Coronavirus Updates April 2023

[missy]

And here we are...in April of 2023 and still in a pandemic situation. I keep hoping one day (soon) this thread won't be necessary.

Some highlights

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DNA samples from Wuhan's Huanan Seafood Marketopens in a new tab or window during the early stages of the COVID-19 outbreak provide no definitive answers to how the virus jumped to humans, according to a Chinese study published in Nature.

Users of liver drug ursodeoxycholic acidopens in a new tab or window were less susceptible to SARS-CoV-2 infection and severe COVID-19 illness. (Journal of Internal Medicine)

The prevalence of sleep problems among long COVID patientsopens in a new tab or window was an estimated 41% at the Cleveland Clinic. (Journal of General Internal Medicine)

The Biden administration summarized its efforts to fight long COVIDopens in a new tab or window in the last year.

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Prepping for Next Winter, Experts Worry About Vaccine Hesitancy​

— FDA official is over mandates, focus should now be on "those who want to have their lives saved"​

by Shannon Firth, Washington Correspondent, MedPage Today April 5, 2023

WASHINGTON -- Leading government scientists and industry experts spoke here on Tuesday about the next COVID vaccine, rising vaccine hesitancy, and what the shots of the future might look like.
Choosing a vaccine for next winter is going to be a challenge, said Peter Marks, MD, PhD, director for the FDA's Center for Biologics Evaluation and Research (CBER), in comments at the World Vaccine Congressopens in a new tab or window.

What's important, "first and foremost," is the vaccine's breadth, and second is its duration, he said. "I think people will get an annual vaccine if they think it's going to protect them broadly. Where we get into problems is when something is a mismatch and we don't have good protection."
It takes 2 to 3 months to manufacture mRNA vaccines. Which means the vaccine's composition will need to be decided sometime around June, Marks explained. Given that tight timeline, he said he doesn't expect the next shot to be "too different" from what's currently available.
Paul Burton, MD, PhD, chief medical officer for Moderna, said every effort should be made to match the vaccine to the virus "as closely as we can, but not let perfection be the enemy of the very good."
Marks said he's hopeful that the next vaccine will protect against severe disease and hospitalization, as it has in the past.

"In the event that the unthinkable happens, which is that some bizarre new reassortment [genetic recombination] occurs with SARS-Coronavirus-2, we'll be looking to the mRNA manufacturers to make something as fast as possible," Marks added.
Burton noted that RNA technology allows a manufacturer the "speed" and "agility" to "step in when things go awry."
As for the ideal vaccine of the future, it would be "nice someday to have a sterilizing vaccine or one that prevents transmission, but I'm not going to hold my breath, because I might become very blue," Marks said.
People have been looking to produce a vaccine to prevent influenza transmission for the last 10 years, and "we still don't have that one," he added.
'Erosion of Confidence in Vaccination'
The CBER director and the other panelists also spoke about what Marks called the "greatest catastrophe" of the pandemic: "the erosion of confidence in vaccination as a major public health tool."

Vaccine hesitancy, instead of waning with the pandemic, appears to be crossing over to other illnesses.
Penny Heaton, MD, Global Therapeutic Area Head for Vaccines at Janssen Pharmaceutical, a subsidiary of Johnson & Johnson, pointed to 2022-2023 flu vaccine dataopens in a new tab or window which show that older adults are returning to pre-pandemic rates of flu vaccination, but for pregnant womenopens in a new tab or window and young children, "rates have dropped dramatically."
One issue is trust. She recalled a 2021 studyopens in a new tab or window that found that the countries with the highest rates of COVID vaccine uptake and the lowest number of deaths were places where the citizens had the most trust in their government.
Gregory Poland, MD, director of the Mayo Clinic's Vaccine Research Group in Rochester, Minnesota and the panel's moderator, also highlighted research out of Denmark, which has the highest uptake of COVID-19 vaccinesopens in a new tab or window and also the highest trust in government.
When Danes were interviewed about vaccination, Poland said, "the response generally was, 'Well, if the government recommends it, why wouldn't we do it?' Which you can hardly imagine here in the U.S."

"But that is a process of decades of trust-building, which can be destroyed within minutes and was in the U.S.," he added.
Burton also commented on the degree of vaccine hesitancy in the U.S., noting that there are grand juriesopens in a new tab or window being established to investigate "the wrongdoings of vaccination."
And, Poland said, in parts of Utah, Idaho, and Florida, residents are trying to make it a misdemeanor for any pharmacist, nurse, or physician to administer a COVID vaccine.
"Right now, there are 88 bills in front of the local and state legislatures to roll back or outlaw any sort of mandate for any kind of vaccine under any condition," Poland added.
That kind of opposition seems unreal to Burton: "Three years ago, the number of deaths in this country was equivalent to 10 jumbo jets falling out of the sky every day and killing everyone -- three and a half thousand people," he said.

Even now, there are still too many people dying of the virus -- at around 350 a day, Burton said.
"I can't honestly believe that we are where we are," he added.
Rebuilding trust in a country as polarized as the U.S. is difficult, Heaton said, but, "I think that's where we have to start ... We have to roll up our sleeves and figure out how the people in these different groups make decisions," she said, speaking of different demographics -- urban areas versus rural, and people of different races and ethnicities.
"There aren't any easy answers," she added.
However, said Burton, loosely quoting Ashish Jha, MD, PhD, who said at a recent meeting of the Massachusetts Medical Society, "Healthcare providers, it really is time to pass that baton back from government agencies back to us as healthcare providers, to step up, step in, and get that trust back."

As for mandates, Marks said that while the U.S. needs a "reset," that isn't a solution.
"I'm past trying to argue with people who think vaccines are bad. I think we just have to take our case that 'This is something that can save your life,' to those who want to have their lives saved."
Isabel Oliver, MD, chief scientific advisor transition lead for the U.K. Health Security Agency, called the loss of trust in vaccines in the U.S. "an absolute tragedy."
While the same cannot be said of the United Kingdom -- booster uptake there has been over 65% -- it is important for countries to "work together," she said. "What happens in the U.S. will end up affecting the U.K. and other parts of the world."
The Next Vaccines
With regard to the next generation of vaccines, Burton spoke about a partnership between Moderna and Vertex focused on aerosolizing mRNA vaccines to treat cystic fibrosis.

Moderna is also working on a personalized cancer vaccine platform and plans to present its data at the American Association for Cancer Researchopens in a new tab or window annual meeting in mid-April.
Meanwhile, Heaton is excited about the potential for artificial intelligence and machine learning to "better understand the antigens that need to be included" in vaccines.
In addition, Janssen is "looking at things like circular RNAopens in a new tab or window, where we can really start to engineer the duration of antigen expression more precisely, where we can even better fine-tune the immune response ... and include the type of immune response that we want," she said.
Heaton said she's also interested in moving beyond lipid nanoparticles to other methods of delivery that may be "potentially less reactogenic, potentially more immunogenic, potentially actually direct[ing] the exact immune response that we want."

