Overcoming Vaccine Hesitancy, Skepticism, and Hostility in Missouri

Similar to the 1918 H1N1 “Spanish flu” pandemic, COVID-19 has manifested as twin public health and economic crises. In the U.S., the first wave of COVID-19 migrated from the Northeast and Pacific Northwest to the Sun Belt, and then the Midwest in 2020. During that first wave, we physicians counselled patients and the public that the elderly and immunocompromised were most vulnerable, and physicians promoted non-pharmaceutical interventions like social distancing and masking. Thus, physicians are also learning to live with uncertainty amid constantly-evolving COVID-19 guidance.

From January–April 2021, Missouri had some of the lowest COVID-19 case rates in the nation. Largely due to the rapid emergence of the Delta (B.1.617.2) variant, however, Missouri was among the top five states with the highest rates of new COVID-19 cases in July. Many Missouri counties still have COVID-19 vaccination rates under 30%,^1,2 partly due to widespread vaccine skepticism and misinformation on social media.

Delta Variant

With several new mutations,^3,4 the Delta variant of SARS-CoV-2 appeared first in India, and continues to evolve and spread throughout the U.S. Delta replicates faster, transmits more easily and to more people, and causes higher viral loads. It also results in more “breakthrough” infections among vaccinated populations, and it causes more severe illness in the unvaccinated. Delta is estimated to be 40–60% more transmissible⁵ than the initial D614G strain or Alpha variant (“UK,” or B.1.1.7 variant), with a basic reproduction number (R_o) of 5–8. For viruses with a R_o of 2.5 spreading in fully-susceptible populations, 10 cycles of transmission results in 9,536 infections. In contrast, viruses with a R_o of 6 result in 60,466,176 infections after 10 cycles of transmission.

By May 2021, India had up to 400,000 cases and up to 4,000 daily deaths. Data from Scotland⁶ suggest that those with Delta were twice as likely to be hospitalized as those with Alpha. Even in highly-vaccinated populations such as Iceland, where 96% of women and 90% of men received at least one vaccine dose, there has been a rise in COVID-19 cases, but no concomitant rise in deaths. It is encouraging that, despite breakthrough infections, the vaccine appears highly protective against death from COVID-19.

The consensus of many surveillance studies is that approximately 80–90% of cases, over 95% of hospitalizations, and over 98% of deaths from COVID-19 occur among those unvaccinated against COVID-19. Those reluctant or unwilling to get vaccinated are most vulnerable, leading some to call this Delta storm a “Pandemic of the Willfully Unvaccinated.” Vaccine hesitancy, skepticism and hostility, coupled with lack of vaccine availability in many nations, increases the likelihood of further mutations, potentially leading to more dangerous “variants of concern” like Delta.

The COVID-19 pandemic has now killed more Americans than the 1918 flu pandemic did. As of September 20, 2021, more than 675,000 people in the United States have died from COVID-19, according to Johns Hopkins University. Above, the Oakland Municipal Auditorium in California was converted to a temporary hospital with volunteer nurses from the American Red Cross in 1918 to help with the patient load. Source: University of California.

In Missouri, many recently-hospitalized COVID-19 patients are under 65 years old, with a median age of 52 in the dedicated COVID ICU at one southwest Missouri hospital.⁷ In the first wave of COVID-19 in 2020, the elderly and those with comorbidities (diabetes, obesity, chronic lung disease) were most vulnerable to SARS-CoV-2. In contrast, Delta has been unpredictable, landing younger and otherwise-healthy patients in intensive care, with deaths in adults as young as 30. Unfortunately, infectious disease experts can no longer predict who becomes severely ill from COVID-19.

On a macro-level, this is not surprising. We know natural selection exerts pressure on viruses and selects for advantageous mutations to target vulnerable populations: the elderly in 2020, unvaccinated groups (severely immunocompromised, hesitant and skeptical individuals, younger populations) today. The second wave of the 1918 pandemic (winter 2018) was the deadliest wave, hitting younger and healthier patient populations than the first wave (spring 2018).

Confronting Vaccine Hesitancy, Skepticism, and Hostility

With our ICUs filling up, it is hard not to feel upset with those who remain willfully unvaccinated; however, vaccine-shaming, scolding, condescension, and finger-wagging are neither helpful nor productive.^8,9 Well-organized anti-vaccine groups are remarkably successful at swaying public opinion against mask mandates, vaccines, and other mitigation measures to protect us. Some politicians are also suing to block mask mandates in our schools and communities, despite evidence-based public health recommendations.⁸

As physicians, it is important to recognize that some may never accept vaccines; on an individual patient level, it is crucial to actively listen empathetically, to allay vaccine fears, and to express understanding of individual patient concerns.^8–10 Not long ago, we proclaimed that children and young adults had no severe consequences from COVID-19. Our main concern was that they might miss school, or infect vulnerable family members; we did not think they would become terribly ill or end up hospitalized. Emerging data on increased childhood hospitalizations, MIS-C, “long COVID,” and myocarditis in athletes has changed our thinking. At this time, neither of the authors would be comfortable sending our children to indoor camps with unvaccinated youth.

