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Saturday, July 17, 2021

More AI Diagnosis: Phone Calls Spot Early Alzheimer's

 Speech patterns in phone conversations can spot people with early to moderate Alzheimer's dementia, a Japanese study suggested.

A machine-learning predictive model correctly identified people with Alzheimer's dementia with about 90% accuracy using audio files of phone conversations of 24 people with confirmed Alzheimer's and 99 healthy controls, reported Akihiro Shimoda, MPH, of McCann Health Worldwide Japan in Tokyo, and co-authors, in PLOS ONE.

People with Alzheimer's disease are more likely to speak more slowly with longer pauses than others, Shimoda and co-authors noted, explaining that people with Alzheimer's spend more time finding the correct word, which produces broken messages that lack speech fluency.

What differentiated this study from others is that it focused on vocal features of everyday speech.

"We did not use text data extracted from voice data," Shimoda told MedPage Today. "We did not use voice data from cognitive tests in a clinical setting, but from daily telephone conversations."

The researchers also assessed pitch and intensity to identify voice characteristics of dementia patients.

"The results show the possibility of incorporating a prediction model into a phone app to conduct an initial assessment of dementia risk in older adults," Shimoda said. "It provides a possible way to identify dementia risk by using voice data of older adults, which are easier to obtain than conventional cognitive tests, biomarkers, or brain imaging."

However, an app based on this model is "far from something that can substitute for current dementia screening methods," he emphasized. "It would be an initial tool that's accessible and low-cost."

The study evaluated data from people 65 and older who participated in a dementia prevention program in Hachioji City from March to May 2020. The program included 1 to 2 months of weekday phone calls from an artificial intelligence (AI) computer program aimed at improving diet, physical activity, and social participation.

The phone interaction included an assessment of cognitive function based on the Japanese version of the Telephone Interview for Cognitive Status (TICS-J) on the first day, then asked participants to talk freely about daily life for 1 minute and answer questions like "What did you do yesterday?"

Alzheimer's was diagnosed using National Institute on Aging-Alzheimer's Association criteria or the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. before the program started. An Alzheimer's diagnosis was used as a binary variable to predict outcome.

People with severe Alzheimer's were excluded from the program. People in the Alzheimer's group had mild/moderate Alzheimer's disease or mild cognitive impairment.

The 99 healthy controls and 24 Alzheimer's patients yielded 1,465 and 151 audio files, respectively, with 81% randomly allocated to the training data set and 19% to validation data. After extracting vocal features from the audio files, the researchers developed models based on extreme gradient boosting (XGBoost), random forest, and logistic regression.

Prediction based on each audio file showed an area under the receiver operating characteristic curve (AUC) of 0.863 (95% CI 0.794–0.931) for XGBoost, 0.882 (95% CI 0.840–0.924) for random forest, and 0.893 (95% CI 0.832–0.954) for logistic regression.

Prediction based on each participant showed an AUC of 1.000 (95% CI 1.000–1.000) for XGBoost, 1.000 (95% CI 1.000–1.000) for random forest, and 0.972 (95% CI 0.918–1.000) for logistic regression. Prediction based on the TICS-J cognitive assessment was 0.917 (95% CI 0.918–1.000).

Both XGBoost and the TICS-J cognitive assessment had 100% sensitivity. XGBoost had 100% specificity, while TICS-J had 83.3% specificity.

The study had several limitations, Shimoda and co-authors acknowledged. The outcome variable was binary -- Alzheimer's disease or healthy controls -- and ignored variations in speech characteristics at different stages of dementia. In addition, the sample size was small, audio quality differed for some participants, and because the TICS-J assessment was conducted by an AI program, its limited speech recognition ability may have affected results.

The researchers also relied on superficial vocal features like pitch and intensity. "Further research could include natural language processing of speech content and sentence structure analysis in order to reduce information loss and increase model prediction performance," the team wrote.


Disclosures

Could COVID Shots in Secret Lure Holdouts?

 In COVID-19 hot spots across the country where the Delta variant is thriving and vaccine hesitancy is high, hospitals have continued to urge for more people to get vaccinated. In the case of Ozarks Healthcare, based in West Plains, Mo., the health system recently issued an impassioned plea for people to get vaccinated, even if it means doing so in secret.

They offered to answer any questions about the vaccine and help with scheduling in a recent statement, addressing the local community.

Notably, the health system added: "If you are afraid of walking into a public area where you might be seen getting your vaccine, we will work to accommodate even more of a private setting for you to receive your vaccine."

With misinformation rampant and vaccination status largely divided by political lines, the concept of making a public appeal to offer the COVID vaccine in private seems to be a unique approach.

