phase I/II and is expected to report interim data in 2023, according to the company's websiteopens in a new tab or window. Arcturus did not respond to a request for comment.
This month, Vertex announced that the FDA approved its investigational new drug application for an inhaled mRNA therapy for cystic fibrosis. The company, which is developing the treatment in partnership with Moderna, said it plans to start a single ascending dose trial in the coming weeksopens in a new tab or window.
There are other mRNA therapies for rare diseases in preclinical trials. Moderna and the Institute for Life Changing Medicines are developing an mRNA therapy for Crigler-Najjar syndrome type 1. Moderna is also conducting preclinical work for OTC deficiency and phenylketonuria.

The Road Ahead
At this time, mRNA appears to be most promising for genetic diseases involving the liver, such as MMA and PA. That's because it's relatively easy to get the mRNA into liver cells.
"When you infuse something into the bloodstream, it gets to the liver first, and then it heads out to the rest of the circulation," Jerry Vockley, MD, PhD, chief of medical genetics at the Children's Hospital of Pittsburgh, told MedPage Today.
The lipid nanoparticles encasing the mRNA "are seen in the highest concentrations by the liver," Vockley said. "To get them into the muscle, for instance, in high enough levels, in clinically meaningful levels, it's just a technical challenge right now."
"We're very interested in finding better ways to deliver mRNA to other cell types," Brooks noted.
Even in PA or MMA, it might be better to deliver mRNA to both the liver and muscle cells, Vockley said. "The liver is only responsible for about a third of the branched chain amino acid metabolism in the body. Muscle is the bigger part. It's more like half to two-thirds."

"If you could get something that hits the muscle and the liver, you probably have something that would be close to curative," he added. "We still don't know if it would fix the brain completely. It's not clear if that's just tied to the metabolic decompensation events, or if it's something that just might show up later in life."
Another limitation to mRNA therapy is that it would need to be re-dosed often.
"It would be a recurrent therapy, and it's unknown how much they're going to need, what the interval is going to be, what the side effects are," Venditti explained.
Gerard Berry, MD, director of the metabolism program at Boston Children's Hospital, said the dosing for the MMA or PA trial could end up being about every 2 weeks.
"We're very enthusiastic about mRNA treatment," Berry said, "but we're paying attention to all of the different nucleic acid therapies."

Vockley echoed that mRNA is just one component of the rare disease therapy space. There's gene therapy, which delivers a copy of the gene that's broken or missing, but it has "had a lot of fits and starts," he said, due to both efficacy issues and side effects, including deaths.
But the gene therapy field has moved on from adenoviral vectors to adeno-associated viral vectors, which should improve safety, Brooks said.
There's also been a move to retroviral and lentiviral vectors for ex vivo gene therapy, which involves removing cells from the body, genetically modifying them, and returning them to the body, he added.
CRISPR also offers another means of gene therapy for rare diseases. Indeed, an ex vivo CRISPR-based treatment for sickle cell disease will be considered by the FDA early next yearopens in a new tab or window.
Four other gene therapies have been approved by the FDA in recent years: voretigene neparvovecopens in a new tab or window (Luxturna) for retinal disease, onasemnogene abeparvovecopens in a new tab or window (Zolgensma) for spinal muscular atrophy, etranacogene dezaparvovecopens in a new tab or window (Hemgenix) for hemophilia B, and nadofaragene firadenovecopens in a new tab or window(Adstiladrin) for a type of bladder cancer. Some approved cancer treatments, known as chimeric antigen receptor (CAR) T-cell therapy, are also considered gene therapy, as they involve ex vivo editing of a patient's own T cells to make them target cancer cells.

In MMA and PA, Venditti's team at the NIH is hard at work on gene therapies that are in the preclinical phase, but other companies are pursuing additional strategies as well. That includes two small-molecule drugs being investigated in human clinical trials: one by CoA Therapeuticsopens in a new tab or window, and another by HemoShear Therapeuticsopens in a new tab or window.
Chertow said the fact that there are three clinical trials that patients with PA can try is "exciting for the families." It's also a significant improvement over the state of research when Jordan was born in 2000, she said.
Since there were almost no research programs then, Chertow and four other families launched the Propionic Acidemia Foundation in 2002 to accelerate research.
The organization has funded about $1.5 million in PA research since then, she said. "A lot of our initial research led to PA being a good option for research like mRNA, because there was a mouse model and ... there was some basic science that was done."
Though that didn't happen quickly enough for Jordan to benefit, the hope is that researchers get closer to a treatment, in whatever form it takes.

"

 

[missy]

"

Autopsies Show COVID-19 in the Brain​

— What this means for neurologic COVID symptoms remains elusive​

by Judy George, Deputy Managing Editor, MedPage Today December 26, 2022

Early this year, leading researchers discussed what we knew -- and didn't know -- about COVID-19 and the brainopens in a new tab or window. Since then, new findings have emerged about SARS-CoV-2 and the nervous system, including the results of an autopsy study that showed the presence of the virus throughout the body and brain.

How can a respiratory pathogen like SARS-CoV-2 cause the nervous system to go haywire? That's the question researchers posed in January, and it's still being asked nearly a year later.



Neurologic complications of COVID are diverse and can be long-lasting, noted Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke, at the time. "They are largely immune-mediated, the brain endothelial cells being a major target," he told MedPage Today.

Research throughout the year supported this view. In July, an autopsy study of nine COVID patientsopens in a new tab or window showed vascular damage with serum proteins leaking into the brain parenchyma, accompanied by widespread endothelial cell activation. Consistent with other studiesopens in a new tab or window, SARS-CoV-2 virus was not detected in the brain.

But in December, an autopsy report of 44 peopleopens in a new tab or window who died with COVID-19 in the first year of the pandemic showed that SARS-CoV-2 virus had spread throughout the body -- including the brain -- and persisted in tissue for months.

Despite this, there was little evidence of inflammation or direct viral cytopathology outside the respiratory tract, reported Daniel Chertow, MD, MPH, of the NIH Clinical Center and the National Institute of Allergy and Infectious Diseases, and co-authors in Nature.



"We did a total of 44 autopsies and in 11 of those, we were able to do a detailed evaluation of the brain," Chertow told MedPage Today. "In most of those individuals where we had brain [samples], we did find evidence of viral RNA and protein across multiple regions we sampled."

"And in one of those patients, using a modified Vero cell line that expresses the human ACE2 and TMPRSS2 receptors, we actually were able to culture virus from the brain," he continued. "So we were able to show not just the presence of viral components -- RNA and protein -- but also live, replication-competent virus."

Several factors set this autopsy study apart from others, Chertow pointed out. The postmortem interval was short, a median of 22 hours, he said.

"In addition, at the time of autopsy, we freshly dissected brain tissue," he added. "We collected tissue from 10 different regions of the brain, and from each of those regions, we preserved tissues in different ways that were amenable for the types of downstream analyses we did."



The findings may not be generalizable, Chertow cautioned. "Everybody in our cohort was unvaccinated because the study was done during the first year of the pandemic, before the vaccine was available," he said. "And most of the people were older and had significant comorbidities." The cohort included predominantly severe and ultimately fatal COVID cases, and results might not apply to younger, healthier, or vaccinated individuals.

Despite its limitations, the study showed that SARS-CoV-2 has the potential to disseminate to cells and tissues throughout the body and the brain, though it leaves important questions unanswered.

"This is a meticulously done detailed study showing that SARS-CoV-2 infection is indeed systemic and involves many organ systems, including the brain," observed Ziyad Al-Aly, MD, of Washington University in St. Louis, who wasn't involved with the research.

"What the study doesn't show is the presence of inflammation, cytopathology, or a clear mechanistic explanation of the neurologic complications of SARS-CoV-2 infection," Al-Aly told MedPage Today.



"Much more needs to be done to help us understand the mechanisms underpinning the neurologic injury we see so vividly in people with COVID-19 both in the acute and the long COVID phase of the disease," he added.

Also contributing to the knowledge of COVID and the brain in 2022 was the case report of a 27-year-old epilepsy surgery patientopens in a new tab or window who recovered from COVID without respiratory compromise.

Extracellular vesicles isolated from her brain biopsy tissue showed the presence of viral nucleocapsid protein, which was associated with endothelial cell activation, fibrinogen leakage, and immune cell infiltration, reported Nath and co-authors in Neurology.

"We never found the virus," Nath told MedPage Today. "We found the viral protein, but no RNA."

Few researchers have found the virus, Nath noted. And when they do find it, "it's not like they're finding overwhelming amounts of virus in the brain," he pointed out. "They find very small amounts of it."

"The question is, really, how significant is it?" he added. "Is it driving the pathology or is it just sitting there? That still remains to be understood."

• Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures
The autopsy study in Nature was financed and supported by the NIH Clinical Center, the National Cancer Institute, the National Institute of Dental and Craniofacial Research, and the National Institute of Allergy and Infectious Diseases. Chertow and co-authors reported no competing interests.
The case report in Neurology was supported by the National Institute of Neurological Disorders and Stroke. Nath and co-authors had no relevant disclosures.
Primary Source
Nature
Source Reference: opens in a new tab or windowStein SR, et al "SARS-CoV-2 infection and persistence in the human body and brain at autopsy" Nature 2022; DOI: 10.1038/s41586-022-05542-y.


Secondary Source

Neurology

Source Reference: opens in a new tab or windowDeMarino C, et al "Detection of SARS-CoV-2 nucleocapsid and microvascular disease in the brain: A case report" Neurology 2022; DOI: 10.1212/WNL.0000000000201682.

"

 

[missy]

Dear @Ella
I am sorry someone is reporting posts here and making more work for you. I am sharing info from medical journals and the like. If someone doesn't like what I am sharing they should just stop reading this thread. I hope others here are finding it useful and informative.

 

[Gloria27]

I reported your post because you are vilifying a group of people that chose differently than you. Pro choice... right.

