Changing recommendations for boosters lead to confusion for the vaccinated and their doctors

Author: Carissa Wolf, Frances Stead Sellers, Ashley Cusick, Kim Mueller  1 day ago

Even in Idaho, which has one of the lowest coronavirus vaccination rates in the country, clinics have been gearing up for an onslaught of calls and emails requesting booster shots.

Administrators at the Primary Health Medical Group updated their website Thursday and then set about revising it Friday when government eligibility recommendations for boosters suddenly changed to include workers in high-risk jobs. Even then, the clinic’s chief executive had to figure out which occupations that meant.

“Who’s at high risk? I had to look it up. Is it firemen? I don’t know,” said David Peterman. “This is so confusing to the public and creates mistrust. And we can’t have that right now. Right now, we need the public to say, ‘Let’s get vaccinated.’ And for those that need boosters, we need to say that ‘This is safe, and this is what we need to do.’”

Confusion over boosters, which has been brewing for months, heightened over the past week as government regulators and advisers met to hash out the pros and cons of administering third doses.

Hours of meetings were followed by a dramatic decision Thursday: The Centers for Disease Control and Prevention’s advisory group narrowed the Food and Drug Administration’s recommendation for who should get a third Pfizer shot, only to be overruled in a late-night announcement by the CDC director: Along with Americans 65 and older, nursing home residents and people ages 50 to 64 with underlying medical conditions, who the advisory panel had suggested should get shots, Rochelle Walensky added the people in high-risk jobs.

“It’s a communications crisis,” said Robert Murphy, executive director of the Institute for Global Health at Northwestern University Feinberg School of Medicine, who said he received worried calls Thursday evening from health-care workers who thought they would not be eligible for the shots, followed by messages Friday from colleagues wondering when and where to go.The deluge of phone calls about booster shots to Primary Health clinics in Southwestern Idaho began weeks ago. On Friday morning, the group’s Garden City clinic, where Maddie Morris fields inquiries, saw an increase in calls, mostly from senior citizens.

“The calls seem pretty nonstop,” the customer service representative said. “It seems like a lot of people are anxious to get a booster.”

Doctors say confusion clouds patients’ willingness to receive boosters. In Idaho, the problem coincides with the primary health-care system’s struggle to meet the demands of the latest covid-19 crush, which earlier this month plunged the state into crisis standards of care — essentially the rationing of health care as demand overwhelms resources.Four patients, two dialysis machines: Rationing medical care becomes a reality in hospitals overwhelmed with covid patients

Peterman expects the new booster guidelines to prompt an increase in inquiries just as the number of providers out sick is at an all-time high.

“We went from 40,000 phone calls daily at 21 clinics to 80,000. Eighty thousand! On top of that, we went from maybe 20 of our employees being out a day to 30 to 40,” Peterman said.

“In the next 72 hours, I want [the CDC] to answer our phones,” he said.

Many newly eligible patients are over 65 and not comfortable using the Internet to find information. So the phones keep ringing at Morris’s desk.

“You really can’t take a breather. You just have to jump to the next call,” she said. And Peterman says he has had to ask staffers to take extra shifts and work long into the night to help close the staffing gap.

Much of the muddle stems from legacy systems at the FDA and CDC that were set up to handle routine drug approvals and childhood vaccinations, not a fast-moving public health crisis involving the entire population, said Jay A. Winsten, the founding director of the Center for Health Communications at the Harvard T.H. Chan School of Public Health.

The CDC’s Advisory Committee on Immunization Practices includes infectious-disease specialists, obstetricians and pediatricians who grappled Thursday with questions in which they have no expertise, such as whether offering boosters might undermine public confidence in the vaccines’ efficacy.

“What’s missing from the equation are communication experts,” said Winsten, including specialists in public-opinion polling and behavior change. “They need a seat at the table.”

Health-care providers across the nation have been helping patients for weeks to filter through not just misinformation and disinformation about boosters but also a surfeit of real-time information.

“That’s the biggest problem,” said Clay Marsh, a pulmonary critical care doctor and executive dean for health sciences at West Virginia University. “The amount of information is dizzying,” Marsh said, “It creates chaos.”

Across the New Orleans metropolitan area, new CDC guidelines had failed to trickle down to many administration sites by Friday morning.

The Louisiana National Guard, which helps to run testing and vaccination sites, was still awaiting clarity.

“We are just administering the first and second doses,” said Sgt. Gaynell Leal, a guard spokeswoman. “As far as the booster part of it, that hasn’t come our way yet.”

“The biggest thing is gaining people’s confidence in science,” Leal said. “My civilian job is I’m a funeral director. So I’ve seen this on both sides.”

On the ground, some National Guard-run sites did offer booster shots Friday, but the eligibility benchmarks they used had not yet caught up with the CDC’s latest guidelines.Tracking the coronavirus vaccine

At a drive-through testing and vaccine site in Meraux, La., just east of New Orleans, medics offered booster shots to those who met the requirements laid out on a “self-risk attestation form” issued in mid-August by the Louisiana Department of Health. That form offered a checklist of reasons one might qualify for a third dose, including active cancer treatment, HIV infection, immunodeficiency issues or the use of immunosuppressants. The form did not account for the age or job-related eligibility factors the CDC announced late this week.

