‘Healthy skepticism,’ shifting protocols may fuel COVID-19 vaccine hesitancy, fatigue
Inconsistent messaging and evolving recommendations surrounding COVID-19 vaccination protocols may have contributed to both hesitancy and fatigue regarding vaccines among patients, according to experts.
“Vaccine hesitancy is not new,” Maria Danila, MD, MSc, MSPH, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham, and physician scientist with the Birmingham Atlanta Geriatrics Research Education and Clinical Center, at the Birmingham VA Medical Center, told Healio. “Vaccine hesitancy was named by the World Health Organization as one of the top 10 threats to global health in 2019.”
Danila co-authored a paper published in October in Rheumatic Disease Clinics of North America that aimed to understand vaccine uptake in the context of COVID-19 and associated misinformation.
In that study, the researchers cited mistrust in the health care system, misinformation related to the vaccine development process, fear of rheumatic disease flares and inconsistent physician recommendations among the “myriad reasons” for low vaccine uptake.
Meanwhile, two randomized controlled trials are currently underway to develop strategies and partnerships to disseminate COVID-19 vaccine information, reduce hesitancy and potentially improve uptake, particularly among under-resourced communities.
“It is hard to generalize about vaccine hesitancy,” Jeffrey Sparks, MD, MMSc, director of immuno-oncology and autoimmunity in the division of rheumatology, inflammation and immunity at Brigham and Women’s Hospital, and associate professor of medicine at Harvard Medical School, told Healio. “Certainly, vaccines are more in the spotlight than ever. For some, the pandemic convinced them of the necessity of vaccines. For others, they weathered the pandemic without vaccination.”
Underlying all of this is the advent of a second President Donald Trump administration, which may introduce different messaging surrounding vaccines.
However, it may be too soon to tell exactly what impact the new administration, and its incoming health officials, may have on vaccine policies and messaging, according to Kevin Winthrop, MD, MPH, a professor of public health and associate professor of infectious diseases and ophthalmology at the Oregon Health and Science University. New faces at the top do not always translate to widespread changes, he noted.
“A lot of those places have institutional memory and have good people who have been working there for years, so it is difficult to say what kind of policy changes may occur,” Winthrop said, adding a bit of advice for those with concerns.
“Whatever happens with those wild cards, keep doing your job and keep working hard,” he said. “Science is science.”
This attention to the science will be critical for most rheumatologists.
“We are still in a place where we are talking about two pandemics, and two different vaccine strategies — the general public vs. highly immunocompromised people,” Winthrop said. “They are two different discussions.”
‘A healthy skepticism’
According to Winthrop, tracing the path of vaccine fatigue over the last half decade means looking back at the recommendations and messaging regarding COVID-19 vaccination.
“The idea of the initial vaccination effort was to slow down or halt the pandemic,” he said. “It allowed people to gain immunity in a more organized fashion. It certainly saved a lot of lives and was a big win.”
However, the equation has changed since the initial products emerged.
“Here we are a few years later, where there were recommendations for boosting every 6 months, which was something different and new,” Winthrop said. “This was not something the public had to deal with before, and fatigue has set in.”
The shifting recommendations may have had another consequence, according to Danila.
“The initial messaging to the public was that one round of vaccinations would be sufficient, and that changed as more information became available,” she said. “That change may have eroded public trust.”
As an infectious disease epidemiologist, Winthrop stressed that 4 years of robust data show that the COVID-19 vaccines are safe and effective, by and large.
“However, the novel nature of the mRNA vaccine construct may have contributed to vaccine hesitancy and fatigue, as well,” he said. “Whenever something new comes out, some people embrace it right away, but there is also a healthy skepticism.”
That skepticism has persisted, but now for other reasons, according to Winthrop.
“A lot of people have had multiple boosters and COVID multiple times — which results in what we call hybrid immunity — who are wondering whether they need to get the vaccine,” he said. “Their skepticism at the moment is perfectly warranted.”
That is not to say that changes to messaging and recommendations have been unwarranted, according to Danila. She added that such messaging has become an increasingly important factor in vaccine uptake.
“In an attempt to improve outcomes and decrease the severity of the pandemic, the communication of what a vaccine can or should do, or how often it should be given, was frequently updated as more knowledge became available,” Danila said. “It was necessary to promote vaccine uptake, when the pandemic was at its peak.”
All these complications were exacerbated by the SARS-CoV-2 virus itself, which demonstrated a spectrum of outcomes ranging from no symptoms to death.
“This highlights the complexity of the issue and that a one-size-fits-all approach to increase vaccine uptake may have had some unintended consequences,” Sparks said.
That complexity continued through August 2024, when the most recent COVID-19 vaccine was released.