 

[missy]

"
Vaccine hesitancy is fueling a resurgence of the measles and chickenpox in the US

Growing vaccine hesitancy fuels measles, chickenpox resurgence in U.S.
Anti-vaccine sentiment has increased since the pandemic, driven by politicization around the coronavirus vaccine


By Lena H. Sun
December 26, 2022 at 6:00 a.m. EST

A rapidly growing measles outbreak in Columbus, Ohio — largely involving unvaccinated children — is fueling concerns among health officials that more parent resistance to routine childhood immunizations will intensify a resurgence of vaccine-preventable diseases.
Most of the 81 children infected so far are old enough to get the shots, but their parents chose not to do so, officials said, resulting in the country’s largest outbreak of the highly infectious pathogen this year.
“That is what is causing this outbreak to spread like wildfire,” said Mysheika Roberts, director of the Columbus health department.
The Ohio outbreak, which began in November, comes at a time of heightened worry about the public health consequences of anti-vaccine sentiment, a long-standing problem that has led to drops in child immunization rates in pockets across the United States. The pandemic has magnified those concerns because of controversies and politicization around coronavirus vaccines and school vaccine mandates.

More than a third of parents with children under 18 — and 28 percent of all adults — now say parents should be able to decide not to vaccinate their children for measles, mumps and rubella (MMR) to attend public schools, even if remaining unvaccinated may create health risks for others, according to new polling by the Kaiser Family Foundation, a health-care research nonprofit.
Public sentiments against vaccine mandates have grown significantly since the pandemic, said Jen Kates, a Kaiser senior vice president. A 2019 poll by the Pew Research Center found that less than a quarter of parents — and 16 percent of all adults — opposed school vaccination requirements.
The growing opposition stems largely from shifts among people who identify as or lean Republican, the Kaiser survey found, with 44 percent saying parents should be able to opt out of those childhood vaccines — more than double the 20 percent who felt that way in 2019.

Adam Moore, a father of three in the Detroit suburbs, said none of his children — 9, 12 and 17 and enrolled in private school — have received routine childhood immunizations, let alone vaccines for the coronavirus or flu. He values personal liberty and says the government has no right telling people what to do with their bodies.
“I find it a hard argument when the government says we’re all for individual liberty on abortion rights and all this other stuff, but when it comes to vaccinations, there’s no such thing as ‘my body, my choice,’” said Moore, 43, an account manager for a marketing company.
Moore, who describes himself as Republican-leaning, said he does not view childhood diseases such as measles and polio, which have resurfaced in recent years, as threats. But if the deadly Ebola virus were circulating, he said, he would want his children to get vaccinated.

Other parents who oppose school immunization mandates echo long-standing misinformation about vaccines that continue to spread via anti-vaccine groups.
Bianca Hernandez, a 37-year-old dog breeder in the Albuquerque metropolitan area, described concerns about the link between vaccine ingredients and autism, a view that has been extensively disproved. She said her two youngest children receive religious exemptions from school vaccination requirements.
CDC expands wastewater surveillance for polio to Michigan, Pennsylvania
Support for immunization mandates has held steady among Democrats, with 88 percent saying that children should be vaccinated to attend public schools because of the potential risk for others when they are not.
Overall, 71 percent of all adults still support school immunization requirements, compared with 82 percent in 2019.
“The situation about increasing negative sentiment about childhood vaccination is concerning, but in absolute terms, vaccines remain the social norm,” said Saad Omer, director of Yale’s Institute for Global Health and an infectious-disease expert who has studied vaccine hesitancy.

Anne Zink, chief medical officer for Alaska’s health department, said that even in a state with historically lower vaccination rates, childhood immunization rates have yet to return to their pre-pandemic levels. In the years before the pandemic, about 65 percent of Alaskan children 19 to 35 months old had completed their routine childhood immunizations. By the end of 2021, 46 percent had.
“I think there is more mistrust of the government, there’s more questioning of vaccines, and we’ve been having a harder time getting people vaccinated,” said Zink, who is also president of the Association of State and Territorial Health Officials.
A few weeks ago, Zink, an emergency room doctor, saw her first case of chickenpox when a young woman walked into the Mat-Su Regional Medical Center in Palmer covered in large, painful lesions. The woman said she and her family did not believe in vaccinations and told Zink she thought chickenpox no longer existed.

A nurse in Mount Vernon, Ohio, administers the measles, mumps and rubella (MMR) vaccine in 2019. (Paul Vernon/AP)
“I was like, ‘Well, it really doesn’t when all of us choose to get vaccinated, but you aren’t vaccinated, your family’s not vaccinated, and the people you hang out with are not vaccinated. Chickenpox has been spreading in your community, and now you’re really sick,’” Zink recalled.

In the past, Zink said, herd immunity would have protected the woman against such childhood diseases. But that protection has waned as anti-vaccine sentiment grows, she said.
To distance its push for vaccination from the current political narrative, the Alaska health department recently brought back images and language from a 1960s promotion for polio vaccination. The new social media campaign uses the vintage Wellbee cartoon and rocket — “Get a booster!” — to remind people that immunization has always been part of the country’s history.

It is too early to see the effects of eroding public support for school vaccination requirements on childhood immunization rates because federal data typically lag by about two years. During the pandemic, routine vaccination rates slipped because of school closures and because children were not going to the doctor.

The growing negative attitudes about school immunization requirements are troubling for health workers. Kentucky officials are urging that people get flu shots after six children — none of whom were vaccinated — died after contracting influenza. South Carolina officials had also promoted childhood vaccinations after two chickenpox outbreaks in March — the first since 2020 — affected nearly 70 people.
A case of paralytic polio in a New York man this summer prompted worry that low childhood immunization rates and rising vaccine misinformation could result in the disease’s resurgence, decades after vaccination had eliminated it in the United States.
“There is definitely a group of parents who have shifted their attitudes,” said Jennifer Heath, immunizations program coordinator for Minnesota’s health department who works on vaccine hesitancy and outreach. “Part of it is true attitude shift. But part is a disconnection to the primary care provider, the human being who’s telling you that vaccines are important.”

School vaccination requirements are among the most effective tools to keep children healthy. All states and the District of Columbia require children to be vaccinated against certain diseases, such as measles, polio and whooping cough, to attend public school. All states grant exemptions based on medical reasons; a growing number allow religious or philosophical exemptions.
D.C. also requires students 12 and older to be vaccinated against covid-19 but has delayed enforcing the mandate until the 2023-2024 school year. California has a pending statewide student coronavirus vaccine mandate that will not take effect until after July 2023. Nearly two dozen states have some form of ban against student coronavirus vaccine mandates.
The Centers for Disease Control and Prevention recommends children get two doses of MMR vaccine, with the first dose at 12 to 15 months, and the second dose between 4 and 6 years old. One dose of the vaccine is about 93 percent effective in preventing measles, one of the most infectious pathogens on the planet that can cause serious complications, including death. Two doses are about 97 percent effective at preventing the disease.

In the Ohio measles outbreak, only three of the 81 children had received a single dose of vaccine, according to state data. None were known to be fully vaccinated.
“I think some of these attitudes were here before the pandemic, and then we probably picked up some additional community members who were accepting of vaccines before but now maybe are more critical about vaccines as a result of what transpired with the coronavirus vaccine,” Roberts said.
Some of the cases occurred in Columbus’s large Somali community, the second-largest Somali population in the United States after the Minneapolis area, Roberts said. Parents have said they “intentionally delayed” giving their children the measles vaccine because of their fear of autism, she said, despite considerable research disproving any relationship between vaccines and autism. Those fears echoed similar concerns of parents in Minnesota’s Somali community during a 2017 measles outbreak that infected 75 children, mostly unvaccinated preschool kids.
Minnesota is also battling a new measles outbreak — 22 cases — as vaccine hesitancy around the MMR vaccine continues to be an issue, said Doug Schultz, spokesman for the Minnesota health department.
Officials are bracing for more cases in the coming weeks as families travel and gather indoors for the holidays. At least 29 of the Ohio children have been hospitalized, some so sick they required intensive care.
Most of the sickened children — 78 percent — are Black, 6 percent are Asian, 6 percent are White, and 4 percent are Hispanic, according to Columbus officials.
Because the measles virus is so contagious, an overall community vaccination rate of about 90 to 94 percent is needed to keep the virus from causing large outbreaks, according to infectious-disease experts. In the United States, nearly 91 percent of children have received at least one dose of the MMR vaccine by age 2. In the Columbus area, Roberts said, the measles vaccination rate is estimated at 80 to 90 percent, but health-care providers are not required to report data to Ohio’s vaccine registry.
Even if overall coverage in a community is high, measles can transmit easily in clusters of under-vaccinated or unvaccinated people. The Columbus outbreak began when one or two unvaccinated people traveled to countries where measles is still common between June and October and infected others in the community, Roberts said.

A sign warns people of measles in the ultra-Orthodox Jewish community in New York's Williamsburg neighborhood in 2019. (Spencer Platt/Getty Images)
In recent years, many of the measles cases reported to the CDC have occurred in underimmunized, close-knit communities, where anti-vaccine misinformation has gained a foothold. In 2019, the United States reported the highest annual number of measles cases — 1,294 — in more than 25 years; three-fourths of those cases occurred among New York’s Orthodox Jewish communities. Outbreaks have also occurred among the Amish in Ohio and Eastern European groups in the Pacific Northwest.
After consulting with counterparts in Minnesota, health officials in Ohio have been working closely with the Somali community to increase vaccination uptake without stigmatizing them. Columbus public health workers have hosted vaccine clinics at a community center and a mosque and are conducting home visits to provide shots. They have also reached out to schools, day-care centers and grocery stores about the importance of vaccination.
The efforts appear to be making a difference.
Nationwide Children’s Hospital in Columbus recently saw a 20 percent increase in the number of parents seeking the MMR vaccine, Roberts said. The health department, too, has seen a small uptick in vaccinations.
“They are trickling in,” she said, “slowly but surely.”

Coronavirus: What you need to know​

Vaccines: The CDC recommends that everyone age 5 and older get an updated covid booster shot. New federal data shows adults who received the updated shots cut their risk of being hospitalized with covid-19 by 50 percent. Here’s guidance on when you should get the omicron booster and how vaccine efficacy could be affected by your prior infections.