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[missy]

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Researchers discover key pathway for COVID organ damage in adults
Published April 6, 2023 | Originally published on MedicalXpress Breaking News-and-Events

Even after three years since the emergence of COVID-19, much remains unknown about how it causes severe disease, including the widespread organ damage beyond just the lungs. Increasingly, scientists are learning that organ dysfunction results from damage to the blood vessels, but why the virus causes this damage is unclear. Now a multidisciplinary team of Emory researchers has discovered what they believe is the key molecular pathway.

Results of their study, published today in Nature Communications, show that COVID-19 damages the cells lining the smallest blood vessels, choking off blood flow. These results could pave the way for new treatments to save lives at a time when hundreds of people are still dying from COVID-19 each day.

Doctors at Emory Healthcare started this study in the early days of the pandemic, to better understand drivers of severe COVID-19, and why adults develop severe disease more often than children. They used a so-called "multi-omics" approach, studying multiple data sets at once, to examine the biochemistry of blood from COVID patients and compared it to non-COVID patients, looking for clues.

"We were surprised by the little overlap between our adult and pediatric patients," says Cheryl Maier, MD, Ph.D., assistant professor in the Department of Pathology and Laboratory Medicine, Emory University School of Medicine, and the study's senior author. "Both groups had abnormalities related to clotting, but one unique pathway that stood out in the adults was related to vessel health and blood flow."

Maier says this finding was particularly interesting given their clinical observations that blood from patients severely ill with COVID-19 was unusually viscous: think maple syrup rather than water.

Maier worked with collaborator and co-senior author Wilbur Lam, professor in the Department of Pediatrics at Emory University and in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, to create cutting-edge models of the smallest blood vessels, expected to be the most sensitive to altered blood flow, which allowed them to visualize how blood from COVID-19 patients versus other patients might be flowing in the human body.

"Watching videos from these microfluidic devices is like seeing how COVID-19 might be affecting our blood vessels in real time," Maier says. "These lab-made blood vessels are lined with real human vascular cells, called endothelial cells. You can put in plasma and red cells, any of the key components of blood and in different combinations, to watch how it behaves and see how the damage happens."

Fibrinogen: A key culprit?

Since the earliest days of the pandemic, physicians have seen that a blood protein called fibrinogen was extremely elevated in patients with severe COVID-19. This protein is often elevated in other acute illnesses, but the elevations seen in the sickest COVID-19 were much higher. The body forms blood clots in part by cutting fibrinogen to form fibrin, a key component of clots, but fibrinogen itself is not thought to form clots and levels are not affected by anticlotting medications.

But the Emory researchers found that in COVID-19 patients, the sky-high levels of fibrinogen cause red blood cells to clump together, altering blood flow and directly damaging the endothelial glycocalyx, a gelatinous protective layer lining the microvessels. "Fibrinogen is one of the top three most abundant proteins in plasma," Maier says. "It's been hiding in plain sight."

When the researchers combined plasma from COVID-19 patients with red blood cells in lab-made blood vessels, they could visualize the cellular aggregation and quantify the destruction of the endothelial cell glycocalyx. "You have these large clusters of red cells that are all stuck together," Maier says. "Normally this wouldn't happen. Capillaries are so narrow that red blood cells must pass through single file. But in COVID, these aggregates stick together even under flow. It's easy to imagine how this mechanically damages the microvasculature."

Much of the new technology was developed by study co-first author Elizabeth Iffrig, MD, PHD, a critical care fellow in Emory's Department of Medicine. "The foundation of what we did was looking at how red blood cells would form these big globules that would gunk up the microvascular system," Iffrig says.

"Our methodology let us look at this in a dynamic process, seeing what happens to these aggregates as we mimic a true physiologic state of blood flow instead of just suspending them in a fluid and measuring how big they are. The methodology allowed us to quantify all those things simultaneously."

Taken together, these data suggest to Maier that the fibrinogen-induced red blood cell aggregation and resulting microvascular damage could be the major pathway by which COVID causes organ damage and even death.

There's presently no medications targeting high fibrinogen in the blood. However the team has done exploratory research using therapeutic plasma exchange: removing plasma with high fibrinogen from COVID-19 patients and replacing it with donor plasma that has normal fibrinogen levels. Maier thinks her team's discovery is critical because it provides a target that might help save lives.

This article was originally published on MedicalXpress Breaking News-and-Events.


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[missy]

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Yes, COVID Is Still Deadlier Than the Flu​

— VA study finds 61% higher mortality rate in hospitalized cases this past winter​

by Ian Ingram, Managing Editor, MedPage Today April 7, 2023

Hospitalizations from COVID-19 during the most recent flu season remained significantly more deadly than those resulting from influenza, but the gap appears to have narrowed substantially since earlier in the pandemic, according to findings from Veterans Affairs' (VA) databases.
Examining over 11,000 hospitalizations due to either of the two infections during this past fall and winter, 5.97% of the COVID-19 patients died within 30 days of admission versus 3.75% of the flu patients, reported Ziyad Al-Aly, MD, of VA St. Louis Health Care System in Missouri, and colleagues.

In a propensity score-matched analysis accounting for age, sex, prior infection, and a host of other factors, this difference translated to a 61% higher risk for death in the group with COVID (HR 1.61, 95% CI 1.29-2.02), the authors detailed in a research letter published in JAMAopens in a new tab or window.
Furthermore, COVID-19 made up the bulk of the hospitalizations during the study period (8,996 vs 2,403 from the flu), resulting in over seven times more patient deaths (538 vs 76).
"However, the difference in mortality rates between COVID-19 and influenza appears to have decreased since early in the pandemic," said Al-Aly and co-authors.
In 2020, mortality rates for hospitalized COVID patients ranged from 17%opens in a new tab or window to 21%opens in a new tab or windowdepending on the study, roughly three times greater than the 6% rate in the current study, the authors noted. For flu hospitalizations, death rates were virtually the same (3.8% in 2020).
"The decline in death rates among people hospitalized for COVID-19 may be due to changes in SARS-CoV-2 variants, increased immunity levels (from vaccination and prior infection), and improved clinical care," the group suggested.

Except for individuals 65 and younger, where death rates at 30 days were nearly identical between COVID and flu patients (1.29% vs 1.33%), all other groups had a higher rate of death after COVID.

Increased risk of death versus the flu was greatest among individuals unvaccinated against COVID (8.75% vs 3.86%; HR 2.32, 95% CI 1.80-3.00), and risk significantly decreased with the number of COVID-19 vaccinations, "findings that highlight the importance of vaccination in reducing risk of COVID-19 death," wrote Al-Aly and colleagues.

