German man got 217 COVID shots over 29 months—here’s how it went

German man got 217 COVID shots over 29 months—here’s how it went

A 62-year-old man in Germany decided to get 217 COVID-19 vaccinations over the course of 29 months —for “private reasons.” But, somewhat surprisingly, he doesn’t seem to have suffered any ill effects from the excessive immunization, particularly weaker immune responses, according to a newly published case study in The Lancet Infectious Diseases.

The case is just one person, of course, so the findings can’t be extrapolated to the general population. But, they conflict with a widely held concern among researchers that such overexposure to vaccination could lead to weaker immune responses. Some experts have raised this concern in discussions over how frequently people should get COVID-19 booster doses.

In cases of chronic exposure to a disease-causing germ, “there is an indication that certain types of immune cells, known as T-cells, then become fatigued, leading to them releasing fewer pro-inflammatory messenger substances,” according to co-lead study author Kilian Schober from the Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene. This, along with other effects, can lead to “immune tolerance” that leads to weaker responses that are less effective at fighting off a pathogen, Schober explained in a news release.

The German man’s extreme history of hypervaccination seemed like a good case to look for evidence of such tolerance and weaker responses. Schober and his colleagues learned of the man’s case through news headlines—officials had opened a fraud investigation against the man, confirming 130 vaccinations over nine months, but no criminal charges were ever filed. “We then contacted him and invited him to undergo various tests in Erlangen [a city in Bavaria],” Schober said. “He was very interested in doing so.” The man then reported an additional 87 vaccinations to the researchers, which in total included eight different vaccine formulations, including updated boosters.

The researchers were able to collect blood and saliva samples from the man during his 214th to 217th vaccine doses. They compared his immune responses to those of 29 people who had received a standard three-dose series.

Throughout the dizzying number of vaccines, the man never reported any vaccine side effects, and his clinical testing revealed no abnormalities related to hypervaccination. The researchers conducted a detailed look at his responses to the vaccines, finding that while some aspects of his protection were stronger, on the whole, his immune responses were functionally similar to those from people who had far fewer doses. Vaccine-spurred antibody levels in his blood rose after a new dose but then began declining, similar to what was seen in the controls.

His antibodies’ ability to neutralize SARS-CoV-2 appeared to be between fivefold and 11-fold higher than in controls, but the researchers noted that this was due to a higher quantity of antibodies, not more potent antibodies. Specific subsets of immune cells, namely B-cells trained against SARS-CoV-2’s spike protein and T effector cells, were elevated compared with controls. But they seemed to function normally. As another type of control, the researchers also looked at the man’s immune response to an unrelated virus, Epstein-Barr, which causes mononucleosis. They found that the unbridled immunizations did not negatively impact responses to that virus, suggesting there were no ill effects on immune responses generally.

Last, multiple types of testing indicated that the man has never been infected with SARS-CoV-2. But the researchers were cautious to note that this may be due to other precautions the man took beyond getting 217 vaccines.

“In summary, our case report shows that SARS-CoV-2 hypervaccination did not lead to adverse events and increased the quantity of spike-specific antibodies and T cells without having a strong positive or negative effect on the intrinsic quality of adaptive immune responses,” the authors concluded. “Importantly,” they added, “we do not endorse hypervaccination as a strategy to enhance adaptive immunity.”

https://arstechnica.com/?p=2008036




CDC ditches 5-day COVID isolation, argues COVID is becoming flu-like

A view of the Centers for Disease Control and Prevention headquarters in Atlanta.
Enlarge / A view of the Centers for Disease Control and Prevention headquarters in Atlanta.

COVID-19 is becoming more like the flu and, as such, no longer requires its own virus-specific health rules, the Centers for Disease Control and Prevention said Friday alongside the release of a unified “respiratory virus guide.”

In a lengthy background document, the agency laid out its rationale for consolidating COVID-19 guidance into general guidance for respiratory viruses—including influenza, RSV, adenoviruses, rhinoviruses, enteroviruses, and others, though specifically not measles. The agency also noted the guidance does not apply to health care settings and outbreak scenarios.

“COVID-19 remains an important public health threat, but it is no longer the emergency that it once was, and its health impacts increasingly resemble those of other respiratory viral illnesses, including influenza and RSV,” the agency wrote.

