COVID-19: Addressing some common concerns contributing to COVID-19 vaccine hesitancy (14 September 2021)
Considerable time has passed since I published my last COVID-19-themed post, a delay due in large part to my professional obligations as a physician executive as well as my other ongoing COVID-19 outreach initiatives (i.e., interviews, lectures, town hall sessions, etc.) that have been keeping me busy during this pandemic. Moreover, with seventeen COVID-19-themed essays written to date, I have been deliberating on what would be a timely and impactful topic for my next post — something about which I have not previously written. Given that as of 7 September, 37.7% of Americans twelve years of age and older are not fully vaccinated, and 26.9% have yet to receive even one dose (1), I thought it might be appropriate to more thoroughly address the issue of vaccine hesitancy (a topic I touch upon in several prior posts). To this end, I have compiled a collection of some of the common statements I have come across in town hall sessions, on social media, etc., along with my responses to each. The compilation is by no means exhaustive (Just recently, a nurse remarked to me that one of our patients told her the vaccine “has aborted babies in it” — something I’ll address below); and I will likely revisit and revise this post as new concerns emerge.
Concern: Approval of the COVID-19 mRNA vaccines was rushed, and corners were cut, and anyone who gets vaccinated is a “guinea pig for an experimental vaccine”.
Reply: To be clear, although vaccine development was expedited, none of the critical steps were omitted. Each of the vaccine candidates was vetted through clinical trials involving tens of thousands of volunteer participants before being granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA); and as with any medical preventative or therapeutic, post-marketing surveillance is ongoing. There are several factors that contributed to the rapid development of the COVID vaccines, none of which have to do with safety or efficacy. Among these is the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative of the National Institutes of Health (NIH). Confronted with myriad pre-clinical and clinical studies, all of which were competing for volunteer participants, and most of which would not advance to market, ACTIV intended to bring the NIH together with other agencies in the Department of Health and Human Services as well as the Department of Defense (DoD), Department of Veterans Affairs (VA), the European Medicines Agency (EMA), and representatives from academia, philanthropic organizations, and more than 15 bio-pharmaceutical companies in order to: 1) develop a collaborative, streamlined forum to identify pre-clinical treatments; 2) accelerate clinical testing of the most promising vaccines and treatments; 3) improve clinical trial capacity and effectiveness; and 4) accelerate the evaluation of vaccine candidates to enable rapid authorization or approval. In short, ACTIV aimed to “establish a collaborative framework for prioritizing vaccine and therapeutic candidates, to streamline clinical trials and tap into existing clinical trial networks, and to coordinate regulatory processes and leverage assets among all partners”. In my mind, ACTIV represents what humankind is capable of when we decide to cooperate and collaborate in pursuit of a common goal. Moreover, despite intense pressure to grant full approval for the three vaccines currently used under EUA in this country (Pfizer, Moderna, Janssen), the FDA has been moving deliberately and methodically in its analysis of the copious amounts of data, and only recently granted full approval to one (Pfizer) after eight months — This is hardly rushing things and cutting corners.
Concern: The Pfizer COVID-19 vaccine did not get FDA approval, only an extended Emergency Use Authorization, and approval was granted only for a yet to be developed vaccine.
Reply: The Pfizer vaccine was indeed granted full FDA approval on 23 August 2021 (2). The FDA approved both the request to manufacture the BioNTech COVID-19 mRNA vaccine as well as the request to label the product with the proprietary name COMIRNATY (a mashup of “COVID”, “mRNA”, and “Community”). The BioNTech COVID-19 and COMIRNATY mRNA vaccines are the same construct, differing only in name, with the former found on vials used pre-authorization and the latter on vials for commercial use. Simply put, BioNTech COVID-19 mRNA vaccine is the product name and COMIRNATY is the trade name. By way of comparison, GlaxoSmithKline marketed its Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine under the trade name Twinrix, and Merck marketed the Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Recombinant Vaccine as Gardasil. (For a comprehensive list of vaccine product and trade names, see reference 3.)
Concern: The Pfizer mRNA COVID-19 vaccine is an experimental vaccine and the manufacturer is still being required by the FDA to monitor for serious side effects.