Tripledemic: Hospitals are overwhelmed by a combination of respiratory illnesses, including flu and RSV, plus the rebounding coronavirus. The simultaneous infection with three or more viruses is keeping people sick for weeks, rather than days. Here’s how to tell the difference between RSV, the flu and covid-19.

Guidance: CDC guidelines have been confusing — if you get covid, here’s how to tell when you’re no longer contagious. We’ve also created a guide to help you decide when to keep wearing face coverings.

Where do things stand? See the latest coronavirus numbers in the U.S. and across the world. In the U.S., pandemic trends have shifted and now White people are more likely to die from covid than Black people. Nearly nine out of 10 covid deaths are people over the age 65.

"

 

[missy]

"

China’s surge​ ​

China’s Covid outbreak appears to be going from bad to worse.​

In recent days, local governments have reported hundreds of thousands of infections a day. Sick patients are crowding hospital hallways, videos obtained by The Times showed. In a video from The Associated Press, a medical worker at a hospital in Zhuozhou, a city near Beijing, asked that a patient be taken elsewhere because the facility was out of oxygen.​

“China’s medical system is already fragile even in the best of times — people rely on hospital E.R.s for even basic care,” said my colleague Isabelle Qian, who covers China for The Times. “Then, the sudden reversal of China’s ‘zero Covid’ policy caught hospitals off guard.”​

The situation is difficult to track in real time because China does not release reliable Covid data. Many experts believe the numbers it does publish are manipulated. But the stories and videos coming out of the country suggest the crisis is worsening.​

The rapid spread of Covid in any country is a concern to health officials around the world because unchecked outbreaks create more opportunities for the virus to mutate into a more contagious or deadlier variant. Those fears are particularly acute for China, a country of 1.4 billion people and the place where the virus originated.​

China recently relaxed its strict “zero Covid” rules, after unusually widespread protests against the measures. The policies had prevented people from leaving their homes if cases were detected in their area and required regular testing for much of the population. They also forced overseas travelers, including Chinese nationals, to stay in quarantine for as long as two months to enter the country. (That requirement is going away, too, officials said on Monday.)​

But the end of the policies exposed two major vulnerabilities that Chinese leaders have not effectively addressed. First, China has not vaccinated large segments of its most vulnerable, older population: While 90 percent of all Chinese were reportedly fully vaccinated as of November, less than 66 percent of those 80 and older were fully vaccinated and only 40 percent had gotten a booster.​

Second, China does not have much natural immunity from past Covid waves. Its lockdown policies have kept the virus out of the country, probably saving lives in the short term. But they have also left its population more vulnerable to the disease than those who have been repeatedly exposed to the virus, as this newsletter previously explained.​

It’s a sharp contrast to the situation in many other countries. Consider the U.S.: Nearly all Americans 65 and older have gotten a Covid vaccine (although less than 37 percent have gotten the latest booster). Americans have also built up natural immunity from prior Covid waves, providing some protection. That combination has allowed American life to return to some sense of normalcy, without recent years’ levels of hospitalization and death.​

Of course, the U.S.’s more lax approach has its own cost: Covid has killed nearly 1.1 million Americans since 2020, according to the C.D.C. China’s strategy has prevented the virus from causing that level of death since it first appeared in Wuhan in late 2019, according to the country’s available data. But without sufficient preparation for the end of “zero Covid,” China is now facing what might be its worst outbreak yet.​

For more​ ​

These videos show how medical staff are outnumbered and working sick as China’s health care system buckles. “Zero Covid” proved China’s government was good at control, but the aftermath has shown it’s not so good at governance, The Times’s Li Yuan writes. "

 

[missy]

"

COVID's Lasting Consequences for Kids​

— Allergist Zachary Rubin, MD, details the post-COVID symptoms presenting at his clinic​

by Emily Hutto, Associate Producer, MedPage Today December 27, 2022
In this video, MedPage Today editor-in-chief Jeremy Faust, MD, sits down with allergist and immunologist Zachary Rubin, MD, of Oak Brook Allergists in Illinois, to discuss the lasting affects of COVID-19 on pediatric health.

Part one of their discussion -- where they discuss the pediatric "tripledemic" of flu, respiratory syncytial virus (RSV), and COVID-19 -- can be viewed hereopens in a new tab or window.

The following is a transcript of their remarks:
Faust: Let me ask you a couple questions about immunology and allergy. I guess I have two questions.

My first one is related to the whole pandemic, like the fact that, for me, I have a little seasonal allergies in the spring and 2020 was my best year ever. There was no pollution, no one was driving, I was masking like crazy, I didn't have a sniffle. Was that kind of common that people's allergies got better?

Rubin: Oh yeah. My practice was very quiet at that time.

People were very healthy because they were masking. So, you're filtering out a lot of the allergens that you're experiencing. People who had outdoor allergens weren't really going outside as much. I mean, the foot traffic -- if you look at some of the data -- people were really staying indoors for quite some time.

Now there was a bump in people with pet allergies because a lot of people were adopting pets, who probably shouldn't have, and they ended up getting indoor pet allergens and things like that. But overall, between allergies and asthma, we were doing quite well in that year.



But once everybody started opening up again and traveling -- more air pollution -- pollen counts have been steadily rising; it seems like every year it's worse and worse and worse now. There's some long-term data to suggest that we're going to have pollen seasons lasting for a month longer in the next 50 to 100 years.

Faust: Your patient population is probably the one I'm interested in with this question: long COVID for kids. I imagine that kids who have allergies or kids that have atopic conditions in general might be a little more predisposed. Tell me what you're seeing with long COVID in terms of how long is it lasting, how common is it? Because, for me, I know this is a major problem, but I also think that the data don't quite match what I'm seeing on the ground. So I'm curious where you fall.



Rubin: Right. So, every physician who deals with long COVID is seeing a different phenotype. That's one of the problems. Some people are dealing with brain fog and some of the neurological issues, some people are dealing with the POTS [postural orthostatic tachycardia syndrome] issues, right? It's not all one clinical entity.

As a pediatric allergist, what I see primarily are skin problems, chronic hives after getting COVID, where it's lasting for like 6 months, where they're getting almost daily hives. That's one phenotype. I have another subset where I just call them COVID coughers, because they get COVID, and they haven't stopped coughing for months. Usually that's lasting for about 6 months is what I'm seeing in my population, and I also take care of adults too. About 30% of my practice is actually adults. I'm certified to take care of all ages.

But in terms of kids, I'm putting a lot of kids on inhaled steroids that I wouldn't have expected, because they didn't have allergic rhinitis. If you skin test them, a lot of them are negative. They don't have that kind of allergic disease that's going on. These aren't kids who started off with eczema and are dealing with chronic hives or chronic cough. So, they're not the typical population. That's what's a little strange to me with what I'm dealing with.



I do have, I'm not seeing this quite as much, but earlier in the pandemic when we had earlier iterations of the virus that was causing a lot of anosmia or lack of smell, I saw a lot of teens and young adults who had problems with smell -- whether they couldn't smell at all or they had parosmia, where they're smelling things that are just rancid and it just didn't quite make sense.

That is something that my ENT colleagues and I have been seeing quite a bit, not quite as much now, because the virus is not really sitting in the nose quite as much, it's kind of in other areas now. But these are people who are having symptoms anywhere between 6 to 12 months or longer, which is a really, really challenging issue for those patients.

Faust: I'm kind of wondering -- let me pursue this just a little bit more because I have two kids and I remember being a kid, there's always a kid or two who had chronic bronchitis. The kid who always had a cold or sniffle and probably, if you think about it, their body, their immune system was just destined to be that way or they had exposures more than the rest of us.



I just wonder, is this COVID causing this increase itself? In other words, the native pathogen meets person, and COVID is just more likely to cause that? Or is this a reaction to the fact that any virus in this sort of echelon of badness for kids would do this -- it's just that COVID is like 100 times more prevalent and contagious than the other ones? So all of a sudden one in a 100 kids who gets "virus" will get this longer-term thing you're describing. But guess what folks, it's just 100 times more common. I mean, which one is it?

Rubin: It's really hard to say that. I mean, I get what you're trying to say and that does make sense, but what concerns me is when you see studies where they're comparing -- this is the type 1 diabetes issue that I'm sure you're familiar with.


So, there are more kids now being diagnosed with type 1 diabetes after COVID compared to if they had another respiratory virus. So we're seeing studies like that when we compare it. That's where I start to say, "Oh gosh, I think COVID is actually causing more severe issues when you start comparing these larger data sets of kids who have gotten COVID compared to kids who got just some other respiratory virus." You age match them and you say, "Okay, actually the diagnosis of type 1 diabetes is higher."

When you see data like that, that's when I say, yeah, I think COVID is actually worse just in general.

Faust: Yeah. Well, I mean, we know it's the mayhem that it's caused. It's just the question of -- I study excess mortality, meaning how many people die compared to how many are expected to, and we talked about this idea of a mortality product. Is each case out of every 100 cases actually deadlier? Yes. Are there more cases? Yes. So, it's both. But I just don't know that for other parts of the spectrum, like for long COVID, for example.


We're running out of time, but do you sense that long COVID or even medium COVID or whatever you want to call it -- 2, 3, 4, or 6 months of misery -- do you sense that this is getting better with higher vaccination rates or is it just too soon to tell?

Rubin: I think it's too soon to tell, honestly. These are things that are going to take the 6- to 12-month, the 24-month range of really just getting larger data and seeing more patients and seeing where this goes, because unfortunately the virus continually mutates, and we are getting these more immune-evasive variants like BQ.1.1 and XBB -- as some people coin "Scrabble" COVID because of these letters that are the highest scoring Scrabble letters -- more and more infections is not necessarily a good thing. We have to see how that ends up playing out.



There is a higher level of population immunity with more exposure and more vaccinations, but what concerns me is the uptake of this bivalent booster. You know, unfortunately this is a type of virus where we do need to be boosted more regularly until we get a better vaccine coming around to try to help protect especially the most vulnerable population.

Faust: Okay. I'm going to ask one more question. It's kind of a hypothetical, but I think I want your take on it.