The most notable change in the new guidance is the previously reported decision to no longer recommend a minimum five-day isolation period for those infected with the pandemic coronavirus, SARS-CoV-2. Instead, the new isolation guidance is based on symptoms, which matches long-standing isolation guidance for other respiratory viruses, including influenza.

“The updated Respiratory Virus Guidance recommends people with respiratory virus symptoms that are not better explained by another cause stay home and away from others until at least 24 hours after both resolution of fever AND overall symptom are getting better,” the document states. “This recommendation addresses the period of greatest infectiousness and highest viral load for most people, which is typically in the first few days of illness and when symptoms, including fever, are worst.”

“Residual risk”

The CDC acknowledged that the eased isolation guidance will create “residual risk of SARS-CoV-2 transmission,” and that most people are no longer infectious only after 8 to 10 days. As such, the agency urged people to follow additional interventions—including masking, testing, distancing, hygiene, and improving air quality—for five additional days after their isolation period.

“Today’s announcement reflects the progress we have made in protecting against severe illness from COVID-19,” CDC Director Dr. Mandy Cohen said in a statement. “However, we still must use the commonsense solutions we know work to protect ourselves and others from serious illness from respiratory viruses—this includes vaccination, treatment, and staying home when we get sick.”

Overall, the agency argued that a shorter isolation period would be inconsequential. Other countries and states that have similarly abandoned fixed isolation times did not see jumps in COVID-19 emergency department visits or hospitalizations, the CDC pointed out. And most people who have COVID-19 don’t know they have it anyway, making COVID-19-specific guidance moot, the agency argued. In a recent CDC survey, less than half of people said they would test for SARS-CoV-2 if they had a cough or cold symptoms, and less than 10 percent said they would go to a pharmacy or health care provider to get tested. Meanwhile, “The overall sensitivity of COVID-19 antigen tests is relatively low and even lower in individuals with only mild symptoms,” the agency said.

The CDC also raised practical concerns for isolation, including a lack of paid sick leave for many, social isolation, and “societal costs.”

The points are likely to land poorly with critics.

“The CDC is again prioritizing short-term business interests over our health by caving to employer pressure on COVID guidelines. This is a pattern we’ve seen throughout the pandemic,” Lara Jirmanus, Clinical Instructor of Medicine at Harvard Medical School, said in a press release last month after the news first broke of the CDC’s planned isolation update. Jirmanus is a member of the People’s CDC, a group that advocates for more aggressive COVID-19 policies, which put out the press release.

Another member of the group, Sam Friedman, a professor of population health at NYU Grossman School of Medicine, also blasted the CDC’s stance last month. The guidance will “make workplaces and public spaces even more unsafe for everyone, particularly for people who are high-risk for COVID complications,” he said.

COVID and flu

But, the CDC argues that the threat of COVID-19 is fading. Hospitalizations, deaths, prevalence of long COVID, and COVID-19 complications in children (MIS-C) are all down. COVID-19 vaccines are safe and effective at preventing severe disease, death, and to some extent, long COVID—we just need more people to get them. Over 95 percent of adults hospitalized with COVID-19 in the 2023–2024 respiratory season had no record of receiving the seasonal booster dose, the agency noted. Only 22 percent of adults got the latest shot, including only 42 percent of people ages 65 and older. In contrast, 48 percent of adults got the latest flu shot, including 73 percent of people ages 65 and older.

But even with the crummy vaccination rates for COVID-19, a mix of past infection and shots have led to a substantial protection in the overall population. The CDC even went as far as arguing that COVID-19 deaths have fallen to a level that is similar to what’s seen with flu.

“Reported deaths involving COVID-19 are several-fold greater than those reported to involve influenza and RSV. However, influenza and likely RSV are often underreported as causes of death,” the CDC said. In the 2022–2023 respiratory virus season, there were nearly 90,000 reported COVID-19 deaths. For flu, there were 9,559 reported deaths, but the CDC estimates the true number to be between 18,000 and 97,000. In the current season, there have been 32,949 reported COVID-19 deaths to date and 5,854 reported flu deaths, but the agency estimates the real flu deaths are between 17,000 and 50,000.

“Total COVID-19 deaths, accounting for underreporting, are likely to be higher than, but of the same order of magnitude as, total influenza deaths,” the agency concluded.

