A high level of RSV vaccination would not only potentially reduce millions of dollars in annual outpatient and hospitalization costs but would also produce an economy of scale with individual shots being delivered at a relatively modest cost of between $117 and $245 per dose, the study said.

The vaccines are currently covered by most private insurers without a patient copay because they are recommended by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices. Some Medicare beneficiaries can also obtain the shots at no cost, but only if they are enrolled in Part D of the program, which deals with drug benefits.

“RSV causes substantial morbidity and mortality among the elderly in the U.S. and globally, but this is the first time that RSV vaccines have been available,” said senior author Alison Galvani, the Burnett and Stender Families Professor of Epidemiology (Microbial Diseases) at the Yale School of Public Health. “We wanted to understand the potential impact of RSV vaccination in terms of averting illness, medical costs, hospitalizations, and deaths.”

RSV is a common respiratory virus that causes mild cold-like symptoms in most people, who usually recover in one or two weeks. But older adults and infants are more likely to develop serious RSV, which can be life-threatening. The current study looked only at the potential impact and cost of RSV vaccines for older adults.

Two RSV vaccines, Arexy and Abrysvo, were approved by the U.S. Food and Drug Administration earlier this year. RSV disease causes an estimated 60,000 to160,000 hospitalizations and 6,000 to 10,000 deaths annually in adults 65 and older, according to the Centers for Disease Control and Prevention (CDC). As of Dec. 1, just 14.8% of people 60 or older in the U.S. said they had obtained an RSV vaccine, CDC records show.

In conducting their study, the researchers created a model for RSV outcomes based on characteristics of the U.S. population 60 or older. Measured outcomes included the annual incidence of cases per 100,000 people requiring outpatient, inpatient, and intensive care, and the death rate for hospitalized patients. The researchers then calculated the medical care costs for these outcomes and lost productivity.

The researchers analyzed how these outcomes would be reduced if 66% of adults 60 and older received an RSV vaccine. That is the typical influenza vaccination coverage for adults 65 years or older in the U.S.

“It would be great if we could achieve even higher levels,” said Galvani, who also serves as the director of Yale’s Center for Infectious Disease Modeling and Analysis. “But if we can achieve that for flu, it makes sense that would be feasible for RSV vaccination as well.”

For comparison, the researchers also analyzed the impact of 100% RSV vaccination coverage. In each scenario, they factored in the efficacy of the vaccine at preventing the need for medical care and death. They looked at the impact of these levels of RSV vaccination over one year and then over two years.

They found that 66% vaccination coverage in the first year reduced outpatient care by 41.4% to 53.6%, hospitalizations by 57.6% to 60.5%, and RSV-related deaths by 58.5% to 60.4%.

Increasing vaccination coverage to 100% reduced outpatient care by 62.9% to 81.2%, hospitalizations by 87.4% to 91.7%, and deaths by 87.6% to 91.3%.

Based on these numbers, the maximum cost-effective price per dose for one season at 66% coverage was $118 to $127. The difference was small — $1 to $3 — for 100% coverage.

With the annual cost savings achieved from vaccination, a program where 66% of adults 60 and older are vaccinated for RSV would cost the U.S. health care system $6.4 to $7.1 billion for one season, and $9.7 to $10.7 billion at 100% vaccination, the researchers found.

The vaccines are intended to protect people over two RSV seasons, as clinical trials for the vaccine showed efficacy for that time. But the researchers felt that until real-world efficacy data are available, a one-season analysis was more appropriate.

“Within the next year or two years, as these vaccines are rolled out, we will get a lot of data on effectiveness and better analysis,” said Seyed Moghadas, the paper’s first author and professor of applied mathematics and computational epidemiology at York University. “This new data will help us better inform vaccination strategies for improved impact against RSV disease.”

If real-world data show strong efficacy over two seasons, Arexvy could be cost effective up to $235 per dose and Abrysvo up to $245 per dose, the researchers found.

These are important issues to understand, Galvani said. Some private insurers have not decided if they will cover the vaccines, and whether Medicare does depends on the plan, she said. People 60 to 64 are not eligible for Medicare and may not have health coverage, she added.

“Accessibility and cost are definitely concerns in the American health care system,” she said. “We hope that our results will inform decision-makers about the health and economic benefits of vaccination, as our results demonstrate the importance of making these vaccines accessible to everyone over 60 years to realize their full benefit.”

The research was published Nov. 30 in Clinical Infectious Diseases.