"Choosing to get vaccinated has been put in a strange light," Ozarks Healthcare wrote. "For some, getting a vaccine may mean losing friendships. But it is a choice that can impact so many lives other than your own."

The need to get more people vaccinated has never been higher. Unfortunately, Ozarks Healthcare wrote in its statement that as of July 7, the health system's COVID patients ranged in age from 30 to 76, and only one had been vaccinated.

"You may think we sound like a broken record," the health system continued. "Conversations about COVID-19 may leave you feeling worn and trampled on, just like this mask, the accessory of 2020 we never wanted to see again. You probably see the exhaustion in our staff's eyes sometimes more than a smile. You likely feel just as disappointed as we are, having to run yet another marathon in a race we never asked to run."

The health system added that it understands getting vaccinated is a personal choice, but doubled down on its plea.

A week after the health system issued its plea, it reported that it had 18 COVID patients hospitalized on Monday, 17 on Tuesday, and 15 that day. The totals marked the highest the health system had seen since early January, and patients ranged in age from 22 to 87.

On July 14, Ozarks Healthcare wrote the following on Twitter: "We administered more than 50 COVID-19 vaccines through our pharmacy yesterday, which is almost double the average we have been seeing! We need many more days like yesterday to make a difference, but we are thankful for those doing their part to help protect our community."

https://www.medpagetoday.com/special-reports/exclusives/93616

States and insurers resurrect barriers to telehealth, putting strain on patients

 Telemedicine is here to stay. But its free-for-all era may be coming to an end.

State-issued emergency declarations and insurer policies that were issued at the start of the Covid-19 pandemic and that were meant to encourage the use of telemedicine are being phased out across U.S. states, one by one. And as they fade away, rules that make telemedicine more complicated — and costly — are setting back in.

Experts say the moves, which come as vaccinations have ramped up and case counts have dwindled, are causing headaches among patients and providers alike. Doctors are scrambling to stay on top of rapidly changing rules. Patients are contorting themselves to keep their virtual appointments — even driving into different states and taking calls from the side of the road so they can legally receive care.

“The party is winding down in subtle ways that are really going to impact patients,” said Ateev Mehrotra, a hospitalist and health care policy researcher at Harvard Medical School who focuses on telemedicine. “And I shouldn’t use the future tense, I should say are currently impacting patients in really, really important ways.”

That was the case for Victoria DeLano and her husband Jim, who were back on the road last week, hauling their two kids and three dogs in a 30-foot RV to visit a doctor with their son James, who has three rare diseases. During the pandemic, they were parked at home. James, 16, was able to receive the specialist care he needed via telemedicine: the cardiologist in Ohio, the geneticist in Atlanta, the gastroenterologist in South Carolina, the neurologist and NIH clinical center in Maryland.

They had saved thousands of dollars, and had to take less time off of work and away from family activities. But most importantly, James didn’t have to handle the exhaustion of constantly traveling with a wheelchair, his service dog, and a cooler of IV medications, fluids, and supplies for his feeding tube.

In May, James had a televisit scheduled with his cardiologist in Ohio. But a week before the appointment, his mom received notice: Telemedicine was off, and they needed to reschedule for in-person. “Now, having that taken away like this,” she said, en route from their Alabama home, “it’s really devastating.”

One of the most visible impacts is playing out on state borders, where the lifting of pandemic restrictions is creating a new phenomenon: the rest stop televisit.

Such visits are becoming more common, especially for patients who see doctors in city centers near state lines, or those who live in New England’s tightly-clustered states. It’s something Stephanie Titus, a primary care physician in Massachusetts, is watching unfold firsthand.

In the last year, Titus has treated patients located in Rhode Island, Vermont, New Hampshire, and even Maine virtually. That would normally require her to obtain a license in each of those states — a process that can take months and cost hundreds of dollars. But thanks to emergency orders from state governors and licensing boards, some of which expedited the application process or extended telehealth licenses to providers in neighboring states, that was no longer necessary.

Many of Titus’ far-flung patients now want to continue televisits whenever they’re practical. “For something as simple as blood pressure checks when they have a reliable blood pressure monitor at home,” said Titus, “it doesn’t make sense to have them travel.” But on July 1, Titus’ network, Mass General Brigham, decided to end telemedicine appointments for patients in states where their providers are not licensed, in anticipation of the lifting of temporary license allowances.

Titus started asking her out-of-state patients to make a choice: come back into the office, or take their telehealth appointments within Massachusetts’ borders. One of her patients from Rhode Island drove just across the border, parked in the lot outside of a BJ’s superstore, and called in from her car.

