By Gary Evans, Medical Writer

Healthcare workers have been designated as the highest priority group to receive the first safe and effective COVID-19 vaccine cleared for use in the United States, according to recent discussions and materials reviewed in a non-voting meeting of top immunization advisors to the Centers for Disease Control and Prevention (CDC).

Facing a dearth of data that awaits clarification in a host of clinical trials, the CDC’s Advisory Committee on Immunization Practices (ACIP) used an ethical framework to make what one member described as a series of Solomonic decisions at its Sept. 22 meeting.

“When and if a safe and effective COVID-19 vaccine is approved by the Food and Drug Administration [FDA], healthcare workers would be tier one recipients,” ACIP recommended. “This group includes some 20 million people who work in hospitals, long-term care facilities, assisted living facilities, skilled nursing facilities, outpatient settings, home healthcare, pharmacies, EMS, public health and other groups.” (More information is available at this link: https://www.cdc.gov/vaccines/acip/meetings/slides-2020-09.html.)

After healthcare workers, the subsequent 1B priority groups for COVID-19 vaccination were open to further refinement, but the order described at the meeting placed non-healthcare essential service workers next, followed by people with high-risk medical conditions, and those older than age 65 years.

Some ethical models for pandemic vaccine uptake have stratified frontline medical workers, but ACIP argued for a broader immunization strategy throughout healthcare. The ACIP healthcare category includes those not directly involved in patient care but potentially exposed to infectious agents while working in a healthcare setting.

“The epidemiology of COVID-19 disease among healthcare personnel demonstrates that cases at risk of disease extend beyond frontline [workers],” said Sara Oliver, MD, MPH, an epidemiologist with the CDC National Center for Immunization and Respiratory Diseases (NCIRD).

Healthcare workers drew 1A status, akin to the military service draft, but the tone of discussions clearly suggested broad reticence to making a such a newly developed vaccine compulsory. Indeed, there was an undercurrent of skepticism about whether healthcare workers would be immunized voluntarily unless safety and efficacy truly can be assured.

In comments before the meeting, ACIP liaison member William Schaffner, MD, professor of preventive medicine at Vanderbilt University, told Hospital Employee Health there is distrust of the vaccine process even in healthcare.

“There is a lot of skepticism in the medical community, and I don’t just mean doctors — I mean nurses and other staff — about the process whereby vaccines will be evaluated both for effectiveness and safety,” says Schaffner, an ACIP liaison member for the National Foundation for Infectious Diseases.

The politicization of the pandemic response threatens to undermine the response even if a safe and effective vaccine is developed.

“I’ve had exchanges with people through email and phone. Virtually everyone around the country is saying, ‘We are seeing medical colleagues express both annoyance and real skepticism about the vaccine evaluation process,’” Schaffner notes. “Even among healthcare workers, we are going to have to do an awful lot of education and provide data and reassurance in order for them to take the vaccine.”

One critical issue will be whether the FDA submits the data for evaluation to its highly regarded Vaccines and Related Biological Products Advisory Committee, he says.

“If that committee speaks to the American public and says, ‘We have reviewed this and think it is appropriate to go forward for emergency use authorization,’ I think practicing doctors, nurses, and others will take much comfort and reassurance in that,” Schaffner says.

Right now, there is little short of open suspicion, including a question during the meeting about whether the eventual ACIP vote and recommendations would have to be signed off by the Department of Health and Human Services (HHS). “Let us get back and confirm that for you,” said ACIP Executive Secretary Amanda Cohn, MD, of the CDC NCIRD. “Typically, the CDC director makes the final decision and informs the HHS director.”

There was some discussion of voting on the matter at a previous meeting, but ACIP Chair José Romero, MD, FAAP, secretary of the Arkansas Department of Health, said the committee would await weigh-in from the FDA before formally voting.

“Once the data are available from Phase III clinical trials, the ACIP Vaccine COVID-19 Work Group will conduct an independent review of safety and efficacy data and present policy options to the full committee,” Romero said. “If and when the FDA authorizes or approves a vaccine, then ACIP will have an emergency meeting and vote on vaccine recommendations and populations for use.”

Ethical Principles

An ACIP work group reviewed ethical principles by several medical groups on allocating a potential vaccine, concluding all ranked vaccine administration to healthcare workers as critical to the pandemic response. The ethical standards ACIP consulted include the World Health Organization’s Strategic Advisory Group of Experts (SAGE), the Johns Hopkins Bloomberg School of Public Health, and the National Academies of Sciences, Engineering, and Medicine (NAM).