In the French Quarter, Tara Thompson, 53, enjoyed a drink in Pirate’s Alley with her husband.

Thompson said that although she took the vaccine to spend time with her elderly parents, she hoped this week’s guidelines would not lead to booster shots soon being pushed on the public.

“I personally don’t want it if I don’t have to have it,” she said. “It’s a matter of trusting the science that seems to be skewed toward the benefit of certain political mind-sets.”

Thompson said she could change her mind if the shots help with travel.

“Or, if the booster shots help Mardi Gras to happen,” she said. “I might consider it then.”

In Chalmette, La., Kerissa Fernandez, 37, wanted more clarity on how the new booster shot guidelines applied to her.

Fernandez, a family nurse practitioner, said she and the staff at the small urgent care clinic she runs with her husband all meet the front-line worker requirement for booster shots. But none of the staffers at the Bayou Urgent Care Clinic had received the Pfizer vaccine, she said.

“I had Moderna. We all got Moderna,” she said. But when the delta variant reached record numbers in Louisiana, she and her husband both ended up with breakthrough infections.

Knowing firsthand the virus’s ability to shape-shift, Fernandez said she and her staff are all eager to get booster shots.

Many newly eligible people say they aren’t waiting for the rules and recommendations to change again. Ann Mackey, 66, qualifies for a booster shot.

“I have a doctor’s appointment next week, so I might see if they can jab me then,” she said from her high-rise apartment in downtown Kansas City, Mo.

The former FDA employee said the government’s conflicting messages have been confusing. She doesn’t understand why she can receive a Pfizer booster, but her friends and family can’t get their third Moderna shot. She is confused about how the government defines “high risk” and who will enforce the newest set of recommendations. And she worries that public confusion will provide another excuse for people to avoid getting their first dose.

“There already is a lot of vaccine hesitancy, and they are just looking for reasons not to get vaccinated,” Mackey said.Americans are sneaking extra coronavirus shots as officials weigh who should get them

Others are considering creative ways to get boosters.

Derek Hoetmer has been following the news closely, hoping he and his wife, a nurse who worked on a covid response team, could get a booster before the Missouri winter.

The problem is that the rules keep changing — and not in the Hoetmers’ favor. They were pleased to wake Friday morning to find the vaccination door had been opened to people in high-risk jobs.

But not wide enough for the Hoetmers, who won’t qualify because their first two doses were Moderna jabs.

With the Missouri winter only two months away, Hoetmer is considering his options. He has heard that other Americans who do not qualify are secretly getting boosters, anyway.

n situation in letter to opposition

Even in Idaho, which has one of the lowest coronavirus vaccination rates in the country, clinics have been gearing up for an onslaught of calls and emails requesting booster shots.© Scott Olson/Getty Images HINES, ILL. – SEPTEMBER 24: Lalain Reyeg administers a coronavirus booster vaccine and an influenza vaccine to Army veteran William Craig at the Edward Hines Jr. VA Hospital on September 24, 2021 in Hines, Ill. (Photo by Scott Olson/Getty Images)

Administrators at the Primary Health Medical Group updated their website Thursday and then set about revising it Friday when government eligibility recommendations for boosters suddenly changed to include workers in high-risk jobs. Even then, the clinic’s chief executive had to figure out which occupations that meant.

“Who’s at high risk? I had to look it up. Is it firemen? I don’t know,” said David Peterman. “This is so confusing to the public and creates mistrust. And we can’t have that right now. Right now, we need the public to say, ‘Let’s get vaccinated.’ And for those that need boosters, we need to say that ‘This is safe, and this is what we need to do.’”

Confusion over boosters, which has been brewing for months, heightened over the past week as government regulators and advisers met to hash out the pros and cons of administering third doses.

Hours of meetings were followed by a dramatic decision Thursday: The Centers for Disease Control and Prevention’s advisory group narrowed the Food and Drug Administration’s recommendation for who should get a third Pfizer shot, only to be overruled in a late-night announcement by the CDC director: Along with Americans 65 and older, nursing home residents and people ages 50 to 64 with underlying medical conditions, who the advisory panel had suggested should get shots, Rochelle Walensky added the people in high-risk jobs.

“It’s a communications crisis,” said Robert Murphy, executive director of the Institute for Global Health at Northwestern University Feinberg School of Medicine, who said he received worried calls Thursday evening from health-care workers who thought they would not be eligible for the shots, followed by messages Friday from colleagues wondering when and where to get them.

“Everyone is kind of confused,” he said. The current discontent has deep roots. In April, Pfizer chief executive Albert Bourla said a third coronavirus dose was “likely” to be needed. In late July, Pfizer-BioNTech announced that their vaccine’s efficacy waned over time. Data from Israel confirmed a drop. Then, last month, as the delta variant of the coronavirus surged and the World Health Organization decried the distribution of third shots in wealthy countries while poor countries were lacking first doses, President Biden announced that most Americans could begin getting boosters of the Pfizer and Moderna vaccines Sept. 20 — subject to the government’s regulatory processes, which unfolded in recent days and focused only on Pfizer. R22egulators already allowed third shots for the immunocompromised who have received Pfizer or Moderna shots but have not yet made recommendations for all recipients of the Moderna and Johnson & Johnson vaccines.People who got Johnson & Johnson’s coronavirus shot feel left behind in push for boosters

The deluge of phone calls about booster shots to Primary Health clinics in Southwestern Idaho began weeks ago. On Friday morning, the group’s Garden City clinic, where Maddie Morris fields inquiries, saw an increase in calls, mostly from senior citizens.