Reply: This statement evinces an incomplete understanding of the FDA approval process for medical devices, therapeutics, and preventatives and presupposes that all approved vaccines are entirely risk-free. FDA approval is granted when 1) data from clinical trials shows that the product has demonstrated sufficient safety and efficacy and 2) the manufacturing process and facilities are shown to conform with established Good Manufacturing Practice (GMP) guidelines. That notwithstanding, it is routine practice to require ongoing surveillance after a product is approved to monitor for very rare serious side effects. In the case of the Pfizer vaccine, there have been rare reports of inflammation of heart muscle (myocarditis) and of the fibrous membrane surrounding the heart (pericarditis) primarily in younger male individuals within a few days after the second vaccination, at an incidence of about 4.8 cases per 1 million doses (4). Given such a low frequency of occurrence, the FDA needs to determine whether observed cases are attributable to the vaccine and if so, whether caution advisories should be issued for certain groups (e.g., young males). No vaccine is entirely safe and effective, and the FDA makes recommendations based on the relative risks and benefits of vaccination versus infection. For example, fifteen cases of cerebral venous sinus thrombosis with thrombocytopenia, a rare and serious condition, were reported in female vaccinees following administration of eight million doses of the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), resulting in a temporary national pause in vaccination with this product on 13 April 2021 (5). However, On 23 April, the Advisory Committee on Immunization Practices concluded that the benefits of resuming Janssen COVID-19 vaccination far outweigh the risks and reaffirmed its interim recommendation under FDA’s Emergency Use Authorization. Included was a new advisory for women aged 18–49 years to discuss the risks and benefits of the vaccine with their physicians (6). Similarly, consider that serious gastrointestinal complications (such as bleeding) occur in 1–2% of people using nonsteroidal anti-inflammatory drugs (NSAIDs). For this reason, cautionary statements are included on the package inserts and individuals at increased risk for a complication (e.g. age greater than 65 years, history of complicated peptic ulcer, and concomitant aspirin or anticoagulant use) may be advised against using NSAIDs. However, their beneficial therapeutic properties are generally accepted (7).
Concern: The Pfizer and Moderna mRNA vaccines cause sterility and infertility.
Reply: This Concern derives from a December 2020 online post in which a German epidemiologist speculated that the SARS-CoV-2 spike protein is structurally similar to human placental protein syncytin-1 and therefore, antibodies against the former (induced by vaccination) might cross-react with the latter, causing miscarriages among vaccinated pregnant women. However, sequence analysis shows that in fact, only a few amino acids are common to both proteins, too few to result in a cross-reactive immune response between the two (8). This was confirmed by studies demonstrating that convalescent serum from patients with COVID-19 does not react with syncytin-1 in vitro (9). It is also worth pointing out that no discernable differences have been observed in either the pregnancy rates or miscarriage rates between vaccinated and unvaccinated women (10). In contrast, pregnant women with COVID-19 infection appear to be at an increased risk of severe disease (requiring ICU admission and mechanical ventilation), death, and pregnancy loss (11); and CDC Director Dr. Rochelle Walensky “encourages all pregnant people or people who are thinking about becoming pregnant and those breastfeeding to get vaccinated to protect themselves from COVID-19” (12).
Lastly, because COVID-19 infection has been associated with decreased sperm counts (13), it has been speculated that the mRNA vaccines might similarly affect sperm (a concern without physiologic basis, given that these are not live vaccines). Nonetheless, a study published in the Journal of the American Medical Association showed no significant decrease in sperm counts among vaccinated men at 75 days after the second dose. On the contrary, significant increases in sperm counts were observed, a finding attributed to a period of abstinence before sample collection (14).
Concern: It is safer to risk COVID-19 infection and to rely on naturally acquired immunity than it is to be immunized with the COVID-19 vaccines.