“These are the right principles. They take the best components of the SAGE, Hopkins, and NAM models,” said ACIP member Peter Szilagyi, MD, MPH, a pediatrics and research professor at the University of California, Los Angeles. “I think one of the challenges we are all facing — and this feels very much like a Solomon’s choice — we have to remember that over [time] the vaccine supply will go up. What we are really talking about is making the decisions for shorter time periods. One of the challenges we feel is that there is a wide diversity of risk in all of these groups. Even in the healthcare group, essential workers, and those with chronic conditions, there is a wide diversity of risk.”

Given the unknowns, the emphasis on safety and trust must be underscored throughout the process, said ACIP member Grace Lee, MD, MPH, professor of pediatrics at Stanford University.

“I agree that it is challenging to communicate around vaccines and vaccine confidence without actually having the clinical trial data in hand,” she said. “But I still think that perhaps what we can do is continue to emphasize the process for decision-making and how much emphasis we are all placing on transparency.”

With transparency placed as the key structural underlying principle, ACIP’s ethical reasons for selecting healthcare workers as priority-one recipients of a COVID-19 vaccine included such factors as maximizing immunization benefits essential to the pandemic response, and equity — because healthcare includes high representation of minorities and low-income workers.

“In terms of feasibility, large health systems have occupational health departments to facilitate vaccine clinics,” said Kathleen Dooling, MD, MPH, a member of the ACIP work group and a medical officer in the CDC’s division of viral diseases.

Healthcare facilities also may use freezers if needed for cold storage of vaccines. Another plus is that influenza vaccine acceptance is fairly high among healthcare workers.

“However, it will be more challenging to reach rural healthcare facilities, long-term care, small, independent clinics, and home healthcare workers,” Dooling noted. Medical workers also have high scientific literacy, a factor ACIP weighed in favor of beginning with healthcare overall.

While healthcare workers may be more open to vaccine receipt than members of the public, particularly vulnerable minority populations, the theme of distrust in the process and the ultimate vaccine that emerges was a common thread through ACIP discussions. Romero warned vaccine hesitancy and distrust will be an ongoing issue.

“I can only speak from my experience within the advisory groups from our department of health for underrepresented minorities,” he said. “There is an extreme disconfidence in this vaccine. I have been trying to reach out to the Latino population primarily by having specific, targeted talks with the leaders of that group. I think we need to begin these now if there is to be any sense of confidence in the vaccine among the minority populations.”

Social Vulnerability and COVID-19

The challenge was underscored by a presentation showing how maps of COVID-19 cases and hospitalizations virtually mirrored maps of ethnic minority and poverty indicators. Megan Wallace, DrPH, MPH, described the Social Vulnerability Index, which was developed by CDC to identify communities that need support before, during, and after public health emergencies. The index measures social determinants of health using census data and ranks each county and census tract on 15 social vulnerability factors. Counties with the highest social vulnerability are at greater risk of COVID-19 outbreaks compared to counties with the lowest social vulnerability. Racial and ethnic minority groups represent 40% of the total U.S. population, but nearly 60% of COVID-19 cases, Wallace explained.

“We need to be very proactive in our educational pieces to reach out to racial and ethnic minorities, essential workers, and people with low economic means,” said Sandra Fryhofer, MD, an ACIP liaison member representing the American Medical Association.

The problem is that medical researchers, even some ostensibly representing the government, have given minority populations multiple historical reasons not to trust them. To cite one of the most infamous, the Tuskegee syphilis experiment studied the progression of the disease in elderly Black men from 1942 to 1972. Astonishingly, their syphilis was allowed to progress, and the experiment continued for decades after the availability of penicillin for effective treatment in the 1940s.1 The education campaign on this vaccine effort faces a steep uphill struggle, in part because of the mixed messaging and waffling that have characterized the federal response to the pandemic.

In addition, the nation’s antivaccine movement has endangered routine immunization rates, as evidenced by measles outbreaks after the measles, mumps, and rubella vaccine was falsely linked to autism. Given this backdrop, one ACIP member said the federal government’s name for its vaccine development push is unfortunate.

“The title ‘Operation Warp Speed’ scares a lot of people,” said Lynn Bahta, RN, MPH, CPH, an immunization consultant in the Minnesota Department of Health. “It would be helpful if our national leaders at the FDA and CDC could talk about what that means in plain language. [That] might help people with some of the anxiety that we have been hearing about vaccinations for COVID-19.”