“On the one hand, through the pandemic, the vaccine was pushed so frequently that eventually it diminished the attention people gave to the issue when hearing about it, and contributed to fatigue,” Danila said. “On the flip side, when the new vaccine was released last August, there was very little promotion or information about the necessity of it, so now many people are not even thinking about it.”
The result is that many immunocompromised patients may not be aware that they are still at risk for severe COVID-19 outcomes.
‘Spectrum of hesitancy’
In a 2023 paper published in The Lancet Rheumatology, on which Sparks was an investigator, Hanberg and colleagues studied 4,305 patients with systemic autoimmune or rheumatic diseases, 3,126 of whom received a fourth dose of a COVID-19 vaccine. Results showed that SARS-CoV-2 infection risk was lower among individuals who received a fourth dose, compared with those who did not (HR = 0.59; 95% CI, 0.47-0-74). In addition, hospitalization or death within 14 days of infection was also lower in the fourth dose group (HR = 0.35; 95% CI, 0.14-0.85).
Despite results like these, vaccine hesitancy persists in rheumatology clinics across the country.
“People using B-cell depleting therapies are clearly among the most vulnerable,” Sparks said. “Even in this group, it has been quite interesting to see the spectrum of hesitancy from both patients and clinicians. Some are highly motivated to receive vaccines for the cellular response, optimize vaccine response by spacing out infusion doses, or pursue pre-exposure prophylaxis. Others decline any risk mitigating strategy at all.”
Danila stressed that vaccines remain recommended for immunocompromised patients and those receiving B-cell depleting therapies.
“The most important consideration is for those receiving B-cell depleting therapies is timing, and that applies to COVID-19, influenza, pneumococcal or shingles vaccines,” she said.
However, messaging — or the lack thereof — may impact hesitancy even in rheumatology populations.
“The last guidance on COVID-19 vaccine from the American College of Rheumatology was released in 2022, which, in the context of the COVID-19 pandemic, is quite a long time ago,” Danila said. “Having that source of information and additional guidance beyond the recommendations from the Centers of Disease Control and Prevention may be impacting uptake across the rheumatology spectrum.”
‘Rationality is critical’
A hard look at the FDA approval process for vaccines — and how it balances scientific rigor with the ability to react quickly to emergencies — may be the first step to rebuilding public trust.
“There has always been a delicate balance in the vaccine regulatory space,” Sparks said. “Requiring large trials may be rigorous but slow. Small studies with surrogate outcomes may be nimble but not convincing of safety or efficacy.”
A companion issue pertains to the likely emergence of yearly COVID-19 vaccine products for the foreseeable future. Although a new FDA approval will not be necessary for the yearly products, hindsight will determine whether the vaccine was effective or not.
“Similar to the seasonal influenza vaccine, COVID vaccines are updated based on projections from circulating strains,” Sparks said. “The current COVID vaccines seem to be a good match, but studies with clinical outcomes are typically performed later, often nearing when a newer vaccine is due.”
However, another complicating factor — specific to the current moment — has been the relatively recent politization of vaccines. Additionally, it remains unclear exactly how the change in presidential administration will impact this new status quo.
“Vaccines have become politicized, so I do envision changes with the new administration,” Sparks said. “Time will tell how drastic these changes will be and their ramifications on public health, particularly for immunosuppressed people.”
Winthrop suggested that the conversations surrounding vaccines are likely to become more difficult for rheumatologists moving forward.
“There is a lot of motivation to spread false information on the internet and via other outlets,” he said. “Some patients will read it and believe it. Others will come in with legitimate questions and concerns about which vaccines they may or may not need. Follow the data and keep talking to your patients.”
What is certain at this time is that the data regarding COVID-19 and its vaccines will continue to evolve, according to Danila.
“Research is dynamic — the way we understand a phenomenon evolves over time,” she said. “We learn from mistakes, or we extend our knowledge, but when that new or additional information starts being disseminated, it may contradict previous information, and this might result in hesitancy.”
This emergence of new information often leads to advice differing from doctor to doctor as they discuss vaccines with their patients.
“Some will provide nuanced vaccine advice, while others may not prioritize the discussion,” Sparks said.
Winthrop, for his part, called on the research community to continue asking — and answering — questions regarding vaccines.
“At this point, the question is how frequently you need to boost in both the general population and in immunocompromised populations,” he said.
Above all, Winthrop encouraged close attention to data and a cool head.
“People on all sides of these debates get very impassioned,” he said. “Rationality is critical.”
References:
Ezeh N, et al. Rheum Dis Clin North Am. 2024;doi:10.1016/j.rdc.2024.09.007.
Hanberg JS, et al. Lancet Rheumatol. 2023;doi:10.1016/S2665-9913(23)00272-2.
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