Structural Contributory Factors Associated with COVID-19 Vaccine Hesitancy Among Americans

A Research Brief

The following is a paper accepted for publication I wrote with a colleague of mine. The acceptance was later reversed. I will not include his name in this post.

Abstract

In December 2019, several unusual respiratory diseases arose in Wuhan, China. This spread quickly from Wuhan to other areas and nations, upon which it was determined that a novel coronavirus was blamable.  Within the context of this background information, the aim of this study is to examine structural factors that may contribute to COVID-19 vaccine hesitancy and acceptance among Americans. It is anticipated that this discussion will proffer information to assist to help identify potential concerns to be addressed to safeguard acceptable uptake among this parameter and enable development of educational programs to teach skills to counsel COVID-19 vaccine-hesitant patients. In addition, it is hopeful that the information presented herein can be used by health educators to understand and accept the validity of the concerns expressed by Americans and others who are COVID-19 vaccine-hesitant. Within this presentation, issues regarding medical mistrust, the COVID-19 vaccine development process, and objective clinical concerns for skepticism.

1.Introduction

In December 2019, several unusual respiratory diseases arose in Wuhan, China1. This spread quickly from Wuhan to other areas and nations, upon which it was determined that a novel coronavirus was blamable. This virus was termed the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCoV) due to its high similarity to SARS-CoV, 2 which caused acute respiratory distress syndrome and resulted in high mortality during 2002–2003. The disease caused by this virus was called Coronavirus disease 19 (COVID-19) and a pandemic was declared as it was determined that human to human transmission played a key part in the consequential outbreak 3.  Since then, COVID-19 has been reported in approximately 200 countries and 4 and by April 2020, around 1,400,000 cases worldwide have been reported according to researchers at John Hopkins University 5. As of the end of September 2021, there were more than 233 million reported cases of COVID-19 and 4.7 million deaths 5.

Li and associates were the first to document a detailed epidemiologic and clinical depiction of the initial 425 cases recorded in the city of Wuhan in Hubei province, China 3.  From a clinical perspective, the majority of patients with COVID-19 display minor to mild symptoms, but around 15% advance to severe pneumonia and around 5% sooner or later cultivate acute respiratory distress syndrome (ARDS) and/or multiple organ failure 6,7.  

SARS-CoV-2 infection can trigger inborn and immune responses and as such, may result in injurious tissue damage 8. Individuals with severe COVID-19, lymphopenia 9 is a common feature, with considerably reduced numbers of CD4+ T cells, CD8+ T cells, monocytes, eosinophils and basophils 10-12. Given features as the aforementioned, efforts to develop a vaccine for the COVID-19 virus were implemented rapidly.

Within the context of this background information, the aim of this study is to examine structural factors that may contribute to COVID-19 vaccine hesitancy and acceptance among Americans. It is anticipated that this discussion will proffer information to assist to help identify potential concerns to be addressed to safeguard acceptable uptake among this parameter and enable development of educational programs to teach skills to counsel COVID-19 vaccine-hesitant patients. In addition, it is hopeful that the information presented herein can be used by health educators to understand and accept the validity of the concerns expressed by Americans and others who are COVID-19 vaccine-hesitant.

2.Medical Mistrust

Vaccine hesitancy remains an obstacle to maximum population inoculation against infectious diseases. Parallel with the speedy advances of COVID-19 vaccines, concerns about the safety of such a vaccine have manifested globally. Health behavior research generally examines medical mistrust from an interpersonal perspective, albeit, it also reflects a belief orientation based on historical and lived experiences. This is particularly consistent for several parameters of the American population 13. What is known is that in general terms, African American men report higher levels of medical mistrust than African American women 13,14. However, with respect to the COVID-19 vaccine, African Americans regardless of gender are not the only parameter hesitant and/or resistant to taking the COVID-19 vaccine.