Reply: This statement is fallacious for two reasons. First, it presupposes that infection with SARS-CoV-2 (the virus that causes COVID-19) is actually safer than the COVID-19 vaccines. Second, it assumes that naturally acquired immunity is protective and long-lasting. With respect to the first assumption, the vaccines are proving to be as safe as they were touted to be when they first received Emergency Use Authorization in December 2020. As of 8 September, 377 million doses of vaccine have been administered in the U.S. at a current rate of 810,715 doses daily (15); and to date, only two serious complications have been identified with the Pfizer, Moderna, or Johnson & Johnson/Janssen vaccines: anaphylaxis and Thrombosis with Thrombocytopenia Syndrome. Anaphylaxis (a severe, potentially life-threatening allergic reaction) can have many causes including food items, insect stings, medications, and vaccines. It is rarely associated with the COVID-19 mRNA vaccines, with an estimated incidence of 2.5 to 11.1 cases per 1 million doses (an incidence of 0.00025–0.00111%), largely in individuals with a history of allergy to one of the vaccine components (16). In comparison, the incidence of anaphylaxis associated with bee envenomation is estimated to be 0.047–0.007% (17) and peanut allergy is present in 0.6% of the U.S. population, and as high as 1.5–3% among children (18,19). The risk of anaphylaxis due to COVID-19 vaccination is mitigated by screening for known allergies to any of the vaccine components beforehand and by a 15–30-minute observation period afterwards (standard protocol for most vaccinations).
The second serious complication that has been rarely associated with the COVID-19 vaccines is Thrombosis with Thrombocytopenia Syndrome (TTS), characterized by blood clots and low platelet counts. TTS has been documented after vaccination with the Johnson & Johnson/Janssen COVID-19 vaccine at a rate of about 7 cases per 1 million vaccinated women between 18 and 49 years old (20). In contrast, a meta-analysis of 42 studies involving 8,271 COVID-19 patients found the incidence of thromboembolic events (i.e. blood clots) to be 21% and included such complications as deep vein thrombosis [20% (95% CI: 13–28%): ICU, 28% (95% CI: 16–41%); postmortem, 35% (95% CI:15–57%)] and pulmonary embolism [13% (95% CI: 11–16%): ICU, 19% (95% CI:14–25%); postmortem, 22% (95% CI:16–28%)], with an attributable mortality of 23% (95%CI:14–32%) (21).
In addition to anaphylaxis and TTS, there are several other complications that may be associated with several of the vaccines, albeit very infrequently. These include myocarditis and pericarditis, which occur with the Pfizer vaccine at an observed incidence of 4.8 cases per 1 million doses (Discussed above), and Guillain-Barre Syndrome (GBS), a generally transient autoimmune disorder characterized by muscle weakness and ascending flaccid paralysis that infrequently complicates certain infections and vaccinations, including vaccination with the Janssen and AstraZeneca vaccines. The observed incidence of GBS associated with the Johnson & Johnson/Janssen vaccine has been reported to be 100 suspected cases among 12.8 million people vaccinated (22) and 833 cases reported worldwide among 592 million administered doses of the AstraZeneca vaccine, as of 25 July (23). Of note, the AstraZeneca COVID-19 vaccine is not currently authorized for use in the United States, but the company does intend to seek FDA approval later this year (24).
Certainly, one should never be cavalier about any vaccine-associated side effect, no matter how uncommonly it occurs. However, an informed decision should include an evaluation of the relative risks and benefits of both vaccination and non-vaccination. When looking at the risks associated with COVID-19 infection, people tend to focus solely on the case fatality rate (CFR), defined as the number of attributable deaths divided by the number of cases, expressed as a percentage, and estimated to be about 1.6% in the United States (25). However, such a myopic approach (of which I was admittedly guilty early in the pandemic) fails to account for the morbidity associated with SARS-CoV-2 infection, something about which I have written previously (26). Indeed, it is increasingly apparent that many patients with COVID-19 experience persistent symptoms, defined as lasting for at least a month after recovery from the acute illness. In one meta-analysis of 45 studies, 72.5% of individuals (interquartile range [IQR], 55.0%-80.0%) experienced at least one persistent symptom, most commonly dyspnea (shortness of breath), fatigue, and insomnia (27). In another meta-analysis of 145 studies, long term complaints were pulmonary (20.70%), neurologic and olfactory (24.13%), and widespread, chiefly fatigue and pain (55.17%); and “Post-COVID-19 Syndrome” is an increasingly recognized phenomenon (28).