“The calls seem pretty nonstop,” the customer service representative said. “It seems like a lot of people are anxious to get a booster.”

Doctors say confusion clouds patients’ willingness to receive boosters. In Idaho, the problem coincides with the primary health-care system’s struggle to meet the demands of the latest covid-19 crush, which earlier this month plunged the state into crisis standards of care — essentially the rationing of health care as demand overwhelms resources.Four patients, two dialysis machines: Rationing medical care becomes a reality in hospitals overwhelmed with covid patients

Peterman expects the new booster guidelines to prompt an increase in inquiries just as the number of providers out sick is at an all-time high.

“We went from 40,000 phone calls daily at 21 clinics to 80,000. Eighty thousand! On top of that, we went from maybe 20 of our employees being out a day to 30 to 40,” Peterman said.

“In the next 72 hours, I want [the CDC] to answer our phones,” he said.

Many newly eligible patients are over 65 and not comfortable using the Internet to find information. So the phones keep ringing at Morris’s desk.

“You really can’t take a breather. You just have to jump to the next call,” she said. And Peterman says he has had to ask staffers to take extra shifts and work long into the night to help close the staffing gap.

Much of the muddle stems from legacy systems at the FDA and CDC that were set up to handle routine drug approvals and childhood vaccinations, not a fast-moving public health crisis involving the entire population, said Jay A. Winsten, the founding director of the Center for Health Communications at the Harvard T.H. Chan School of Public Health.

The CDC’s Advisory Committee on Immunization Practices includes infectious-disease specialists, obstetricians and pediatricians who grappled Thursday with questions in which they have no expertise, such as whether offering boosters might undermine public confidence in the vaccines’ efficacy.

“What’s missing from the equation are communication experts,” said Winsten, including specialists in public-opinion polling and behavior change. “They need a seat at the table.”

Health-care providers across the nation have been helping patients for weeks to filter through not just misinformation and disinformation about boosters but also a surfeit of real-time information.

“That’s the biggest problem,” said Clay Marsh, a pulmonary critical care doctor and executive dean for health sciences at West Virginia University. “The amount of information is dizzying,” Marsh said, “It creates chaos.”

Across the New Orleans metropolitan area, new CDC guidelines had failed to trickle down to many administration sites by Friday morning.

The Louisiana National Guard, which helps to run testing and vaccination sites, was still awaiting clarity.

“We are just administering the first and second doses,” said Sgt. Gaynell Leal, a guard spokeswoman. “As far as the booster part of it, that hasn’t come our way yet.”

“The biggest thing is gaining people’s confidence in science,” Leal said. “My civilian job is I’m a funeral director. So I’ve seen this on both sides.”

On the ground, some National Guard-run sites did offer booster shots Friday, but the eligibility benchmarks they used had not yet caught up with the CDC’s latest guidelines.Tracking the coronavirus vaccine

At a drive-through testing and vaccine site in Meraux, La., just east of New Orleans, medics offered booster shots to those who met the requirements laid out on a “self-risk attestation form” issued in mid-August by the Louisiana Department of Health. That form offered a checklist of reasons one might qualify for a third dose, including active cancer treatment, HIV infection, immunodeficiency issues or the use of immunosuppressants. The form did not account for the age or job-related eligibility factors the CDC announced late this week.

In the French Quarter, Tara Thompson, 53, enjoyed a drink in Pirate’s Alley with her husband.

Thompson said that although she took the vaccine to spend time with her elderly parents, she hoped this week’s guidelines would not lead to booster shots soon being pushed on the public.

“I personally don’t want it if I don’t have to have it,” she said. “It’s a matter of trusting the science that seems to be skewed toward the benefit of certain political mind-sets.”

Thompson said she could change her mind if the shots help with travel.

“Or, if the booster shots help Mardi Gras to happen,” she said. “I might consider it then.”

In Chalmette, La., Kerissa Fernandez, 37, wanted more clarity on how the new booster shot guidelines applied to her.

Fernandez, a family nurse practitioner, said she and the staff at the small urgent care clinic she runs with her husband all meet the front-line worker requirement for booster shots. But none of the staffers at the Bayou Urgent Care Clinic had received the Pfizer vaccine, she said.

“I had Moderna. We all got Moderna,” she said. But when the delta variant reached record numbers in Louisiana, she and her husband both ended up with breakthrough infections.

Knowing firsthand the virus’s ability to shape-shift, Fernandez said she and her staff are all eager to get booster shots.

Many newly eligible people say they aren’t waiting for the rules and recommendations to change again. Ann Mackey, 66, qualifies for a booster shot.

“I have a doctor’s appointment next week, so I might see if they can jab me then,” she said from her high-rise apartment in downtown Kansas City, Mo.

The former FDA employee said the government’s conflicting messages have been confusing. She doesn’t understand why she can receive a Pfizer booster, but her friends and family can’t get their third Moderna shot. She is confused about how the government defines “high risk” and who will enforce the newest set of recommendations. And she worries that public confusion will provide another excuse for people to avoid getting their first dose.