People with COVID were also at higher risk of death versus the flu if they were over 65 or received no outpatient treatment -- e.g., nirmatrelvir-ritonavir (Paxlovid), molnupiravir (Lagevrio), or remdesivir (Veklury).

For their study, Al-Aly's team used electronic health databases from the VA, enrolling all individuals hospitalized from October 2022 to January 2023 with an admission diagnosis for COVID-19 or influenza, along with a positive test 2 days before or up to 10 days after admission. Individuals with dual infections were excluded.



After propensity weighting, patients had an average age of 73 years, 71% were white, 23% were Black, and 95% were men. Average body mass index was 28, and mean estimated glomerular filtration rate was 64-65. About one in five had previously had COVID, and about 63% were current or former smokers.

For vaccination history, a little less than two-thirds had received the flu vaccine and three-fourths received at least two doses of COVID vaccine, with 55% having received a booster as well.

Only 2% of the hospitalized COVID-19 cases had received antivirals in the outpatient setting, while 24% received remdesivir during inpatient care. In the cases of influenza, oseltamivir was administered to 6% in the outpatient setting and to 82% during hospitalization.

Limitations cited by the study authors included the common one seen with most VA studies (an older, predominantly male population), along with the fact that the results may not reflect the risk differences for non-hospitalized cases. Also, causes of death were not analyzed and residual confounding may have occurred.

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  Ian Ingram is Managing Editor at MedPage Today and helps cover oncology for the site.
  
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[missy]

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Researchers reveal why viruses like SARS-CoV-2 can reinfect hosts, evade the immune response
Published April 7, 2023 | Originally published on MedicalXpress Breaking News-and-Events


The human body is capable of creating a vast, diverse repertoire of antibodies—the Y-shaped sniffer dogs of the immune system that can find and flag foreign invaders. Despite our ability to create a range of antibodies to target viruses, humans create antibodies that target the same viral regions again and again, according to a new study led by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, and Harvard Medical School. These "public epitopes" mean that the generation of new antibodies is far from random and that a virus may be able to mutate a single amino acid to reinfect a population of previously immune hosts. The team's findings, which have implications for our understanding of immunity and public health, are published in Science.

"Our research may help explain a lot of the patterns we've seen during the COVID-19 pandemic, especially in terms of re-infection," said corresponding author Stephen J. Elledge, Ph.D., the Gregor Mendel Professor of Genetics at the Brigham and HMS. "Our findings could help inform immune predictions and may change the way people think about immune strategies."

Before the team's study, there were hints, but no clear evidence, that people's immune systems didn't target sites on a viral protein at random. In isolated examples, investigators had seen recurrent antibody responses across individuals—people recreating antibodies to home in on the same viral protein location (known as an epitope). But the study by Elledge and colleagues helps explain the extent and underlying mechanisms of this phenomenon.

The team used a tool the Elledge lab developed in 2015 called VirScan, which can detect thousands of viral epitopes—sites on viruses that antibodies recognize and bind to—and give a snapshot of a person's immunological history from a single drop of blood. For the new study, the researchers used VirScan to analyze 569 blood samples from participants in the U.S., Peru, and France. They found that recognition of public epitopes—viral regions recurrently targeted by antibodies—was a general feature of the human antibody response. The team mapped 376 of these commonly targeted epitopes, uncovering exactly where antibodies bind their targets. The team found that antibodies recognized public epitopes through germline-encoded amino acid binding (GRAB) motifs—regions of the antibodies that are particularly good at picking out one specific amino acid. So, instead of randomly choosing a target, human antibodies tend to focus on regions where these amino acids are available for binding, and thus repeatedly bind the same spots.

A small number of mutations can help a virus avoid detection by these shared antibodies, allowing the virus to reinfect populations that were previously immune.

"We find an underlying architecture in the immune system that causes people, no matter where in the world they live, to make essentially the same antibodies that give the virus a very small number of targets to evade in order to reinfect people and continue to expand and further evolve," said lead author Ellen L. Shrock, Ph.D., of the Elledge lab.

Interestingly, the team notes that nonhuman species produce antibodies that recognize different public epitopes from those that humans recognize. And, while it is more likely for a person to produce antibodies against a public epitope, some people do produce rarer antibodies, which may more effectively protect them from reinfection. These insights could have important implications for treatments developed against COVID-19, such as monoclonal antibodies, as well as for vaccine design.

"The more unique antibodies may be a lot harder to evade, which is important to consider as we think about the design of better therapies and vaccines," said Elledge.

This article was originally published on MedicalXpress Breaking News-and-Events.

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[missy]

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Keeping COVID-19 in check will likely require periodic boosters
Published April 4, 2023 | Originally published on MedicalXpress Breaking News-and-Events


Between natural infection and a global vaccination campaign, most people now have some immunity against the virus that causes COVID-19. This widespread immunity hasn't stopped people from getting infected, but it has dampened the massive waves of illness and death that roiled the globe in the early years of the pandemic. Keeping the virus in check requires maintaining this level of immunity, a difficult task because the virus is constantly spinning off new variants that can partially evade antibodies elicited by vaccines and prior infections.

New research from scientists at Washington University School of Medicine in St. Louis suggests that updated booster shots will be important for shoring up population immunity as new variants emerge—but there's a caveat.

Their research, published April 3 in Nature, shows that vaccinating people against the original strain of the virus and then boosting with a shot that targets a new variant can elicit a broad antibody response capable of neutralizing a wide array of variants, including ones that have not yet emerged. The trick is to target a variant for the booster that is so different from the original strain of the virus that it triggers the maturation of new and diverse antibody-producing cells.

"The challenge with COVID-19 is that the virus keeps mutating," said senior author Ali Ellebedy, Ph.D., an associate professor of pathology & immunology, of medicine, and of molecular microbiology. "It's not that the vaccines don't elicit a lasting antibody response. They do. The problem is that the virus changes and the existing antibodies become irrelevant. Here we showed that it's possible to design a variant-specific booster that doesn't just strengthen the antibodies people already have but elicits new antibodies. This means that periodically giving boosters targeting new variants would allow population-level protection to be maintained even as the virus evolves."

The first COVID-19 vaccines reduced the risk of severe illness and death by more than 90%. But then the virus changed. The antibodies that had worked so well against the original strain proved less effective at recognizing and neutralizing emerging variants, leading to breakthrough infections. The obvious solution was to update the vaccines to target new variants, but the success of the first vaccines against the original strain made designing an effective variant booster shot tricky, Ellebedy said.

"The whole point of making boosters against new variants is to teach the immune system to recognize features in the new variants that are different from the original strain," Ellebedy said. "But the new variants still share a lot of features with the original strain, and it's possible that the response to these shared features could dominate the response to new features. The boosters could end up just engaging immune memory cells that are already present rather than creating new memory cells, which is what we need for protection against new variants."