There are a lot of people out there who are really concerned about the lost year of school and the terrible outcomes in terms of that. But I often think about, why don't we have the outcome of interest for all of our interventions just be days in class, how many days kids are in school? Do you think that if we could test kids weekly for RSV and flu and COVID and have them put masks on during surges that would lead to kids being in school more?



Rubin: I think so. I think if we're able to try to slow the spread by identifying who's sick, taking them out, and continually masking when there are surges. Like right now, this would be the time to have masks back in school. I mean now we're going to be in winter break, right? But in the few weeks that come after winter break, it may be a good idea to do that so that kids don't come back and spread a bunch of virus -- whether it's COVID, RSV, influenza, or this newer concern that we're going to start seeing in national media now, the concern of strep A and invasive group A strep.

When I see that it's 10 times higher in Colorado right now, that is very alarming to me. You don't want kids getting invasive group A strep in the setting of an antibiotic shortage.



I think we need to pick and choose when we do in these types of interventions. They can be short-term, but there's a lot of potential for success. We have seen in Boston, there was a really good studyopens in a new tab or window from the New England Journal, that the schools that held onto those mass mandates longer had lower COVID transmission compared to those that dropped it earlier. I'm sure you probably heard of that study. That was a very impactful one. I think we can take lessons from that and not forget how certain mitigation strategies can be helpful when we pick and choose it.

Unfortunately, we haven't invested enough in our schools to have improved ventilation, because I think that's an area that's not been tapped into well. If we improve ventilation in these older buildings, I actually think that would be a big deal in helping keep kids in school as well.



Faust: Yeah, I think that's right. I think the simple stuff is actually pretty consensus.

I talked to Joseph Allen about thisopens in a new tab or window, if you only open the window for 10 minutes, an hour, you actually have an air change that makes a huge difference. Keep the kids in school, throw the mask on for a week here and there, we don't have to have the debate about whether having it on for a year hurt them or helped them -- I think it probably helped, but at this point that's in the past.

But if you throw these things on for a week, you can really break a circuit. Then, the teacher's not out, or then half the class isn't out. We have had schools where classrooms just shut down, because we're not doing the things that we know prevent the spread. Actually, slowing these things down is not delaying the inevitable, it's keeping the overall environment relatively safe. So, I think we see eye-to-eye on a lot of issues.



Zach, tell us where to find you on social media.

Rubin: So my handle is the same for all of my social media. It's @rubin_allergy. I'm on TikTokopens in a new tab or window, Twitteropens in a new tab or window, Instagramopens in a new tab or window, YouTubeopens in a new tab or window. I'm debating about what I'm doing with Twitter with everything going on with Elon Musk, so I have a Med-Mastodon too. It's the same thing, but I don't know what I'm going to do with that, but I'm primarily on TikTok and Instagram at this point.

I'm happy to collaborate with you in the future. This has been great. I know we've kind of followed each other over the last few years, but it's nice to be able to finally talk with you.

Faust: Absolutely, and I know this audience will have a lot of questions, so we'll loop them back to you. I want to thank everyone for joining us, and have a great night.

Rubin: You too. Take care.

Faust: Thanks a lot.

Rubin: Bye.

"

 

[missy]

As 2022 draws to a close I was hoping we wouldn't need this thread anymore but unfortunately looks like we still do

"

The US will require airline passengers coming from China to show negative Covid-19 tests as health experts fear the virus’s unchecked spread across that country could imperil the world. Since Xi Jinping abruptly droppedhis restrictive “Covid-zero” policies amid protests and economic worries, tens of millions of Chinese have been infected daily while scientists predict millions may die. The Biden administration has been especially concernedabout a lack of transparency coming from China, where Covid-19 first appeared three years ago. The high number of people affected over a very short period of time raises the chances of a new variant emerging, one that could possibly circumvent defenses in nations that have already suffered multiple infection waves and millions of deaths. The US said it will also expand its viral genomic surveillance program of travelers to keep watch for new versions of the pathogen. The new testing requirement will apply to all passengers regardless of nationality or vaccination status and will go into effect Jan. 5. But the fallout from Beijing’s decision to suddenly lift precautions is already spreading: In Milan, Italian authorities said 50% of people arriving from China tested positive. —David E. Rovella



Some extra news stories fyi

Here are today’s top stories​

Stocks fell for a second day as investors grew worried about the global implications of the surge in Covid-19 cases across China. Hopes of ending 2022 on a high note may seem increasingly misplaced. Global equities have lost one fifth of their value this year, the largest decline since 2008 on an annual basis, and an index of global bonds has slumped 16%. Here’s your. markets wrap.


US companies had a lot to overcome in the latter half of the year, what with rising interest rates, budget-conscious consumers and a sagging stock market. That’s left some of them in very tough spots for the start of 2023. These five should be watched closely.

Multiple stress points are emerging in credit markets, from banks stuck with piles of buyout debt to a UK pension blow-up and real-estate troubles in China and South Korea. With cheap money a thing of the past, those problems may be just the start. Distressed debt in the US alone jumped more than 300% in 12 months, high-yield issuance has become more challenging in Europe and leverage ratios have reached a record by some measures. Globally, almost $650 billion of bonds and loans are in distressed territory. It’s all adding up to the biggest test of corporate credit since the financial crisis—and it may spark a wave of defaults.


Solana, the cryptocurrency backed by indicted crypto mogul Sam Bankman-Fried, tumbled 12% on Wednesday amid concerns that large holders may be about to dump the token.

Exxon Mobil is suing the European Union in a bid to kill a new windfall tax on oil groups. The fossil fuel industry has reaped record profits this year thanks to Vladimir Putin’s war on Ukraine. If successful, the oil giant could jeopardize the levy, which is aimed at bringing down skyrocketing consumer energy costs.

South Africa’s power utility Eskom has had 13 chief executives in the past decade. Now, after a year in which the nation saw 200 days of power cuts, the debt-ridden state utility is looking for a new CEO. But finding someone who can do the job and actually wants it is another story.

After Xi Jinping ordered his unprecedented assault on China’s housing market, restrictions on developer borrowing managed to lower financial risk, kneecapping over-leveraged companies like China Evergrande. But when it comes to the key metric of housing—affordability—the results are mixed. For all the pain inflicted on bondholders and real estate companies, housing remains stubbornly expensive in the world’s most unaffordable market. Now China homebuyers are questioning if it was all worth it.


Bloomberg continues to track the global coronavirus pandemic. Click here for daily updates.

​

"

 

[missy]

From the NYT December 28th 2022

"
As Covid-19 Continues to Spread, So Does Misinformation About It
Doctors are exasperated by the persistence of false and misleading claims about the virus.



Tiffany Hsu
By Tiffany Hsu
Dec. 28, 2022
Nearly three years into the pandemic, Covid-19 remains stubbornly persistent. So, too, does misinformation about the virus.

As Covid cases, hospitalizations and deaths rise in parts of the country, myths and misleading narratives continue to evolve and spread, exasperating overburdened doctors and evading content moderators.

What began in 2020 as rumors that cast doubt on the existence or seriousness of Covid quickly evolved into often outlandish claims about dangerous technology lurking in masks and the supposed miracle cures from unproven drugs, like ivermectin. Last year’s vaccine rollout fueled another wave of unfounded alarm. Now, in addition to all the claims still being bandied about, there are conspiracy theories about the long-term effects of the treatments, researchers say.

The ideas still thrive on social media platforms, and the constant barrage, now a yearslong accumulation, has made it increasingly difficult for accurate advice to break through, misinformation researchers say. That leaves people already suffering from pandemic fatigue to become further inured to Covid’s continuing dangers and susceptible to other harmful medical content.


“It’s easy to forget that health misinformation, including about Covid, can still contribute to people not getting vaccinated or creating stigmas,” said Megan Marrelli, the editorial director of Meedan, a nonprofit focused on digital literacy and information access. “We know for a fact that health misinformation contributes to the spread of real-world disease.”

Twitter is of particular concern for researchers. The company recently gutted the teams responsible for keeping dangerous or inaccurate material in check on the platform, stopped enforcing its Covid misinformation policy and began basing some content moderation decisions on public polls posted by its new owner and chief executive, the billionaire Elon Musk.

Dig deeper into the moment.
Special offer: Subscribe for $1 a week.
From Nov. 1 to Dec. 5, Australian researchers collected more than half a million conspiratorial and misleading English-language tweets about Covid, using terms such as “deep state,” “hoax” and “bioweapon.” The tweets drew more than 1.6 million likes and 580,000 retweets.

The researchers said the volume of toxic material surged late last month with the release of a film that included baseless claims that Covid vaccines set off “the greatest orchestrated die-off in the history of the world.”

Naomi Smith, a sociologist at Federation University Australia who helped conduct the research with Timothy Graham, a digital media expert at Queensland University of Technology, said Twitter’s misinformation policies helped tamp down anti-vaccination content that had been common on the platform in 2015 and 2016. From January 2020 to September 2022, Twitter suspended more than 11,000 accounts over violations of its Covid misinformation policy.





Now, Dr. Smith said, the protective barriers are “falling over in real time, which is both interesting as an academic and absolutely terrifying.”

The Spread of Misinformation and Falsehoods
Covid Myths: Experts say the spread of coronavirus misinformation — particularly on far-right platforms like Gab — is likely to be a lasting legacy of the pandemic. And there are no easy solutions.
Midterms Misinformation: Social media platforms struggled to combat false narratives during the 2022 U.S. midterm elections, but it appeared most efforts to stoke doubt about the results did not spread widely.
A ‘War for Talent’: Seeing misinformation as a possibly expensive liability, several companies are angling to hire former Twitter employees with the expertise to keep it in check.
A New Misinformation Hub?: Misleading edits, fake news stories and deepfake images of politicians are starting to warp reality on TikTok.
“Pre-Covid, people who believed in medical misinformation were generally just talking to each other, contained within their own little bubble, and you had to go and do a bit of work to find that bubble,” she said. “But now, you don’t have to do any work to find that information — it is presented in your feed with any other types of information.”


Several prominent Twitter accounts that had been suspended for spreading unfounded claims about Covid have were reinstated in recent weeks, including those of Representative Marjorie Taylor Greene, a Georgia Republican, and Robert Malone, a vaccine skeptic.