“There already is a lot of vaccine hesitancy, and they are just looking for reasons not to get vaccinated,” Mackey said.Americans are sneaking extra coronavirus shots as officials weigh who should get them

Others are considering creative ways to get boosters.

Derek Hoetmer has been following the news closely, hoping he and his wife, a nurse who worked on a covid response team, could get a booster before the Missouri winter.

The problem is that the rules keep changing — and not in the Hoetmers’ favor. They were pleased to wake Friday morning to find the vaccination door had been opened to people in high-risk jobs.

But not wide enough for the Hoetmers, who won’t qualify because their first two doses were Moderna jabs.

With the Missouri winter only two months away, Hoetmer is considering his options. He has heard that other Americans who do not qualify are secretly getting boosters, anyway.

“I won’t lie. I’ve thought about that option,” Hoetmer said. “I would rather go about it the right way and not take away someone’s booster shot.”

Study Finds Teenage Boys Six Times More Likely To Suffer Heart Problems From Vaccine Than Be Hospitalized by COVID

Authors; Paul Joseph Watson via Summit News,

Research conducted by the University of California has found that teenage boys are six times more likely to suffer from heart problems caused by the COVID-19 vaccine than to be hospitalized as a result of COVID-19 itself.

“A team led by Dr Tracy Hoeg at the University of California investigated the rate of cardiac myocarditis – heart inflammation – and chest pain in children aged 12-17 following their second dose of the vaccine,” reports the Telegraph.

“They then compared this with the likelihood of children needing hospital treatment owing to Covid-19, at times of low, moderate and high rates of hospitalisation.”

Researchers found that the risk of heart complications for boys aged 12-15 following the vaccine was 162.2 per million, which was the highest out of all the groups they looked at.

This compares to the risk of a healthy boy being hospitalized as a result of a COVID infection, which is around 26.7 per million, meaning the risk they face from the vaccine is 6.1 times higher.

Even during high risk rates of COVID, such as in January this year, the threat posed by the vaccine is 4.3 times higher, while during low risk rates, the risk of teenage boys suffering a “cardiac adverse event” from the vaccine is a whopping 22.8 times higher.

The research data was based on a study of adverse reactions suffered by teens between January and June this year.

In a sane world, such data should represent the nail in the coffin for the argument that teenagers and children should be mandated to take the coronavirus vaccine, but it obviously won’t.

In the UK, the government is pushing to vaccinate 12-15-year-olds, even without parental consent, despite the Joint Committee on Vaccination and Immunisation (JCVI) advising against it.

Meanwhile, in America, Los Angeles County school officials voted unanimously to mandate COVID shots for all

NIH orders $1.67M study on how COVID-19 vaccine impacts menstrual cycle

Authors: By Hannah Sparks September 7, 2021

The National Institutes of Health has announced a $1.67 million study to investigate reports that suggest the COVID-19 vaccine may come with an unexpected impact on reproductive health.

It’s been a little over six months since the three COVID-19 vaccines in the US — Pfizer, Moderna and Johnson & Johnson — became widely available to all adults. But even in the early days of vaccine rollout, some women were noticing irregular periods following their shots, as reported first by the Lily in April.

Shana Clauson, 45, spoke to the Washington Post’s women’s news site at the time, and again this week, about her experience after getting the jab — revealing that her period arrived earlier and heavier than what she considers normal. She was one of many who gathered on social media to share what they were seeing.

“Is this not being discussed, or is it even being looked at or researched because it’s a ‘woman’s issue?’ ” Clauson speculated to the Lily last spring.

Women, those under 40 more likely to have side effects to COVID vaccine, expert says

It would appear that the NIH heard Clauson and others’ reports, as they announced on Aug. 30 that they intended to embark on just such research — aiming to incorporate up to half a million participants, including teens and transgender and nonbinary people.

Researchers at Boston University, Harvard Medical School, Johns Hopkins University, Michigan State University and Oregon Health and Science University have been enlisted to embark on the study, commissioned by the NIH’s National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women’s Health.

The approximately yearlong study will follow initially unvaccinated participants to observe changes that occur following each dose. More specifically, some groups will exclude participants on birth control or gender-affirming hormones, which may have their own impact on periods.

“Our goal is to provide menstruating people with information, mainly as to what to expect, because I think that was the biggest issue: Nobody expected it to affect the menstrual system, because the information wasn’t being collected in the early vaccine studies,” said NICHD director Diana Bianchi in a statement to the Lily — reportedly crediting their early coverage for helping to make the NIH aware.

‘We were worried this was contributing to vaccine hesitancy in reproductive-age women.’

NICHD director Diana Bianchi

The NIH suggests that changes to the menstrual cycle could arise out of several of life’s circumstances during a pandemic — the stress of lifestyle changes or possibly contending with illness. Moreover, the immune and reproductive systems are intrinsically linked, and the notion that the immune-boosting vaccine may disrupt the typical menstrual cycle is plausible, as demonstrated by previous studies concerning vaccine uptake.

It’s also worth noting the vaccine does not cause infertility and the Centers for Disease Control and Prevention recommends the shot even for pregnant women.

As changes to the menstrual cycle are “really not a life and death issue,” explained Bianchi, the Food and Drug Administration — fast-tracking their work — prioritized only the most critical risks associated with the COVID-19 vaccine.