To gauge the effectiveness of boosters at eliciting new antibodies, Ellebedy and colleagues studied people who received a COVID-19 vaccine targeted against the original strain, followed by a combined booster targeting two of the early variants—beta and delta—or a booster targeting the newer omicron variant. Along with Ellebedy, the research team included co-corresponding author Jackson Turner, Ph.D., an instructor in pathology & immunology, and co-first authors Wafaa B. Alsoussi, a graduate student, and Sameer Kumar Malladi, Ph.D., a postdoctoral researcher, both in Ellebedy's lab.

The first studies were discouraging, Ellebedy noted. The researchers looked at 39 people who had received the two-shot primary sequence of the Pfizer/BioNTech or Moderna COVID-19 vaccines, followed by an experimental booster shot targeting the beta and delta variants. All participants produced antibodies that neutralized the original virus strain and the beta and delta variants. But none of the antibodies studied were unique to beta or delta. The absence of such antibodies indicates that the variant booster had failed to trigger the development of detectable new antibody-producing cells, Ellebedy said.

"This was disappointing but not surprising," said Ellebedy, who is also an expert on influenza vaccines. "If you look at the sequences for the beta and delta spike proteins, they are not really very different from the original strain. If we saw this degree of difference among influenza strains, we would say there's no reason to update the annual vaccine. But the omicron variant is a different matter."

The omicron variant, dominant worldwide since late 2021, carries dozens of new mutations relative to the original strain of the virus. Ellebedy and colleagues recruited eight people who had received the Pfizer/BioNTech or Moderna COVID-19 vaccine and gave them a booster targeted against the omicron variant alone. The CDC later recommended the use of updated boosters that target both the omicron variant and the original strain. Such bivalent boosters became available to the public in fall 2022, manufactured by both Pfizer/BioNTech and Moderna.

Studying blood samples provided by participants four months after their boosters, the researchers identified more than 300 distinct antibodies capable of neutralizing the original strain, or one or more of the variants. Of those, six neutralized omicron but not the original strain, an indication that the booster successfully triggered the creation of new antibodies optimized for omicron. One such new antibody even neutralized BA.5, a subvariant of omicron that is circulating widely now but had not yet emerged at the time the booster was made.

"This booster engaged naive B cells and created new memory cells, which means it expanded people's immune repertoire and equipped them to respond to a greater diversity of variants," Ellebedy said. "Designing boosters to maintain immunity to the evolving virus is not going to be easy. The extent of the difference between the old and the new variants is clearly important. But if we are careful about how we choose which variants to include in boosters, I think we can stay ahead of this virus."

More information: SARS-CoV-2 Omicron boosting induces de novo B cell response in humans., Nature (2023). DOI: 10.1038/s41586-019-0000-0. www.nature.com/articles/s41586-023-06025-4

This article was originally published on MedicalXpress Breaking News-and-Events.

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[missy]

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New study shows SARS-CoV-2 infection accelerates the progression of dementia
Published April 5, 2023 | Originally published on MedicalXpress Breaking News-and-Events


Infection with SARS-CoV-2 has a significant impact on cognitive function in patients with preexisting dementia, according to new research published in the Journal of Alzheimer's Disease Reports. Patients with all subtypes of dementia included in the study experienced rapidly progressive dementia following infection with SARS-CoV-2.

Since the first wave of COVID-19, neurologists have noticed both acute and long-term neurological syndromes and neuropsychiatric sequelae of this infectious disease. Insights into the impact of COVID-19 on human cognition has so far remained unclear, with neurologists referring to "brain fog."

A group of researchers driven to gain a better understanding of and dissipate this fog investigated the effects of COVID-19 on cognitive impairment in 14 patients with preexisting dementia (four with Alzheimer's disease [AD], five with vascular dementia, three with Parkinson's disease dementia, and two with the behavioral variant of frontotemporal dementia), who had suffered further cognitive deterioration following COVID-19.

Lead investigators Souvik Dubey, MD, DM, from the Department of Neuromedicine, Bangur Institute of Neurosciences (BIN), Kolkata, West Bengal, India, and Julián Benito-León, MD, Ph.D., from the Department of Neurology, University Hospital "12 de Octubre," Madrid, Spain, explained, "We speculated there must have been some deleterious effect of COVID-19 in patients with preexisting dementia extrapolating our understanding from the cognitive impact of this viral infection in patients without dementia. However, post-COVID-19 evaluation of cognitive impairments in patients with preexisting dementia is difficult due to multiple confounders and biases."

In addition to finding that that all subtypes of dementia, irrespective of patients' previous dementia types, behaved like rapidly progressive dementia following COVID-19, the team of investigators found that the line of demarcation between different types of dementia became remarkably blurry post-COVID-19.

Co-investigator Ritwik Ghosh, MD, Department of General Medicine, Burdwan Medical College and Hospital, Burdwan, West Bengal, India, expressed his concern about dementia subtyping. "It is more difficult in the post-COVID-19 era, where the history of this viral infection plays the most important role. Few patients with a history of COVID-19 without preexisting dementia have phenotypically and imaging-wise similar brain changes mimicking other degenerative and vascular dementias."

Researchers also found that the characteristics of a particular type of dementia changed following COVID-19, and both degenerative and vascular dementias started behaving like mixed dementia both clinically and radiologically. A rapidly and aggressively deteriorating course was observed in patients having insidious onset, slowly progressive dementia, and who were previously cognitively stable.

Cortical atrophy was also evident in the study's subsequent follow-ups. Coagulopathy involving small vessels and inflammation, which were further correlated with white matter intensity changes in the brain, was considered the most important pathogenetic indicator.

The rapid progression of dementia, the addition of further impairments/deterioration of cognitive abilities, and the increase or new appearance of white matter lesions suggest that previously compromised brains have little defense to withstand a new insult (i.e., a "second hit" like infection/dysregulated immune response and inflammation).

According to Dr. Dubey and his co-investigators, "'Brain fog' is an ambiguous terminology without specific attribution to the spectrum of post-COVID-19 cognitive sequelae. Based on the progression of cognitive deficits and the association with white matter intensity changes, we propose a new term: 'FADE-IN MEMORY' (i.e., Fatigue, decreased Fluency, Attention deficit, Depression, Executive dysfunction, slowed INformation processing speed, and subcortical MEMORY impairment)."

Co-investigator Mahua Jana Dubey, MD, Department of Psychiatry, Berhampur Mental Hospital, Berhampur, West Bengal, India, added, "Amidst various psychosocial impacts of COVID-19, cognitive deficits, when accompanied by depression and/or apathy and fatigue in patients with or without preexisting dementia, require meticulous evaluation because it imposes added stress and burden on caregivers, one of the most important but often forgotten issues that may have the potential to hamper treatment."