Cobbling together cross-state care can be especially challenging for patients using virtual mental health visits. While weekly, conversation-based mental health services have been a natural fit for telemedicine, their frequency also makes them uniquely susceptible to the impacts of expiring rules.

After Minnesota’s governor rescinded a number of executive orders on May 28, Doug Anderson, clinical services director at Sioux Falls Psychological Services in neighboring South Dakota, had to start asking patients to drive across the border to continue telecare. Even if patients agree, providers are stuck in an ethical bind: Without a reliable way to verify location, do you trust your patient, or do you try to protect yourself from accidentally practicing illegally? Some of his colleagues, Anderson said, have been asking patients to take a screenshot of their location on Google Maps and share it at the beginning of the appointment.

“Frankly, it leaves an awful lot of people in the lurch,” said Anderson. “It makes life difficult for clients, as well as therapists.”

For some, driving across a state border just isn’t an option. In Massachusetts, independent clinical social worker Cooper McCullough has been seeing a client who lives in New York via telehealth. He made clear that they might not be able to continue working together after New York lifted its temporary license waivers, and kept a close eye on regulatory websites so he could be sure to give the client notice. July 5, he read on the site, would be the last day of the waiver.

But on June 24, the governor ended the disaster emergency, immediately taking with it the executive order that allowed McCullough to see his client. They had to cancel their exit session.

“This person is not somebody who would’ve entered therapy lightly,” said McCullough. “I don’t know if he’s going to be comfortable continuing that with somebody he doesn’t know.”

With behavioral health accounting for more than half of all telehealth visits during the pandemic, the end of license waivers could have a dramatic impact on patients. “The restriction across states is bad for clients: bad for access to care and very much bad for continuity of care,” said Roy Huggins, a counselor and founder of Person Centered Tech, a consulting company that helps mental health providers navigate telehealth. “Needing to switch a therapist is unhelpful at best, or harmful at worst,” he added.

To many providers, the reversion to pre-pandemic regulations on telehealth is nonsensical.

“One of the big benefits of what happened during the pandemic was an expansion, but it was also a sense of clarity. You knew what the rules were, because everything was fine,” said Mehrotra in a recent symposium on telehealth. “We’re about to enter a time where it’s very, very confusing because everyone’s going to potentially have a different set of rules. And for a telehealth provider, that makes things 10 times worse because you have 10 sets of rules for every state you’re in.”

Based on current executive orders, Titus could still legally see some of her out-of-state patients via telehealth, but her health network decided to implement a single cutoff date because it was just too complicated to keep track. “Elaborating that to the thousands and thousands of patients that we have this is just too burdensome, and the risk is not worth it,” said Titus.

There are good reasons for states to issue their own licensure requirements. States want to protect their patients, and so do providers. With individualized licenses, states decide what level of experience, certification, and continuing education is required to practice. They also provide a clear path to discipline doctors who harm patients. And with more state-specific knowledge, providers might have a better chance of being able to direct in-person services to a patient who has a medical crisis during a video appointment.

Those arguments have led to one set of solutions: interstate compacts, which would streamline the process of applying for cross-state or state-specific licenses. For physicians, there’s the Interstate Physician Licensure Compact, which 30 states have signed onto since 2017; physicians still have to pay for each state’s license, but the process moves faster. Psychologists have PSYPACT; providers licensed in its 26 states can apply for a dedicated, cross-member telepsychology authorization. Social workers will start developing their own compact soon, with funding from the Department of Defense, whose frequent transfers have made it a proponent of interchangeable licenses for military spouses who practice medicine.

Some states are also passing legislation to extend temporary telehealth provisions without burdening physicians with new license applications. Connecticut will continue to acknowledge out-of-state licenses for two years for telemedicine, and Arizona will do so in perpetuity; others are allowing physicians to hold onto their emergency licenses for as long as it takes for their new, long-term licenses to be approved.

All those solutions keep states in charge of license issuance, theoretically providing better protection for patients. But Mehrotra sees a different motivation at work in states’ possessiveness. “I think the much bigger issue and concern is that state medical boards are focused on protecting their members from the outside competition,” he said.

While federal licensure is viewed by most as an unlikely solution, telehealth’s impact on interstate commerce could open up a path to a comprehensive federal solution, perhaps legislation requiring license reciprocity between states, Mehrotra wrote in a recent perspective in the New England Journal of Medicine. “I would love a telemedicine-only license that would allow me to take care of any established patient anywhere in the U.S.,” said Titus, a sentiment echoed by many of the providers who spoke with STAT.