In all, the CDC was ready to fold SARS-CoV-2 into the gang of common seasonal respiratory viruses, with most cases mild and undiagnosed. “Viruses cause most acute respiratory illnesses, but it is rarely possible to determine the type of virus without testing, and oftentimes testing does not change clinical management,” the agency wrote.

https://arstechnica.com/?p=2007434




Can you sanitize the inside of your nose to prevent COVID? Nope, FDA says.

Can you sanitize the inside of your nose to prevent COVID? Nope, FDA says.

More than four years after SARS-CoV-2 made its global debut, the US Food and Drug Administration is still working to clear out the bogus and unproven products that flooded the market claiming to prevent, treat, and cure COVID-19.

The latest example is an alcohol-based sanitizer meant to be smeared inside the nostrils. According to its maker, the rub can protect you from becoming infected with SARS-CoV-2 and other nasty germs, like MRSA, and that protection lasts up to 12 hours after each swabbing. That all sounds great, but according to the FDA, none of it is proven. In a warning letter released Tuesday, the agency determined the sanitizer, called Nozin, is an unapproved new drug and misbranded.

While ethyl alcohol is used in common topical antiseptics, like hand sanitizers, the FDA does not generally consider it safe for inside the nostrils—and the agency is unaware of any high-quality clinical data showing that Nozin is safe, let alone effective. The FDA also noted that, for general over-the-counter topical antiseptics, calling out specific pathogens it can fight off—like SARS-CoV-2 and MRSA—is not allowed under agency rules without further FDA review. Making claims about protection duration is also not allowed.

The FDA’s warning letter is nothing to sneeze at; the letter threatens seizure and injunction for failing to adequately respond.

Nozin’s maker, Maryland-based Global Life Technologies Corp., did not immediately respond to a request for comment from Ars. On its website, the company touts its product’s effectiveness with a link to a published study from 2014, indicating that use of Nozin lowered the colonization levels of S. aureus and other bacteria in the noses of 20 healthy health care workers. The study did not address protection from infection or carriage of any viruses. The company also lists unpublished studies indicating that the product can kill bacteria in laboratory conditions, does not irritate skin, and lowered bacterial growth in the noses of 30 people over a 12-hour period.

This is far from the first dubious, nasal-based COVID product the FDA has called out. There was the Corona-cure nasal spray of 2020, and the Halodine and NanoBio Protect nasal antiseptics of 2021. That year, the Federal Trade Commission sued a company called Xlear over allegedly false claims that its nasal spray can prevent and treat COVID-19. At least two more nasal spray makers received FDA warning letters in 2022.

To date, the FDA has not approved any nasal sprays to prevent or treat COVID-19, and the scant data on their efficacy remains inconclusive. But there are still plenty of such products for sale online. Most, like Nozin, claim to work by killing bacteria and viruses directly. One product, a nitric oxide nasal spray called Sanotize, is currently in a Phase III clinical trial to test whether it can prevent SARS-CoV-2 infections. Others claim to work by coating the nasal passage with the gelling agent iota-carrageenan to provide a barrier to viral entry. A pilot clinical trial of 400 health care workers in Argentina published in 2021 found that the use of an iota-carrageenan nasal spray led to a 4 percent absolute risk reduction in SARS-CoV-2 infection.

https://arstechnica.com/?p=2003503




CDC to update its COVID isolation guidance, ditching 5-day rule: Report

CDC to update its COVID isolation guidance, ditching 5-day rule: Report

The Centers for Disease Control and Prevention is preparing to update its COVID-19 isolation guidance, moving from a minimum five-day isolation period to one that is solely determined by symptoms, according to a report from The Washington Post.

Currently, CDC isolation guidance states that people who test positive for COVID-19 should stay home for at least five days, at which point people can end their isolation as long as their symptoms are improving and they have been fever-free for 24 hours.

According to three unnamed officials who spoke with the Post, the CDC will update its guidance to remove the five-day minimum, recommending more simply that people can end their isolation any time after being fever-free for 24 hours without the aid of medication, as long as any other remaining symptoms are mild and improving. The change, which is expected to be released in April, would be the first to loosen the guidance since the end of 2021.

In an email to Ars, a CDC spokesperson did not confirm or deny the report, saying only: “There are no updates to COVID guidelines to announce at this time. We will continue to make decisions based on the best evidence and science to keep communities healthy and safe.”

The Post notes that the proposed update to the guidance matches updated guidance from California and Oregon, as well as other countries.