"As the aging population and dementia are increasing globally, we believe pattern recognition of COVID-19-associated cognitive deficits is urgently needed to distinguish between COVID-19-associated cognitive impairments per se and other types of dementia. This understanding will have a definitive impact on future dementia research," Dr. Souvik Dubey concluded.

"Increasing epidemiological evidence of the association of COVID-19 and AD is the heightened risk of AD with COVID-19, and of increased COVID-19 in patients with AD points to shared pathogenesis. Dubey et al further clarify this connection in demonstrating COVID-19 fundamentally alters the course of dementia no matter the cause," remarked George Perry, Ph.D., Editor-in-Chief, Journal of Alzheimer's Disease, and Semmes Distinguished University Chair in Neurobiology at The University of Texas at San Antonio.

This article was originally published on MedicalXpress Breaking News-and-Events.

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[missy]

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Long COVID Hitting Some States, Minorities, Women Harder​

Lisa Rapaport
April 10, 2023


More than 3 years into the COVID-19 pandemic, lasting symptoms are becoming quite common, with residents of certain states, women, Hispanic people, and transgender people more at risk, a new report shows.
More than one in four adults sickened by the virus go on to have long COVID, according to a new report from the U.S. Census Bureau. Overall, nearly 15% of all American adults — more than 38 million people nationwide — have had long COVID at some point since the start of the pandemic, according to the report.
The report, based on survey data collected between March 1 and 13, defines long COVID as symptoms lasting at least 3 months that people didn't have before getting infected with the virus.

It is the second recent look at who is most likely to face long COVID. A similar study, published last month, found that women, smokers, and those who had severe COVID-19 infections are most likely to have the disorder

The Census Bureau report found that while 27% of adults nationwide have had long COVID after getting infected with the virus, the condition has impacted some states more than others. The proportion of residents hit with long COVID ranged from a low of 18.8% in New Jersey to a high of 40.7% in West Virginia.

Other states with long COVID rates well below the national average include Alaska, Maryland, New York, and Wisconsin. At the other end of the spectrum, the states with rates well above the national average include Kentucky, Mississippi, New Mexico, Nevada, South Carolina, South Dakota, and Wyoming.

Long COVID rates also varied by age, gender, and race. People in their 50s were most at risk, with about 31% of those infected by the virus going on to have long COVID, followed by those in their 40s, at more than 29%.


Far more women (almost 33%) than men (21%) with COVID infections got long COVID. And when researchers looked at long COVID rates based on gender identity, they found that transgender adults were more than twice as likely to have long COVID than cisgender males. Bisexual adults also had much higher long COVID rates than straight, gay, or lesbian people.

Long COVID was also much more common among Hispanic adults, affecting almost 29% of those infected with the virus, than among White or Black people, who had long COVID rates similar to the national average of 27%. Asian adults had lower long COVID rates than the national average, at less than 20%.

People with disabilities were also at higher risk, with long COVID rates of almost 47%, compared with 24% among adults without disabilities.

Sources:


U.S. Census Bureau: "U.S. Adult Population Grew Faster Than Nation's Total Population From 2010 to 2020."


CDC: "Long COVID."

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[missy]

Catch-up quick: COVID-19​

KATELYN JETELINA APR 18

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Surveillance​

SARS-CoV-2 continues to decline after a small Spring Break bump. Wastewater levels are the lowest they’ve been in over a year! Hospitalizations and deaths continue to decline as well, but we are still losing 1,300 people per week.

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SARS-CoV-2 Wastewater U.S., over time. Source here.
As expected, COVID-19 continues to mutate. Interestingly, scientists are finding that mutations not on the spike protein are becoming more and more influential in the virus’s ability to continue to spread.

XBB.1.16 (which social media has deemed “Arcturus”) has created a huge wave in India, which is finally peaking. But this isn’t necessarily what will happen elsewhere. The last wave in India was nine months ago; there were a lot of susceptible people. In the U.S., XBB.1.16 accounts for 7% of cases. If growth continues, this could create a bump in transmission in weeks to come, but we do not expect a tsunami.

Another up-and-coming Omicron subvariant could provide competition—XBC.1.6. This is a recombination of Delta and Omicron first detected in Southern Australia. It has since caused a wave of cases and hospitalizations there. This may be also one to follow.

​

Noteworthy pieces of COVID-19 news​

• Operation Next Gen. The Biden administration announced Operation Next Gen— an allocation of $5 billion dollars to speed up the testing and development of second-generation COVID-19 vaccines and therapies. This is a much needed investment, as a pan-coronavirus or mucosal vaccine could be a game changer. Unfortunately, they are incredibly challenging to make.
• Spring boosters. The FDA has been very quiet on this end. Word on the street is they’re deciding on a spring policy and a few other decisions for the future of COVID-19 vaccines (instead of waiting for fall). This would make sense given that ACIP has scheduled a meeting for tomorrow. I’ll be back with Cliff notes if anything noteworthy happens.
• End of the emergency. The National Emergency ended last week, which was the first of five “buckets” of pandemic provisions ending. It mainly had implications for Medicaid eligibility. KFF found that adults impacted are most concentrated in Texas (41%), followed by Florida (20%), and Georgia (13%). Next month, the Public Health Emergency ends, which will mean quite a lot.

​

Interesting science updates​

• SARS-CoV-2 is mutating to escape Paxlovid. Scientists have found instances in which SARS-CoV-2 mutated to resist Paxlovid protection. These mutations have not taken off, but it’s a concerning sign. It would really hurt if we lost Paxlovid as a tool.
• Where you live matters. Not all states struggled equally in the pandemic. In fact, a Lancet study found a 4-fold difference in deaths between states, even after adjusting for age and key health conditions. Arizona had the highest rate.
  

  ​

  Cumulative COVID-19 infection and death rates by US state. Figure from: Bollyky et al., Lancet.
• Half of COVID-19 symptomatic healthcare workers went to work sick. Given that masks are dropping at hospitals, this may be a bad sign for hospital-acquired COVID-19 infections, which are increasing and already have a high mortality rate (~10.6%). (Note: This rate of going to work while sick is about the same for flu.)
• U.K.’s bet on vaccine timing worked. The U.K. saved ~10,000 lives and 58,000 hospital admissions by separating doses of the primary series by 12 weeks, instead of 3 weeks. This strategy was intended to increase the reach of first doses. Despite the success, I still think it was the right move in the States to stick to the clinical trial protocol (3 weeks), given rising vaccine skepticism.

Bottom line​

We are entering a lull in transmission, but COVID-19 continues to show its colors. A big shift is coming in our response as the emergency ends in the next month. Will keep you updated.
"

 

[missy]

New Variant Jumps to Second Place on COVID List​

"
The new COVID-19 strain known as "Arcturus" has increased in the U.S. so much that it has been added to the CDC's watch list.