A study conducted by Murphy (2021) examined vaccine hesitancy/resistance using nationally representative data from the general adult populations of Ireland and the United Kingdom and established that vaccine hesitancy behavior was manifested for 35% and 31% of these populations correspondingly 15. They concluded that respondents in Ireland and the UK, although diverged on multiple health associated and sociodemographic variables were less likely to value information about the pandemic from institutional government sources and had comparable levels of mistrust in these institutions regarding vaccine information. In the U.K., data notes that as of 15 January 2021, less than 21 percent of Blacks over 80 and 36.8 percent of Black healthcare workers had received the COVID-19 vaccine 16,17. 

Similar observations have been observed with other communities. Based of self-report data, research in Michigan found that among a sample of medical students, of which the majority projected positive views and attitudes towards vaccines and knowing they face likely higher risk of exposure to COVID-19, just 53% indicated they would participate in a COVID-19 vaccine trial and 23% were unwilling to take a COVID-19 vaccine immediately upon FDA approval 18. Statistically the investigators concluded that the concern for serious side effects was independently predictive of lower probability to participate in a COVID-19 vaccine trial or instantaneously upon FDA endorsement.

The major factor for most is the pace at which the COVID-19 vaccines were developed and distributed among the general population. It has been statistically demonstrated via nonparametric estimation of duration based on the hazard ratio between two treatment regimens that standard clinical trials last between 5 to 5.6 years 19. In addition, there is the concern associated with employing new technologies for vaccine development, specifically mRNA cell therapies 20.

3.COVID-19 Vaccine Development

The development of the COVID-19 vaccine began in April of 2020 and involved the use of a range of technologies, many of these, which were not “the basis for licensed vaccines 21.” Of these, it was concluded that platforms that employed technique’s typically employed in the field of cancer treatment based on DNA or mRNA were of priority given their flexibility with respect to antigen manipulation 22,23. Consequently, from the publication of the first SARS-CoV-2 sequences to the final vaccine product occurred in an astounding period of six months. In December 2020, the US Food and Drug Administration (FDA) issued emergency use authorizations for coronavirus disease 2019 (COVID-19) vaccines from Pfizer-BioNTech and Moderna. Presently, these two mRNA vaccines are in use for the prevention of coronavirus disease 2019 (COVID-19). Both of these contain and employ polyethylene glycol 2000 as the PEG-micellar carrier system for the vaccine.

Cabanillas and Novak (2021) describe the process of the carrier system that employ this technology as follows: “The mRNA vaccines BNT162b2 and mRNA-1273 are based on the same technology of mRNA that encodes the viral spike (S) glycoprotein of SARS-CoV-2. The mRNA molecule in these vaccines is surrounded by lipid nanoparticles (LNPs) to provide stability to the mRNA molecules. The LNPs have been additionally subjected to the chemical process of PEGylation, which consists on the chemical attachment of polyethylene glycol (PEG) to the surface of the LNPs in order to increase its efficiency and delivery to the target cells 24.” In short, this approach enables the mRNA vaccine to use genetic material to make proteins inside of your body by having the RNA wrapped in a coating that makes delivery easy and keeps the body from damaging it.

4.Objective Clinical Concerns for Skepticism

As of date, there are no studies that can accurately state what the long-term effects of any of the COVID-19 vaccines on the market, regardless if they are from the U.S., China or Russia. This serves as a valid issue of consternation for many COVID-19 hesitant African Americans.  Although considered rare, the side effects documented thus far give many African Americans concern and consequently have contributed to the very low rate of COVID-19 vaccines administered to date to this population. These include Thrombocytopenia 25, cutaneous reactions 26, Anaphylaxis 27, Myocarditis and Pericarditis 28.