For patients like James DeLano, who have benefited the most from telehealth provisions during the pandemic, reform can’t come soon enough. His mom is grateful for the care he receives — the visit in Ohio went well — but she hopes that new regulations will make it easier to use telehealth when it’s practical. “I kind of feel like we didn’t know what we didn’t have until we had it,” said Victoria DeLano, in the middle of a 12-hour stretch in the RV. “We didn’t recognize the value of telehealth until the shutdown.”

https://www.statnews.com/2021/07/13/telehealth-provisions-emergency-patients/

Decline in Covid-19 preceded vaccines. But we need jabs to finish the job

 As coronavirus infections decline in the U.S., it seems appropriate to celebrate the triumph of vaccines over viruses. But how much of the credit do vaccines deserve? Less than you might expect.

Don’t get me wrong: I believe in vaccines. I got vaccinated was soon as I was eligible and am 100% behind the goal of getting everyone on the planet vaccinated. Yet there are other factors also at work in quelling a pandemic.

Following patterns from previous pandemics, the precipitous decline in new cases of Covid-19 started well before a meaningful number of people had been vaccinated.

Nearly 50 years ago, medical sociologists John and Sonja McKinlay examined death rates from 10 serious diseases: tuberculosis, scarlet fever, influenzae, pneumonia, diphtheria, whooping cough, measles, smallpox, typhoid, and polio. In each case, the new therapy or vaccine credited with overcoming it was introduced well after the disease was in decline. More recently, historian Thomas McKeown noted that deaths from bronchitis, pneumonia, and influenza had begun rapidly falling 35 years before the introduction of new medicines that were credited with their conquest.

These historical analyses are relevant to the current pandemic.

New cases of Covid-19 peaked in early January 2021. Since then, cases retreated from more than 300,000 per day on Jan. 8 to around 55,000 on Feb. 21. Vaccines were first given emergency use authorization toward the end of December 2020. By Feb. 21, only 5.9% of Americans had received two shots, yet there had been an 82% decline in new cases.

Daily Covid Cases
New cases of Covid-19 peaked on Jan. 8, 2021. By Feb. 21, only 5.9% of the population had been fully vaccinated, but cases had fallen 82%.J. EMORY PARKER/STAT

To be sure, coronavirus vaccines are a remarkable accomplishment. But even a vaccine that’s 95% effective can’t take full credit if it is introduced on the back of a naturally receding epidemic. Timing is everything.

There are two ways to develop immunity: natural infection and vaccination. The best explanation for declining rates of Covid-19 appears to be previous infections, which vary considerably from state to state.

Individuals with confirmed Covid-19 diagnoses are only the tip of the iceberg. Although estimates vary, the most recent study from the National Institutes of Health suggests that about five people were infected with SARS-CoV-2, the virus that causes Covid-19, for each person with a confirmed case. Multiplying known cases by five yields a rough estimate of the number of people who may have been infected. I performed a simple calculation of what I call the natural immunity rate by dividing my estimate of the number of people naturally infected by SARS-CoV-2 by the population of the state.

By mid-February 2021, an estimated 150 million people in the U.S. (30 million times five) may have had been infected with SARS-CoV-2. By April, I estimated the natural immunity rate to be above 55% in 10 states: Arizona, Iowa, Nebraska, North Dakota, Oklahoma, Rhode Island, South Dakota, Tennessee, Utah, and Wisconsin. At the other end of the continuum, I estimated the natural immunity rate to be below 35% in the District of Columbia, Hawaii, Maine, Maryland, New Hampshire, Oregon, Puerto Rico, Vermont, Virginia, and Washington.

The table below summarizes how these two groups of states with high and low natural infection rates differ. By the end of 2020, new infections were already rapidly declining in nearly all of the 10 states where the majority may have had natural immunity, well before more than a minuscule percentage of Americans were fully vaccinated. In 80% of these states, the day when new cases were at their peak occurred before vaccines were available.

In contrast, the 10 states with lower rates of previous infections were much more likely to experience new upticks in Covid-19 cases in March and April. The date with the highest number of new cases occurred before vaccines were available in only 30% of these states. By the end of May, states with fewer new infections had significantly lower vaccination rates than states with more new infections.

In other words, states with low natural immunity, like Oregon, Vermont, and Washington, that had vaccinated more of their citizens were also experiencing more new Covid-19 cases. And despite lower vaccination rates, high natural immunity states like North Dakota, Tennessee, and Utah may have had fewer cases because more of their citizens were protected through natural immunity from previous infections.