Officially labeled XBB.1.16, Arcturus is a subvariant of Omicron that was first seen in India and has been on the World Health Organization's watchlist since the end of March. The CDC's most recent update now lists Arcturus as causing 7% of U.S. coronavirus cases, landing it in second place behind its long-predominant Omicron cousin XBB.1.5, which causes 78% of cases.

Arcturus is more transmissible but not more dangerous than recent chart-topping strains, experts say.


"It is causing increasing case counts in certain parts of the world, including India. We're not seeing high rates of XBB.1.16 yet in the United States, but it may become more prominent in coming weeks," Mayo Clinic viral disease expert Matthew Binnicker, PhD, told The Seattle Times.

"

"

Second Omicron Booster Authorized​

— Here's the FDA's latest update on COVID vaccines​

by Kristina Fiore, Director of Enterprise & Investigative Reporting, MedPage Today April 18, 2023

Certain groups are now eligible for another dose of the bivalent COVID-19 vaccine, and the updated shots have now fully replaced the monovalent shots, the FDA announcedopens in a new tab or window.
The agency scrapped the emergency use authorizations (EUAs) for the monovalent Moderna and Pfizer-BioNTech mRNA vaccines, and has authorized the bivalent boosters (original plus Omicron BA.4/BA.5 strains) for all doses starting at age 6 months.
People age 65 and up can now get a second bivalent dose at least 4 months after their initial bivalent dose. FDA said a second bivalent dose for this group is supported by data showing that immunity wanes in this population over time, but that an additional dose restores it.

In addition, those who are immunocompromised can get an additional dose at least 2 months after their initial bivalent shot, FDA said. They can have additional doses at the discretion of their healthcare provider, who can also determine the interval at which these doses are received, the agency said.
For young kids who are immune compromised (ages 6 months through 4 years), however, eligibility for additional doses will depend on the vaccine they previously received, the agency noted.
Most people who only had monovalent shots in the past can now get a single dose of a bivalent booster dose. The agency intends to make decisions about future vaccination after an FDA advisory committee meeting in June regarding the fall strain.
As for the unvaccinated, a single dose of the bivalent vaccine will now suffice, rather than multiple doses of monovalent vaccines, the agency said.
Kids ages 6 months through 5 years who've had one, two, or three doses of a monovalent vaccine can get a bivalent shot but the number of doses will depend on the vaccine and their vaccination history, FDA said.

Unvaccinated kids ages 6 months through 5 years can get a two-dose series of the Moderna bivalent vaccine. Unvaccinated kids ages 6 months through 4 years can get a three-dose series of the Pfizer-BioNTech bivalent vaccine, and for this brand, 5-year-olds can get a single dose of the bivalent shot.
"Evidence is now available that most of the U.S. population 5 years of age and older has antibodies to SARS-CoV-2, the virus that causes COVID-19, either from vaccination or infection that can serve as a foundation for the protection provided by the bivalent vaccines," Peter Marks, MD, PhD, director of FDA's Center for Biologics Evaluation and Research, said in a statement. "COVID-19 continues to be a very real risk for many people, and we encourage individuals to consider staying current with vaccination, including with a bivalent COVID-19 vaccine."

• 
  
  Kristina Fiore leads MedPage’s enterprise & investigative reporting team. She’s been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to [email protected].
  "

 

[missy]

"

Severe COVID-19 Linked to New Diabetes Diagnoses​

Lisa O'Mary
April 19, 2023



COVID can more than triple the chance of being diagnosed with type 2 diabetes within a year of being infected, according to a new Canadian study.
Men who had even a mild case of COVID were significantly more likely than non-infected men to be diagnosed with type 2 diabetes, which is a chronic condition that affects how the body turns food into energy. Women didn't have an increased risk unless they were severely ill.
Both men and women who had severe cases were at the highest risk. People who were hospitalized for COVID treatment had more than a doubled risk of being diagnosed with type 2 diabetes, and those who were admitted to intensive care units had more than a tripled risk.

"This is definitely a concern in terms of long-term outcomes," researcher and University of British Columbia professor Naveed Z. Janjua, PhD, told The New York Times. "With a respiratory infection, you usually think, 'Seven or eight days and I'm done with it, that's it.' [But] here we're seeing lingering effects that are lifelong."

The study was published on Tuesday in JAMA Network Open. Researchers analyzed health data from 2020 and 2021 for 629,935 people, 20% of whom were diagnosed with COVID during that time. Most people in the study had not been vaccinated because vaccines were not widely available then. The health information came from a registry maintained by public health officials in British Columbia, Canada. The follow-up period was 257 days.

The authors cautioned that their findings could not say that COVID causes type 2 diabetes; rather, in a commentary published along with the study, Pamela B. Davis, MD, PhD, said the link makes sense because COVID is known to impact the pancreas, which makes insulin. Insulin is a hormone that helps the body regulate blood sugar — a process that doesn't work properly in people with diabetes.

"Such a stress may move a patient from a prediabetic state into diabetes," wrote Davis, who is a former dean of the Case Western University School of Medicine in Ohio, where she is now a professor.


The researchers estimated that the increased pattern of diagnoses of diabetes following COVID infection could increase the rate of the disease occurring in the general population by 3% to 5% overall.



"

 

[missy]

"

AstraZeneca Confident New COVID Antibody Protects Against Known Variants​

By Maggie Fick
April 19, 2023

BARCELONA (Reuters) - AstraZeneca is confident that its new version of COVID-19 antibody treatment could protect immunocompromised patients against all known virus variants, its vaccines head said.
Laboratory studies show the antibody, called AZD3152, neutralizes all known variants of COVID-19 and AstraZeneca has support from regulators to make the treatment available by the end of this year, Iskra Reic said in an interview on Tuesday.
AstraZeneca plans, pending more positive data and regulatory approval, to make the antibody available by the end of 2023.
These types of therapies are most needed for people with compromised immune systems, either because of underlying conditions or because they are undergoing immune suppressing treatments. They account for nearly 2% of the global population.

In January, the U.S. health regulator withdrew its emergency use authorization for AstraZeneca's original COVID-19 antibody cocktail Evusheld, as new dominant variants made it obsolete.

The U.S. Food and Drug Administration's (FDA) decision resonated with concerns raised by Europe's health regulator.

AstraZeneca's AZD3152, it new COVID-19 antibody, was acquired through a $157 million deal last year with British biotech start-up RQ Bio.

The British drugmaker will likely make future investments like its current partnerships with RQ Bio but did not have any deals to announce, said Reic, a longtime AstraZeneca executive who has led the company's vaccines and immune therapies unit since it was formed in late 2021, during the pandemic.