The NIH, too, pulled together the initiative at breakneck speed. Funding for such a study would typically take years to see approval.

“We were worried this was contributing to vaccine hesitancy in reproductive-age women,” said Bianchi.

COVID-19 live updates: Vaccine protection against hospitalization is dropping slightly, CDC says

The CDC initially said 97% of people hospitalized with COVID-19 are unvaccinated

Authors: By Julia Jacobo and Ivan Pereira Last Updated: August 30, 2021, 5:18 PM ET

The COVID-19 vaccines’ ability to keep people out of the hospital appears to be dropping slightly, particularly for those 75 and older, the Centers for Disease Control and Prevention announced Monday during an advisory panel.

The CDC has previously estimated that 97% of people in the hospital being treated for COVID-19 are unvaccinated, but that data was collected before the spread of delta, a hyper-transmissible variant that many doctors have warned appears to be making people sicker.

The latest CDC analysis estimates that the ability of the COVID vaccines to keep a person out of the hospital is now between 75% to 95%.

For people older than 75 in particular, vaccine effectiveness against hospitalization experienced the steepest decline, from more than 90% to 80% between June and July.

Health experts are also concerned that a person’s immunity could be waning over time, particularly among older people whose bodies are less likely than younger people to develop a strong immune response to the vaccines.

However, the vaccine still remain highly effective at preventing serious illness, according to the briefing.

Scientists push back on call to endorse booster shots for all

Authors: By Ariel Hart,  Helena Oliviero– The Atlanta Journal-Constitution

Responding to the resurging pandemic and breakthrough infections, President Biden and some top health officials are pushing for the U.S. to begin vaccine booster shots by Sept. 20. But the committee of scientists who officially recommend whether to take such steps met Monday and pushed back.

The scientists said they still had fundamental questions to answer, such as whether the increase in COVID-19 infections after vaccination, so-called breakthrough cases, was related at all to waning effectiveness of the vaccines.

When the Sept. 20 date was announced “it led everyone—it led physicians, it led the public—to believe that they had access to information about these vaccines and the need for boosters that had not yet been publicly released,” said Dr. Sandra Fryhofer of Atlanta, a nonvoting member of the committee. “And to me, that kind of opened the door to a lot of confusion.”

The group, the Advisory Committee on Immunization Practices, advises the Centers for Disease Control and Prevention on whether scientific data merit approval or warnings on vaccines. From the moment its chairwoman opened Monday’s meeting, members made blunt statements that they would follow scientific data and processes on booster shots, regardless.

Other scientists were glad to hear it.

“There is a process that is being undermined by ‘science by leak,’” said Dr. Felipe Lobelo of Emory University, an epidemiologist and associate professor told the AJC. “We don’t really have strong data on when the waning starts; on whether the increased rates of infection and so called breakthrough infections…are occurring because of this waning effect— or is it because delta is more transmissible? Or is it because people are changing behaviors?”

Dr. Carlos del Rio, professor of medicine at Emory University, agreed. “The problem is by focusing on boosters we’re distracting from the biggest problem, which is all the unvaccinated people,” he said.

Without calling them “booster shots,” the FDA has authorized an extra shot for certain people with compromised immune systems, like organ transplant recipients, after they have completed their original coronavirus vaccine regimen. But no decisions have been made for other vulnerable groups, much less the general public.

That leaves Georgians who are now eager for a booster shot not knowing what comes next.

In Avondale Estates, Carolyn Chandler, 80, has marked her calendar for Oct. 16, the day she should get a booster if they’re recommended eight months from initial vaccination, as federal officials have touted.

Ever since Chandler started to see reports showing waning immunity from the vaccines, there was no question for her that she would get a booster.

“I just would like to stick around for a while,” Chandler said.

FDA Issues Warning About Increased Risk Of Heart Inflammation Caused By Moderna Jab

Authors: BY TYLER DURDENMONDAY, AUG 30, 2021 – 02:14 P

Earlier this month, we reported on leaked data from a Canadian study which arrived at a disturbing conclusion: the risk of rare side effects like myocarditis and pericarditis – types of heart inflammation that are potentially deadly in some patients – was at least 2.5x higher in the Moderna jab than in its main competitor, produced by Pfizer-BioNTech.

The leaking of the data to the press was an embarrassment for the FDA and CDC, and so they pledged to investigate. Now, less than two weeks later, the FDA has just announced that it has updated its “fact sheet” to reflect the higher risk of heart inflammation in male patients under the age of 40.

For all patients, the “post-marketing” data examined by the FDA show that the risk of experiencing these side effects is highest within 7 days of receiving the second dose.

Only Pfizer has received full approval from the FDA; the Moderna jab is still technically under the emergency authorization. Whether this will delay or in any way impact the FDA’s approval of the Moderna jab remains unclear.

Here’s the full updated text:

Myocarditis and Pericarditis Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. The observed risk is higher among males under 40 years of age than among females and older males. The observed risk is highest in males 18 through 24 years of age. Although some cases required intensive care support, available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management. Information is not yet available about potential long-term sequelae. The CDC has published considerations related to myocarditis and pericarditis after vaccination, including for vaccination of individuals with a history of myocarditis or pericarditis

Questions about the link between the mRNA jabs and heart inflammation have been circulating since these side effects were first uncovered in a group of American soldiers reporting acute chest pain after their vaccinations.