Public policy may have also played an unexpected role. In the 2020 presidential election, Donald Trump carried seven of the 10 states with high natural immunity, while Joe Biden carried all 10 states with low natural immunity. Among the 10 states with high natural immunity, 90% did not have active mask policies, while 90% of states with low natural immunity had mask policies in place through May.

Variable10 States with Highest Natural Immunity Rates10 States with Lowest Natural Immunity Rates
Estimated previous infections (confirmed cases x 5)61%26%
Fully vaccinated39%45%
14-day change in cases-9%+9%
States won by Trump70%0%
States with mask policy in effect10%90%
States with peak infections before vaccines available (Jan. 1, 2021)80%30%

Data from The New York Times, values through May 2021

So, what happened? First, states that enacted mask and related policies had fewer new cases of Covid-19. That is certainly good news. But there may have been a downside: Mask and other mandates that successfully lowered infections may have left unvaccinated people vulnerable to SARS-CoV-2 because fewer had acquired natural immunity. Conversely, states without mask policies suffered higher rates of infection that resulted in more natural immunity, offering more protection before vaccines were available.

Although vaccines and previous infections are alternative pathways to immunity, vaccines are by far the safer route to it. The cost for some states to achieve high natural immunity was the heartbreak of intolerable rates of illness, hospitalization, and death. Suggesting that people risk getting infected to achieve immunity is unacceptably irresponsible.

To be prepared for future pandemics, the U.S. — and other countries — need to learn what really happened across the course of this one. The answer is not likely to be simple, since there is plenty of nuance overlaid on ever-changing trends.

For example, in contrast to my analysis, the Washington Post reported on June 14 that coronavirus infections are falling where people are vaccinated and rising where they are not. The Post’s analysis is correct: There is a modest correlation between current state-level vaccination rates and the most recent reports of new cases. But it ignores longer-term trends.

States with low natural immunity, despite administering more vaccines, were more likely to have surges of Covid-19 in the spring. As the pandemic was receding, declines in low natural immunity states may have appeared larger because they were falling from higher spring peaks. Most states with high natural immunity had achieved low new case rates by December, leaving less room to observe declines. A set of graphs is available here.

Some analyses also concentrate on small geographic areas. Sweetwater County, Wyo., where only about 27% of residents are fully vaccinated, has received significant media attention. The county recently led Wyoming for increases in new cases. Wyoming, in turn, leads the U.S. in new infections. But Sweetwater County has only 42,343 residents. Minor — and perhaps transitory — changes in the number of cases can appear as a large percentage change.

In contrast to the suggested spike, data from the New York Times show that Sweetwater’s seven-day average for new cases has been relatively steady for the last few months and recently declined from a high on June 1. And though Wyoming has a very low statewide vaccination rate, new cases had dropped by mid-February — before many people could have been vaccinated — and have remained fairly steady through the spring.

Epidemiology is rarely simple and it will take some time to sort through these conflicting interpretations.

But one trend appears to be clear. As in previous pandemics, the rapid fall in new cases preceded the widespread distribution of vaccines. Although vaccines deserve much credit for declining rates of Covid-19, the protection provided by natural infection has been underappreciated. Emerging evidence shows that previously infected people have effective and durable immunity that rivals or exceeds the benefits of vaccines.

When historians look back at this pandemic, they might report that credit for its resolution should be shared by vaccines, natural immunity, and other public health measures. But even though vaccines did not initiate the decline in Covid-19 cases, they are the best tool available for assuring that the smoldering fire of it is extinguished.

Robert M. Kaplan is a faculty member at Stanford Medicine’s Clinical Excellence Research Center and a distinguished professor emeritus at the UCLA Fielding School of Public Health.

https://www.statnews.com/2021/07/12/covid-19-decline-preceded-vaccines-still-need-jabs-finish-the-job/

Next Covid-19 Battle Will Be About Vaccinating Kids

 ON MONDAY, THE Tennessee Department of Health fired its top vaccine official, Michelle Fiscus. Her transgression: In May, she had sent a memo to pharmacies and physicians in the state, relaying a Tennessee Supreme Court decision that allows teens to seek medical care, including vaccinations, without their parents’ consent. At the time, the Food and Drug Administration had just authorized the Pfizer vaccine for 12- to 17-year-olds, and one for the Moderna vaccine was soon to follow.

Fiscus’ memo was approved by the governor’s staff, and it contained no policy changes. The legal ruling it discussed was handed down in 1987. State legislators, though, accused her of “prodding” children to seek the vaccine. She was summoned to two hearings; at one, a legislator proposed dissolving the entire state health department in retaliation.