Last year, the unit made $4.8 billion in revenues. However, demand for COVID-19 vaccines have dramatically declined with competition from mRNA vaccines and given many countries already have an oversupply of COVID-19 shots.

(Reporting by Maggie Fick in Barcelona; Additional reporting by Natalie Grover in London; Editing by Alexander Smith)

"

 

[missy]

"

ACIP meeting: Spring booster Cliff notes​

KATELYN JETELINA APR 20

​

​

The ACIP meeting for spring boosters convened yesterday. You know the drill; here are your Cliff notes.

Bottom line upfront​

CDC and FDA are trying to simplify COVID-19 vaccine recommendations. (Verdict is out if they actually did this for kids). From now on, people are “up-to-date” if:

• 6+ years old: 1 bivalent (i.e. fall Omicron vaccine) dose. Regardless of vaccine history. Period.
• <6 years old:
  • Moderna: at least 2 doses, including 1 bivalent.
  • Pfizer:
    • 5 years: 1 bivalent.
    • Under 5 years: at least 3 doses, including 1 bivalent.

If you meet this criteria, there is nothing you need to do right now. You can stop reading.
But this happens to be only 1 in 6 Americans (2 in 5 of those who 65 years and older). A ridiculous number of Americans are not up-to-date with COVID-19 vaccines. This means a lot of people need to keep reading.
Also, adults 65+ years and/or immunocompromised who got the fall booster may now choose to receive a spring booster (the timing varies, see figure below). This YLE post is for you.

​

Bivalent safety​

Safety data was presented at the ACIP meeting in detail. There were no surprises; it continues to look great.
There are two questions the CDC is trying to get clarity on, though, for those over 65:

• 3-6 weeks after the fall booster, the rate of strokes was lower among vaccinated than unvaccinated. In other words, there may be a secondary protective effect, which is great news.
• Getting the flu and COVID-19 vaccines simultaneously may be a problem. While not statistically significant, there is an elevated rate of stroke within 21 days. (It’s pretty darn close to being statistically significant, too.) I hope we get more clarity before the upcoming fall vaccine campaign.

Bivalent effectiveness​

Why do I need a spring booster? CDC presented data that shows vaccine effectiveness waning against hospitalization. Efficacy for bivalent vaccines among those over 65 years decreased from 64% to 39%.

​

CDC slide here
While 39% seems low, there are two important points to keep in mind:

1. We need to think of effectiveness as “relative” now—relative to some combination of prior vaccination, prior infection, or both. This means the 39% is the benefit above and beyond whatever underlying immunity an individual has. We’re going to see lower numbers than we were used to because of this, but it doesn’t mean we’re not getting protection (i.e., hospitals are not filling up).
2. We are getting more hospitalized “with” COVID-19 (vs. “for”) than before, making it harder to understand what it means when someone is hospitalized and has a COVID-19 diagnosis. One way to know if hospitalization is “for” COVID-19 is to look at ventilator use. Protection against ventilator use has not waned.

​

Source: CDC slide
So the majority of people are still protected against severe disease from COVID-19. However, among older people with comorbidities, risk for hospitalization “with” COVID-19 likely increases with time. (I go through the why and how in more depth on this YLE post.) We don’t know what this risk is prospectively, but getting a spring booster is one way to avoid finding out.

Lingering ACIP questions with some answers​

• What about people who didn’t get the mRNA vaccine? If someone doesn’t want the mRNA booster or is allergic to some component, there is no option for them at this time. Novavax said they should have a bivalent vaccine by fall.
• What about immunocompromised kids under 5 years old? They are not eligible for a spring booster. FDA said that it’s because they just don’t have data to justify it. Pediatricians in the meeting were not happy with this answer and rightfully so. These vulnerable children are being left behind.
• What about pregnancy? Pregnant people are not eligible for a spring booster. There’s a good chance this will change in the future. A CDC decision should be made in the coming weeks.
• What if I just had an infection? The CDC is still not providing recommendations based on infection history. (I was surprised.) Canada took this route, which I agreed with.
• Are the recommendations for children really more simple? No. Parents are supposed to follow the figure below, which is confusing. We need to fix this.

​

What’s next?​

The FDA meets in June to discuss the fall vaccine plan, including the vaccine variant formula. I expect everyone will be eligible for a booster in the fall, but time will tell.

Bottom line​

Anyone who hasn’t had a bivalent vaccine (i.e. fall Omicron booster) needs to get one. A small group of Americans are now eligible for a spring booster. This is important given the continued unpredictability of COVID-19—prepare for the worst, and hope for the best.


"

 

[missy]

Do I need a spring booster?​

KATELYN JETELINA APR 25

"

Level of urgency​

The level of urgency for a spring booster should be dependent on two things:

1. Risk factors. Ninety percent of people in the hospital “for” or “with” COVID-19 do not have a bivalent vaccine (i.e. fall booster). This group has the highest level of urgency.

If you had the fall booster, you’re in pretty good shape against acute severe disease. Will this change with time? We don’t know. The U.S. (and a handful of other countries) don’t want to risk finding out, so a spring booster is “permissible”.

People in the hospital today for COVID-19 are older adults and/or those with a comorbidity. (If you want to know why, read more here.) This means groups with the second highest level of urgency for a spring booster are those with a fall booster and:

• Adults over 75 years;
• Adults over the age of 65 years with a comorbidity; and,
• Moderate or severely immunocompromised.

If you’re not in one of these groups, your level of urgency is significantly reduced. You could time a booster for maximum protection. If I were over 65 without a comorbidity, I would, especially since wastewater concentration is nosediving. For example, four weeks before a really big event you don’t want to miss, like a wedding, get a booster. Or wait to get a booster on the chance that another variant of concern comes (and get it right before a wave).

​

2. Timing. If you’re in one of the urgent groups, the next question is: When was your last infection or vaccine?

• 6+ months ago: Go get a spring booster today.
• 4-6 months: Schedule one, but you don’t need to rush to the pharmacy.
• <4 months: Wait. But do not wait until past May/June, so that you enough runway time before the (anticipated) fall vaccine.

Potential individual-level risks​

People are wondering about risks of spring boosters. The risks are small, especially when we compare them to risks resulting from infection. Perhaps the following risks should really only be considered for those who are not in the high-urgency groups above.

• Myocarditis. This is the biggest risk of COVID-19 vaccines but is really only a problem for adolescents. (Benefits still outweigh risks. There is also a risk of myocarditis from COVID-19 infection.)
• Flu vaccine. There may be an increased risk of stroke if you get flu and COVID-19 vaccines at the same time. This shouldn’t be a problem for your spring decision.
• Side effects. Some people get their butt kicked from side effects immediately after the vaccine. Some just don’t have the ability to be out of commission for a few days.
• Imprinting. We know imprinting is a thing with COVID-19. And, we should expect imprinting. (Read a deep dive here.) The biggest influence of imprinting occurs after first exposure to the virus (through vaccine or infection). We still don’t have good evidence that imprinting is harming protection, though.
• Unknown unknowns. We simply don’t know the risks of stimulating the immune system with 6 shots in 2 years, too. There are always unknown risks, albeit small.