The officials who spoke with the outlet noted that the loosened guidelines reflect that most people in the US have developed some level of immunity to the pandemic coronavirus from prior infections and vaccinations.

A report earlier this month found that the 2023–2024 COVID-19 vaccine was about 54 percent effective at preventing symptomatic COVID-19 when compared against people who had not received the latest vaccine. However, the CDC estimates that only about 22 percent of adults have received the updated shot.

Currently, the CDC recommends that people wear a mask for 10 days after testing positive unless they have two negative tests 48 hours apart. The Post reported that it’s unclear if the CDC will update its mask recommendation.

https://arstechnica.com/?p=2003150




US verges on vaccination tipping point, faces thousands of needless deaths: FDA

A child with measles.
Enlarge / A child with measles.

The US may be heading to a “dangerous vaccination tipping point,” with immunization rates falling so low that population-level immunity is now at risk, and we will likely see thousands of needless deaths this respiratory virus season, two top officials for the Food and Drug Administration warned in a recent JAMA commentary.

FDA Commissioner Robert Califf and top FDA vaccine regulator Peter Marks noted the profound benefits of lifesaving vaccines—which save millions of lives in the US each year—and their established safety, which is monitored both passively and actively through multiple, overlapping federal safety monitoring systems. And yet, “an increasing number of people in the US are now declining vaccination for a variety of reasons, ranging from safety concerns to religious beliefs,” thanks to the rise of anti-vaccine misinformation spread on social media and elsewhere on the Internet.

Data from the Centers for Disease Control and Prevention last year found that, for the third consecutive year, vaccination rates among kindergartners had continued to slip, with rates of non-medical vaccination exemptions rising to an all-time high. There are now 10 states with vaccination exemption rates over 5 percent, meaning that even if clinicians and health officials manage to vaccinate all non-exempt children, the state will not be able to reach the target of 95 percent coverage needed to curb the spread of disease on a population level.

Califf and Marks lamented that the efficacy of vaccines has meant that the “disturbing” suffering and deaths from vaccine-preventable diseases, such as the extremely contagious measles, are no longer visible to people in the US. Thus, vaccines’ benefits are underappreciated. But that reality is changing as vaccination rates slip, particularly in small pockets of the country.

“Regrettably, pediatric vaccine hesitancy now has been responsible for several measles outbreaks in the US, including a recent one in central Ohio involving local-acquired cases in 85 children, 36 of whom (42 percent) had to be hospitalized for complications,” Califf and Marks write.

A measles outbreak is ongoing in Philadelphia, where an unvaccinated person who contracted the virus outside the US exposed other unvaccinated people at the Children’s Hospital of Philadelphia and an area daycare. So far, eight cases have been confirmed (one adult and seven children), six of which were hospitalized. Some of the cases occurred when an infected, unvaccinated child broke quarantine and attended the daycare.

While childhood vaccination rates suffer and bygone diseases flare, there’s also concern for older people and more familiar diseases. The respiratory virus season is now peaking. Influenza-like illness activity—which can capture not just flu but also RSV and COVID-19—is high and rising throughout much of the country, posing a high risk to older people. Flu is infecting the most people right now, but COVID-19 is causing more than six times more deaths, with over a thousand deaths a week in recent weeks. Yet, the CDC estimates that only about 19 percent of adults have gotten the latest COVID-19 vaccine booster so far, while nearly 45 percent have gotten their annual flu shot.

Califf and Marks pose the question of what can be done to reverse course, and they point to a possible solution of calling on doctors, nurses, and even pharmacists to speak up about the benefits and importance of vaccination. Clinicians who provide care remain the most trusted sources of information for health decisions, they write.

“We believe that the best way to counter the current large volume of vaccine misinformation is to dilute it with large amounts of truthful, accessible scientific evidence,” they conclude. They called on health care providers to take every chance to help people make well-informed decisions about vaccinations. “By doing so, we can both help prevent pediatric infectious diseases and dramatically reduce the harm from pathogens such as COVID-19, influenza, and respiratory syncytial virus [RSV] disease before we have another large wave of any of these vaccine-preventable illnesses.”

https://arstechnica.com/?p=1995211




Contact-tracing software could accurately gauge COVID-19 risk

A woman wearing a face mask and checking her phone.