The news is weighing on Moderna’s share price, which has fallen substantially since its Aug. 9 peak. It was down more than 3% on Monday afternoon.

Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines

Authors: Bryant, Andrew MSc1,*; Lawrie, Theresa A. MBBCh, PhD2; Dowswell, Therese PhD2; Fordham, Edmund J. PhD2; Mitchell, Scott MBChB, MRCS3; Hill, Sarah R. PhD1; Tham, Tony C. MD, FRCP4 American Journal of Therapeutics: July/August 2021 – Volume 28 – Issue 4 – p e434-e460doi: 10.1097/MJT.0000000000001402

Abstract

Background: 

Repurposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials.

Areas of uncertainty: 

We assessed the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemoprophylaxis, among people with, or at high risk of, COVID-19 infection.

Data sources: 

We searched bibliographic databases up to April 25, 2021. Two review authors sifted for studies, extracted data, and assessed risk of bias. Meta-analyses were conducted and certainty of the evidence was assessed using the GRADE approach and additionally in trial sequential analyses for mortality. Twenty-four randomized controlled trials involving 3406 participants met review inclusion.

Therapeutic Advances: 

Meta-analysis of 15 trials found that ivermectin reduced risk of death compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.19–0.73; n = 2438; I2 = 49%; moderate-certainty evidence). This result was confirmed in a trial sequential analysis using the same DerSimonian–Laird method that underpinned the unadjusted analysis. This was also robust against a trial sequential analysis using the Biggerstaff–Tweedie method. Low-certainty evidence found that ivermectin prophylaxis reduced COVID-19 infection by an average 86% (95% confidence interval 79%–91%). Secondary outcomes provided less certain evidence. Low-certainty evidence suggested that there may be no benefit with ivermectin for “need for mechanical ventilation,” whereas effect estimates for “improvement” and “deterioration” clearly favored ivermectin use. Severe adverse events were rare among treatment trials and evidence of no difference was assessed as low certainty. Evidence on other secondary outcomes was very low certainty.

Conclusions: 

Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally.

For More Information:https://journals.lww.com/americantherapeutics/Fulltext/2021/08000/Ivermectin_for_Prevention_and_Treatment_of.7.aspx

Further evidence supports controversial claim that SARS-CoV-2 genes can integrate with human DNA

Authors: By Jon CohenMay. 6, 2021 , 2:45 PM

Science’s COVID-19 reporting is supported by the Heising-Simons Foundation.

A team of prominent scientists has doubled down on its controversial hypothesis that genetic bits of the pandemic coronavirus can integrate into our chromosomes and stick around long after the infection is over. If they are right—skeptics have argued that their results are likely lab artifacts—the insertions could explain the rare finding that people can recover from COVID-19 but then test positive for SARS-CoV-2 again months later.

Stem cell biologist Rudolf Jaenisch and gene regulation specialist Richard Young of the Massachusetts Institute of Technology, who led the work, triggered a Twitter storm in December 2020, when their team first presented the idea in a preprint on bioRxiv. The researchers emphasized that viral integration did not mean people who recovered from COVID-19 remain infectious. But critics charged them with stoking unfounded fears that COVID-19 vaccines based on messenger RNA (mRNA) might somehow alter human DNA. (Janesich and Young stress that their results, both original and new, in no way imply that those vaccines integrate their sequences into our DNA.)

Researchers also presented a brace of scientific criticisms, some of which the team addresses in a paper released online today by the Proceedings of the National Academy of Sciences (PNAS). “We now have unambiguous evidence that coronavirus sequences can integrate into the genome,” Jaenisch says.

SARS-CoV-2, the virus that causes COVID-19, has genes composed of RNA, and Jaenisch, Young, and co-authors contend that on rare occasions an enzyme in human cells may copy the viral sequences into DNA and slip them into our chromosomes. The enzyme, reverse transcriptase, is encoded by LINE-1 elements, sequences that litter 17% of the human genome and represent artifacts of ancient infections by retroviruses. In their original preprint, the researchers presented test tube evidence that when human cells spiked with extra LINE-1 elements were infected with the coronavirus, DNA versions of SARS-CoV-2’s sequences nestled into the cells’ chromosomes.

Many researchers who specialize in LINE-1 elements and other “retrotransposons” thought the data were too thin to support the claim. “If I would have had this data, I would have not submitted to any publication at that point,” says Cornell University’s Cedric Feschotte, who studies endogenous retrovirus chunks in the human genome. He and others also said they expected higher quality work coming from scientists of the caliber of Jaenisch and Young. In two subsequent studies, both posted on bioRxiv, critics presented evidence that the supposed chimeras of human and viral DNA traces are routinely created by the very technique the group used to scan for them in chromosomes. As one report concluded, the human-virus sequences “are more likely to be a methodological product, [sic] than the result of genuine reverse transcription, integration and expression.”

In their new paper, Jaenisch, Young, and colleagues acknowledge that the technique they used accidentally creates human-viral chimeras. “I think it’s a valid point,” Jaenisch says. He adds that when they first submitted the paper to a journal, they knew it needed stronger data, which they hoped to add during the review process. But the journal, like many, requires authors to immediately post all COVID-19 results to a preprint server. “I probably should have said screw you, I won’t put it on bioRxiv. It was a misjudgment,” Jaenisch says.