The panel survey, fielded with over 1,600 U.S. adults, finds that many have a base of knowledge about the flu but there is a reservoir of uncertainty about other consequential information about the flu, Covid-19, and vaccination. Among the findings of the ASK survey, which also inquired more broadly about attitudes toward vaccine mandates and the continuing “return to normal”:

• Nearly half of Americans (49%) do not know it is safe to get a flu shot during pregnancy.
• Over half of Americans (53%) say the Army should be able to require Covid-19 vaccination for soldiers who do not have a medical or religious exemption – and a plurality (45%) say public schools should be able to require Covid-19 vaccination of all children who do not have a medical or religious exemption.
• Only 10% of those who had heard of NFL player Damar Hamlin’s on-field collapse think that vaccination was connected to his cardiac arrest – but many more are not sure whether the rate of heart-related deaths has increased among young athletes over the past three years.
• More than half of Americans (52%) now say their lives have returned to a pre-pandemic normal, up significantly from 47% in October 2022.

“Although the CDC indicated that seasonal flu activity is now low nationally, the fact that the level of reported flu vaccination in our panel was roughly the same in January of this year as a year before is concerning,” said Kathleen Hall Jamieson, director of the Annenberg Public Policy Center. “Because this has been a more severe flu season than the one a year ago, we expected an increase in the reported vaccination rate.”

The nationally representative panel of 1,657 U.S. adults surveyed by SSRS for the Annenberg Public Policy Center (APPC) of the University of Pennsylvania from January 10-16, 2023, was the tenth wave of an Annenberg Science Knowledge survey whose respondents were first empaneled in April 2021. The margin of sampling error (MOE) is ± 3.2 percentage points at the 95% confidence level. See the Appendix and Methodology for question wording and additional information.

What the public knows: The flu and flu shot

The latest wave of the ASK survey finds that many people know the basics about the flu:

• Handwashing: 93% of respondents know that washing your hands helps you avoid getting sick from or spreading the seasonal flu.
• Getting the flu again: 83% know it’s possible to get the flu more than once in a flu season.
• Vaccine effectiveness: 77% know that the effectiveness of the seasonal flu shot in the United States can vary from year to year.
  • However, 19% of respondents also think, incorrectly, that the effectiveness of the measles vaccine can vary from year to year and 40% are not sure.
  • Nearly three-quarters of those surveyed (73%) think the seasonal flu shot is effective at reducing the risk of getting the flu this year.
• Mask-wearing: 77% know that wearing a high-quality, well-fitting mask helps limit the spread of flu.
• Contagion: 76% know it’s possible to spread the seasonal flu to others even if you have no symptoms.
  • 14% of our respondents say they have had the flu this season. Of this group, 8% had no symptoms; 29% had mild symptoms; 43% had moderate symptoms; and 19% had severe symptoms.

A majority of the public knows that the following claims are false:

• Flu vaccine and Covid-19: Three-quarters (77%) know it’s false to say that the seasonal flu shot increases your risk of getting Covid-19 – though 6% incorrectly think this is true and 17% are not sure whether it is true or false. (See APPC’s project FactCheck.org to learn more about the false claim linking the flu shot and Covid-19.)
• Better late than never: 71% know it’s false to say that if you haven’t gotten your flu shot by November, there’s no value in getting it – though 11% incorrectly think this is true and 18% are not sure. (The CDC recommends vaccination even after November because significant flu activity can continue into May.)
• Cold weather: Nearly two-thirds (65%) know it’s false to say that cold weather causes the flu – but a third either incorrectly think this is true (22%) or are not sure (13%).
• The flu can be treated: 64% of respondents know it’s false to say there is no treatment for the flu – but 23% incorrectly think this is true and 13% are not sure if it is true.

Areas of uncertainty

But there are important claims about the flu that substantial parts of the public are confused about:

• Pregnancy: Almost half (49%) do not know that it is safe to get a flu shot during pregnancy, including the 10% who think it is not safe and 39% who are unsure. Just 51% know it is safe.
• Get flu from the shot? 46% do not know you cannot get the flu from the flu shot, including 29% who think you can get the flu from the shot and 16% who are not sure.
• Antibiotics and the flu: 45% do not know that the flu cannot be treated with antibiotics, including 25% who think it can be treated with antibiotics and 20% who are unsure.
• Antibiotics and viruses: 40% do not know that antibiotics do not work on viruses such as those that cause colds, the flu, and Covid-19 – including 20% who think it is false to say antibiotics don’t work on viruses, and 20% who are unsure.