Among women, there have been reports of hemorrhage, blood clots and thrombocytopenia following administration of COVID-19 vaccines as well as post-vaccination menstrual irregularities, including vaginal hemorrhages 29. Some have noted that polyethylene glycol, an ingredient found in the Pfizer and Moderna vaccines, have been observed to position a “potential toxicity risk” to ovaries in women 30.  These findings were based on trials run on rodents after intravenous administration. This is in strong consideration as to why we presently observe many menstrual anomalies and miscarriages being reported by women who have received the Pfizer and Moderna vaccines. This is in strong consideration as to why we presently observe many menstrual anomalies and miscarriages being reported by women who have received the Pfizer and Moderna vaccines. Pfizer has even published findings indicating of the possibility of ‘mRNA vaccine shedding’ and concerns regarding women that are pregnant and breastfeeding 31.

Researchers have also described cutaneous reactions to the vaccines. Although not considered to be a serious adverse event, McMahon and associates recorded 414 cutaneous reactions to the messenger RNA COVID-19 vaccines noting that the most common morphologies were delayed large local reactions and local injection site reactions 32. Others have documented the occurrence of maculopapular rash 33 and mucocutaneous reactions, such as pruritus, urticaria, and angioedema after receiving the COVID-19 messenger RNA (mRNA) vaccination 34.

Another side effect documented in the literature to possible occur after receiving the COVID-19 vaccine is anaphylaxis. Anaphylaxis can be potentially life-threatening. In this case, it is an allergic reaction to the vaccine itself 35.  As of January 10, 2021, 108 case reports of anaphylaxis from the Moderna COVID-19 vaccine were submitted to the Vaccine Adverse Event Reporting System (VAERS) 36. Some have suggested that the polyethylene glycol lipid nanoparticle (LNP) delivery system, could be responsible for this bodily reaction 37. 

The most problematic reported health issue recorded in the present body of scientific literature is the presentation of Myocarditis and Pericarditis post vaccination. Myocarditis is an inflammation of the heart muscle (myocardium) and Pericarditis refers to swelling and irritation of the thin tissue surrounding the heart called the pericardium. Das and associates confirmed 29 published cases of acute myopericarditis following COVID-19 mRNA vaccination, most of which manifested within 1–5 days after the second dose of mRNA COVID-19 vaccination 38. It has been estimated that myocarditis presentation occurs in about 12.6 cases per million doses of second-dose mRNA vaccine, particularly among individuals 12 to 39 years of age 39.

5.Experimental Vaccine Ingredients and Hesitancy

The mass media’s lack of interest to support alternative solutions to COVID-19 can make the consumer feel leery about the true mission of the healthcare industry. The patent protocol game has led drug companies to be less open about their ingredients to protect intellectual property rights. As stated earlier, it normally takes 5 to 5.6 years for standard clinical trials for new drugs/vaccines to be completed, so “Operation Warp Speed” can increase hesitant perspectives.  The partnership between an untrustworthy government and a profiteering public-private sector can make consumers hesitant about the agenda.  Supposedly, the money-making endeavor is to facilitate and accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics. The Operation Warp Speed initiative may seem benevolent until we see the subsequent forced mandates to take these experimental agents, and the revenue being generated from both vaccine production and testing for COVID-19.  Adding more to the game of making a person hesitant, the CDC modified the definition of the words vaccine and vaccination in the Fall of 2021after realizing the experimental agents were neither fully safe nor 100% effective.

To make wise decisions, consumers should know the ingredients they are putting into their bodies. However, the medical pharmaceutical industrial complex is constructed to not share proprietary rights for a product until the companies reap the profits. Therefore, there are controversies that can swirl on a scientific level, and this increases vaccine hesitancy.

It is common knowledge that nanotechnology and bioengineering are now major investments in drug delivery. The public concern about graphene oxide utilization in mRNA experimental vaccines has led many consumers to question the need to have this nanotechnology in their body. The companies and constituents who are marketing this technology emphasize safety and indicate that this new mRNA concoction is efficacious with the use of nanotechnology.

