Physician Outlook

Rethinking Covid-19 Vaccine Mandates


The Scientific Justification, Ethics and Legality of Vaccination Policies for Schools and Universities

SARS-CoV2, the virus that causes the disease COVID-19, has indubitably caused tremendous disease burden in USA, EU, UK, India, South Africa, Brazil and several other countries. SARS-CoV2 is perhaps the greatest public health crisis in one hundred years. As of the time of this writing, CDC’s officially confirmed COVID-19 numbers indicate 33 million ‘cases’ and about 598 thousand deaths in the US alone. Furthermore, an estimated 100M-150M people have been infected with SARS-CoV2 (about four times the officially confirmed PCR numbers in the general population). Hard metrics such as hospitalizations and deaths are easier to track and report to inform public health policy. While difficult to define and quantify, SARS-CoV2 has also caused long term symptoms in countless survivors (“long COVID” or Post Acute COVID Syndrome, PACS). PACS ought to be part of our assessment of disease burden and we are only now beginning to better quantify the disease burden across age groups.

Early in 2020, as were just learning about the disease, it’s full clinical manifestations and impact, due to limited testing capacity and under recognition of mild and moderate illness, many people with COVID-like illness were not tested.  The initial focus of our testing, diagnostic, and therapeutic modalities were almost exclusively on hospitalized patients, based upon the concerns of inadequate ICU capacity, ventilator supply, limited supply of personal protective equipment (PPE). Much of the initial projections and extrapolations were based upon critically and severely ill hospitalized patients. As we now have amassed vast data enabling a more comprehensive and representative description of clinical spectrum of clinical disease, as we are better contextualizing organ specific disease burden, and as we have almost irrefutable evidence of clearly defined risk stratification, it behooves us to also reassess our approach(es) to pandemic control.

DEFINING THE EMERGENCY

Exposure to and subsequent infection with SARS-CoV2 does not carry the same risk across all populations. We have known from the early studies evaluating the hospitalization data from Wuhan, from the Italian Health Ministry data, and from the CDC MMWR on COVID-19 hospitalizations in April and then again in June 2020 that there is a predictable risk stratification for who suffer the highest risk of severe COVID-19 complications (hospitalization, need for mechanical ventilation, and death). Since the June 2020 CDC MMWR on COVID-19 hospitalizations, our initial understanding of risk stratification has not only remained unchanged, repeated studies have further underscored it across most Western populations. The unequivocal number one risk factor is age ≥ 65 years old. For the younger population, severe COVID complication in the “young otherwise healthy” is incredibly rare, and more than 99% of them are not even hospitalized, having no symptoms or just have a mild cold with rapid and complete recovery. For persons 18 – 49 years old who do suffer a more severe course, BMI ≥30 has been shown repeatedly to be one of the top risk factors, along with diabetes, heart disease, and high blood pressure. Absent any of these risk factors, severe complications are very rare for young otherwise healthy people under 50 years old. For those ≥75 years old, underlying medical problems no longer add incremental risk (age itself is the most potent risk factor).

80% of all COVID-19 deaths have occurred in those ≥ 65 years old. Children represent 2% of all COVID-19 hospitalizations and 0.8% of all COVID+ ‘cases’ in the pediatric population result in hospitalization. Children represent 0.06% of all COVID-19 deaths, with a case fatality rate of 0.01% and an infection mortality rate likely much lower. The following graphs (COVID-19 mortality and hospitalizations by age group) best summarize the risk stratification by age.
 

Source of data: https://data.cdc.gov

Graph from: https://covid.cdc.gov

As the second graph demonstrates, not only are deaths rare in younger people, so too are hospitalizations due to COVID. Two recent studies[1][2] even suggest that pediatric COVID hospitalizations may be over estimated by 40% (distinguishing hospitalization due to COVID pneumonia from incidental COVID+ identified from PCR screening while hospitalized for other causes like trauma and fracture). COVID-19 is clearly a pandemic that disproportionately affects the elderly and warrants public action to protect the vulnerable. However, is there any “emergency” in children and young adults warranting similar action across all age groups and risk profiles?

Determining whether COVID-19 disease burden constitutes an “emergency” in children and young adults can be assessed from several metrics. First, excess deaths may be evaluated, comparing 2020 excess deaths to prior years. CDC’s own analysis of indicates there were no excess deaths in 2020 compared to prior years for the 0- 24 year-old age group, suggesting COVID-19 did not cause any increased disease burden.

Source of graph: https://www.cdc.gov

Secondly, comparing to other causes of death in children and young adults, COVID-19 is not only not a leading cause of death, it is no worse than influenza. One recent study[3] even suggests COVID-19 may be less severe than influenza in pediatric population.