It’s summer 2021. You rent a house in the countryside with a bunch of friends for someone’s birthday. The weather’s gorgeous that weekend, so mostly you’re all outside—pool, firepit, hammock, etc.—but you do all sleep in the same house. And then on Tuesday, you get an alert on your phone that you’ve been exposed to SARS-CoV-2, the virus that causes COVID-19. How likely are you to now have it?

To answer that question, a group of statisticians, data scientists, computer scientists, and epidemiologists in the UK analyzed 7 million people who were notified that they were exposed to COVID-19 by the NHS COVID-19 app in England and Wales between April 2021 and February 2022. They wanted to know if—and how—these app notifications correlated to actual disease transmission. Analyses like this can help ensure that an app designed for the next pathogen could retain efficacy while minimizing social and economic burdens. And it can tell us more about the dynamics of SARS-CoV-2 transmission.

Over 20 million quarantine requests

The NHS COVID-19 app was active on 13 to 18 million smartphones per day in 2021. It used Bluetooth signals to estimate the proximity between those smartphones while maintaining privacy and then alerted people who spent 15 minutes or more at a distance of 2 meters or less from a confirmed case. This led to over 20 million such alerts, each of which came with a request to quarantine—quite a burden.

The researchers found that the app did, in fact, accurately translate the duration and proximity of a COVID-19 exposure to a relevant epidemiological risk score. The app assessed a contact’s risk by multiplying the length of contact, the proximity of contact, and the infectiousness of the index case as determined by how long it had been since the index case started showing symptoms or tested positive.

There was an increasing probability of reported infection as the app’s risk score increased: more contacts whom the app deemed were at a high transmission risk did go on to test positive for COVID-19 within the following two weeks than those who were notified but had lower risk levels. (That’s positive tests that were reported by using the app. Some of the high-risk people probably did not test at all, did not report their test results, or did not report them within the allotted time. So this is an underestimation of the correlation between notification of risk and infection.)

More exposure = higher risk

When the researchers separated the factors contributing to the risk of an exposure, they found that duration was the most important indicator. Household exposures accounted for 6 percent of all contacts but 41 percent of transmissions.

One caveat: The app didn’t record any contextual variables that are known to impact transmission risk, like if people live in an urban or rural area, was the meeting indoors or outdoors, was it during the week or over the weekend, was anyone vaccinated, etc. Including such data could make risk assessment more accurate.

Based on their work, the researchers suggest that an “Amber Alert” stage could have been introduced to the app, in which people deemed to have an interim degree of risk would be guided to get a PCR test rather than immediately jumping to quarantine. Including this intermediate Amber Alert population could have significantly reduced the socioeconomic costs of contact tracing while retaining its epidemiological impact or could have increased its effectiveness for a similar cost. Performing analyses like this early on in the next pandemic to determine how it is transmitted might minimize illness and strain on society.

Nature, 2023.  DOI:  10.1038/s41586-023-06952-2

https://arstechnica.com/?p=1992331




Fall COVID shot uptake is an “abysmal” 7%; wastewater testing impaired

Fall COVID shot uptake is an “abysmal” 7%; wastewater testing impaired

More than a month since US health officials recommended updated COVID-19 vaccines for all Americans, only 7.1 percent of US adults have rolled up their sleeves for the shot and just 2.1 percent of children have been immunized.

The uptake is sluggish at best, and the current rates were dubbed “abysmal” Thursday by one immunization adviser for the Centers for Disease Control and Prevention. The CDC’s advisory panel got an update yesterday on the fall campaign to boost protection against COVID-19 ahead of the winter respiratory illness season.

The current uptake is far short of survey data from last month that indicated more than half of American adults planned to get the shots. And survey data presented yesterday to the CDC advisory committee didn’t differ dramatically from that. In a National Immunization Survey-Adult COVID Module that ran from October 8 to 14 that polled 14,715 adults, 24.6 percent said they “definitely will” get vaccinated, and an additional 30.6 percent said they “probably will.” That’s on top of the 7.1 percent who reported they were already vaccinated. The remaining 37 percent said they will definitely or probably not get vaccinated.

The disappointing vaccination rate so far may partly reflect a rocky rollout for this year’s updated shots, which were for the first time distributed on the commercial market rather than via a federal distribution system. In the earliest days of this year’s rollout, people seeking the updated shots reported encountering limited supplies, cancelled pharmacy appointments, and billing chaos. Some insurance companies were slow to update their billing codes to include the updated vaccines, leading some insured people facing erroneous $200 bills.