While commending a practical CDC “playbook” for eventual administration of a vaccine by state and local health officials, ACIP member Paul Hunter, MD, of the City of Milwaukee Health Department, questioned the lack of security planning.

“The one thing I didn’t see is security at the sites,” he said. “I’m a bit worried at the threats of violence that have been perpetrated against visible leaders of public health. These have led in part to the resignation of commissioners of health, like my commissioner of health in Milwaukee — that is part of the reason she resigned.”

CDC officials at the meeting clarified they have worked with the administration in running some tabletop security exercises and will be adding more details in future iterations of the immunization planning playbook.

Even a relatively routine public health measure for a new vaccine — the planned heightened surveillance for adverse effects and text message monitoring of immunized healthcare workers’ symptoms — took an ominous tone.

“With all the discussions going on around the country and some people expressing concerns [about] the process of assessing the safety and effectiveness of these vaccines, requiring continued monitoring for safety after the vaccine is rolled out may be a cause of concern to some,” said ACIP member Robert Atmar, MD, of the Baylor College of Medicine in Houston. “We want the public to be reassured that any vaccine that is rolled out has gone through the appropriate review process, and this additional safety collection is what we do with all vaccine products. Again, it is voluntary for the initial recipients of the vaccine.”

Tom Shimabukuro, MD, MPH, MBA, of the CDC’s COVID-19 Vaccine Safety Team, said text message monitoring of healthcare workers will not be mandatory, and they can opt out after initial contact. The vaccine safety assessment for essential workers (V-SAFE) is a smartphone-based survey program for early vaccine recipients, he explained.

“It is reassuring to me that many healthcare workers, including myself, are already participating in daily symptom monitoring within our own healthcare systems,” Szilagyi said. “I think people are getting used to this very quick daily monitoring.”

The existing Vaccine Adverse Event Reporting System (VAERS) also will include a COVID-19 vaccine component. That includes a requirement that COVID-19 vaccine-related deaths be reported in one day, serious incidents in three days, and non-serious reports within five days.

The FDA has said it would accept a vaccine with 50% efficacy as long as there was high confidence that it would be no lower than 30% effective.2

“I never heard the FDA say that before — and the FDA is not exactly the most trusted agency anymore. None of them are,” says Richard Wenzel, MD, MSc, emeritus chairman and professor of internal medicine at Virginia Commonwealth University. “If it is only 50%, I think there will be some reluctance.”

Wenzel is not a member of the ACIP committee, but the veteran epidemiologist is closely following the vaccine process.

“I think one of the questions people will have is if the [first one] is sort of 50% to 60% efficacy, do they wait for data to come in on vaccine number two, which might have 70% or higher efficacy?” he asks. “Another question healthcare workers will ask is how safe is it? If it is sort of borderline effective and people say, ‘I felt like I had the worst flu for two or three days,’ that will obviously influence the level of acceptance.”

That said, Wenzel is confident a SARS-CoV-2 vaccine will be developed, in part due to lingering signs of immunity in people infected with the original SARS in 2003. Infectious antibodies faded within a few months, but “there is T cell recognition 17 years after SARS in some patients,” he says.

There is precedent for a disastrous rollout of a pandemic vaccine. In 1976, the H1N1 “swine flu” vaccine was linked to paralysis and fatalities in the infamous “pseudo-pandemic.” One adverse effect was an increase in Guillain-Barré paralytic syndrome (GBS), a rare autoimmune disease in which the body turns on its own nerve cells. In 1976 — responding to a feared H1N1 pandemic that never materialized — public health officials immunized more than 40 million people with a newly developed vaccine. Several hundred cases of GBS included a reported 25 deaths, prompting the enduring observation that the vaccine killed more people than the disease did. The adverse reactions were not fully recognized until a large rollout of the vaccine program, which was then halted.3

REFERENCES

  1. Centers for Disease Control and Prevention. U.S. Public Health Service syphilis study at Tuskegee. Last reviewed March 2, 2020. https://www.cdc.gov/tuskegee/timeline.htm
  2. Food and Drug Administration. Coronavirus (COVID-19) update: FDA takes action to help facilitate timely development of safe, effective COVID-19 vaccines. June 30, 2020. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-takes-action-help-facilitate-timely-development-safe-effective-covid
  3. Evans G. Foul spirit of ‘76 haunts H1N1 response. Hospital Infection Control & Prevention. Nov. 1, 2009. https://www.reliasmedia.com/articles/114698-foul-spirit-of-76-haunts-h1n1-response