Ethical Considerations Surrounding Employment Mandated Coronavirus Disease 2019 Vaccination and Allergy Skin Testing for the Coronavirus Disease 2019 Vaccine.

Abstract

To the Editor: The first coronavirus disease 2019 (COVID-19) vaccine administered in the United States was on December 14, 2020. A nurse working in the intensive care unit at Long Island Jewish Medical Center in New York received the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine on national television.1 As of December 7, 2021, more than 447 million doses of COVID-19 vaccines had been administered in the United States, and 8.24 billion doses had been administered worldwide.2,3 Approximately 588 million doses of COVID-19 vaccines were distributed in the United States, and 237 million people (71.5% of the US population) have received at least one dose of a COVID-19 vaccine.4 In addition, booster doses of the vaccines have been administered to 49.9 million individuals (24.9% of the fully vaccinated US population).4 While the vaccines have been demonstrated to help prevent the spread of the SARS-CoV-2 virus and alleviate the symptoms of COVID-19, only 200.7 million (60.5% of eligible individuals in the United States) were fully vaccinated as of December 7, 2021.5 Among the remaining 39.5% of eligible Americans, some remain hesitant about receiving the vaccine for various reasons. Reasons commonly provided for vaccine hesitancy include but are not limited to religious beliefs, concerns regarding autonomy and personal liberties with respect to making decisions about one’s own medical care, notions of political conspiracy, the potential for short- and long-term adverse effects, and possible allergic reactions caused by the vaccine components. For example, many allergists and immunologists believe that individuals who were previously exposed to polyethylene glycol (PEG) in drugs such as PEG 3350 (also known as MiraLAX®) may have high levels of immunoglobulin E antibodies to PEG.6 This may put them at risk for anaphylaxis after COVID-19 immunization because PEG is a novel vaccine ingredient in the Moderna and Pfizer mRNA COVID-19 vaccines. On August 16, 2021, former New York State Governor Andrew Cuomo mandated that all hospital personnel and staff at long-term care facilities—including nursing homes, adult care, and other congregate care settings—receive the first dose of a COVID-19 vaccine series by September 27, 2021.7 All unvaccinated staff members were expected to have documented an approved medical exemption; otherwise, these individuals were not permitted to work. In addition, New York City Mayor Bill de Blasio announced that employees and customers of establishments in the city such as restaurants, gyms, and performance venues must receive at least one dose of the COVID-19 vaccine series by September 13, 2021.8 Mayor de Blasio also required city municipal employees, such as police officers, firefighters, and sanitation workers, be vaccinated with at least the first dose by October 29, 2021.9 Similarly, President Joseph Biden also enacted COVID-19 vaccination mandates for federal workers to be fully vaccinated or request an exemption by November 22, 2021,10 but the deadline was later revised to January 4, 2022.11 An initial population-based study determined that before the introduction of COVID-19 vaccines, allergic reactions to vaccines generally occurred at a rate of 1.31 cases per million vaccine doses.2 However, later studies for the different COVID-19 vaccines demonstrated higher incidence of anaphylaxis in the immediate postvaccination period than initially expected from preliminary safety studies as follows: Moderna vaccine, 2.5 per million doses; Pfizer-BioNTech vaccine, 24 per million doses; and AstraZeneca vaccine, 23 per million doses.3,12,13 We hypothesized that the individuals with hesitancy to receive the vaccine will seek allergy testing for the COVID-19 vaccine, temporally related to the impending vaccination mandates, and will eventually decide to receive the vaccine if no adverse reactions were elicited. This study aimed to investigate (1) how the demand for COVID-19 vaccine allergy testing was affected by the New York State employee vaccination mandates and (2) the percentage of individuals who selected to receive the vaccine after the risk of immediate allergic response (e.g., anaphylaxis) was obviated by allergy testing. METHODS We retrospectively reviewed the deidentified medical records of 13 patients who presented to the allergy and immunology practice and expressed their concerns regarding the COVID-19 vaccine. During the initial patient encounter, patients were interviewed for known allergies, including to determine whether they had ever experienced a prior allergic hypersensitivity reaction after exposure to PEG or any PEG 3350 products in the past, and