By Leo Lam, Taylor Nichols, Hannah Larson.

We thank Tracy Beth Høeg, et al. for their reply to our response paper ‘Ethics of college vaccine mandates, using reasonable comparisons’. Our paper showed that the risk-benefit calculation to mandate vaccines on college campuses benefits students and the community and is ethical. We performed risk-benefit analyses using the risk and benefit of comparable risk profiles that erred on minimizing the vaccine’s benefit to be conservative of the risk. The authors claim that one of our comparisons is inappropriate, and they continue to assert that the vaccine/booster is a net harm to college-age students. Our response is as follows.

Definition of SAEs vs Actual SAEs

In the first original comparison that the authors performed, they weighed the predicted number of COVID-19 hospitalizations prevented (benefit) with vaccine-associated Severe Adverse Events (SAEs) (risk) from Pfizer’s randomized trial. The comparison is inappropriate because the risk profiles between the benefit and risk are biased heavily toward the risk given that the reported SAEs were transient, self-resolved, and have no long-term consequences. The authors, in their response, argued that because the FDA definition of the SAEs included “death, hospitalization, disability, permanent damage, life-threatening event or condition, which required medical or surgical intervention to prevent a serious outcome”, their comparison is appropriate and is “more reasonable” than ours. We strongly disagree with this assertion because this subset of severe SAEs from the FDA’s definition did not occur and ethical comparisons cannot be made with imaginary events. The 3 cases of SAEs during the Pfizer trial were fully reported and well-defined, and the resources required to treat those three conditions are much more comparable to a mild COVID-19 infection, which we used in our comparison. The infection rate value we used to calculate the infection risk came directly from the same reference as the authors.

The authors further argued that the booster vaccine “will only offer transient (if any) protection against infection” and that it only amounts to “postponing an infection for a few months”. We disagree on two points. First, the cited reference contains outdated information from the original Pfizer vaccine instead of the updated bivalent vaccine. Secondly, we fundamentally disagree that an infection is inevitable and that a vaccine serves only to delay future infection. Preventing COVID-19 infection and reducing the number of severe illnesses is the goals of having public health policies, and waning protection can be, and has been remedied using booster vaccinations. The argument presented by the authors is based on flawed assumptions and is not congruent with basic public health principles, therefore we do not consider their self-defeating argument to be valid in the context of public health.

As such, our argument stands that when reasonably comparing the risk and benefits of preventing COVID-19 infections versus the risk of experiencing transient, self-resolving SAEs, there is a net benefit to vaccination for the college-age group.

Vaccine-associated myocarditis and the “net harm” claim

In the risk and benefits comparison for myocarditis, the risk of vaccine-related myocarditis (VRM) (risk) was compared to the number of COVID-19 hospitalizations prevented (benefit). We discounted the number of cases of post-vaccine myocarditis the authors used because vaccine-caused myocarditis is mild and generally self-resolved with minimal intervention in over 90% of the cases. We used the remaining 10%, an overestimate of the more severe cases, to compare to the COVID-19 hospitalization prevented, which are more clinically equivalent in terms of resources needed to treat and found a net benefit. The authors argue that there have been deaths from VRM and that another study showed that “post diagnosis of vaccine-associated myocarditis, over 25% were still taking medications for the myocarditis diagnosis” and there are other sequelae after 90 days.

While there have been deaths from VRM, since we are determining the risk and benefits, note that there have been far more deaths in this age group from the COVID-19 virus. In the most extensive VRM study as of this writing (n= 44,276,704), the VRM rate for the 12-29 age group is 2.52 per 100,000. The VRM mortality rate is 0.000047% and 0.000042% overall and for the 12-29 age group respectively. The rates of this study are similar to another large study in Israel (n= 9,289,765). The mortality rate for the 18-29 age group from COVID-19 in the United States is approximately 0.016% (6,956/43M), over 380 times higher than the VRM mortality rate. Besides, arguing that the risk of the only serious side effect from vaccination is higher than the risk of getting infected by the SARSCoV2 virus judging by the mortality rate alone is inaccurate given that death is not the only negative outcome of a SARS-CoV-2 infection, including the fact that COVID-caused myocarditis is 7X more frequent and comes with much higher mortality rate. It is worth noting that two of the four references provided by the authors did not establish causality between the vaccine and myocarditis.

Children and Young People (CYP) experience Long COVID symptoms at a rate of 25% with life-disrupting symptoms such as fatigue, sleep disorders, headache, respiratory symptoms, cognitive symptoms, exercise intolerance, and altered smell and taste. As much as 16% of the young individuals suffering from Long COVID reported absenteeism at 8 months post-infection. Treatment options are scarce as the medical community continues to learn about Long COVID. We would assert that the clinical risk profile of the Long-COVID sequelae is more severe than the treatable and mostly self-resolved consequences of most VRM cases. Even if we consider the two sequelae equal, the difference in mortality rates alone should render the claim of a “net harm” invalid.

Considering VRM and the benefits of preventing severe illness with COVID-19 alone, the vaccination mandate is an overwhelming net benefit to the students’ age group and the surrounding community.

COVID-19 Hospitalization Prevented versus ≥Grade 3 Reactogenicity

Given the transient and self-resolving nature of reactogenicity, we are pleased that the authors agreed that this comparison group was originally unreasonable. The authors argue that the reactogenicity symptoms are a “relevant source of harm and morbidity” based on their “net harm” claim a priori. We disagree given the invalid claim of “net harm” as we outlined above. Once again, the authors ignored the sequelae of Long COVID, which has far more severe consequences in “preventing normal activities”. As such, our original point stands that the benefit far outweighs the risk concerning reactogenicity.

Ethical Analysis

The authors assert that we did not engage in their ethical analysis. This was intentional, as their ethical analysis was based on the vital principle of proportionality and thus their ethical argument was based on the risk and benefit analyses performed. Their ethical arguments were invalid absent the support of such analyses, as we have responded to above. Besides, attending a specific university is a privilege and not a right, and that students and parents are free to choose a university without a mandate. An individual institution should be free to decide upon a vaccine mandate for their students given the overall net benefit, rather than harm, as we have demonstrated, and that this is not an overall impediment to the pursuit of higher education. The authors further argue that some recent European policy changes are consistent with their conclusions. Policy changes do not always follow accurate science or ethics. Policymakers also consider public sentiment and how policy changes affect their political future. Citing selective policy changes does not change the balance of the scientific evidence of risk and benefit analyses, as we have analyzed here.

Conclusion

We have demonstrated that the COVID-19 vaccines and their mandate in universities clearly benefit the student age group based on clinically sound science and conservative risk assessment. We find the claim of “net harm” by the authors to be scientifically inaccurate and that this claim minimizes the sequelae of COVID-19 infections, mortality in youths, and Long COVID. Based on comprehensive clinical criteria, it is evident that the COVID-19 vaccine and vaccine mandate is a clear net benefit for the 18-29-year-old age group. As such, the conclusion of our paper holds, and that their claims of net harm are scientifically false.

Paper title: The ethics of college vaccine mandates, using reasonable comparisons

Authors: Leo Lam, Taylor Nichols, Hannah Larson

Affiliations: University of Washington (LL), University of San Francisco (TN), Shoreline Community College (HL)

Competing interests: None declared

Social media accounts of post authors: @SeattleiteLeo @tnicholsmd