Flu data rom CDC Estimated Influenza burden: https://www.cdc.gov/flu/about/burden/2019-2020.html

Pediatric COVID data from https://services.aap.org

Flu data from CDC Estimated Influenza burden: https://www.cdc.gov

Pediatric COVID data from https://services.aap.org

COVID-19 NOT a PEDIATRIC or ADOLESCENT EMERGENCY

COVID-19 therefore does not seem to qualify as an “emergency” in children and young adults necessitating unprecedented suspension of risk-benefit analysis for any mandated interventions. Although we hear public health officials repeatedly state that “the benefits outweigh the risks” for adolescents (and young adults) being vaccinated against COVID-19, I have yet to see any formal analysis of relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) to prevent one hospitalization or death in this younger cohort. If the risk of severe COVID-19 complications is dramatically lower in this cohort, the risk-benefit analysis must also be approached differently. For those who are ≥ 65 years old, have BMI ≥ 30, or have any of the aforementioned underlying medical conditions, the risk-benefit of these EUA COVID vaccines is probably very favorable. We should continue to encourage people with these high-risk factors to be vaccinated. The dramatic drop in hospitalizations after mass vaccination in the elderly (in Israel, US, and UK) alone strongly suggests a tremendous benefit of mass vaccination in high-risk groups against COVID-19. However, for children and young adults, the risk-benefit analysis may not be favorable and warrants a more cautious and meticulous analysis.

LIFTING THE VEIL ON HERD IMMUNITY

Even those who concede that children and young adults rarely suffer severe COVID complications, suggest that we cannot reach the Herd Immunity Threshold (HIT) of >70% entire general population vaccinated unless children are also vaccinated. They also raise concerns that unvaccinated children can infect vulnerable adults and elderly. Neither of these claims have been sufficiently debated and analyzed transparently to warrant unquestioned vaccination mandates for children and young adults in schools and universities. The formula for HIT (1 – 1/R0) presumes several conditions which not only have not been proven for SARS-CoV2, but have actually been refuted by prevailing knowledge.  

First, the HIT formula presumes “everyone is equally susceptible.” Age distribution and risk profile according to BMI and underlying medical conditions clearly refute the presumption that “everyone is equally susceptible.” Secondly, the HIT formula presumes population homogeneity (random and equal chance of anyone interacting with anyone else). Human beings most certainly do not behave this way. Our family, social, and professional networks as well as our living situation significantly increase our chances of interacting with certain members of society (clusters) with virtually no chance of interacting with other members of society. At least one model attempted to adjust for population heterogeneity and arrived at a proposed 40-45% HIT[4]. Thirdly, HIT formula presumes no one has immunity prior to the epidemic. This understanding focuses almost exclusively on adaptive immunity (that part of our immune system that responds to a novel infection and develops B cells, T cells, and antibodies specific to that infection). This conceptual approach completely neglects innate immunity (that part of our immune system which has preexisting nonspecific antibodies and immune cells). A publication last May 2020[5], explored why children’s innate immune system renders them less likely to suffer severe COVID complications. Admittedly, we cannot know with certainty until a pandemic has already completed what precisely the HIT is for SARS-CoV2, we can state with confidence that underlying presumptions in the HIT are not applicable. Therefore, the HIT is likely less than 70% of the general population (i.e., children and young adults do not need to be vaccinated against COVID to control the pandemic trajectory). 

EUA for COVID vaccinations was extended to adolescents in mid May 2021. The graph below depicts COVID hospitalizations through third week of May in several counties in California, before mass vaccination in adolescents had reached any significant percentage. At this time, the highest percent population vaccinated was indeed in the elderly, with decreasing percent population vaccinated with each younger age group. A similar phenomenon was demonstrated in Israel, where they had successfully controlled the pandemic by emphasizing mass vaccination in elderly without mass vaccination in children at that time.

Source of graph: https://covidactnow.org

In the subsequent weeks more of the population is vaccinated in California, and the disparity between counties with highest percent vaccinated and lowest percent vaccinated continues. However, with increasing percent population vaccinated, the shapes and parallel nature of the curves remains unchanged.

California now has the among the lowest per capita COVID+ cases, hospitalizations, and deaths in the country. While much media attention has been given to the success of the mass vaccination efforts as the cause of controlling the pandemic trajectory, California is currently 20th in states by percent population vaccinated (as of the time of the first graph above, it was 26th).