Having very briefly discussed the relative risks of both the COVID-19 vaccines and COVID-19 itself, I would like to quickly comment about duration of immunity following SARS-CoV-2 infection and after vaccination. The human immune system is incredibly complex, and whether or not an individual is protected against infection or reinfection is determined by both the kinetics and nature of the immune response (e.g. humoral or cellular), as well as features of the pathogen itself. For some pathogens (e.g. measles, mumps, and rubella viruses), immunity is essentially lifelong. For some, such as Clostridium tetanus (causative agent of tetanus) and Bordetella pertussis (the bacterium that causes whooping cough), immunity is long-lived, but vaccine boosters are required; and for others, like Treponema pallidum (syphilis) and coronaviruses (which cause respiratory infections), infection does not confer immunity and reinfection is common. With respect to SARS-CoV-2 (the coronavirus that causes COVID-19), it is simply too early to confidently predict if either infection or vaccination induce lasting immunity. Studies of convalescent serum (i.e. blood taken from recovered COVID-19 patients) and from vaccinated patients show that neutralizing antibody titers persist but wane over time (29). However, these studies do not address the role, if any, of cellular immunity in COVID-19. Nonetheless, cases of reinfection, as well as infection after vaccination have both been described (30,31), and it is quite possible that SARS-CoV-2 (as with many other coronaviruses) will persist in circulation and that periodic boosters will be necessary (akin to seasonal influenza vaccination). However, unlike reinfection, boosters mitigate the risk of severe COVID-19 and of the Post-COVID-19 syndrome.
Concern: It is preferable to rely on supplements rather than on vaccines to prevent COVID-19.
Reply: Certainly, good nutrition is necessary for a healthy immune system and undernourished individuals are at increased risk of infection as well as a more severe and prolonged course. However, unlike with the COVID-19 vaccines, there is currently no convincing data that nutritional supplements either protect against COVID-19 or attenuate the severity of infection. For example, the use of vitamin D has been promoted as both a preventative of and remedy for COVID-19, based on a small number of retrospective studies that showed lower serum vitamin D levels in COVID-19 patients (32,33). However, such studies do not prove causation. Moreover, a more definitive randomized control study of hospitalized COVID-19 patients dosed with vitamin D3 did not demonstrate benefit (34). Similarly, in a multicenter randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, neither zinc, ascorbic acid (vitamin C), nor a combination of the two significantly decreased the duration of symptoms (35). The bottom line is that while supplements may be beneficial, any role in preventing COVID-19 or treating patients with COVID-19 is unproven and likely to be modest at best; and to date, only vaccines have proven benefit in the prevention of COVID-19 and severe COVID-19.
Concern: Major religious denominations oppose use of the COVID-19 vaccines.
Reply: According to the Pew Research Center, just over 40% of Americans identify as religious (36), with 70.6% of them identifying as Christian (46.6% Protestant, 20.8% Catholic, 1.6% Mormon) and 5.9% identifying as non-Christian, including Jewish (1.9%), Muslim (0.9%), Buddhist (0.7%), and Hindu (0.7%), as well as unaffiliated (22.8%) (37). Certainly, there is considerable variability on specific issues both between (e.g. Christian and Jewish) and within (e.g. Catholic and Protestant) major denominations. That notwithstanding, COVID-19 vaccination is condoned, if not endorsed, by most major religious denominations. For example, The Vatican’s doctrinal office, the Congregation for the Doctrine of the Faith (CDF), has determined that these vaccines are “morally acceptable” for Catholics (36). Of note, two vaccines (AstraZeneca and Janssen/Johnson & Johnson) were researched using cell lines remotely derived from aborted fetal tissue. However, even these vaccines are condoned, with the CDF stating:
All vaccinations recognized as clinically safe and effective can be used in good conscience with the certain knowledge that the use of such vaccines does not constitute formal cooperation with the abortion from which the cells used in production of the vaccines derive…The morality of vaccination depends not only on the duty to protect one’s own health, but also on the duty to pursue the common good.