Attitudes toward flu vaccination

• Tamiflu: Nearly two-thirds of those surveyed (65%) disagree with the statement that there’s no need for a flu shot because they can always use Tamiflu to treat flu symptoms.
• Breakthrough infections: 58% disagree with the statement that breakthrough seasonal flu infections are evidence that flu shots don’t work – though 15% agree and 26% neither agree nor disagree.
• Danger to children: 57% disagree with the statement that children do not need the seasonal flu shot because they are at a low risk of death from the flu – though 18% agree and 25% neither agree nor disagree.
• Flu shots for all: Just 41% agree that every person older than six months should get a flu shot every year – 33% disagree and 26% neither agree nor disagree. The CDC recommends a flu shot every season for nearly everyone six months and older.

How many have had a flu shot and why

The ASK survey in January 2023 finds that 49% of respondents say they have had a seasonal flu shot, statistically unchanged from 47% in our January 2022 survey and 50% in April 2021. According to the Centers for Disease Control and Prevention (CDC), nearly 46% of U.S. adults 18 and older had a flu shot as of December 31, 2022.

The CDC actively promoted flu vaccination amid concerns that the 2022-23 season would be severe.

When the 49% of survey respondents who said they got the flu vaccine were asked in January why they got the shot (multiple responses were permitted):

• 69% said I get it every year (down from 78% in January 2022)
• 64% said to protect myself against catching the flu (up from 44% in January 2022)
• 8% said to protect myself against Covid-19 (unchanged from 9% in January 2022)
• 25% said because it is recommended by the CDC (this response was not previously offered)

Concerns: The flu, Covid-19, RSV, polio, myocarditis

Worries about family members contracting flu, Covid, or RSV: About a third of those surveyed say they are somewhat or very worried about family members contracting Covid-19 (36%), the seasonal flu (35%), or RSV, respiratory syncytial virus (33%). Only 11% say they are somewhat/very worried about a family member contracting polio, which reemerged as a public health threat in July 2022 after a case was reported in New York State. (FactCheck.org has more about poliovirus being found in New York City sewage.)

Myocarditis: Rare cases of myocarditis, an inflammation of the heart muscle, have been reported among those who have had mRNA Covid-19 vaccines, particularly young males following a second vaccine dose. (FactCheck.org has more on the Covid-19 vaccine and myocarditis.) The connection between myocarditis and the vaccine has drawn attention on social media and in news media.

The survey found that over a third of respondents (37%) think that Covid-19 poses a higher risk for myocarditis than the vaccine against Covid-19. But 17% think that is false and nearly half of those surveyed (47%) are not sure which poses a higher risk.

Damar Hamlin and young athletes dying of heart problems

Much of the public rejects the notion that Damar Hamlin’s collapse during an NFL game had anything to do with the vaccine against Covid-19. But the survey finds that many people are uncertain about the broader unsupported claim that more young athletes are dying of heart problems these days.

Hamlin, a safety on the Buffalo Bills, suffered a cardiac arrest during the Jan. 2, 2023, game against the Cincinnati Bengals, triggering a spate of unfounded, anti-vaccine conspiracy theories on social media about the cause. The overwhelming majority of those in our survey (87%) said they had heard, read, or seen reports of his collapse.

But those respondents overwhelmingly reject the idea that a Covid-19 vaccine caused Hamlin’s injury. Only 10% of those who had heard of the incident attribute it to factors connected with the vaccine. Nearly half (49%) say that based on what they had heard of it, Hamlin’s cardiac arrest was most likely caused by being hit hard in the chest; 17% say an underlying heart condition; and 21% say they are not sure. (FactCheck.org writes about what was known about Hamlin’s injury.)

While social media posts with millions of views quickly associated Hamlin’s collapse with vaccination, mainstream media sources noted the lack of evidence for such claims or dismissed them as misinformation. See, for example, stories such as The inevitable, grotesque effort to blame vaccines for Damar Hamlin’s collapse (Washington Post, Jan. 3) and Hamlin’s collapse spurs new wave of vaccine misinformation (Associated Press, Jan. 5).

However, 26% of those surveyed say they think that the number of young athletes dying of heart problems increased over the past three years, and nearly half (49%) are not sure whether the number has increased or decreased. Only 23% say that the numbers of deaths have remained virtually unchanged. (See FactCheck.org’s article No Surge in Athlete Deaths, Contrary to Widespread Anti-Vaccine Claims on why this claim is unfounded.)

Covid-19 and MMR vaccine mandates

Schools and military: The ASK survey finds stronger support for a Covid-19 vaccine mandate in the military than in public schools, with over half supporting a military mandate:

• 53% of those surveyed strongly or somewhat agree that the U.S. Army should be able to require Covid-19 vaccination of all soldiers who do not have a medical or religious exemption and 30% strongly or somewhat disagree (asked of a survey half-sample).
• 45% strongly or somewhat agree that public schools should be able to require Covid-19 vaccination of all children who do not have a medical or religious exemption and 38% strongly or somewhat disagree (asked of a half-sample).