Source of percent population vaccinated: https://www.nytimes.com

IMMUNITY FROM PRIOR INFECTION

As stated above, an estimated 100M – 150M people in US have been infected by SARS-CoV2 (four times the officially confirmed PCR+ ‘cases’). During the winter surge in December and January, Los Angeles County had among the highest per capita hospitalizations in the world. CDC’s most recent seroprevalence study suggest > 50% of Southern California residents have antibodies to SARS-CoV2[6]. Several studies have demonstrated that immunity from natural infection is comparable (or better) than immunity from vaccination[7][8][9]. Other studies have demonstrated that reinfection in those with prior immunity is quite rare and no worse than ‘breakthrough’ cases in those who are vaccinated[10][11]. Because the shape of the per capita hospitalizations in several CA counties is almost identical and parallel regardless of percent population vaccinated (27-55% through third week of May), immunity from natural infection is most certainly contributing to controlling the pandemic trajectory much more than the public narrative by public health experts who continue to emphasize that we “need” to have children and young adults vaccinated to reach Herd Immunity Threshold.

RISK OF MYOCARDITIS AFTER EUA COVID VACCINATION IN CHILDREN AND YOUNG ADULTS

Recently, myocarditis (inflammation of the heart) has received increasing attention in media and by public health officials. CDC even had an emergency meeting scheduled for June 18th to review the data and consider if updated recommendations were needed (the meeting was unfortunately postponed at the last minute due to the federal holiday). Israel has a more centralized health care system enabling a more comprehensive and accurate active surveillance of post vaccine complications. By comparison US relies mostly on passive surveillance like VAERS. There have been concerns raised about under reporting in VAERS. To what degree these concerns may be applicable to severe adverse events after EUA COVID vaccines is worthy of further evaluation and analysis. For now, we can use data from Israel for comparison. Data from Israel suggest the risk of myocarditis after mRNA vaccination in males less than 30 years old to be 1 in 3,000 to 1 in 6,000. There is no known reason to believe the risk would be dramatically different in US population in the absence of formal analysis comparing risk matched cohorts.

Source: https://www.fda.gov

While data from CDC and FDA in the images above do support the statement that “the vast majority” have a mild course of myocarditis, there are cases with a more severe course that warrant further evaluation. Mild cases of myocarditis usually result in complete recovery with a very favorable prognosis[12]. However, severe myocarditis cases can result in cardiomyopathy necessitating heart transplant. There is also a paucity of longitudinal follow-up data (beyond five years) on long term outcomes for myocarditis in children. Thus, erroring on the side of caution until we have a more comprehensive analysis of the risk of myocarditis is wiser than the ongoing push to have all adolescents urgently vaccinated.

LOW RISK IS ETHICALLY DIFFERENT THAN MANDATED RISK

COVID-19 itself poses a risk of severe long-term complications. Balancing the risks of COVID-19 versus the risk-benefit of EUA COVID vaccines will require age and risk factor specific analysis (which to my knowledge has not yet but transparently performed or published by public health officials for risk of myocarditis in those less than 30 years old versus the putative benefits of EUA COVID vaccination in the younger cohorts). Children and young adults can suffer from severe long term COVID-19 complication including (but limited to) myocarditis, MIS-C, and PACS. Risk stratification analysis again reveals that Type 1 diabetes, obesity, and congenital circulatory disorders are among the highest risk factors for severe COVID-19 complications in the younger cohorts.

Source: https://covid.cdc.gov

Myocarditis can occur from several causes, the most common ones being infections, autoimmune disorders, hypersensitivity and toxins12.  Among others, some common infections causing myocarditis include adenovirus (usually causes common cold), parvovirus (can cause mild rash in children), coxsackie virus, influenza, HIV, and Epstein-Barr virus (the virus that causes ‘mono’). COVID-19 itself can cause myocarditis. While initial concerns from a study[13] using cardiac MRI suggested risk of myocarditis and “long term heart damage” in COVID survivors may be greater than 60%, numerous subsequent studies suggest the risk of myocarditis is 0.3-2.5% (comparable to influenza)[14][15][16] [17]. The background rate of myocarditis worldwide is about 22 cases per 100,000 persons[18].