In a statement she gave to The Tennessean Monday evening, Fiscus said that, to protect itself, the department has shut down all its communication campaigns about vaccination. “Not just Covid-19 vaccine outreach for teens, but ALL communications around vaccines of any kind,” she wrote. “No back-to-school messaging to the more than 30,000 parents who did not get their children measles vaccines last year due to the pandemic. No messaging around human papillomavirus vaccine to the residents of the state with one of the highest HPV cancer rates in the country.” (On Tuesday, The Tennessean confirmed that vaccine promotion, and vaccination clinics held at schools, had been shut down.)

Fiscus’ firing came two days after a crowd at the Conservative Political Action Conference in Dallas cheered an announcement that the Biden administration hasn’t achieved its goal of getting one dose of vaccine into 70 percent of Americans by July 4th. It also came three days after the Centers for Disease Control and Prevention relaxed the agency’s previous guidelines about wearing masks inside school buildings. Add those events together, and they’re a storm siren for the next Covid battle, this time over vaccinating children—which will arrive as the virus’s Delta variant advances and the school year is about to begin.

Clinical trials underway now are testing the safety, efficacy, dosing, and timing of mRNA vaccines for kids between the ages of 11 years and 6 months; about 4,500 children are in Pfizer’s trial, and about 7,000 in Moderna’s. A Pfizer official said in June that the first request for emergency authorization should be sent to the FDA in September or October. (Johnson & Johnson is only now beginning trials in teens and has not yet included younger kids.)

Those trials are scattered across medical centers in the US and several European countries—more sites than were initially planned for, according to several principal investigators, because the companies feel it’s urgent to gather data and move toward approval as rapidly as possible. That's because, now that adults can get vaccinated, children make up a larger proportion of those getting sick from Covid.

Kids represented 14.2 percent of all US cases in July, compared to 2 percent in April 2020, according to the American Academy of Pediatrics. Just in the US, more than 4 million children have fallen ill from Covid. And though most experience only mild illness, 16,623 had been hospitalized as of July 8, and 344 had died. As of the end of June, 4,196 children and teens had developed MIS-C, the perplexing and sometimes fatal inflammation that occurs after Covid infection and affects the heart, lungs, kidneys, and brain.

“Covid is a risk for children,” says Mark Sawyer, a professor of pediatrics at the UC San Diego School of Medicine and temporary voting member of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), which reviewed evidence submitted on behalf of the Covid vaccines. “The reported deaths are at least as bad as the worst influenza season in terms of pediatric deaths, and probably a little worse than that. That doesn't even get us into what long-term consequences could occur, either from MIS-C or so-called long-haul Covid. And that doesn't even touch the public health argument, which is that we need children not to be bringing Covid to their grandparents and others who are at extremely high risk.”

As many researchers have pointed out over the years, children aren’t just small adults. Once past the teen years, adults have mostly achieved their final height and size—barring big gains or losses in fat and muscle—and, crucially, a settled immune balance with the world. But children are changing all the time, not just in size and muscle mass, but in how their immune systems defend them against the world.

“The spectrum and the strength of the immune response changes over years,” Inci Yildirim, a vaccinologist and associate professor of pediatrics and global health at the Yale School of Medicine, told WIRED by email. “For example, a healthy 13-month-old child usually has a higher number of lymphocytes, which is one of many components of the immune system playing a role in how we respond to the vaccines, compared with a healthy 15-year-old teenager.”

Even though we have data on how adults respond to the Covid vaccines—from the clinical trials that got the vaccines their emergency authorizations, and also from real-world observations—we can’t assume that children’s reactions will be the same. Weirdly, they might be better. For instance, after the introduction of the HPV vaccine (which prevents cancers of the cervix, neck, and throat), federal authorities decided that 9- to 14-year-olds need only two doses, not three as older teens and adults do, because the younger kids’ response to the vaccine was so strong.

But because Covid is still a new and under-researched disease, we have to do clinical trials to explore what those reactions might be. As the World Health Organization highlighted in a meeting in May, we still have not identified the “correlates of protection” that define immunity. Those would be agreed-upon metrics for immune response—a minimum number of antibodies, for instance, or measurements of the presence of T cells— that would indicate when someone who has received a vaccine is protected against infection. If we could define those correlates, we could skip placebo-controlled trials for head-to-head studies comparing different vaccines, or even use blood tests. Since we don’t, full trials in kids, patterned on the adult ones, are necessary.

(Talaat and other principal investigators said many of the parents enrolling their kids turned out to be faculty from medical schools and other parts of universities conducting the trials, who happened to hear about the trials early because of their jobs. That could turn out to be a problem, because it may have accidentally created trial populations that are low on diversity—not necessarily of race or national origin, but of economic status and living conditions, both of which affected who was vulnerable during Covid’s first wave.)