It is also worth mentioning that neither of the mRNA vaccines (i.e. Pfizer and Moderna) were researched using fetal tissue cell lines. Among the non-Catholic Christian denominations, support for the vaccines falls along a spectrum. Although no church officially opposes vaccinations in general, and very few openly discourage them, positions range from open endorsement (e.g. Anglican, Episcopalian, The Church of Jesus Christ of Latter-day Saints) to more reluctant (Evangelical Protestant, Dutch Reformed, The Church of Christ, Scientist) (39). Among the non-Christian denominations, the COVID-19 vaccines are generally (but not universally) condoned or endorsed. In Judaism, for example, vaccination is perceived as a Mitzvah (i.e. a positive commandment), exampled as a way of both taking care of the body we were gifted and of protecting others (40). There has been some vaccine resistance among some ultra-Orthodox Jewish communities, owing to distrust of government mandates (e.g., Social distancing is anathematic to tight-knit religious communities), concern for the possibility that there are non-kosher components of the vaccine (There are none), as well as concerns that the vaccines cause infertility (They do not; see my previous comments on this topic). To this end, there have been extensive efforts both in the United States and in Israel to reach out to ultra-Orthodox communities in order to dispel Concerns and provide reassurance about the vaccines (41); and several ultra-Orthodox rabbis have stepped forward to exhort their followers to get vaccinated (42). Like Judaism, Islam perceives life as a gift from The Creator, and the preservation and protection of life is deemed to be a religious obligation (43). There is some vaccine hesitancy amongst Muslims, owing to distrust of the government (especially among African American Muslims for whom the Tuskegee experiments still resonate), as well as concerns about porcine products in the vaccines (There are none) (44); and as with outreach to Jewish leaders, Muslim leaders have been engaged to reassure their adherents that the COVID vaccines are both compatible with Islamic principles and that they are Halal (45). Regarding Hinduism, there do not appear to be any significant reservations about the vaccines, other than reassurance that they do not contain bovine products; and India is one of the world’s largest producers of COVID-19 vaccines. Low vaccination rates there seem to derive more from logistical challenges than from vaccine hesitancy (46).
(Note: I am not a theologian, and I am not knowledgeable about the nuanced positions of every religious denomination on vaccines in general and COVID-19 vaccines in particular. At a glance, the major denominations do appear to weigh in on supporting the vaccines. Nonetheless, the reader is encouraged to consult with his or her own religious leaders for guidance on this topic.)
Concern: Vaccination should be a personal choice and mandated vaccination is an attempt to erode individual autonomy.
Reply: This is a thorny issue, but there is no denying that distrust of the government, coupled with a perception that vaccine coercion is an attempt to erode individual autonomy, are contributing to COVID-19 vaccine hesitancy. In the United States, with our libertarian tradition enshrined in the Constitution, efforts to cajole (or mandate) people to get vaccinated often elicit a paradoxical and unintended response (i.e. The harder the push, the harder the push-back); and for some people, refusal to get vaccinated is seen as defiance against tyranny (47). This is complicated by the reality that COVID-19 vaccination is perceived by some people to be more of a partisan political issue than a public health one. Admittedly, I am not a Constitutional lawyer, a political scientist, a philosopher, or a sociologist, all of whom could likely better opine about whether COVID-19 vaccination should be compulsory. I do, however, understand the nature of communicable diseases, and this is what I endeavor to share with people in an apolitical manner.
Like all viruses, SARS-CoV-2 can only replicate in the cells of a susceptible host. The viral genome is smaller than that of bacteria and of eukaryotes, at the expense of some of the genes necessary for replication, and viruses must rely instead on the replicative machinery of host cells to make copies of themselves. Once the progeny viruses are assembled, they are released from the host cell and in turn, each invades another cell and the process continues. Because viruses can only be propagated by means of nonimmune individuals, collective immunity (either natural or acquired) makes it increasingly unlikely that the virus will encounter a susceptible host, and assuming there is not a reservoir (such as an animal) that can reintroduce the virus into a human population, transmission ends. The percentage of the population that must be immune in order to interrupt spread of the virus (i.e. herd immunity) depends upon a number of variables to include how contagious a disease is. Recently, Dr. Anthony Fauci said that the U.S. will not be able to reach herd immunity against COVID-19 without vaccine hesitant people “either getting the jab or getting the virus” (48). Unfortunately, the estimated percentage of the population believed to be required for COVID-19 herd immunity is now believed to be well over 80% (49), and vaccine hesitancy, along with the emergence of variants and a current lack of COVID-19 vaccines authorized for use in young children, are raising doubts about whether herd immunity is still even achievable (50). That notwithstanding, the only feasible strategy currently on the table for ending the COVID-19 pandemic remains a combination of vaccination and social measures (i.e., masking, distancing, staying home if ill, etc.). Currently, however, 20% of Americans say that they are unlikely to get the COVID-19 vaccine, with 14% saying they are very unlikely to get vaccinated (51). Their reasons (some of which I address above) are varied, but some people cite a distrust of the government and opposition to any vaccine mandates as an intrusion on civil liberty (52).