With those problems largely worked out, CDC Director Mandy Cohen remains hopeful that vaccination rates will increase—at least hitting last year’s disappointing rate of 17 percent.

But poor vaccination uptake is one challenge to fortifying the country against another COVID-19 wave this winter. Another is the ongoing erosion of surveillance and data reporting. With cases low, state reporting on the decline, and testing data scant, the CDC has a dramatically reduced view of SARS-CoV-2 circulation compared with previous points in the pandemic. The agency mainly relies on surveillance of emergency department visits, hospitalization admissions, and deaths to assess transmission. One other remaining surveillance system that has proven useful for signaling upcoming surges is wastewater testing—but even that has been hampered.

Offline surveillance

Politico reported Thursday that a quarter of the country’s wastewater testing sites are offline amid a contract dispute. In September, the CDC attempted to replace the Boston-based firm, Biobot, with Verily, a subsidiary of Google’s parent company, Alphabet. But Biobot filed a protest with the Government Accountability Office, halting the transition until the GAO weighs in, which it isn’t expected to do until January.

It’s unclear why exactly the CDC wanted to switch from Biobot to Verily for its wastewater surveillance needs, but costs may have played a role. Verily’s contract is for $38 million over five years, while Biobot’s was $31 million for less than a year and a half.

For now, of the 1,200 wastewater testing sites in the CDC’s nationwide network, around 400 in a “handful of states and territories” are shutdown indefinitely. And, even when they do come back online, state epidemiologists suggested to Politico that switching over to new methods and data systems might take some additional time. “It’s not as easy as just handing the keys to Verily,” one state official told the outlet.

Overall, surveillance will likely be hindered this winter, and if vaccination rates don’t pick up considerably, the population overall won’t have high levels of protection. Though previous vaccinations and infections do provide some long-lasting protection against severe disease and death, protection from infection and mild to moderate disease declines over a few months. Older people are particularly more vulnerable without a boost. Data presented to the CDC Thursday suggested that 20.5 percent of people age 75 and older have gotten a vaccine so far, and just 15.4 percent of people age 65 and older have gotten vaccinated.

Meanwhile, though the circulation of SARS-CoV-2 is relatively quiet now, a genetic analysis published this week indicates that the pandemic virus is continuing to adapt to our immune responses and is evolving significantly faster than other respiratory viruses, including influenza and other human coronaviruses.

According to the latest CDC data, around 16,000 weekly hospitalizations and 1,200 weekly deaths from COVID-19 are being reported in the US.

https://arstechnica.com/?p=1979385




Pfizer hikes price of COVID antiviral Paxlovid from $530 to nearly $1,400

A box of Paxlovid, the Pfizer antiviral drug.
Enlarge / A box of Paxlovid, the Pfizer antiviral drug.

Pfizer on Wednesday revealed that it raised the list price of a course of Paxlovid—its lifesaving antiviral drug used to reduce the risk of severe COVID-19 in those most vulnerable—to nearly $1,400, more than double the roughly $530 the US government has paid for the treatment in the emergency phase of the pandemic.

Pfizer CEO Albert Bourla had noted in an investor call at the beginning of the week that the company would increase the price of Paxlovid as it moves from government distribution to the commercial market at the end of this year. But, he did not announce the new list price then. Instead, the company revealed the more than twofold increase in a letter to pharmacies and clinics dated Wednesday. The Wall Street Journal was the first to report the list price of $1,390 after viewing the letter.

A Pfizer spokesperson told the Journal that “pricing for Paxlovid is based on the value it provides to patients, providers, and health care systems due to its important role in helping reduce COVID-19-related hospitalizations and deaths.”

A cost-effectiveness analysis last year determined the value of Paxlovid at between $563 and $906 per treatment course, according to nonprofit drug-pricing watchdog The Institute for Clinical and Economic Review.

The list price is not necessarily what people and insurers will pay for the drug. The cost will be negotiated with pharmacy benefit managers (PBMs), independent middle-managers who oversee prescription drug benefits and copays for health insurers, federal programs, and other payers. A person familiar with Pfizer’s pricing decision told the Journal that the company set the higher list price so that it can offer larger discounts and rebates to PBMs and insurers.