Mr. Musk himself has used Twitter to weigh in on the pandemic, predicting in March 2020 that the United States was likely to have “close to zero new cases” by the end of that April. (More than 100,000 positive tests were reported to the Centers for Disease Control and Prevention in the last week of the month.) This month, he took aim at Dr. Anthony S. Fauci, who will soon step down as President Biden’s top medical adviser and the longtime director of the National Institute of Allergy and Infectious Diseases. Mr. Musk said Dr. Fauci should be prosecuted.

Twitter did not respond to a request for comment. Other major social platforms, including TikTok and YouTube, said last week that they remained committed to combating Covid misinformation.

YouTube prohibits content — including videos, comments and links — about vaccines and Covid-19 that contradicts recommendations from the local health authorities or the World Health Organization. Facebook’s policy on Covid-19 content is more than 4,500 words long. TikTok said it had removed more than 250,000 videos for Covid misinformation and worked with partners such as its content advisory council to develop its policies and enforcement strategies. (Mr. Musk disbanded Twitter’s advisory council this month.)


But the platforms have struggled to enforce their Covid rules.

Newsguard, an organization that tracks online misinformation, found this fall that typing “covid vaccine” into TikTok caused it to suggest searches for “covid vaccine injury” and “covid vaccine warning,” while the same query on Google led to recommendations for “walk-in covid vaccine” and “types of covid vaccines.” One search on TikTok for “mRNA vaccine” brought up five videos containing false claims within the first 10 results, according to researchers. TikTok said in a statement that its community guidelines “make clear that we do not allow harmful misinformation, including medical misinformation, and we will remove it from the platform.”
Image
A man in a black shirt and green medical scrub pants sits looking at the camera.
Dr. Anish Agarwal, an emergency physician in Philadelphia, said some patients continued to believe “crazy” claims about Covid-19 vaccines.Credit...Michelle Gustafson for The New York Times

In years past, people would get medical advice from neighbors, or try to self-diagnose via Google search, said Dr. Anish Agarwal, an emergency physician in Philadelphia. Now, years into the pandemic, he still gets patients who believe “crazy” claims on social media that Covid vaccines will insert robots into their arms.

“We battle that every single day,” said Dr. Agarwal, who teaches at the University of Pennsylvania’s Perelman School of Medicine and serves as deputy director of Penn Medicine’s Center for Digital Health.

Online and offline discussions of the coronavirus are constantly shifting, with patients bringing him questions lately about booster shots and long Covid, Dr. Agarwal said. He has a grant from the National Institutes of Health to study the Covid-related social media habits of different populations.

“Moving forward, understanding our behaviors and thoughts around Covid will probably also shine light on how individuals interact with other health information on social media, how we can actually use social media to combat misinformation,” he said.

Years of lies and rumors about Covid have had a contagion effect, damaging public acceptance of all vaccines, said Heidi J. Larson, the director of the Vaccine Confidence Project at the London School of Hygiene & Tropical Medicine.


“The Covid rumors are not going to go away — they’re going to get repurposed, and they’re going to adapt,” she said. “We can’t delete this. No one company can fix this.”

Some efforts to slow the spread of misinformation about the virus have bumped up against First Amendment concerns.

A law that California passed several months ago, and that is set to take effect next month, would punish doctors for spreading false information about Covid vaccines. It already faces legal challenges from plaintiffs who describe the regulation as an unconstitutional infringement of free speech. Tech companies including Meta, Google and Twitter have faced lawsuits this year from people who were barred over Covid misinformation and claim that the companies overreached in their content moderation efforts, while other suits have accused the platforms of not doing enough to rein in misleading narratives about the pandemic.
Image

Dr. Graham Walker, an emergency physician in San Francisco, quit Twitter this month over frustrations with Covid misinformation.Credit...Jason Henry for The New York Times

Dr. Graham Walker, an emergency physician in San Francisco, said the rumors spreading online about the pandemic drove him and many of his colleagues to social media to try to correct inaccuracies. He has posted several Twitter threads with more than a hundred evidence-packed tweets trying to debunk misinformation about the coronavirus.

But this year, he said he felt increasingly defeated by the onslaught of toxic content about a variety of medical issues. He left Twitter after the company abandoned its Covid misinformation policy.

“I began to think that this was not a winning battle,” he said. “It doesn’t feel like a fair fight.”


Now, Dr. Walker said, he is watching as a “tripledemic” of Covid-19, R.S.V. and influenza bombards the health care system, causing emergency room waits in some hospitals to surge from less than an hour to six hours. Misinformation about easily available treatments is at least partly responsible, he said.

“If we had a larger uptick in vaccinations with the most recent vaccines, we probably would have a smaller number of people getting extremely ill with Covid, and that’s certainly going to make a dent in hospitalization numbers,” he said. “Honestly, at this point, we will take any dent we can get.”
Tiffany Hsu is a tech reporter covering misinformation and disinformation. @tiffkhsu


"

 

[missy]

From the NEJM December 28th 2022

"

VV116 versus Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19​

List of authors.

• Zhujun Cao, M.D., Ph.D.,
• Weiyi Gao, M.D., Ph.D.,
• Hong Bao, M.D., Ph.D.,
• Haiyan Feng, M.D.,
• Shuya Mei, M.D., Ph.D.,
• Peizhan Chen, Ph.D.,
• Yueqiu Gao, M.D., Ph.D.,
• Zhilei Cui, M.D., Ph.D.,
• Qin Zhang, M.D., Ph.D.,
• Xianmin Meng, Ph.D.,
• Honglian Gui, M.D., Ph.D.,
• Weijing Wang, M.D., Ph.D.,
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
• 
  
• et al.

BACKGROUND​

Nirmatrelvir–ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

METHODS​

We conducted a phase 3, noninferiority, observer-blinded, randomized trial during the outbreak caused by the B.1.1.529 (omicron) variant of SARS-CoV-2. Symptomatic adults with mild-to-moderate Covid-19 with a high risk of progression were assigned to receive a 5-day course of either VV116 or nirmatrelvir–ritonavir. The primary end point was the time to sustained clinical recovery through day 28. Sustained clinical recovery was defined as the alleviation of all Covid-19–related target symptoms to a total score of 0 or 1 for the sum of each symptom (on a scale from 0 to 3, with higher scores indicating greater severity; total scores on the 11-item scale range from 0 to 33) for 2 consecutive days. A lower boundary of the two-sided 95% confidence interval for the hazard ratio of more than 0.8 was considered to indicate noninferiority (with a hazard ratio of >1 indicating a shorter time to sustained clinical recovery with VV116 than with nirmatrelvir–ritonavir).

RESULTS​

A total of 822 participants underwent randomization, and 771 received VV116 (384 participants) or nirmatrelvir–ritonavir (387 participants). The noninferiority of VV116 to nirmatrelvir–ritonavir with respect to the time to sustained clinical recovery was established in the primary analysis (hazard ratio, 1.17; 95% confidence interval [CI], 1.01 to 1.35) and was maintained in the final analysis (median, 4 days with VV116 and 5 days with nirmatrelvir–ritonavir; hazard ratio, 1.17; 95% CI, 1.02 to 1.36). In the final analysis, the time to sustained symptom resolution (score of 0 for each of the 11 Covid-19–related target symptoms for 2 consecutive days) and to a first negative SARS-CoV-2 test did not differ substantially between the two groups. No participants in either group had died or had had progression to severe Covid-19 by day 28. The incidence of adverse events was lower in the VV116 group than in the nirmatrelvir–ritonavir group (67.4% vs. 77.3%).

CONCLUSIONS​

Among adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir–ritonavir with respect to the time to sustained clinical recovery, with fewer safety concerns. (Funded by Vigonvita Life Sciences and others; ClinicalTrials.gov number, NCT05341609. opens in new tab; Chinese Clinical Trial Registry number, ChiCTR2200057856.)

The coronavirus disease 2019 (Covid-19) pandemic continues to spread rapidly worldwide,1,2 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into variants with increasing transmissibility and capability of evading human immunity (e.g., the B.1.1.529 [omicron] variant).3-5 A widespread and timely distribution of efficacious antiviral therapy is an important part of the response.6,7
Currently, nirmatrelvir–ritonavir8 is recommended by World Health Organization (WHO) guideline for treating mild-to-moderate Covid-19.9 Nirmatrelvir is an oral inhibitor of the SARS-CoV-2 3-chymotrypsin–like cysteine protease enzyme that can be dispensed at community pharmacies and has been authorized for emergency use by many countries. However, access to nirmatrelvir is limited worldwide, and its effectiveness depends on ritonavir,10 which has multiple drug–drug interactions warranting specialized assessment before prescription. Remdesivir is also recommended11 but needs to be administered intravenously, which limits its widespread use during the pandemic. Therefore, several oral analogues of remdesivir have been developed to address this issue, including GS-621763,12 ATV006,13 and VV116.14,15

VV116 is a deuterated remdesivir hydrobromide with oral bioavailability and potent activity against SARS-CoV-2 in studies in animals15 and satisfactory safety and side-effect profiles in phase 1 trials.16A preliminary small-scale study has shown a shorter viral shedding time in patients with Covid-19 who received VV116 within 5 days after the first positive test than in those who received regular care.17 However, the efficacy of VV116 for clinical recovery, symptom resolution, and prevention of disease progression remains unknown, particularly as compared with nirmatrelvir–ritonavir. In addition, the safety profiles of VV116 have not been fully assessed. Here, we report the results of a phase 3 trial of VV116 as compared with nirmatrelvir–ritonavir for oral treatment of symptomatic participants at high risk for progression to severe Covid-19 during the omicron outbreak.