In the new PNAS paper, the team provides evidence that artifacts alone can’t explain the detected levels of virus-human chimeric DNA. The scientists also show that portions of LINE-1 elements flank the integrated viral genetic sequence, further supporting their hypothesis. And they have collaborated with one of the original skeptics, Stephen Hughes of the National Cancer Institute, who suggested an experiment to clarify whether the integration was real or noise, based on the orientation of the integrated viral sequences relative to the human ones. The results support the original hypothesis, says Hughes, a co-author of the new paper. “That analysis has turned out to be important,” he says.

“The integration data in cell culture is much more convincing than what was presented in the preprint, but it’s still not totally clean,” says Feschotte, who now calls Jaenisch’s and Young’s hypothesis “plausible.” (SARS-CoV-2, he notes, can also persist in a person for months without integrating its genes.)

The real question is whether the cell culture data have any relevance to human health or diagnostics. “In the absence of evidence of integration in patients, the most I can take away from these data is that it is possible to detect SARS-CoV-2 RNA retroposition events in infected cell lines where L1 is overexpressed,” Feschotte says. “The clinical or biological significance of these observations, if any, is a matter of pure speculation at this point.”

Jaenisch’s and Young’s team do report hints of SARS-CoV-2 integration in tissue from living and autopsied COVID-19 patients. Specifically, the researchers found high levels of a type of RNA that is only produced by integrated viral DNA as the cell reads its sequence to make proteins. But, Young acknowledges, “We do not have direct evidence for that yet.”

Harmit Malik, a specialist in ancient viruses in the human genome at the Fred Hutchinson Cancer Research Center, says it’s a “legitimate question” to ask why people who should have cleared the virus sometimes have positive polymerase chain Reaction tests for its sequences. But he also remains unconvinced that the explanation is integrated virus. “Under normal circumstances, there is so little reverse transcription machinery available” in human cells, Malik says.

The controversy has grown decidedly more civil since December. Both Young and Jaenisch say they received more intense criticism for their preprint than any studies in their careers, in part because some researchers worried it played into the hands of vaccine skeptics spreading false claims about the newly authorized mRNA vaccines. “If there ever was a preprint that should be deleted, it is this one! It was irresponsible to even put it up as a preprint, considering the complete lack of relevant evidence. This is now being used by some to spread doubts about the new vaccines,” Marie-Louise Hammarskjöld, a microbiologist at the University of Virginia, posted in a comment on bioRxiv at the time.

And what of the original journal submission? “They rejected it,” Jaenisch says.

Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants

  1. Authors: ViewAmarendra Pegu1,†, Sarah O’Connell1,† View ORCID ProfileStephen D. Schmidt1,, Sijy O’Dell1,View ORCID ProfileChloe A. Talana1, Lilin Lai2, Jim Albert Science  12 Aug 2021: eabj4176m OI: 10.1126/science.abj4176

Abstract

SARS-CoV-2 mutations may diminish vaccine-induced protective immune responses, particularly as antibody titers wane over time. Here, we assess the impact of SARS-CoV-2 variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.526 (Iota), and B.1.617.2 (Delta) on binding, neutralizing, and ACE2-competing antibodies elicited by the vaccine mRNA-1273 over seven months. Cross-reactive neutralizing responses were rare after a single dose. At the peak of response to the second vaccine dose, all individuals had responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6-months after the primary series of the mRNA-1273 vaccine. Across all assays, B.1.351 had the lowest antibody recognition. These data complement ongoing studies to inform the potential need for additional boost vaccinations.

SARS-CoV-2, the virus that causes COVID-19, has infected millions of people worldwide fueling the ongoing global pandemic (1). The combination of RNA virus mutation rates, replication and recombination, in a very large number of individuals is conducive to the emergence of viral variants with improved replication capacity and transmissibility, as well as immunological escape. Of particular interest are the Variants of Concern B.1.1.7 (20I/501Y.V1 or Alpha), B.1.351 (20H/501Y.V2 or Beta), P.1 (Gamma; first identified in Brazil), B.1.429 (Cal20 or Epsilon; first identified in California), and B.1.617.2 (Delta; first identified in India); and Variant of Interest B.1.526 (Iota; first identified in New York). In multiple studies, B.1.351 is the most resistant to neutralization by convalescent or vaccinee sera, with 6-15 fold less neutralization activity for sera from individuals immunized with vaccines based on the virus strain first described in January 2020 (Wuhan-Hu-1, spike also called WA1) (29). Most of these prior studies evaluated sera from vaccinated individuals at timepoints soon after the first or second dose, and had limited data on the durability of such responses. Likewise, clinical studies have reported somewhat reduced efficacy and effectiveness against the B.1.1.7, B.1.351, and B.1.617.2 variants (1012). Although such data provide critical insights into the performance of the vaccines against viral variants, they have not fully addressed the durability of cross-reactive binding and functional antibodies.