But these rebates and discounts, which are currently not transparent, aren’t always passed on from PBMs to insurers and other payers. Thus, they can add to the overall skyrocketing costs of health care in the US—which by far spends more on health care than any other high-income country despite having many of the worst health outcomes of any other high-income country.

For now, those covered by Medicare or Medicaid and those who are uninsured will continue to have free access to Paxlovid through 2024 via a government program. And the government and Pfizer will offer assistance programs to reduce the price for several years afterward. Without assistance, people who are uninsured would face the steeply increased list price.

Still, with assistance and rebates, doctors and other advocates say higher list prices will lead to lower use of the drug, which is already inequitably distributed globally and underused in the US, particularly in settings where it is most beneficial.

https://arstechnica.com/?p=1977187




“Church of Bleach” family gets years in prison for deadly “miracle” solution

Bottles of MMS, a bleach product sold by Genesis II Church of Health and Healing.
Enlarge / Bottles of MMS, the bleach product that Genesis II Church of Health and Healing was ordered to stop selling.

A federal judge in Miami has handed down years-long prison sentences to a Florida father and his three adult sons who were convicted in July of using a faux church to sell an industrial-strength bleaching agent as a “miracle” solution they falsely claimed could cure serious illnesses such as cancer, HIV/AIDS, and COVID-19.

Father Mark Grenon, 66—the patriarch of the so-called “Church of Bleach”—and one of his sons, Joseph Grenon, 36, were sentenced to 60 months in prison (five years). That’s the statutory maximum sentence for their conviction of conspiring to defraud the US by distributing an unapproved and misbranded drug.

Jonathan Grenon, 37, and Jordan Grenon, 29, received longer sentences of 151 months in prison (12 years and seven months), because they were convicted of contempt of court as well as conspiring to defraud the US.

Mark and Joseph Grenon were also initially charged with contempt but did not ultimately face the charges due to an extradition deal. After the US government filed charges in 2020, Mark and Joseph fled to Colombia, and the contempt charges against them were dropped as part of an agreement to extradite them back to the US.

“A Waco”

During the jury trial, federal prosecutors described the Grenons as “con men” and “snake-oil salesmen” who, in 2010, began selling their dangerous bleach product—”Miracle Mineral Solution (MMS)”— through a non-religious “church” called the Genesis II Church of Health and Healing. They sold MMS as a “sacrament” in exchange for mandatory “donations” to the church, while claiming MMS could treat serious conditions, including cancer, Alzheimer’s, diabetes, autism, malaria, hepatitis, Parkinson’s, herpes, HIV/AIDS, and COVID-19.

Prosecutors said the family sold tens of thousands of bottles of MMS, making more than $1 million over the years.

MMS is consumed as chlorine dioxide, a powerful bleaching agent that can cause severe vomiting, diarrhea, and life-threatening low blood pressure. The Food and Drug Administration, which warned consumers of the product in 2019, received reports of people requiring hospitalizations, developing life-threatening conditions, and even dying after drinking MMS, according to prosecutors.

When federal authorities first filed charges against the Grenons in 2020, the Grenons sent letters threatening a federal judge and warned they would “pick up guns” and stage “a Waco.”

Grenons speak

Throughout the trial, the Grenons represented themselves but did not speak in their defense, seemingly as a form of protest. They had court-appointed defense attorneys who stood by during the trial, but the Grenons did not allow them to speak for them.

In July, it took a Miami jury just 30 minutes to return the guilty verdicts for the four men, according to the Miami Herald.

The Herald reported that the men broke their silence during sentencing last week to plead for mercy and protest their prison terms.

Father Mark Grenon reportedly argued to the judge that he was a victim in the case and that his three years in custody so far amounted to “kidnapping.” As such, he said the US government owed him compensation of $5.76 million for being “held unlawfully.”

He apparently put the deal to the judge, asking “yes or no?” US District Judge Cecilia Altonaga called it a “nonsensical question,” and said, “I won’t answer that.”

The three sons, meanwhile, said they did not “consent” to the judicial proceedings and claimed their time in custody was already enough.

“I have lost everything,” Jonathan Grenon told the court, noting that he was married with five sons. “I believe I should be released to my family.”