MMR vaccine: Asked their views on the childhood vaccines for measles, mumps, and rubella (MMR), 63% agree that healthy children should be required to get the MMR vaccine in order to attend public schools, while 22% say parents should be able to decide whether to vaccinate their children who attend public schools and 15% are not sure.

Getting back to ‘normal’

The return to normal: Asked when they expect to be able to return to “your normal, pre-Covid-19 life,” more than half of Americans (52%) say they already have – up from 47% in October 2022. More than 1 in 5 Americans (22%) continue to say “never,” which is statistically unchanged since July 2022.

Mask-wearing: Six in 10 people (61%) say they never or rarely wear masks, statistically unchanged from the 60% who said this in October 2022. And 18% say they always or often wear a mask, also statistically unchanged from the 17% who said so in October.

See the Appendix for question wording and data and the Methodology for additional i

“It’s always very exciting to discover a new site of vulnerability on a virus because it paves the way for rational vaccine design,” says co-senior author Andrew Ward, PhD, professor of Integrative Structural and Computational Biology at Scripps Research. “It also demonstrates that despite all the years and effort of influenza vaccine research there are still new things to discover.”

“By identifying sites of vulnerability to antibodies that are shared by large numbers of variant influenza strains we can design vaccines that are less affected by viral mutations,” says study co-senior author Patrick Wilson, MD, who was previously at the University of Chicago and recently recruited to Weill Cornell Medicine as a professor of pediatrics and a scientist in the institution’s Gale and Ira Drukier Institute for Children’s Health. “The anchor antibodies we describe bind to such a site. The antibodies themselves can also be developed as drugs with broad therapeutic applications.”

In a typical year, influenza affects more than 20 million people in the United States and leads to more than 20,000 deaths. Vaccines against influenza typically coax the immune system to generate antibodies that recognize the head of hemagglutinin (HA), a protein that extends outward from the surface of the flu virus. The head is the most accessible regions of HA, making it a good target for the immune system; unfortunately, it is also one of the most variable. From year to year, the head of HA often mutates, necessitating new vaccines.

Researchers have designed experimental influenza vaccines to be more universal, spurring the body to create antibodies against the less-variable stalk region of HA, which extends like a stem between the influenza virion and the HA head. Some of these universal flu vaccines are currently in early clinical trials.

In the new study, a collaborative team of scientists characterized 358 different antibodies present in the blood of people who had either been given a seasonal influenza vaccine, were in a phase I trial for an experimental, universal influenza vaccine, or had been naturally infected with influenza.

Many of the antibodies present in the blood of participants were antibodies already known to recognize either the HA head or stalk. But a collection of new antibodies stood out; the antibodies bound to the very bottom of the stalk, near where each HA molecule is attached to the membrane of the flu virion.

The co-first authors of the manuscript — Julianna Han, a staff scientist in the Ward lab, and Jenna Guthmiller, a postdoctoral fellow at the University of Chicago — named this section of HA the anchor, and began studying it further. In all, the scientists identified 50 different antibodies to the HA anchor, from a total of 21 individuals. The antibodies, they discovered, recognized a variety of H1 influenza viruses, which account for many seasonal flu strains. Some of the antibodies were also able to recognize pandemic H2 and H5 strains of influenza in lab tests. And in mice, the antibodies successfully protected against infection by three different H1 influenza viruses.

“In order to increase our protection to these highly mutating viruses, we need to have as many tools as we can,” says Han. “This discovery adds one more highly potent target to our repertoire.” Importantly, these antibodies appear to be fairly common in people, and belong to a class of antibodies that any person’s body can produce — an important consideration in designing a vaccine to spur their development.

“The human immune system already has the ability to make antibodies to this epitope, so it’s just a matter of applying modern protein engineering methods to make a vaccine that can induce those antibodies in sufficient numbers,” adds Guthmiller.

The researchers say that future, improved iterations of a universal vaccine could more purposefully aim to generate anchor antibodies. Until now, scientists designing universal vaccines hadn’t paid attention to whether the anchor region of the stem was included as a target. Ideally, a universal influenza vaccine will lead to antibodies against multiple sections of the virus — such as both the HA anchor and the stalk — to increase protection to evolving viruses.

The researchers are planning future studies on how to design a vaccine that most directly targets the HA anchor of different influenza strains.