Methods​

TRIAL DESIGN AND RANDOMIZATION​

In this multicenter, observer-blinded, randomized, controlled trial, symptomatic participants at high risk for progression to severe Covid-19 were randomly assigned in a 1:1 ratio to receive either oral VV116 (600 mg every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5) or oral nirmatrelvir–ritonavir (300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days) (Fig. S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). VV116 was manufactured and provided by Vigonvita Life Sciences. The selection of nirmatrelvir–ritonavir as the active control for comparison with VV116 was based on the established superiority of nirmatrelvir–ritonavir to placebo12 and on its recommendation as the standard treatment for our target population by the WHO guideline.11
Randomization was performed with the use of a centralized, interactive Web response system. All the site investigators, site staff (except for those who administered the trial drugs), and those who were involved in end-point assessments were unaware of the trial-group assignments until unblinding on May 20, 2022. Participants remained aware of the trial-group assignments throughout the trial. Additional details are provided in the Supplementary Appendix.
The data-cutoff date for the primary analysis was May 13, 2022, when the target number of primary end-point events (>724 events) was reached in the full analysis population. The data-cutoff date for the final analysis was August 18, 2022.​

TRIAL OVERSIGHT​

The trial was approved by the National Human Genetic Resources Committee in China and the institutional review board or ethics committee at each trial site before the start of recruitment and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. One of the sponsors, Vigonvita Life Sciences, designed and monitored the trial and collected and analyzed the data in collaboration with the site investigators. Safety oversight was performed by Vigonvita Life Sciences and the institutional review board or ethics committee at each site. The first author drafted the manuscript, and the writing committee revised the manuscript and made the decision to submit it for publication. All the authors had data confidentiality agreements with Vigonvita Life Sciences and vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol, available at NEJM.org.​

PARTICIPANTS​

After written informed consent was obtained, participants from seven hospitals in Shanghai, China, that were designated by the Chinese government for the treatment of Covid-19 were assessed for eligibility between April 4, 2022, and May 2, 2022. Adults 18 years of age or older were eligible if they had mild-to-moderate Covid-19 with a total symptom score of 2 or more as determined on the basis of definitions adapted from the Food and Drug Administration.18 Symptom scores range from 0 to 3 (with higher scores indicating greater severity) for each of 11 symptoms; total symptom scores range from 0 to 33 (Table S1). Other key inclusion criteria were a positive SARS-CoV-2 reverse-transcriptase–polymerase-chain-reaction (RT-PCR) test with an additional finding indicating early infection or high viral activity (the findings are listed in the Supplementary Appendix), and at least one risk factor for progression to severe Covid-19.
Key exclusion criteria were confirmed or suspected severe or critical Covid-19 or an anticipated need for mechanical ventilation before randomization, an alanine aminotransferase or aspartate aminotransferase level that was more than 1.5 times the upper limit of the normal range, an estimated glomerular filtration rate (eGFR) of less than 60 ml per minute, or the use of contraindicated drugs listed in the package insert of nirmatrelvir–ritonavir. Although nirmatrelvir–ritonavir is not contradicted in persons with an eGFR of 30 to less than 60 ml per minute, we excluded these participants to avoid a potential overdose in the updated protocol (version 3.0; April 10, 2022). Before that date, a total of 38 participants with an eGFR of 30 to less than 60 ml per minute had been enrolled in the trial (16 in the VV116 group and 22 in the nirmatrelvir–ritonavir group). Full eligibility criteria are provided in the Supplementary Appendix and protocol.​

ASSESSMENT​

Covid-19–related symptom scores (described above) and scores on the WHO Clinical Progression Scale (range, 0 to 10, with higher scores indicating a worse clinical condition) (Table S2) were determined by investigators on day 1 before the trial-drug administration, followed by assessment at approximately the same time every day until the resolution of Covid-19–related target symptoms or day 28, whichever was earlier. SARS-CoV-2 RNA from nasopharyngeal swabs was measured by RT-PCR assay at each site, with both qualitative data (positive or negative) and quantitative data (cycle-threshold value) obtained if available. More details of assessment and data collection are provided in the protocol.​

END POINTS​

The primary efficacy end point was the time from randomization to sustained clinical recovery through day 28. Sustained clinical recovery was defined as the alleviation of all Covid-19–related target symptoms to a total symptom score of 0 or 1 (range, 0 to 33, with higher scores indicating greater severity) for 2 consecutive days. The first day of the 2-consecutive-day period was considered to be the event date. Secondary efficacy end points included progression to severe or critical Covid-19 or death from any cause; the change in Covid-19–related symptom score and the score on the WHO Clinical Progression Scale through day 28, the time to sustained resolution of all target symptoms and to a first negative SARS-CoV-2 test, and clinical recovery, symptom resolution, and a negative SARS-CoV-2 test by prespecified days. Safety end points included adverse events and serious adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Any adverse event that emerged or worsened from the time of informed consent through day 28 was actively recorded and reported for trial-regimen recipients. Details of the end points are provided in the Supplementary Appendix and Table S3. The primary end point was assessed in the primary analysis (data-cutoff date, May 13, 2022), and the data were updated in the final analysis (data-cutoff date, August 18, 2022).​

STATISTICAL ANALYSIS​

The primary efficacy hypothesis was that VV116 would be noninferior to nirmatrelvir–ritonavir with respect to sustained clinical recovery. Owing to the lack of data on the time to clinical recovery in participants with omicron infection treated with nirmatrelvir–ritonavir, the reference duration of 5.5 days was estimated on the basis of the duration of acute symptoms in persons infected with SARS-CoV-2 during the omicron wave19 and an overall vaccination rate of more than 90% in the general population in Shanghai.20 To satisfy the noninferiority hypothesis, the lower boundary of the two-sided 95% confidence interval for the hazard ratio of the primary end point had to be above 0.8. The noninferiority margin corresponds to a duration of 6.875 days to sustained clinical recovery, which is 25% longer than 5.5 days. A minimum of 724 events were required to ensure a statistical power of 85%.
The noninferiority hypothesis was tested in the full analysis population — that is, the modified intention-to-treat population (all the participants who underwent randomization and received at least one dose of VV116 or nirmatrelvir–ritonavir). Sensitivity analyses involved participants who started a trial regimen within 5 days after symptom onset and the per-protocol population. The intention-to-treat population (all the participants who underwent randomization) was analyzed post hoc. Details of the analysis populations are provided in Tables S4 and S5.
For all the other efficacy analyses, data were analyzed in the full analysis population. The Kaplan–Meier method was used to estimate the median time to sustained clinical recovery, with the 95% confidence interval estimated by means of the Brookmeyer–Crowley method with log–log transformation. The hazard ratio for time to sustained clinical recovery and its 95% confidence interval were estimated with the use of the Cox proportional-hazards model. Data for participants without sustained clinical recovery were censored on the last day on which Covid-19–related symptoms or signs were recorded. Participants with missing end-point data were considered to have not had clinical recovery on that day, and a sensitivity analysis was performed with the use of the multiple-imputation method. Subgroup analyses of the primary end point were prespecified to assess the consistency of the intervention effect. For efficacy results other than the primary end point in the full analysis population, 95% confidence intervals have not been adjusted for multiplicity and should not be used to infer treatment effects. Additional details are provided in the statistical analysis plan, available with the protocol.​

Results​

PARTICIPANTS​

Figure 1.

Screening, Randomization, and Follow-up.
A total of 997 participants were screened from April 4 through May 2, 2022, and 822 were randomly assigned to receive VV116 (411 participants) or nirmatrelvir–ritonavir (411 participants). Of these 822 participants, 741 (90.1%) completed 28-day follow-up, 51 (6.2%) did not receive VV116 or nirmatrelvir–ritonavir, and 30 (3.6%) had discontinued the trial by the time of the final analysis (data-cutoff date, August 18, 2022) (Figure 1 and Table S6).
Table 1.

Demographic and Clinical Characteristics of the Full Analysis Population.
The characteristics of the full analysis population at baseline were balanced between the VV116 group (384 participants) and the nirmatrelvir–ritonavir group (387 participants) (Table 1) and were largely representative of the expected patient population (Table S7). The median age of the participants was 53 years (interquartile range, 38 to 66), and approximately half were women. Most participants (92.1%) had mild Covid-19, and three quarters were fully vaccinated or boosted. The most common risk factor for progression to severe Covid-19 at baseline was an age of 60 years or older (37.7%), followed by cardiovascular disease (including hypertension) (35.1%), a body-mass index (weight in kilograms divided by the square of the height in meters) of 25 or higher (32.9%), current smoking (12.5%), and diabetes (10.1%). Most participants (77.3%) received trial regimens within 5 days after symptom onset. Medication adherence was similar in the two groups, with a mean (±SD) of 9.7±1.6 doses taken in the VV116 group and 9.4±2.0 doses taken in the nirmatrelvir–ritonavir group. More information on received vaccines, coexisting conditions, and adherence is provided in Tables S8, S9, and S10.​

PRIMARY END POINT​

In the primary analysis involving the full analysis population, sustained clinical recovery occurred in 377 participants in the VV116 group and 378 participants in the nirmatrelvir–ritonavir group. The hazard ratio for the time from randomization to sustained clinical recovery (VV116 vs. nirmatrelvir–ritonavir) was 1.17 (95% confidence interval [CI], 1.01 to 1.35; lower boundary, >0., which indicates that the noninferiority of VV116 to nirmatrelvir–ritonavir was established.
Figure 2.

Time to Sustained Clinical Recovery.Table 2.

Primary and Secondary Efficacy End Points (Full Analysis Population).
In the final analysis of this population, the hazard ratio for the time to sustained clinical recovery (VV116 vs. nirmatrelvir–ritonavir) was 1.17 (95% CI, 1.02 to 1.36; lower boundary, >0.; the estimated median time to sustained clinical recovery was 4 days and 5 days, respectively, and the 25th percentile of the time to sustained clinical recovery was 4 days (95% CI, 3 to 4) in both groups (Figure 2A and Table 2). Consistent results were also found in a sensitivity analysis with imputation of missing end-point data (hazard ratio, 1.17; 95% CI, 1.01 to 1.35). Noninferiority of VV116 to nirmatrelvir–ritonavir was also observed in the per-protocol population (Figure 2B), among participants who started treatment within 5 days after symptom onset (Figure 2C), and in the intention-to-treat population (Fig. S2). In most prespecified subgroups, the point estimates of the hazard ratio were greater than 1 regardless of age, sex, and vaccination status (Fig. S3).​

SECONDARY END POINTS​

By the time of the final analysis, no participants in this trial had died or had had progression to severe Covid-19. The estimated median time from randomization to sustained resolution of Covid-19–related target symptoms was 7 days (95% CI, 7 to in both groups (hazard ratio, 1.06; 95% CI, 0.91 to 1.22) (Table 2 and Fig. S4). The percentage of participants with sustained clinical recovery was higher in the VV116 group than in the nirmatrelvir–ritonavir group by each prespecified time point (Table 2). The median time from randomization to a first negative SARS-CoV-2 test was 7 days (95% CI, 6 to 7) in both groups (hazard ratio, 0.99; 95% CI, 0.85 to 1.14) (Fig. S5). The percentages of participants with negative SARS-CoV-2 tests by prespecified time points and the changes in viral cycle-threshold values and target symptom scores from baseline were similar in the two groups (Table 2 and Tables S11 and S12).​

SAFETY​

Table 3.