It is revealed that there is a lipid nanoparticle sheath enveloping the mRNA technology in the vaccine, so we have the evidence that nanotechnology is being used.  The use of graphene oxide as a delivery system is the likely candidate to facilitate the delivery of this experimental technology into the biology of a person. Graphene is one atom thick, and it is an efficient electrical conductor used in microchips.  Graphene oxide is a unique material that can be viewed as a single monomolecular layer of graphite with various oxygen-containing functionalities.  When you add gold (Msezane et al., 2012) and oxygen doping to the equation (Suggs, Person and Wang, 2011), you have a compound to tailor the electronic structure of oxygen doped carbon nanomaterials, and chemically modifying single-walled carbon nanotubes can be manipulated for numerous devices.   

With knowledge and scientific evidence that companies are investing in nanotechnology to bioengineer products, consumers have hesitancy to receive these experimental products. Not all COVID vaccines are using the mRNA technology, so it is not as though all the vaccine options are the same. It does not mean there is not the same level of hesitancy with non mRNA experimental vaccines, but it is the content that is the concern for the consumer in any of these products.

The negative consequences or potential danger of having these items circulate in the human body are factors that make the consumer hesitant to get vaccinated. Without a reliable and honest discussion, consumers do not know if the mRNA technology is harmless or dangerous. On too many occasions, the scientific community may not reveal the negative consequences of a product until years later.  Putting experimental chemicals in your body can be problematic for a host of biological reasons related to autoimmune responses, allergic reactions, neurodegenerative links, and the fear of potential tracking devices circulating in your body.

Beyond vaccine technology, this nanotechnology is being used for cancer drug delivery and experiments to study neural circuits. Magnetogenetics is another experimental approach that has a base in animal studies. Essentially, genetically encoded nanoparticles can be used in vivo to remotely regulate cellular activity (Stanley, et al., 2015). Both animal and human studies have demonstrated the efficacy of a novel platform for using nanotechnology to remotely control cellular response and regulate the physiology of specific neural populations or circuits.

The amazing concern is that cells can be controlled by external devices outside of the body the same way a remote control device can turn a television on and off or change stations. People have hesitancy with COVID-19 vaccines because radiofrequency fields can be used to eventually control people. In addition, photostimulation of gold nanorods (AuNRs) using a tunable near infrared (NIR) laser at specific longitudinal surface plasmon resonance wavelengths can induce the selective and temporal internalization of calcium in HEK-293T cells via TRPV1 activation leading to gene expression (Sanchez-Rodriguez et al., 2016). In other words, genes can be triggered from an external device and alter behavior.

With sparse knowledge of what is officially in the patented products, the manipulation of nanotechnology can be enhanced to impact biological systems. Consumers are rightfully hesitant about receiving this mRNA technology in their bodies for fear of unknown long-term consequences.  These current factors in conjunction with past history (e.g., the 1976 swine flu vaccine damages) are a matter of life and death, and this is a valid reason for vaccine hesitancy.  There are reports (Silberner, 2009) reminding us that the government recalled 800,000 doses of vaccine targeted to children.  The recall, which was based on potency concerns, may lead to fresh worries that the government rushed to get the product on the market too quickly.

6.Disregard for Vitamin D has an Influence on Consumer Hesitancy

The exclusion of natural elements to treat and heal a person should raise caution about the true agenda of vaccine mandates. To explain here, we can utilize the common metaphor that there is no one shoe size that fits all. Moreover, not all drugs are effective for every ethnic group. These vaccines may cause differential effects that can be detrimental, whereas low-cost items like vitamin D are safe and harmless.  Vaccine hesitancy exists because allopathic medicine can cause iatrogenic illnesses.  In simplified words, doctors can kill.

