By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: The world waits eagerly for a COVID-19 vaccine. But the supply of vaccine is unlikely to initially meet the demand. Ethical issues are important as individuals and groups are prioritized for early vaccination.

SOURCE: Persad G, Peek ME, Emanuel EJ. Fairly prioritizing groups for access to COVID-19 vaccines. JAMA 2020; Sept. 10. doi: 10.1001/jama.2020.18513. [Online ahead of print].

There is optimism about the coming availability of SARS-CoV-2 vaccines. However, supplies are likely to be limited, at least initially. Thus, various groups have suggested prioritization schemes to allocate limited vaccine supplies.

In a viewpoint article, Persad et al suggest that three main ethical issues relate to vaccine allocation, and they discuss these issues in light of COVID-19. First, they claim that providing benefit while limiting harm is a universal value and that a vaccine could reduce illness and death while also mitigating unemployment, poverty, and educational deprivation. Second, they believe that it is fundamental to prioritize disadvantaged populations, including the medically vulnerable who risk earlier death if infected, as well as those who have been subject to socioeconomic deprivation and oppression. Third, they suggest that differences of race, gender, and religion should not enter into consideration in simplistic ways that could actually harm or de-prioritize disadvantaged population groups — while, of course, not ignoring relevant differences.

The authors point out that the vaccine allocation plan proposed by the U.S. National Academy of Medicine also valued reciprocity, the recognition of past good behavior to justify earlier vaccination. This principle encourages that previous organ donors be prioritized to receive organs if they subsequently are in need, and the National Academy of Medicine applies this principle to COVID-19 vaccination as well. However, the authors propose that reciprocity be subordinate to the greater values of preventing harm and helping disadvantaged groups. The authors see the assignment of worth to past good behavior as too difficult and controversial to be implemented fairly.

The viewpoint authors believe that their main ethical principles support individual and societal benefit when prioritized immunization is targeted for healthcare workers, people in high transmission settings, and medically vulnerable individuals who have medical conditions that put them at risk of poorer outcomes if they were to be infected with SARS-CoV-2. Focusing on healthcare workers would reduce iatrogenic spread of illness and provide reduced risk for patients with risk factors who frequent healthcare settings and live in medical housing situations. Focusing on people working in high transmission settings would reduce direct harm and minimize spread; this would include school personnel, childcare providers, and food supply workers. It is reported that 200 million people in the United States have high-risk medical conditions, so further prioritization within the high-risk groups also will be necessary.

The authors stress that it is important to be careful not to harm disadvantaged populations by the choice of “high risk” individuals prioritized for early vaccination. For instance, although it is true that the risk of poor COVID outcomes increases after age 65 years, 30% of non-white people who die as a result of COVID are younger than 65 years of age, while only 13% of whites who lose their lives to COVID are younger than 65 years of age. The risk of death in a healthy older person who can shelter in place in a single-family residence is significantly less than that of a similarly aged person with medical comorbidities who lives in crowded housing. Prioritizing all older people also would lead to some younger people being relatively more likely to become ill and succumb, with the resulting loss of many more total years of remaining life.

Others, applying the principle of reciprocity, have suggested that participants in vaccine research studies should be prioritized for vaccination when good vaccines become available. The authors point out that this approach is problematic since vaccine studies have tended to include people who are unlikely to live or work in high transmission settings, and vaccine studies have included relatively few people with either medical conditions or backgrounds in racial and ethnic minority groups.

The authors of this viewpoint article go on to caution against prioritizing vaccine allocation based on racial and ethnic background. They accurately claim that the statistical risk of poor COVID outcomes is less the result of genetics and more because of the consequences of structural racism that have left some racial and ethnic groups more likely to work or live in crowded settings where social distancing is particularly difficult.

Thus, the authors urge that COVID-19 vaccines be allocated to prevent harm, prioritize those who are disadvantaged, and achieve equal treatment. They caution against simplistic schemes that prioritize only the elderly or those of certain racial groups without considering the individual’s actual risk factors for becoming infected or suffering extreme illness if infected. They then practically propose that the vaccine be allocated so that half the supply goes to frontline healthcare workers, with one-fourth of the initial vaccine supply going to people living and working in high-risk settings, and the final fourth going to other people. Within those categories, priority would be given to individuals with high-risk medical conditions.

COMMENTARY

Believing in individualized medicine, we often select diagnostic testing and therapeutic interventions based on what is deemed best for each individual patient. Early in the COVID-19 pandemic, however, it became shockingly clear that resources were not infinite and that even resource-rich societies needed to think through priorities of allocating limited resources. With at least 25 vaccines currently being evaluated, and even as we anticipate the availability of COVID-19 vaccines, our consideration of vaccine delivery systems must go beyond infection and immunity, beyond safety and efficacy.1 We will need to consider the ethics of allocation of limited vaccine supplies.

How much safety and efficacy data will be enough to begin widespread vaccination? Even moving at “warp speed,” scientific processes should be respected. Sadly, a review of the initial nine months of COVID-19 research data revealed 33 papers that were deemed “unsuitable for public use” and had to either be retracted, withdrawn, or labeled as concerning.2 The desire to quickly control the pandemic should not prompt acceptance of rushed or incompletely vetted research findings. And, even after licensing and widespread vaccination are achieved, post-marketing surveillance will be needed; the dangers of an initial rotavirus vaccine and an early dengue fever vaccine were not recognized until large population groups had been vaccinated.