Here we investigate the impact of SARS-CoV-2 variants on recognition by sera from individuals who received two 100 mcg doses of the SARS-CoV-2 vaccine mRNA-1273. mRNA-1273 encodes the full-length stabilized spike protein of the WA1 and was administered as a two-dose series 28-days apart. We previously described the binding and neutralization activity against the WA1 SARS-CoV-2 spike longitudinally over 7 months from the first vaccination in volunteers from the Phase 1 trial of the mRNA-1273 vaccine (1316). In the current study, we demonstrate the utility of employing multiple methodologies to assess SARS-CoV-2 vaccine-elicited humoral immunity to variant viruses over time. We tested sera from a random sample of 8 volunteers in each of three age groups: 18-55, 55-70, and 71+ years of age, all of whom had samples available from four timepoints: 4 weeks after the first dose, and two weeks, 3 months, and 6 months after the second dose (Days 29, 43, 119, and 209 after the first dose, respectively).

Three functional assays and two binding assays were used to assess the humoral immune response to the SARS-CoV-2 spike protein. SARS-CoV-2 neutralization was measured using both a lentivirus-based pseudovirus assay, and a live-virus focus reduction neutralization test (FRNT) (17). The third functional assay was a MSD-ECLIA (Meso Scale Discovery-Electrochemiluminescence immunoassay)-based ACE2 competition assay. This method measured the ability of mRNA-1273 vaccine-elicited antibodies to compete with labeled soluble ACE2 for binding to the specific RBD (WA1 or variant) spotted onto the MSD plate. Antibody binding to cell-surface expressed full-length spike was analyzed by flow cytometry. Binding to soluble protein was measured by interferometry in the MSD-ECLIA platform. All samples were assessed against WA1 and the B.1.1.7 and B.1.351 variants in each of these orthogonal serology assays. In addition, all samples were tested against WA1 containing the D614G mutation in both neutralization assays, as well as binding in the cell-surface assay. Further variants were tested in binding assays as follows: S-2P and RBD binding, P.1 against all samples; cell-surface spike binding, P.1, B.1.429, B.1.526, and B.1.617.2 against all samples. A subset of samples – Day 43 to capture the peak response, and Day 209 to look at durability – were evaluated by pseudovirus neutralization against P.1, B.1.429, B.1.526, and B.1.617.2. The specific sequences used in each assay are defined in table S1.

We first assessed the patterns of antibody activity over time. Consistently across assays, low-level recognition of all variants was observed after a single dose (Day 29) (Fig. 1). Activity against all variants peaked two weeks after the second dose (Day 43) with moderate declines over time through Day 209 (Fig. 1). Notably, the values obtained for each assay on a per-sample basis correlated with each other (fig. S1). We next evaluated the relative impact of each variant, considering all timepoints together. Employing the pseudovirus assay, the neutralizing activity was highest against D614G and lowest against B.1.351, with values for all other variants tested falling in between those two variants (Fig. 1A and Fig. 2A). Similar to previous reports from our group (15) and others (18), pseudovirus neutralization ID50s to D614G were 3-fold higher than to WA1 (Fig. 2G). In contrast, using the live-virus FRNT neutralization assay (Fig. 1B and Fig. 2B), titers to WA1 were higher than to D614G, consistent with previous reports for that assay (19). For all other variants, the impact in the live-virus and pseudovirus neutralization assays were concordant: titers against B.1.1.7 were similar to D614G and lower against B.1.351. ACE2 competition was highest for WA1 RBD, intermediate for B.1.1.7, and lowest for B.1.351 (Fig. 1C and Fig. 2C). Spike-binding antibodies were measured using two different methodologies. In the cell-surface spike binding assay, serum antibodies were bound to full-length, membrane-embedded spike on the surface of transfected cells and measured by flow cytometry (20). In this assay (Fig. 1D and Fig. 2D), WA1 and D614G were nearly indistinguishable, with ~1.5-fold reduced binding to B.1.1.7, B.1.526, B.1.617.2, and 2.4 to 3.0-fold reduced binding to P.1, and B.1.429, and B.1.351. We also used the MSD-ECLIA multiplex binding assay to simultaneously measure IgG binding against both the stabilized soluble spike protein S-2P (21) and RBD proteins derived from WA1 and the B.1.1.7, B.1.351, and P.1 variants. The ECLIA assay showed slightly reduced binding to the variant S-2P (Fig. 1E and Fig. 2E) and RBD (Fig. 1F and Fig. 2F) proteins, with the rank order of highest to lowest binding as follows: WA1, B.1.1.7, P.1, and B.1.351. The overall effect of each variant in each assay is tabulated in Fig. 2G, which shows the geometric mean of the ratios between values for WA1 and variant or D614G and variant. In all assays, B.1.351 was the variant that caused the greatest reduction in titers compared to WA1 or D614G.

For More Information: https://science.sciencemag.org/content/early/2021/08/11/science.abj4176.full

Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people

  1. Julia Hippisley-Cox1, Duncan Young2,3, Carol Coupland4, Keith M Channon5, Pui San Tan6, David A Harrison7, Kathryn Rowan8,  Paul Aveyard6, Ian D Pavord9, Peter J Watkinson5,10
  2. Correspondence to Prof Julia Hippisley-Cox, Primary Care Health Sciences, University of Oxford, Oxford OX1 

Abstract

Background 

There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission.

Methods 

This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20–99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care.

Findings 

Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.

There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group.

Interpretation 

ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.