If the government and medical pharmaceutical industrial complex were truly interested in your health and welfare, then all treatments (even low cost) should be available for consideration. Since the pandemic is reported to be severe, a trustworthy agenda would ensure equal protection with all treatments and remedies beyond a vaccine. Hesitancy exists because consumers do not hear or see mass media attention on factors that are obviously important, such as sunlight. The key to sunlight is the regulation of vitamin D synthesis in the body.

The neglect of regularly measuring vitamin D levels as well as providing standard supplementation demonstrates a neglect in the scientific community. Vitamin D is a critical factor that is essential to maintain overall health and fight against disease. It is documented that melanin dominant people living away from the equator have low levels of vitamin D, so there should be an intense interest to boost those levels.

The science community does not show much interest in simple solutions to enhance life, so this can raise vaccine hesitancy. Not every condition requires a drug or a vaccine. It should be logical to understand that nature is superbly prepared to maintain our health at an optimal level. To propagandize the support and marketing that only vaccines are equipped to manage this specific coronavirus is upsetting and polarizing. No recently developed vaccine is a treatment or a cure for COVID-19. This is an established fact since vaccinated people have contracted the coronavirus as breakthrough cases and even died.

The vitamin D story is not the only neglected science approach to critique. It is mentioned here because of how easy it is to think about sunlight and/or supplements. Obviously, there is no millions and billions of dollars in it for the vaccine developers, but there is a richness in the health benefits for consumers. One can become hesitant about government sponsored mandates when profiteering from vaccines is more important than divulging common cures.

It appears vitamin D has been overlooked as a significant component of life. Since it is primarily generated in our skin following ultraviolet radiation exposure from the sun, we can find great value in the importance of being outdoors. During the pandemic, many people were forced into isolation to remain indoors and away from the sun, and this could have attributed to more illnesses.

The receptors for vitamin D are ubiquitously spread through the brain and body. It is estimated that approximately 5% of the human genome is under the influence of vitamin D (Heikkinen, Vaisanen, Pehkonen, Seuter, Benes, and Carlberg, 2011; Ramagopalan, et al., 2010). The main physiological function of vitamin D is in regulating calcium levels by influencing calcium absorption, storage, and retention in the intestines, bowels, and kidneys. However, there is an updated view of the vitamin D-folate hypothesis (Jones, Lucock, Veysey and Beckett, 2020) that could explain some interactions with being healthy during the pandemic in addition to side effects from vaccines. Folate or vitamin B9 is required for the body to make DNA and RNA and to assist with cell division. A link between the folate status and adverse pregnancy outcomes is well established, particularly with respect to the influence of this vitamin on the occurrence of neural tube defects (Pitkin, 2007). Folate can affect maternal and embryonic physiology as well as paternal fertility reducing sperm counts and motility (Jones et al., 2020). COVID-19 vaccines using the mRNA technology may be impairing both male and female reproductive physiology to give more hesitancy concerning the unknown effects stemming from these experimental agents.

More closely related to the symptoms associated with COVID19, vitamin D supplementation (400 IU/day; 2000 IU/day; single parenteral dose 100,000 IU) was given in randomized clinical trials (Charan, Goyal, Saxena and Yadav, 2012).  According to this systematic review and meta-analysis, vitamin D significantly reduces the respiratory tract infection related events as compared to placebo. Beneficial effect of vitamin D was observed in children as well as adults according to fixed model. Beneficial effect of vitamin D was observed only in children according to random model.  This vitamin D study by Charan and colleagues was analyzed 10 years ago, so we have evidence that it works.

African Americans may be hesitant because research on melanin dominant bodies has been exploited in past research (Washington, 2006). In a more recent review (Paria et al., 2020), it was reported that vitamin D induces immunity, vitamin D production may be influenced by melanin, and both vitamin D and melanin may have significant impact in management of COVID-19. Vitamin D is known to enhance the rate of melanin synthesis; and this may concurrently regulate the expression of furin. Furin is responsible for the activation of several virus particles. Increased furin activity enhances the role of TMPRSS2 in viral entry into the host cells. Negative regulation of vitamin D may bring down the furin activity and associated TMPRSS2 action thereby decreasing the chances of coronavirus infection.