Source: https://pubmed.ncbi.nlm.nih.gov

Using the Israeli data of 1 in 3,000 to 1 in 6,000, the risk of vaccine associated myocarditis (16-33 per 100,000) may be comparable or slightly more than the risk of myocarditis in the general population from other causes. The risk of myocarditis occurring after vaccination may be comparable or less than the risk of myocarditis after COVID-19 (0.3-2.5%). But we must be careful in this methodology of assessing the risk. First, the risk profile is different for myocarditis after vaccination compared to myocarditis after COVID-19 itself. Children and young adults suffering from severe COVID complications tend to have serious underlying medical conditions. The overall data on COVID complications in hospitalized patient is skewed by the fact that the majority were greater than 65 years old. By comparison, those suffering from myocarditis after vaccination are younger and often do not have any of these medical problems. Secondly, exposure to other infections or etiologies (see table above) that can cause myocarditis is not mandated. By comparison, exposure to COVID vaccination may become mandated by many schools and universities. Also, even after direct exposure to a COVID+ patient in a hospital setting (the highest risk setting), not everyone becomes ‘infected’[19]. Most go on to have no symptoms or only mild symptoms. Many do not even have seroconversion after direct exposure. However, after mandated vaccination there is 100% chance of immunogenicity. A seroprevalence preprint study[20] (subsequently published as a CDC MMWR in Mar 2021) earlier this year suggested ten times more children may be infected from SARS-CoV2 than officially confirmed PCR+ ‘cases’. If this study is generalizable across other regions in the US, this would further reduce the already low officially confirmed hospitalization rate (0.8%) and Case Fatality Rate (0.01%) in the pediatric population. Thus, many children and young adults may already have immunity from natural infection and may not derive any incremental benefit from mandated COVID vaccination policies. Low risk of any COVID vaccine associated myocarditis is ethically very different than mandated risk, especially since those who are highest risk of these complications are least likely to have any severe COVID complications. 

LEGAL ISSUES

Several legal opinion pieces have already been written on the topic. It is outside the scope of this paper to explore that in detail. Suffice it to say that Emergency Use Authorization does not prohibit private organizations from mandating COVID vaccination. Full FDA BLA approval may be granted to Pfizer and Moderna mRNA vaccines by end of year (some expect by end of summer). This would also undermine any arguments that government agencies cannot mandate EUA vaccines, the terms of which explicitly stipulate a person has the right to refuse. One federal judge has already upheld the employer mandate by Houston Methodist in Texas. The burden may ultimately fall upon State Legislatures and / or state Governors to balance the needs of public safety motivating public schools and universities to implement mandated COVID vaccination polices versus individual right to not have mandated risk in the context of rapidly evolving data severe vaccine associated side effects in adolescents and young adults.

SUMMARY

COVID-19 is real. It is not a hoax. For high-risk population it carries a high risk of morbidity and mortality. One year ago, the pandemic was continuing to spread uncontrolled in the US, with rising hospitalizations and deaths almost everywhere. The Spring, Summer, and Winter surges in various US regions overwhelmed many hospital systems who had to implement surge protocols. Almost six hundred thousand people died of COVID in the US. Many who survived still suffer long term consequences. Front line workers faced tremendous psychological burden with ongoing threat of personal danger and bringing infection home to vulnerable family. The toll and trauma of this pandemic is indeed tremendous both individually and collectively.

But we are not now where we were one year ago. COVID+ cases, hospitalizations and deaths have continued to decline since beginning of January. In states such as California, COVID+ numbers are lower than at any time during the pandemic. Many states have lifted COVID restrictions for weeks or months, without any subsequent surge of hospitalizations or deaths. The state of emergency that began last March 2020 and continued through January 2021 most certainly does not exist now. There also is no indication that in the US it will return anytime in the near future. Therefore our calculus and methodology of risk-benefit analysis for children, young adults, and those with prior infection out to reflect ought to also reflect the change in transmission dynamics and not impose the risk of 2020 onto the epidemiological reality of 2021.

A word of caution to all employers, schools, and universities considering mandates: just because one can legally implement such mandates, doesn’t mean one ought to implement them. There is no scientific or ethical justification for mandating vaccination in those who have had prior infection. They already have immunity. There is also no scientific and ethical justification for COVID mandated vaccination policies for children and young adults – they have increased risk of recently identified vaccine associated complications and are the very cohorts with the lowest risk of severe COVID complications. Vulnerable adults and elderly who feel unsafe around children and young adults can choose to be vaccinated and continue to wear high quality masks.

We should not be mandating risk in young healthy people to protect vulnerable older adults when alternatives exist.

For the record: I am generally pro vaccination. I have been fully vaccinated with all recommended FDA approved vaccines, including those recommended for overseas travel as appropriate for that region. I recommend vaccination to all my cardiac patients as they are certainly high risk. One can simultaneously understand and accept the tremendous benefit of vaccination programs in controlling vaccine preventable diseases, while also urging caution in certain lower risk subsets of the population when the risk-benefit analysis may not be favorable for vaccines which have been available to the general population less than 6 months. As scientists it is our moral imperative and professional responsibility to consider all variables in our recommendations and be willing to adapt them to patient specific situations to maximize individual safety.

Source: https://www.kff.org

Source: https://www.kff.org

 


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20)https://www.medrxiv.org/content/10.1101/2021.02.05.21250792v1

 

 

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