The Grenons had previously stated that they plan to appeal their convictions.

https://arstechnica.com/?p=1974517




After being demoted and forced to retire, mRNA researcher wins Nobel

Katalin Karikó and Drew Weissman.
Enlarge / Katalin Karikó and Drew Weissman.

Biochemist Katalin Karikó and immunologist Drew Weissman won the Nobel Prize in Physiology or Medicine Monday for their foundational research showing that chemical modifications to the molecular building blocks of messenger RNA (mRNA) could enable its use for therapeutics and vaccines—a realization crucial to the rapid development of the life-saving mRNA COVID-19 vaccines during the deadly pandemic.

The pair’s prize-winning and tenacious work on different types of RNA culminated in a 2005 breakthrough study showing that chemical modifications of mRNA bases (nucleosides)—adenine (A), cytosine (C), uracil (U), and guanine (G)—could keep them from igniting innate immune responses and inflammation reactions, which had foiled previous efforts to use mRNA for therapeutics.

In our cells, mRNA is an intermediate molecule, a single-stranded copy of coding from the genes in our DNA blueprints that is then translated into functional proteins. (DNA uses bases A, C, G, and thymine (T), which is structurally similar to RNA’s U.) The mRNA is copied (aka transcribed) from DNA in a cell’s nucleus and then moves to the cytoplasm for its code-deciphering translation into proteins. Thus, mRNA is critical for protein production and is more accessible than DNA—features that made it an appealing target for developing therapeutics.

But, mRNA is considered unstable compared to DNA, and early work using synthetic strands of mRNA found it sparked inflammatory responses and led to only low levels of target proteins. This is where Karikó and Weissman’s work came in.

mRNA toiling

Karikó had long been interested in using mRNA for therapies. After receiving her PhD at Hungary’s Szeged University in 1982, Karikó did two post-doctoral research stints in the US before landing a tenure-track professor position at the University of Pennsylvania in 1989. There, she began experimenting with different types of RNA but with little success. She could not win scientific grants to fund her work and, in 1995, after years of toiling, her bosses at UPenn gave her the choice of either leaving or getting demoted. She chose the demotion.

In 1997, Weissman joined UPenn and, with his funding, the two began collaborating on mRNA research. Weissman, an immunologist, was interested in developing a vaccine against HIV and had been focusing on priming immune responses with dendritic cells—an immune cell with the main function of presenting bits of foreign substances (antigens) to T cells to train immune responses against those antigens.

Together, the two realized that synthetic (un-modified) mRNA triggered the dendritic cells to activate inflammatory responses. The finding led them down the path of realizing that RNA in mammalian cells was frequently chemically modified, while DNA and RNA from bacteria and viruses were frequently unmodified. Around the same time, other researchers found evidence that some key proteins that regulate inflammation—toll-like receptors (TLRs)—specifically detect modifications on DNA and RNA to trigger inflammation responses. TLRs are known for recognizing molecular patterns that uniquely identify pathogens.

In their breakthrough 2005 paper, Karikó and Weissman showed that synthetic RNA activates several TLRs, leading to inflammation responses. And, crucially, adding modifications to the bases in the synthetic mRNA—specifically, pseudouridine (Ψ), 5-methylcytidine (m5C), N6-methyladenosine (m6A), 5-methyluridine (m5U) or 2-thiouridine (s2U)—suppressed the inflammation responses. They subsequently showed the modifications could also improve protein production.

Kicked off and kicked out

The finding kicked off the field of mRNA therapeutics and spurred the formation of both Moderna and BioNTech, the two companies that would go on to develop lifesaving mRNA vaccines against COVID-19. Today, m1 Ψ is the most common modified base used in mRNA vaccine production and is present in Moderna and Pfizer-BioNTech’s vaccines.

However, the finding received little fanfare among much of the scientific community at the time, and Karikó’s research and contribution continued to go largely unappreciated before the pandemic. In 2013, Karikó said she was forced to leave UPenn.

“Ten years ago, I was here in October, because I was kicked out from Penn, was forced to retire,” she said in an early morning interview Monday with the Nobel Assembly. She went on to work with BioNTech, doing hands-on benchwork. She became vice president and later senior vice president there. Since 2021, she went back to being a professor, working at Szeged University and as adjunct faculty at UPenn.

Weissman is also still at UPenn, as the Roberts Family professor in vaccine research and director of the Penn Institute for RNA Innovations.

https://arstechnica.com/?p=1972598