In sum, the function of our inherent immune system depends on vitamin D content that in turn leads to the protection of our health and well-being (Paria et al., 2020). Individuals showing low levels of vitamin D (less than 30 ng/ml) were bound to complain about constant infections in the upper respiratory track than individuals possessing adequate vitamin D levels, depending on their age, gender, body mass, race, and season (Aranow, 2011). Likewise, there is no one vaccine that is appropriate for everyone, and this additional fact contributes to vaccine hesitancy.

7.Conclusion

Americans are not vaccine hesitant nor are the ant-vaccine. However, many are COVID-19 vaccine hesitant for many of the aforementioned reasons presented herein. The increased risk of Myocarditis and Pericarditis post vaccination has caused Sweden’s Public Health Agency to suspended the use of Moderna’s COVID-19 vaccine for those ages 30 and under. Likewise, the Danish Health Authority stated that it would not offer the Moderna vaccine to people under the age of 18.

There are also the mixed messages that are being presented in public by U.S federal government health officials. It has been stated that if one is vaccinated, they can still contract the virus from the unvaccinated and that both can carry and/or spread the virus equally regardless of vaccine status. This messaging has resulted in high levels of consternation for a major segment of the population. Then there is the observation that the latest Public Health data from the UK shows that COVID-19 vaccinated people have accounted for 81% of COVID-19 deaths over summer 2021 40. Even with high rates of vaccinated in the UK, COVID-19 deaths are over 11 times higher than this time 2020 and that since teens were first given the COVID-19 vaccine there has been a 63% increase in deaths among teen boys compared to the same time in 2020.

The effectiveness of the Pfizer-BioNTech COVID-19 vaccine falls below 50 percent after five months, according to a new study published in The Lancet medical journal on Oct. 4 41.

Similar findings have been reported in Singapore where more than 83% of the population is fully vaccinated. Hirschmann (2021) has reported that although such a high proportion of the population is fully vaccinated, the nation has seen an increase in COVID-19 infections reflected in a seven-day rolling average of near 3,000 newly confirmed cases 42. This may be due to the complex structure of the virus. Researchers in India discovered four insertions in the spike glycoprotein unique to the 2019-nCoV that are not found in other coronaviruses all they suggest are similar to amino acid remains observed in main structural proteins of HIV-1.

There is also what has been reported in the Vaccine Adverse Event Reporting System (VAERS) database co-managed by the U.S. Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). VAERS Summary for COVID-19 Vaccines through October 1, 2021 has documented 778,685 adverse reactions to the COVID-19 vaccines from the period of December 2020 to present vaccines compared to 723,780 for all other vaccines from 1990 to present.

In summary, the motives for COVID-19 vaccine acceptance and/or hesitancy is multifaceted as most human behavior. In the future, it will be vital for health professionals to measure the manner in which information is communicated. The present environment molded by an incessant 24-hour media cycle has not assisted but rather aimed to shame the hesitant or employ fear tactics to encourage others to get the COVID-19 vaccine. Moreover, Government agencies should be transparent about their COVID-19 response programs and openly share all information, positive and negative if the goal is to ensure the existence of a healthy populous. This includes the reporting of adverse events that occur after some take the vaccine because many are neither anti-vaccine or vaccine hesitant, they just question its safety given how rapidly these specific vaccines were produced; therefore, additional scientific inquiry on COVID-19 vaccine acceptance and hesitancy should be a priority and should be employed to inform contextualized campaigns and information-sharing that will provide information that address all issues individuals may have pertaining to the COVID-19 vaccines. It is our aim that this research brief will add to the discussion regarding behavior affiliated with COVID_19 by demonstrating the need for an educational curriculum designed to enhance student knowledge about the COVID-19 vaccine and to teach vaccine counseling skills.

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