With respect to the latter, there is precedent for compulsory vaccination, and since Jacobson vs. Massachusetts (1905), the judiciary has consistently upheld vaccination mandates. In this landmark case, the Supreme Court upheld the authority of states to enforce compulsory vaccination laws, with a 7–2 majority agreeing that mandated vaccination does not violate the Fourteenth Amendment. The Court held that:
In every well-ordered society charged with the duty of conserving the safety of its members the rights of the individual in respect of his liberty may at times, under the pressure of great dangers, be subjected to such restraint, to be enforced by reasonable regulations, as the safety of the general public may demand and that Real liberty for all could not exist under the operation of a principle which recognizes the right of each individual person to use his own (liberty), whether in respect of his person or his property, regardless of the injury that may be done to others. Furthermore, the Court held that Mandatory vaccinations are neither arbitrary nor oppressive so long as they do not go so far beyond what was reasonably required for the safety of the public (53).
With this line of judicial reasoning, one could make the argument that mandated COVID-19 vaccination is justifiable (That is to say, that 1. the pandemic poses a significant public health threat and 2. the vaccines have been sufficiently demonstrated to be safe); and no doubt, the current Administration is examining this in close consultation with Constitutional law attorneys. From an infectious disease perspective, while universal vaccination would be ideal for curtailing the pandemic, at a minimum, vaccination must be compulsory in certain settings, such as for employees of hospitals and nursing homes. On this issue, I believe there should be no compromise. Those of us who have chosen healthcare as a profession have an ethical and moral obligation to provide care for patients, to safeguard them, and to do them no harm (Primum non nocere). We were not compelled to enter this field, and did so willingly, fully recognizing the risks and obligations beforehand. As for mandating vaccines for everyone, others with a better grasp than mine of Constitutional law can argue legality, applying the key considerations of proportionality, precedent, context, and sufficiency of access (54). My tack will remain explaining the science, addressing concerns, dispelling myths, and appealing to a sense of civic responsibility. As with my prior COVID-19-themed posts, my intention here is not to politicize, sensationalize, or trivialize the pandemic, but only to provide information and thoughtful commentary.
Until my next update — regards.
Michael Zapor, MD, PhD, CTropMed, FACP, FIDSA
(14 September 2021)
References
1. https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-total-admin-rate-total (Accessed 8 September 2021)
2. https://www.fda.gov/media/151710/download
3. https://www.fda.gov/vaccines-blood-biologics/vaccines/vaccines-licensed-use-united-states
4. Diaz GA, Parsons GT, Gering SK, Meier AR, Hutchinson IV, Robicsek A. Myocarditis and Pericarditis After Vaccination for COVID-19. JAMA. Published online August 04, 2021. doi:10.1001/jama.2021.13443
5. See I, Su JR, Lale A, et al. US Case Reports of Cerebral Venous Sinus Thrombosis with Thrombocytopenia after Ad26.COV2.S Vaccination, March 2 to April 21, 2021. JAMA. 2021;325(24):2448–2456. doi:10.1001/jama.2021.7517
6. https://www.cdc.gov/mmwr/volumes/70/wr/mm7017e4.htm