Within the trials, child entrants are stratified—separated into groups—according to age ranges. The Stanford University School of Medicine, for instance, joined the Pfizer Phase I safety trial for infants and toddlers, who were divided into groups of kids between the ages of 6 months and 2 years, and then kids who were at least 2 but younger than 5. Stanford now is one of the sites hosting Phase II efficacy trials for the under-5 group, and also is running part of the Phase II and III trials for the 5- to 11-year-olds. (A Phase III trial also tests efficacy, but in a larger group, because some rare effects are only observable when more participants are added.)

The Pfizer trial those studies are part of is already returning information showing that the vaccines may create stronger immunity in kids than in adults, according to Yvonne Maldonado, a pediatrician and professor of epidemiology and population health and principal investigator of the Stanford trial site. “The first data that was put out in May, that was submitted to FDA, showed that the Pfizer vaccine had elicited much higher antibody titers in children than it did in adults,” Maldonado says. Those findings could well lead, in the final authorizations, to vaccines containing much smaller doses of active ingredients than are present in the adult vaccines.

Overall, it seems there have been no major setbacks. But there’s a difficult challenge approaching. Once trial data determining children’s doses and shot schedule passes the FDA—as either an emergency use authorization or a full new drug approval—the campaigns that distribute the shots will be run by the individual states, in the same way that the adult vaccines were. This spring, that was chaotic.

What might save the child vaccine, and the health of vulnerable elderly and immunocompromised people in contact with children, is that the system to distribute the shots won’t have to be built from scratch. American public health agencies already recommend that children and teens receive 16 different vaccines by the time they turn 18—against measles, mumps, rubella, diphtheria, pertussis, two types of hepatitis, rotavirus, chicken pox, flu, and so on—and many of those vaccines require multiple doses. A massive infrastructure delivers, tracks, and pays for those shots: physician practices, commercial pharmacies, health department clinics, and county health fairs; health department registries and state school-entry standards; private insurers and an array of federal buying programs. (Outside the US, the mix of funding comes from national governments and international philanthropies, and the vaccinators may be doctors’ offices, public health clinics, or volunteer-run sites.) Adding a Covid vaccine into that distribution would not be trivial, but it should not be impossibly hard.

“If you want to get vaccines out to a population, the most practical way to do that is through pediatric immunization,” says Ofer Levy, a pediatric infectious disease clinician and director of the Precision Vaccines Program at Boston Children’s Hospital, and also a temporary voting member of VRBPAC. “The majority of the world’s infrastructure for delivering vaccines is directed at children, and vaccines that are given to children around the globe get a population penetration of 80 percent to 90 percent.”

Yet any legislation that makes Covid vaccines available to children—or mandates them—is also a matter for every individual state government to decide. And in the seven months since the adult versions were released, openness to vaccination has split into a red-blue divide. That could lead to more of the politicization that exploded in Tennessee this week, and fewer kids able to access the shots. And that means ongoing vulnerability, the emergence of more variants, and a longer pandemic in the end..

https://www.wired.com/story/the-next-covid-19-battle-will-be-about-vaccinating-kids/

Israel offers 3rd Pfizer shot amid spiking cases, U.S. says not yet needed

 Israel will allow adults with severe pre-existing medical conditions to receive a third dose of the Pfizer vaccine against Covid-19, making it the first country in the world to do so. 

The Israeli government’s decision comes as coronavirus infections rise due to the spread of the delta variant, but also stands in contrast to a recent statement from top U.S. health authorities regarding its own citizens that a booster shot isn’t actually needed.  

Israel’s health ministry this week said that the booster will be offered to adults considered to be at risk, and specifically mentioned people with severe immunodeficiency or who have recently undergone an organ transplant. 

It was not immediately clear whether the booster shot would also be made available to Palestinians living in Israeli-occupied territory. 

Jury remains open

Covid cases in Israel jumped to more than 400 per day in early July after staying in the single digits for most of June — despite the fact that the country has been praised for executing one of the fastest vaccination campaigns in the world. More than 5 million of its 9 million citizens have been fully vaccinated against the disease. 

But after fully reopening its economy in the spring, Israel has brought back some restrictions, including mandatory mask-wearing indoors and on public transport. 

Still, despite the rise in case volume, Israel’s health ministry said during the first week of July that only 47 of the 4,000 registered active cases in the country were considered serious.

Meanwhile, the debate continues as to whether a third dose of any vaccine is necessary and will make a significant difference in protecting people from the virus. Health officials in the U.S. don’t take that to be the case so far.