Bottom line​

Anyone who hasn’t had a bivalent vaccine (i.e. fall Omicron booster) needs to get one. If you have your bivalent already, there is a spectrum of urgency. Try not to overthink it too much.


"

 

[missy]

"

Evolution of Florida vaccine analysis​

KATELYN JETELINA
AND
KRISTEN PANTHAGANI, MD, PHD
APR 27, 2023

Last October, the Florida Surgeon General issued new guidance around the COVID-19 vaccines: men aged 18-39 should not receive COVID mRNA vaccines. This policy change was based on an analysis they performed that found “an increased risk of cardiac-related death among men 18-39.”

This finding was alarming and inconsistent with analyses from CDC and independent scientists. So, two outside epidemiologists, Drs. Kat Wallace and Jon Laxton and the Tampa Bay Times requested the unreleased drafts through the Freedom of Information Act. They were curious how Florida came to this conclusion because if true, it was a huge revelation.

Those records tell a dramatic story of how science should not be done.

Drafts​

There were at least six versions of this analysis and report. The drafts show very different results and conclusions compared to the final version of the report released last October. Here’s how it changed.

Version 1: Completely opposite results​

Version 1 of the report is the most distinct from all the others. Importantly, this first version found no increased risk of death in any age/vaccine group.

The table below summarizes the key results in version 1 compared to the final version using color codes:

• Green: analysis found vaccination is associated with reduced risk of death;
• Red: vaccination is associated with increased risk of death; and
• Gray: there was no association either way.

In version 1, you see ALL GREEN AND GRAY—none of the results, for any of the ages or subgroups analyzed, showed any increased risk of death after vaccination. But in the version that was released in October, many of those results changed to red.

​

Why is there a lot of red now? The study design changed over time.

• In version 1, the risk period was weeks 1-6 after vaccination, and the control period was weeks 7-18 after vaccination.
• In subsequent versions, the risk period was weeks 1-4 post-vaccine, and the control period was weeks 5-25 after vaccination.

​

It’s hard to say which risk period is “right.” Sometimes there are clear reasons why you should pick a certain subgroup or risk period. Other times researchers pick a reasonable cut-off and just go with it.

However, knowing the results from both designs, we do have reason to be concerned. The fact that this slight change in study design yielded opposite results suggests the results aren’t reliable. If you tweak your design parameters slightly, without a clear hypothesis-driven reason to do so, and the whole thing falls apart, that suggests your results may not be real but rather are just statistical noise.

Version 2: What about COVID infection?​

One of the major criticisms back in October was the analysis failed to look at the risk of COVID infection and balance that with any risk of vaccination. It turns out, they did run that analysis—they just didn’t include it in their report.

In version 2, they evaluated risk of death after COVID-19 infection. They found the risk of death after infection was higher than risk after vaccination, for all age groups (even young men). The same pattern held true when they looked at only cardiac-related deaths.

In version 2, authors included this in the study’s text. But, in all subsequent versions, this text and analysis was removed.

Versions 3-5: mRNA vaccines have two doses​

In versions 3-5, the authors added a sensitivity analysis. Sensitivity analyses are used to determine how reliable results are by switching up certain parameters or assumptions and seeing if the key results hold true.

In this case, they performed a sensitivity analysis that accounts for both doses of the mRNA vaccines.

The study design they chose is meant for single dose vaccines, because the risk and control periods are muddled when people get multiple doses. In the main analysis of the study, they ignored the first mRNA vaccine dose and only analyze results based on the last vaccine dose.

But when the sensitivity analysis accounted for the multi-dose scheduling, the significant results disappear. They found no association between vaccination and cardiac-related death in any of the subgroups analyzed.

Version 5 has the same data as versions 3 and 4, but includes the discussion/conclusion and limitations sections. Here is the last paragraph of the discussion/conclusion section:

​

When we get to the final, publicly posted, version of the study: The sensitivity analysis was completely removed. In fact, no mention of it was made.

Instead, the final version (version 6) concludes that COVID vaccines are associated with an “increased risk for cardiac-related mortality 28 days following vaccination.”

Evolution of conclusions​

Throughout the drafts, there was a clear evolution of conclusions. Starting with no risk of death to young men to significant risk.

​

At its most basic level, science’s goal is to figure out what’s true about reality. It is common practice for scientific analyses to evolve over time. But when that happens, there must be clear methodological reasons for the changes. In this case, the study design, results, and conclusions were altered with no scientific explanation, no transparency, no hypothesis-driven reason provided, and no opportunity for formal peer-review.

Bottom line​

This is not how science or evidence-based policy is done.



"

 

[Betty Baguette]

Sorry if I'm not putting this article in the right thread.

COVID will eventually evade Paxlovid, former White House advisor Deborah Birx says

She worries that the virus' evolution is outpacing U.S. development of vaccines and treatments—and that it could soon render popular antiviral Paxlovid useless.

fortune.com

 

[missy]

"

What’s going on with booster shots?​

Is there another booster available for seniors? Robert, Stamford, Connecticut For a little while there, it looked like booster shots had become a part of our regular routine. Personally, I felt like I was getting them more often than I remembered to floss. As Covid started becoming less of an immediate threat for healthy adults, our vaccine strategy started shifting. Health officials have started thinking about Covid like they do influenza — which requires an annual shot, right before sniffle season kicks off. However, their approach to keeping seniors healthy is different. The US Centers for Disease Control and Prevention said last week that older and medically vulnerable people should get another dose of the bivalent shot as soon as possible. “The vaccine’s primary job is to reduce the risk of hospitalization, severe illness and death from Covid. The people that are most at risk for these bad outcomes are people that are over 65 years old and those who have compromised immune systems,” says Katrine Wallace, an epidemiologist at University of Illinois at Chicago. “We still are losing over 1,000 people per week to Covid and mostly these are people in high-risk groups,” she says. That subset of people will benefit from another shot, according to recent data. Protection against emergency department visits for those 65 and older waned to 25% six months after their first bivalent booster, compared to 61% in the first 60 days, researchers found. “It makes sense on a population level to target additional protections towards this vulnerable group,” says Wallace. The CDC also recommends that anyone older than six who hasn’t received a bivalent booster (and most people haven’t) go get one. “If you have not had a Covid vaccine since September, you have not had the updated mRNA vaccine,” says Wallace. “So you should go get one.” If you’re all up to date, well, then just sit tight for now. You’re likely not due for another until fall. — Kristen V. Brown "