Adverse Events (Safety Population).
Through 28 days of follow-up, participants who received VV116 reported fewer adverse events than those who received nirmatrelvir–ritonavir (67.4% vs. 77.3%), as well as fewer grade 3 or 4 adverse events (2.6% vs. 5.7%) (Table 3). Seven participants in the VV116 group were taking concomitant medications that have potential drug interactions with ritonavir (three were taking estazolam, one diazepam, and three nifedipine), and four of them (one taking estazolam and three nifedipine) had concomitant medications withheld during the active treatment phase. Seven participants in the nirmatrelvir–ritonavir group were taking concomitant medications that have potential drug interactions with ritonavir (three were taking estazolam and four nifedipine), and three of them (one taking estazolam and two nifedipine) had concomitant medications withheld during the active treatment phase. Two serious adverse events (acute cerebral infarction and a deterioration of the preexisting interstitial lung disease) were reported in two participants in the nirmatrelvir–ritonavir group. One serious adverse event was reported in a participant in the VV116 group who was readmitted for repeat positivity for SARS-CoV-2 on RT-PCR assay. None of the three serious adverse events were considered by the investigators to be related to the assigned drugs (Table 3). The most frequently reported adverse events (occurring in ≥5% of the participants in either group) were dysgeusia (3.6% with VV116 and 25.8% with nirmatrelvir–ritonavir), hypertriglyceridemia (10.7% and 20.9%, respectively), and hyperlipidemia (3.1% and 9.6%) (Table S13); all these frequent adverse events were nonserious.​

Discussion
In light of the preliminary positive findings of a reduction in viral shedding time among patients with SARS-CoV-2 infection who were taking VV116,17 the current trial compared VV116 with nirmatrelvir–ritonavir to assess clinical end points and adverse events. This trial showed that in symptomatic adults hospitalized with mild-to-moderate Covid-19 who were at high risk for severe disease, a 5-day course of oral treatment with VV116 was noninferior to nirmatrelvir–ritonavir in shortening the time to sustained clinical recovery. This noninferiority in efficacy was seen in the full analysis population, the per-protocol population, and in participants who started treatment within 5 days after symptom onset. The point estimates of secondary end points also suggested that VV116 was better than or similar to nirmatrelvir–ritonavir with respect to the time to sustained symptom resolution and to a first negative SARS-CoV-2 test. No participants in either group died or had progression to severe or critical Covid-19. Participants in the VV116 group had a lower incidence of adverse events than those in the nirmatrelvir–ritonavir group.
The administration of oral antiviral agents is feasible early in infection. Such therapies, if given promptly, could help mitigate hospitalization burden, facilitate postexposure prophylaxis, and potentially minimize household transmission.
This trial was performed in Shanghai, China, during an outbreak of Covid-19 (March through June 2022) involving more than 600,000 infections.21 SARS-CoV-2 genomic analysis of specimens from 129 patients in this period showed the BA.2.2 sublineage in all of them,20 which suggests that the major variant involved in our trial was omicron. In this population, the median time to sustained clinical recovery or symptom resolution in both trial groups was shorter than those reported in other trials, such as those evaluating REGEN-COV (14 days)22 and bamlanivimab with or without etesevimab (8 days).23
Another feature of this trial is that 75.7% of the participants had been vaccinated against SARS-CoV-2, which reflects the current reality of population immunity; vaccinated persons have been excluded from most trials, given the rapidly changing landscape of the Covid-19 response.8 Therefore, we prespecified and conducted subgroup analyses according to vaccination status. The results were similar in participants with previous vaccination and those without previous vaccination. Recent studies have shown that treatment with nirmatrelvir–ritonavir in vaccinated patients with Covid-19 is associated with a reduced risk of hospitalization or progression to severe Covid-19, as well.24-26
In this trial, fewer adverse events occurred in the VV116 group than in the nirmatrelvir–ritonavir group. Unlike nirmatrelvir–ritonavir, which has drug–drug interactions with multiple medications,9VV116 does not inhibit or induce major drug-metabolizing enzymes or inhibit major drug transporters, so interaction with concomitant medications is less likely. Transient dysgeusia was reported in one quarter of the participants receiving nirmatrelvir–ritonavir in this trial, a proportion higher than that previously reported in the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial (5.6%)9; this adverse event warrants more attention in future trials. In addition, the incidence of dyslipidemia was relatively high among both nirmatrelvir–ritonavir recipients and VV116 recipients. Although this adverse reaction has been noted with long-term use of ritonavir in patients with human immunodeficiency virus infection,27 the possible effect of nirmatrelvir or VV116 on lipid metabolism needs further investigation.
The trial has several limitations. First, we were not able to conduct this trial with a double-blind and double-dummy design because the production of the placebo tablet for nirmatrelvir–ritonavir was not completed before the trial began owing to the omicron outbreak. Second, the trial involved Chinese adults infected with omicron subvariants in a single geographic area, so the results require validation in more heterogeneous populations with greater diversity of viral variants. Third, it is possible that symptoms could have recurred after 2 consecutive days without symptoms. Fourth, the WHO ordinal scale that was used to evaluate outcomes was not ideal for detecting differences among participants with mild Covid-19, especially when discharge decisions may be driven by factors other than clinical improvement. Fifth, no conclusions can be made about the efficacy of VV116 for the prevention of progression to severe or critical Covid-19 or death, because no events occurred in either group. Possible efficacy for this outcome is planned to be evaluated in a separate trial (ClinicalTrials.gov number, NCT05242042. opens in new tab). Sixth, we did not recognize SARS-CoV-2 rebound after nirmatrelvir–ritonavir treatment until the release of the Centers for Disease Control and Prevention advisory on May 24, 2022.28 Data on such rebounds were very limited and not suitable for analysis in our trial.
In this trial, early administration of oral VV116 was noninferior to nirmatrelvir–ritonavir in shortening the time to sustained clinical recovery in participants with mild-to-moderate Covid-19 who were at high risk for progression to severe disease. VV116 also had fewer safety concerns than nirmatrelvir–ritonavir.​

Supported by Vigonvita Life Science and partially supported by the Science and Technology Commission of Shanghai Municipality (22YJ1900600), a Lingang Laboratory emergency project (LG-YJ-202204-01), the National Key Research and Development Program of China (2021YFC0865000), the National Natural Science Foundation of China (82088102, 8200058, a Shanghai Shenkang Three-Year Action grant (SHDC2022CRS031), and Shanghai Municipal Key Clinical Specialty (shslczdzk01103).
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Drs. Cao, W. Gao, Bao, Feng, and Mei and Drs. Xie, Xu, Ning, Yuan Gao, and Zhao contributed equally to this article.
This article was published on December 28, 2022, at NEJM.org.

"

 

[missy]

Japan to Require Negative COVID Test Upon Arrival for Chinese Travelers China to Scrap COVID Quarantine Rule for Inbound Travellers India Makes COVID Test Mandatory for Arrivals From Some Countries, Including China Medical Staff on Frontline of China's COVID Fight Say Hospitals Are 'Overwhelmed' Beijing, Shanghai Residents Back to Work as China Limps Towards Living With COVID Omicron Subvariant XBB Jumps to 18% of US COVID Cases: CDC China Estimates COVID Surge Is Infecting 37 Million People a Day India Plans to Make COVID-19 Negative Test Mandatory for Passengers From High Caseload Countries BioNTech's COVID Booster Vaccine Approved in Hong Kong for Individuals From Age 12​

 

[missy]

"

Japan Marks Record 415 COVID-19 Deaths: Health Ministry​

By Reuters Staff
December 29, 2022

TOKYO (Reuters) - Japan on Wednesday recorded 415 COVID-19 deaths, the highest-ever count for a single day, health ministry data showed.
The country counted 216,219 newly confirmed coronavirus cases on Wednesday, up 4% from a week earlier, the data also showed, approaching the record high of some 260,000 a day in August.
In the past seven days, Japan had the world's largest confirmed COVID-19 infections and the second-most deaths after the United States, according to a tally by the World Health Organization.
(Reporting by Kantaro Komiya; Editing by Chang-Ran Kim)
"

"
MILAN (Reuters) - Italy has ordered COVID-19 antigen swabs and virus sequencing for all travellers coming from China, where cases are surging, the health minister said on Wednesday.

Italy, which was the first nation in Europe to be hit hard by the virus in February 2020 after it emerged in China, is now the first to impose mandatory tests on people arriving from the Asian country grappling with a new wave.

Milan's main airport, Malpensa, had already started testing passengers arriving from Beijing and Shanghai on Dec. 26, and the results showed almost one in two passengers was infected.

"The measure is essential to ensure surveillance and detection of possible variants of the virus in order to protect the Italian population", minister Orazio Schillaci said, announcing mandatory testing for all passengers.


The minister did not say what measures would be imposed on travellers testing positive, but the local health chiefs in the Lombardy region around Milan and the Lazio region around Rome said they would have to quarantine in buildings set aside by the local health authorities.





Chinese hospitals and funeral homes were under intense pressure on Wednesday as its COVID-19 wave drained resources, while the scale of the outbreak and doubts over official data prompted some countries to consider new travel rules on Chinese visitors.

Japan has said that from Dec. 31 it will require a negative COVID-19 test upon arrival for travellers from mainland China, while Taiwan will test arrivals from China from Jan. 1.