In one author’s (ALH) reproductive endocrinology and infertility practice, half his patients (and their partners) remain unvaccinated. Some patients now seek medical exemption waivers for pregnancy or preconception, because of employer mandates for COVID-19 vaccinations. For pregnant patients, he reviews national guidance^12,13 from the American College of Obstetricians and Gynecologists (ACOG), recommending all pregnant and lactating individuals to be vaccinated against COVID-19: “ACOG encourages members to enthusiastically recommend vaccination … emphasizing known [vaccine] safety and increased risk of severe complications associated with COVID-19 infection, including death, during pregnancy.” For infertility patients, he quotes national guidelines^10,14 from the American Society for Reproductive Medicine (ASRM) stating “COVID-19 vaccination does not impact male or female fertility or fertility treatment outcomes,” so we are to “encourage vaccination for all patients during evaluation and treatment for infertility.” ALH will not provide medical exemption waivers for COVID-19 vaccinations to his pregnant or preconception patients.

There is also rampant misinformation¹³ about COVID-19 vaccines and infertility. For couples in which the female partner is under 35, infertility is defined as the inability to conceive after one year of regular, unprotected heterosexual intercourse – so COVID-19 vaccines simply haven’t been around long enough to determine any (positive or negative) effects of vaccines on fertility. However, SARS-CoV-2 may negatively impact male fertility. After SARS-CoV-2, there is evidence for virions in both semen samples and testicular biopsies,^15–17 as well as reports of men with testicular pain, orchitis, epididymitis, and/or testicular damage.¹⁵ Studies also suggest that hypogonadism, oxidative stress, and disruption of the hypothalamic-pituitary-testicular axis may occur after SARS-CoV-2 infection in men.^15–17 COVID-19 vaccines may actually protect male fertility, by decreasing risks of hypogonadism and testicular damage.¹³

Limitations to Science, as a Persuasive Argument

At the time this was writing, (August 30, 2021), FDA had just formerly approved the Pfizer COVID-19 vaccine (beyond emergency use), with recommendations for a booster (third dose). While these developments reassure many, ASRM¹⁰ and others^8,9 note “for some patients, conveying evidence-based scientific information will not be enough to provide reassurance of the importance of vaccination. Appealing to patients with empathy and personal reassurance can go a long way towards allaying fears and encouraging them to be vaccinated.”

Best practices for discussing vaccine hesitancy¹⁸ are to genuinely seek out specific patient concerns through open-ended questions.⁹ It is also critical to approach discussions with grace and humility; it has been challenging for us all to keep up with rapidly-evolving information⁸ throughout this pandemic. Whatever your personal opinion on vaccines, civility is critical for an open and constructive dialogue, free from “vaccine shaming,” bullying, and virtue-signaling.

While a hardcore 10–15% of the population is unlikely to ever receive COVID-19 vaccines, many remain “on-the-fence” with unanswered questions.¹⁷ Given the rise in COVID-19 cases, our Missouri State Medical Association (MSMA) has recommended¹⁹ “consulting your physician for questions about the vaccine,” and encouraged “simple acts to help stop the virus: practice social distancing when possible, voluntarily wear a mask in public places, and get tested if you feel sick.” This recommendation is partly due to emerging data^20,21 on breakthrough infections in fully-vaccinated individuals.

While COVID-19 vaccines are 95% effective against symptomatic disease from the original wild-type SARS-CoV-2 (and Alpha variant), mRNA vaccines are less effective²² in preventing symptomatic infection from Delta. These data are often used by anti-vaccine forces as proof that “those vaccines don’t work,” however, a low death rate despite a high incidence of infection shows vaccines indeed work. The vaccine will not prevent car accidents in recently-vaccinated persons, and there will indeed be other unintended deaths in vaccinated patients, unrelated to the vaccine. Vaccines do not prevent having someone cough in your face; the best mitigation measures for “someone coughing in your face” are masking and social distancing, which also protected people during the 1918 pandemic. Not much has changed!

Conclusion

We have seen a parade of COVID-19 treatments go by, from hydroxychloroquine to ivermectin, from convalescent plasma to monoclonal antibodies. While some monoclonal antibodies are spectacular, and while steroids help the severely ill, we will not emerge from this pandemic with medical treatments: vaccination and non-pharmacologic mitigation measures (hand-washing, crowd-avoidance, social distancing, mask-wearing) are the fastest way to put this pandemic behind us.

Another important issue is our crumbling public health infrastructure. Without good surveillance, a tiny spark of highly-contagious disease easily becomes an inferno. We have an excellent multi-layered global surveillance system for influenza, which we should replicate for SARS-CoV-2 and its variants. Our wonderful public health partners must also be empowered, not threatened.

The COVID-19 pandemic has created unparalleled medical, social, political, and economic challenges. Constantly-evolving guidelines have resulted in a public that is understandably uncertain, fearful, and suffering from “COVID fatigue.” There are many sources^{8, 13, 18} of vaccine hesitancy; having a script of responses can be a useful tool to address common questions. In this edition of Missouri Medicine, MSMA provides a guide to address common concerns and misconceptions about COVID vaccines. See page 404.

Amid evolving public health guidelines, COVID-19 has helped health care providers develop a finer appreciation of the anxiety, uncertainty, feelings of helplessness, and fears of the unknown, that regularly complicate decision-making for our patients. For those who see things as “black-and-white,” and were perhaps overly dependent on algorithms, it has likely been a particularly difficult time. All of us could likely be a little less dogmatic, as we start appreciating the nuances⁸ and gray areas in medicine. In learning to live with uncertainty, we should learn that with every plan, we must be flexible, able to absorb new information, and ready to change direction with little notice. While not typically part of medical education, we must learn to communicate uncertainty and nuance to patients and the public. We will learn from this pandemic and evolve as physicians, as communicators, as patient advocates, and as humans.