7. Sostres C, Gargallo CJ, Lanas A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther. 2013;15 Suppl 3(Suppl 3):S3. doi:10.1186/ar4175
8. Kloc M, Uosef A, Kubiak JZ, Ghobrial RM. Exaptation of Retroviral Syncytin for Development of Syncytialized Placenta, Its Limited Homology to the SARS-CoV-2 Spike Protein and Arguments against Disturbing Narrative in the Context of COVID-19 Vaccination. Biology (Basel). 2021;10(3):238. Published 2021 Mar 19. doi:10.3390/biology10030238
9. Lu-Culligan, A. & Iwasaki, A. The false rumours about vaccines that are scaring women. New York Times (26 Jan 2021)
10. Male, V. Are COVID-19 vaccines safe in pregnancy? Nat Rev Immunol 21, 200–201 (2021). https://doi.org/10.1038/s41577-021-00525-y
11. Delahoy MJ, Whitaker M, O’Halloran A, et al. Characteristics and Maternal and Birth Outcomes of Hospitalized Pregnant Women with Laboratory-Confirmed COVID-19 — COVID-NET, 13 States, March 1–August 22, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1347–1354. DOI: http://dx.doi.org/10.15585/mmwr.mm6938e1
12. https://www.cdc.gov/media/releases/2021/s0811-vaccine-safe-pregnant.html (Accessed 8 September 2021)
13. Best JC, Kuchakulla M, Khodamoradi K, et al. Evaluation of SARS-CoV-2 in human semen and effect on total sperm number: a prospective observational study. World J Men’s Health. 2021;39(e12)
14. Gonzalez DC, Nassau DE, Khodamoradi K, et al. Sperm Parameters Before and After COVID-19 mRNA Vaccination. JAMA. 2021;326(3):273–274. doi:10.1001/jama.2021.9976
15. https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/ (Accessed 9 September 2021)
16. Blumenthal KG, Robinson LB, Camargo CA, et al. Acute Allergic Reactions to mRNA COVID-19 Vaccines. JAMA. 2021;325(15):1562–1565. doi:10.1001/jama.2021.3976
17. Lee EJ, Ahn YC, Kim YI, Oh MS, Park YC, Son CG. Incidence Rate of Hypersensitivity Reactions to Bee-Venom Acupuncture. Front Pharmacol. 2020;11:545555. Published 2020 Oct 7. doi:10.3389/fphar.2020.545555
18. Boyce JA, Assa’ad A, Burks AW, et al. (December 2010). “Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel”. J. Allergy Clin. Immunol. 126 (6 Suppl): S1–58. doi:10.1016/j.jaci.2010.10.007. PMC 4241964
19. Chen M, Welch M, Laubach S (March 2018). “Preventing Peanut Allergy”. Pediatric Allergy, Immunology, and Pulmonology. 31 (1): 2–8. doi:10.1089/ped.2017.0826
20. TTS with Janssen’s COVID-19 vaccine. Reactions Weekly. 2021;1855(1):12. doi:10.1007/s40278–021–95688–3
21. Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis. EClinicalMedicine. 2020 Dec;29:100639. doi: 10.1016/j.eclinm.2020.100639. Epub 2020 Nov 20. PMID: 33251499; PMCID: PMC7679115
22. https://www.yalemedicine.org/news/covid-vaccine-guillain-barre-syndrome (Accessed 9 September 2021)
23. https://www.ema.europa.eu/en/documents/covid-19-vaccine-safety-update/covid-19-vaccine-safety-update-vaxzevria-previously-covid-19-vaccine-astrazeneca-8-september-2021_en.pdf (Accessed 9 September 2021)
24. https://apnews.com/article/europe-business-health-coronavirus-pandemic-072cc116cfb443f64321a6e39400fa93 (Accessed 9 September 2021)
25. https://coronavirus.jhu.edu/data/mortality (Accessed 9 September 2021)
27. Nasserie T, Hittle M, Goodman SN. Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19: A Systematic Review. JAMA Netw Open. 2021;4(5):e2111417. doi:10.1001/jamanetworkopen.2021.11417
28. https://www.frontiersin.org/articles/10.3389/fmed.2021.653516/full