In the medical field, we often espouse a “do no harm” approach. Of course, risks and benefits must be balanced carefully. Almost no medical intervention carries zero risk of harm, and new rapidly produced interventions should be recognized as inherently risky.

How much effectiveness is enough to warrant widespread immunization? Malaria vaccines offering children 30% protection for up to four years have not been seen as effective enough to warrant widespread use. One hopes the COVID-19 vaccines will have better efficacy than the current malaria vaccine candidates.

The authors of the viewpoint article wisely look beyond race in considering the prioritization of vaccination. Clearly, race is related to poor outcomes with COVID-19, and new data confirm this finding.3 But race is, to at least some degree, a marker for risk factors rather than a fully independent risk factor. Even in the county where I live, recent pre-publication epidemiologic data suggest that COVID-19 is, indeed, more common in minority racial groups, but the geospatial clustering of cases reveals that the risk actually is associated with living in crowded housing (apartment buildings and trailer parks) and with neighborhoods with lower socioeconomic levels.4 Race is a statistical marker for risk, but considering race alone would lead decision-makers to inappropriately include many low-risk individuals (those of racial minority groups who have high socioeconomic status and live in single-family dwellings) in the “high risk” category.

Well-intentioned, ethics-based research regulations also can hinder research for appropriately studying vulnerable populations. Although incarcerated individuals are at particularly high risk of infection and poor outcomes with SARS-CoV-2, it is not likely that prisoners will be included in COVID-19 vaccine trials.5

Children are at risk of becoming ill with COVID-19, and they also are at risk of becoming asymptomatic “super spreaders” as schools open. One could wonder if children should be mandated to receive vaccines, even as other vaccines are mandated through school systems. However, careful review of the situation reveals that more data are needed before deciding if children should be prioritized for early or mandated vaccination.6

Another ethical issue has been raised about a few of the candidate COVID-19 vaccines. As with some routine childhood vaccines, some of the adenovirus vector-based COVID-19 vaccines have used decades-old cell lines from aborted fetal tissue during the manufacturing process.7 “Moral complicity” is the notion that using the products of an unethical act, as some see abortion, makes one complicit to the initial act. Moral complicity was a major concern in past generations when execution rates seemed to increase when “justified” by the use of victims’ bodies “for science.”8 Does the use of abortion-derived vaccines make vaccinators and vaccine recipients complicit with and “guilty of” the initial abortion? A similar issue was raised when the popular press realized that researchers were benefitting from studies involving HeLa cell lines that had been used without the patient’s consent. Most of us do not see the moral complicity argument as a limitation to the use of specific vaccines any more than we see a kidney transplant recipient who received an organ from a deceased murder victim as being complicit with or guilty of the murder of the organ donor.

Already, governments of some wealthy countries have purchased huge stocks of not-yet-produced COVID-19 vaccines, with more than 2 billion doses already bought.9 The World Health Organization recommends that richer nations ensure that resource-limited countries receive early access to vaccines, too.10 It is hoped that national and international law will serve as a means, rather than as a barrier, to just and equitable distribution of vaccines around the globe.11

REFERENCES

  1. Poland GA, Ovsyannikova IG, Crooke SN, Kennedy RB. SARS-CoV-2 vaccine development: Current status. Mayo Clin Proc 2020;95:2172-2188.
  2. Bramstedt KA. The carnage of substandard research during the COVID-19 pandemic: A call for quality. J Med Ethics 2020; Oct. 1. doi: 10.1136/medethics-2020-106494. [Online ahead of print].
  3. Goyal MK, Simpson JN, Boyle MD, et al. Race and/or ethnic and socioeconomic disparities of SARS-CoV-2 infection among children. Pediatrics 2020;146:e2020009951.
  4. Juhn Y. Personal communication. Oct. 2, 2020.
  5. Wang EA, Zenilman J, Brinkley-Rubinstein L. Ethical considerations for COVID-19 vaccine trials in correctional facilities. JAMA 2020;324:1031-1032.
  6. Opel DJ, Diekema DS, Friedman Ross L. Should we mandate a
    COVID-19 vaccine for children? JAMA Pediatr 2020; Sept. 14. doi: 10.1001/jamapediatrics.2020.3019. [Online ahead of print].
  7. Wadman M. Abortion opponents protest COVID-19 vaccines’ use of fetal cells. Science. June 5, 2020. https://www.sciencemag.org/news/2020/06/abortion-opponents-protest-covid-19-vaccines-use-fetal-cells
  8. Cheshire WP. Turning a blind eye: An ethical assessment. Ethics Med 2011;27:7-15.
  9. Callaway E. The unequal scramble for coronavirus vaccines by the numbers. Nature 2020;584:506-507.
  10. Subbaraman N. Who gets a COVID vaccine first? Access plans are taking shape. Nature 2020;585:492-493.
  11. Phelan AL, Eccleston-Turner M, Rourke M, et al. Legal agreements: Barriers and enablers to global equitable COVID-19 vaccine access. Lancet 2020;396:800-802.