On the first flight to Malpensa that tested passengers from China out of 62 passengers 35 were Covid positive, Lombardy's health chief Guido Bertolaso said on Wednesday, while on the second 62 were positive out of 120.


He added that virus sequencing procedures had been activated to analyse variants, and the results are expected on Thursday.

(Reporting by Emilio Parodi, editing by Gavin Jones and David Gregorio)
"

 

[missy]

"

Triple Winter Epidemic: How Do We Deal With This Extraordinary Season?​

Véronique Duqueroy
December 29, 2022

According to Benjamin Davido, MD, PhD student (infectious disease specialist, Raymond-Poincaré Hospital, Garches, France), the hospital once again finds itself in an unprecedented and worrisome situation: a triple epidemic. It is experiencing a particularly early flu season, an explosion of cases of respiratory syncytial virus (RSV), and a resurgence of SARS-CoV-2. How can this epidemic situation be explained, and what solutions (such as masking, social distancing, and new vaccination and prevention campaigns) should be considered? Medscape Medical News raised these questions with Davido.

Medscape: There is currently a worrisome epidemic situation in several countries. Was it foreseeable, in your opinion?

Davido: Factually, there is indeed a triple epidemic of flu, RSV infections, and COVID-19. Some numbers are chilling, and it seems no country can escape them: more than 20% of positive flu cases are being reported in the United States, with largely insufficient flu vaccination coverage around the world, and especially in Europe. This scenario had been predicted, because there was a very large wave of flu in Australia this summer. Added to this is the European Center for Disease Prevention and Control alert on bronchiolitis and the resumption of circulation of SARS-CoV-2, with a consequent increase in hospitalizations (+18% in intensive care units in France currently). And that's not counting what is happening in China. We've endured the BQ1.1 variant worldwide, whereas the population is hardly immune anymore, since few people have received the Omicron-targeted bivalent booster (about 10% in France).


This situation is, therefore, particularly worrisome. We are witnessing a season with a significant number of respiratory infections of all kinds, and this is unprecedented in the post-COVID era. Every day, I am called on for hospitalizations for pulmonary infections, including bacterial ones. Over the past 3 months, we've seen a few elderly patients come into the department. Today, the average age of my patients is between 50 and 60 years, and some are occasionally in their thirties, like a patient who, with no comorbidities, arrived last week for pneumonia (severe flu) and had to go through the intensive care unit. I am once again seeing admissions to the ICU, including a 60-year-old woman who had never been vaccinated against COVID. The ICU is logically seeking downstream beds.... We once again need to remember that with Omicron, the risk of death in hospitalized patients is 7%, compared with 12% during the Delta wave.





Medscape: Why is the speed of this epidemic so exceptional?

Davido: Before the COVID-19 pandemic, hospitalizations for flu began between the end of December and the beginning of January, with a peak in late January. Today, 1 in 2 patients I am called to see have the flu. I'm amazed at how quickly it is evolving. We were in a gray area for a while, since we weren't testing for the flu in primary healthcare settings, so it was difficult to assess the arrival of this unprecedented wave of hospital flu in the COVID era. But we are now in an epidemic crisis management situation — we are meeting this week to list the beds available in geriatrics, in anticipation.

As for COVID, with the current variant (BQ1.1), which is even more contagious than the previous one (BA.5), the wave hits very quickly (+37% of cases in 1 week). This is perhaps the only good news. It should pass quickly, but the corollary, of course, will be the hospital overload inherent in severe forms. And once again, if only 10% to 20% of the target population is protected against BA.5, we'll find ourselves in a frankly very embarrassing situation, given the total lack of protective measures, such as masking and social distancing, in day-to-day life.


Regarding RSV, I think we underestimated the situation. We mobilized medical and paramedical staff on bronchiolitis at the hospital to counter a pediatric epidemic, while a double epidemic had just been added in adults. One of our mistakes was that for the past 2 years, we focused so closely on COVID that we couldn't imagine the overflow coming from somewhere else.

Medscape: What solutions can currently be envisioned to limit hospital strain in these unprecedented winter circumstances?

Davido: The faster the waves crash, the faster they'll inundate the hospital, that's for sure. But what's almost astonishing is that, while treatments (such as nirmatrelvir and ritonavir) and vaccines are now available, nothing has been put in place. We've gone from one extreme to the other, namely, from an almost hygienist society — rightly or wrongly — with restrictions going as far as wearing a mask outdoors with no scientific basis for it, to a general exasperation where we no longer want to hear about either COVID or masks. As we lifted all these mitigation measures, we stoked the fire for these viruses of yesteryear (that is, flu and RSV). We are in a completely different place than we were last year, and I'm not even talking about 2020, when there were only about 30 serious cases of flu identified.... Today, whether it's the vaccine or the mitigation measures or both, there are no more rules, no more compass! However, I think that as soon as the meteorological winter arrives, that is to say, December 1, we have to start putting the masks back on in crowded places and anticipate the vaccination of people at risk.

It seems completely crazy to get to this winter period without calibrating our epidemic surveillance tools, whether that means screening tests, vaccine booster campaigns, the use of protective measures, such as masking and social distancing, etc. If we continue like this, the next waves are really going to bury the hospital.





Medscape: Do you think people are sufficiently informed about vaccination or mitigation measures?


Davido: I don't think it's being explained well. Regarding vaccination, we have to stop thinking in terms of the number of doses and rather think in terms of new-generation vaccines. I've heard many accounts of people who don't know that people under 60 can be vaccinated. Some would like to get the boosters but think they aren't allowed to! We clung to the idea of a vaccination that targeted the elderly; it's a very bad message, because you can be 50 years old and have had a myocardial infarction and therefore be at risk. In addition, last year, the vaccination campaigns against the flu and against COVID came out at the same time, whereas today, everyone "manages" as best they can to get vaccinated. If there are no guidelines, no accelerated and outlined path, people are lost. A message like, "Vaccination with the new Omicron vaccine is open to everyone," would have more weight than talking about a fourth vaccine dose.


In the world before, we managed only one disease ― it was the flu ― and there were no mitigation measures. It all ran well. Today, we should probably be making more of an effort. When the bronchiolitis epidemic happened, it should have been said very clearly to put the mitigation measures back in place. However, the Ministry of Health has been completely silent on this subject. We were somehow engulfed by energy and political news. We are no longer "at war" against these viruses (just as we should be against bacteria, since, as a recent Lancet study reminds us, bacterial infections remain the second leading cause of death worldwide).


The moral is that we cannot, overnight, abandon campaigns to fight and prevent infectious diseases; it's not rational. We have to remember and explain basic hygiene. For example, the "energy sobriety" so acclaimed today encourages closing all the windows to save on heating.... However, if there is no more ventilation of the spaces, we are bound to increase the likelihood of contamination. And how does that play out currently in doctor's offices, where we increasingly see patients not wearing masks?

Medscape: How do we envision the future of the fight against these epidemics?


Davido: We have to relaunch strong campaigns to fight against infectious diseases every year, like they do, for example, with breast or colon cancer. And, as in oncology, we must continue to improve and simplify diagnostic tools and optimize treatments. Next year, we expect to see a new arsenal in the fight against bronchiolitis, through RSV vaccines. One example is that there are tools to screen for the flu, COVID, and RSV all at once. We'll have to explain it and put it in place and make all these new tools available, including to the primary care doctor.


There is also real work to be done on the collaboration between primary care and hospital infectious diseases. We will need to optimize the channels, eg, to call on and expand the field of competence of pharmacists and professionals in contact with patients. And more generally, we need to organize care in a broader way and imagine, for example, a "European conductor" for European health.


Medscape: Reinstate unvaccinated caregivers to bail out hospital departments, like they did in Italy?


Davido: I think it's a phony debate, because the real underlying question that is not being asked is, will this solve the hospital's problem? The answer is no. We're talking about around 4000 people, and among them, there are a lot of administrative staff, paramedics, etc. There are hardly any doctors. So, we have to be very careful when we talk about these "caregivers."





Nevertheless, I understand the subtlety of saying that vaccination does not prevent contamination and that everyone wears a mask in the hospital, so as a result, the vaccine becomes optional because it has no protective effect on patients. Beyond this shortcut, if we reinstate these people, I believe that a tacit agreement should be put in place with them: in the event of a wave of unprecedented magnitude and given the availability of new mRNA vaccines which significantly reduce the likelihood of becoming infected, including with new variants, these people will have to submit to the science and vaccination.


We don't say it enough, but this vaccination of caregivers has largely made it possible, when the waves occur, on the one hand to avoid absenteeism, but also to "unmask" those who claim to be caregivers but do not rely on scientific data. Because I don't think you can be at the bedside of a patient who is suffering from COVID or the flu and tell him, "You were right not to get vaccinated and to end up in intensive care." There are ethics in medical care that are essential.


But we must be extremely clear: to say that the hospital is collapsing because staff were ousted who did not comply with vaccination is completely false. Their reinstatement is certainly possible, but it will not solve the problem in either the short or the long term.


This article was translated from the Medscape French edition.

"

 

[missy]

"
Three years of Covid


It’s been three years, but the coronavirus pandemic that’s claimed millions of lives all over the world is still very much with us. The virus is now rampaging across the country where it was first discovered, with tens of thousands being infected each day and potentially millions more lives at risk. Nations around the world this week said they are implementing measures to test or restrict travelers from China, where an unprecedented wave was unleashed this month when Xi Jinping abandoned his “Covid zero” policy in the face of widespread protests and spreading economic malaise. Xi contends his strategy is “optimized” to protect lives and minimize economic costs. But the country’s economy is showing more strain as the surge grows. China’s vaccination programs lagged other parts of the world as it pursued years of testing and lockdowns. Now health experts say they’re worried the virus’s unchecked spread in a nation of 1.4 billion could spawn new variants that will circumvent protections people elsewhere have gained through vaccination or previous infections. While no new variants have emerged from China so far, it’s still early days.

"

 

[dk168]

England decided to join other countries in having precautionary and temporary measures for travellers from China from ahead of borders re-opening next week:

https://www.gov.uk/government/news/...uced-to-improve-covid-surveillance-from-china

The table has turned and they do not like it, judging by some of the reactions I have read!

DK