29. Ariel Israel, Yotam Shenhar, Ilan Green, Eugene Merzon, Avivit Golan-Cohen, Alejandro A Schäffer, Eytan Ruppin, Shlomo Vinker, Eli Magen Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection medRxiv 2021.08.19.21262111; doi: https://doi.org/10.1101/2021.08.19.21262111
30. Wang J, Kaperak C, Sato T, et alCOVID-19 reinfection: a rapid systematic review of case reports and case series Journal of Investigative Medicine 2021;69:1253–1255
31. Michela Antonelli, Rose S Penfold, Jordi Merino, Carole H Sudre, Erika Molteni, Sarah Berry, Liane S Canas, Mark S Graham, Kerstin Klaser, Marc Modat, Benjamin Murray, Eric Kerfoot, Liyuan Chen, Jie Deng, Marc F Österdahl, Nathan J Cheetham, David A Drew, Long H Nguyen, Joan Capdevila Pujol, Christina Hu, Somesh Selvachandran, Lorenzo Polidori, Anna May, Jonathan Wolf, Andrew T Chan, Alexander Hammers, Emma L Duncan, Tim D Spector, Sebastien Ourselin, Claire J Steves. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. The Lancet Infectious Diseases, 2021
32. Meltzer DO, Best TJ, Zhang H, Vokes T, Arora VM, Solway J. Association of Vitamin D Levels, Race/Ethnicity, and Clinical Characteristics With COVID-19 Test Results. JAMA Netw Open. 2021 Mar 1;4(3):e214117. doi: 10.1001/jamanetworkopen.2021.4117. PMID: 33739433; PMCID: PMC7980095
33. Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA Netw Open. 2020 Sep 1;3(9):e2019722. doi: 10.1001/jamanetworkopen.2020.19722. PMID: 32880651; PMCID: PMC7489852
34. Murai IH, Fernandes AL, Sales LP, Pinto AJ, Goessler KF, Duran CSC, Silva CBR, Franco AS, Macedo MB, Dalmolin HHH, Baggio J, Balbi GGM, Reis BZ, Antonangelo L, Caparbo VF, Gualano B, Pereira RMR. Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients with Moderate to Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021 Mar 16;325(11):1053–1060. doi: 10.1001/jama.2020.26848. PMID: 33595634; PMCID: PMC7890452
35. Thomas S, Patel D, Bittel B, Wolski K, Wang Q, Kumar A, Il’Giovine ZJ, Mehra R, McWilliams C, Nissen SE, Desai MY. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2021 Feb 1;4(2):e210369. doi: 10.1001/jamanetworkopen.2021.0369. PMID: 33576820; PMCID: PMC7881357
36. https://www.pewforum.org/2021/01/14/measuring-religion-in-pew-research-centers-american-trends-panel/ (Accessed 10 September 2021)
37. https://www.pewforum.org/religious-landscape-study/ (Accessed 10 September 2021)
38. https://www.cacatholic.org/CCC-vaccine-moral-acceptability (Accessed 10 September 2021)
39. https://www.eastidahonews.com/2021/08/where-do-major-us-religions-stand-on-the-covid-19-vaccination/ (Accessed 10 September 2021)
40. https://www.chabad.org/library/article_cdo/aid/2870103/jewish/What-Does-Jewish-Law-Say-About-Vaccination.htm (Accessed 10 September 2021)
43. https://ifyc.org/article/faith-and-covid-19-vaccine-muslims-were-among-first-believe-vaccines
44. https://www.nextavenue.org/covid-vaccine-hesitancy-muslim-americans/
45. https://www.thehastingscenter.org/islamic-ethics-covid-19-vaccination-and-concepts-of-harm/
50. https://covid19-projections.com/path-to-herd-immunity/
51. https://www.ipsos.com/en-us/news-polls/axios-ipsos-coronavirus-index
52. David A. Broniatowski, Amelia M. Jamison, Neil F. Johnson, Nicolás Velasquez, Rhys Leahy, Nicholas Johnson Restrepo, Mark Dredze, and Sandra C. Quinn, 2020: Facebook Pages, the “Disneyland” Measles Outbreak, and Promotion of Vaccine Refusal as a Civil Right, 2009–2019. American Journal of Public Health 110, S312_S318, https://doi.org/10.2105/AJPH.2020.305869
53. https://supreme.justia.com/cases/federal/us/197/11/
54. https://journalofethics.ama-assn.org/article/when-are-vaccine-mandates-appropriate/2020-01