Journal Reference:

1. Jenna J. Guthmiller, Julianna Han, Henry A. Utset, Lei Li, Linda Yu-Ling Lan, Carole Henry, Christopher T. Stamper, Meagan McMahon, George O’Dell, Monica L. Fernández-Quintero, Alec W. Freyn, Fatima Amanat, Olivia Stovicek, Lauren Gentles, Sara T. Richey, Alba Torrents de la Peña, Victoria Rosado, Haley L. Dugan, Nai-Ying Zheng, Micah E. Tepora, Dalia J. Bitar, Siriruk Changrob, Shirin Strohmeier, Min Huang, Adolfo García-Sastre, Klaus R. Liedl, Jesse D. Bloom, Raffael Nachbagauer, Peter Palese, Florian Krammer, Lynda Coughlan, Andrew B. Ward, Patrick C. Wilson. Broadly neutralizing antibodies target a hemagglutinin anchor epitope. Nature, 2021; DOI: 1038/s41586-021-04356-8

Researchers say the findings should renew efforts to assure flu vaccination is a routine part of quality cardiovascular care.

“As a nation, the U.S. health care system must do a better job protecting a population that is at very high risk for serious complications and death from the flu,” said Varayini Pankayatselvan, MD, an internal medicine resident at Beth Israel Deaconess Medical Center in Boston and the study’s lead author. “As physicians, it is our job to help patients take these simple but effective preventative measures as well as to determine what the barriers to vaccination are, so we can help our patients get around them.”

The study, which used data from the 2018-2019 Behavioral Risk Factor Surveillance System survey conducted by the Centers for Disease Control and Prevention, provides the first real-world look at national flu vaccination patterns in adults with cardiovascular disease. Pankayatselvan said earlier studies in this area have been limited to inpatient samples from hospitalized patients.

A total of 101,210 respondents with a physician diagnosis of heart attack, coronary heart disease or stroke were included in the analysis. They were asked if they got a flu shot “within the past year.” Only 50.4% of this population reported being up to date with flu vaccination, which is strikingly low given that the ACC and other leading health organizations strongly recommend that anyone with cardiovascular disease get a flu shot every year.

Key findings showed no difference in vaccination rates between women and men. People who went to college were more likely to have received a flu shot within the past year when compared with those who had less education. Black and Hispanic adults were about 20% less likely to report getting a flu vaccine compared with whites.

“We haven’t made much progress when it comes to closing persistent vaccination gaps among racial and ethnic groups, and preliminary data on the COVID-19 vaccination also points to disparities still being an issue, which is concerning,” Pankayatselvan said, adding that people with cardiovascular disease are also being urged to get the COVID-19 vaccine. “We need more research to better understand vaccine reluctance, inequities in access to vaccines as well as the value of seeking out community partnerships to improve vaccinations across the board.”

Patients with chronic obstructive pulmonary disease, chronic kidney disease and diabetes were significantly more likely to have gotten a flu shot. Pankayatselvan said this suggests these patients may have more routine access to providers who administer the flu vaccine in their office; she said earlier studies have shown that compared with pulmonary and endocrinology practices, cardiology offices are much less likely to have the flu vaccine on-site. Additionally, when people think of the flu or COVID-19, they more readily think of lung issues, even though these infections can cause heart troubles too. These infections can place added stress on the body and heart by quickening heart rate, ramping up the body’s fight or flight response and triggering inflammation.

What is Pankayatselvan’s message to people with heart disease? “Next time you see a doctor–any doctor–ask about getting your flu shot. Your physician can answer any questions you have and help you make a plan to get it every year,” she said. “It’s an easy, fast and safe way to prevent a lot of potential complications including severe illness, pneumonia, heart attacks, heart failure, hospitalization and even death.”

There are other benefits too, Pankayatselvan said. “Even flu aside, we know that getting the flu shot may be a cardioprotective measure for hospitalized patients with influenza. Previous research has shown that, among hospitalized patients with influenza, the flu vaccine is linked to a lower risk of acute heart failure and acute ischemic heart disease. Additionally, some research indicates the protective effect of getting the flu vaccine may be similar to smoking cessation and some heart medications,” she said.

Getting a flu shot also prevents people from transmitting the flu to others, something researchers are hoping will prove true for the COVID-19 vaccine too.

This study is limited in that it relies on people’s recollection of getting a flu shot. It also only gives a snapshot of vaccination patterns in 2018-2019; it remains to be seen whether the threat of COVID-19 may have prompted more people with heart disease to get vaccinated against the flu.

Pankayatselvan will present the study, “Influenza Vaccination Among Patients with Cardiovascular Disease in the United States,” on Monday, May 17, at 12 p.m. ET / 16:00 UTC.