“Americans who have been fully vaccinated do not need a booster shot at this time,” the U.S. Food and Drug Administration and Centers for Disease Control said in a joint statement on July 8.

“We continue to review any new data as it becomes available and will keep the public informed. We are prepared for booster doses if and when the science demonstrates that they are needed.”

In a press release issued on the same day, Pfizer and BioNTech said that a third dose of their vaccine “has the potential to preserve the highest levels of protective efficacy against all currently known variants including Delta.”

The American and German companies are currently developing a new version of their shot “that targets the full spike protein of the Delta variant,” the statement said. 

‘A dangerous trend’

Pfizer has said it would request regulatory approval for its booster shot, while some countries where Chinese-made vaccines were widely administered are now offering a Pfizer booster amid doubts over the efficacy of Chinese vaccines. Bahrain and the United Arab Emirates are among the countries now offering a Pfizer booster for people who have received two doses of China’s Sinopharm, despite the jury remaining open as to whether the practice is ultimately safe.  

On Monday, chief WHO scientist Soumya Swaminathan warned against mixing vaccines. 

“It’s a little bit of a dangerous trend here … we’re in a data-free, evidence-free zone as far as mix and match (of vaccines),” she said during a press conference.

“There is limited data on mix and match, there are studies going on, we need to wait for that, maybe it will be a very good approach, but at the moment we only have data on the AstraZeneca followed by Pfizer. So, it will be a chaotic situation in countries if citizens start deciding when and who should be taking a third and fourth dose.”

Criticism over vaccine delivery to Palestinians

The West Bank’s ruling Palestinian Authority in June canceled a vaccine swap deal with Israel, under which it would have received 1 million doses of an ageing stock of Pfizer vaccines from Israel that needed to be used up, and would in exchange give Israel a similar number of Pfizer doses it planned to receive from the company later in the year. 

But the stock’s expiry date was in June — the same month it was meant to be delivered to Israel — and the Palestinians rejected them, saying they were initially told the shots would expire in July and August. Israel denies this and says they were clear about the expiry dates.

Israel in January sent 5,000 vaccine doses to Palestinian health workers living in the West Bank, which rights activists and Palestinians say is insufficient and a dereliction of Israel’s duty of care as an occupying state.

Israel’s foreign ministry did not immediately reply to a CNBC request for comment. 

Just over 30% of eligible Palestinians in the West Bank and Gaza have received at least one vaccine dose, Palestinian officials say, largely thanks to the COVAX vaccine sharing initiative and donations from various countries.

https://www.cnbc.com/2021/07/13/israel-is-offering-a-third-pfizer-shot-amid-spiking-cases.html

Friday, July 16, 2021

Can dietary supplements help the immune system fight coronavirus infection?

 Johns Hopkins Medicine gastroenterologist Gerard Mullin, M.D., and a team of co-authors published an article May 11, 2021, in Advances in Experimental Medicine and Biology that details the scientific rationale and possible benefits—as well as possible drawbacks—of several dietary supplements currently in clinical trials related to COVID-19 treatment.

According to business analysts, the U.S. nutritional supplement industry grew as much as 14.5% in 2020, due in large part to the COVID-19 pandemic.

Mullin, associate professor of medicine at the Johns Hopkins University School of Medicine, and his colleagues shine a light on melatonin, vitamin C, vitamin D, zinc and several plant-based compounds, such as green tea and curcumin. For instance, the authors explain that ascorbic acid—also known as vitamin C—"contributes to immune defense by supporting cell functions of both the innate and adaptive immune systems."

In the journal article, they discuss the mechanics of how each of the supplements works and how each might benefit a patient fighting COVID-19.

Zinc, they write, has been shown "to inhibit coronavirus RNA replication." They also note that, when administered at symptom onset, zinc "can reduce the duration of symptoms from illness attributed to more innocuous coronavirus infections, such as the common cold."

Finally, Mullin and his colleagues provide short explanations of the clinical trials underway to test each supplement's effectiveness in fighting COVID-19.

For example, Mullin says that, "to date, there are abundant data associating low vitamin D status to higher vulnerability to COVID-19 and poor clinical outcomes."

The authors caution that "any benefit of dietary supplements against COVID-19 depends on results of randomized controlled trials" and peer-reviewed literature.


Explore further

Multivits, omega-3, probiotics, vitamin D may lessen risk of positive COVID-19 test

More information: Gerard E. Mullin et al, Dietary Supplements for COVID-19, Coronavirus Disease - COVID-19 (2021). DOI: 10.1007/978-3-030-63761-3_29
https://medicalxpress.com/news/2021-07-dietary-supplements-immune-coronavirus-infection.html