patients were advised about the risks and benefits of the different COVID-19 vaccines by a board-certified allergist/immunologist. The physician offered allergy skin testing with the COVID-19 vaccine if despite having no personal history of allergy, including allergic hypersensitivity to PEG or PEG 3350, patients continued to have concerns about possible allergic reactions, including anaphylaxis. Vital signs (blood pressure, heart rate, oxygen saturation) were evaluated before any allergy testing was initiated. The Pfizer-BioNTech (BNT162b2) mRNA COVID-19 vaccine was used as the vaccine for all allergy testing procedures. All the patients were advised not to take any medications with antihistamines at least 7 days before presenting for allergy testing. Patients were first skin tested percutaneously on one of their forearms using the Pfizer-BioNTech COVID-19 vaccine to observe any possible allergic reactions that may be triggered. A negative saline control that produces a 0-mm wheal and a positive histamine control that produces a 5-mm wheal was used on the same forearm. A drop of the vaccine or control was applied to the surface of the skin in accordance with the procedure described in Patel et al14 for percutaneous skin testing in allergy. An epinephrine injector was readily available in case of anaphylaxis or any other severe allergy symptoms. The patients’ forearms were evaluated after 15 minutes for any wheals induced, specifically for a ≥ 5-mm wheal or a flare caused by the COVID-19 vaccine. The diameter of any wheals or flares produced were measured and then recorded. The allergy testing results were confirmed if the negative saline control produced a less than 1-mm wheal and the positive histamine control produced ≥5-mm wheal. If the percutaneous skin prick testing was negative for the Pfizer-BioNTech COVID-19 vaccine, the patients proceeded with intradermal allergy testing on bilateral forearms. The COVID-19 vaccine and the negative saline control (with a predicted 0-mm wheal) were injected under the surface of the skin on both forearms; no positive histamine control was used in the intradermal allergy testing. The forearms were re-evaluated for the presence of wheal or flare reactions elicited by the COVID-19 vaccine and the diameters of any were recorded. Wheal diameter ≥5 mm was defined as a positive intradermal test result. RESULTS In the cohort of 648 patients who presented to the allergy and immunology center inquiring about COVID-19 vaccination—that is, the total number of patients seeking vaccination, allergy testing to the vaccine, or seeking medical exemption from vaccination—between March 25 and December 7, 2021, only 13 (2.0%) refused to receive the COVID-19 vaccine, expressing concerns about the safety of the COVID-19 vaccine. These 13 patients stated that they were required to either complete a COVID-19 vaccination series or obtain either medical or religious exemption to continued employment due to the impending statewide vaccination mandate. When alternatives to the Pfizer-BioNTech COVID-19 vaccine offered at the allergy-immunology center were discussed, all 13 patients denied that they would be more comfortable receiving a different COVID-19 vaccine, including a non-mRNA vaccine, such as the Johnson & Johnson viral vector COVID-19 vaccine. In attempting to receive medical exemption from state-mandated COVID-19 vaccination, 9 of those 13 patients requested allergy testing for the vaccine whereas the remaining 4 declined any allergy testing. The 4 patients who declined to be allergy tested stated various reasons, such as trypanophobia (extreme fear of medical procedures involving injections and hypodermic needles) or only requesting a medical exemption from the New York State vaccination mandate for their employers, not necessarily related to an allergy to the COVID-19 vaccine. Although the COVID-19 vaccines were available to the US population as early as December 2020, no patients presented to the allergy and immunology practice to express concerns regarding potential allergic reactions and anaphylaxis caused by COVID-19 vaccines until August 17, 2021—approximately 8 months after the vaccines were introduced. The study’s first COVID-19 vaccine allergy testing was performed on September 3, 2021. Previous studies indicate confirmed anaphylaxis caused by COVID-19 vaccines is rare,15,16 likely because of a lack of preexisting immunoglobulin E antibodies against the novel COVID-19 mRNA vaccine excipient PEG and other vaccine components.17 Similarly, a cohort study found that 98% of a group of highly allergic individuals had no allergic reaction after COVID immunization, 1% had mild allergic responses, and only 0.7% had anaphylactic reactions.18 None of the patients had an allergic reaction or anaphylaxis during the allergy testing procedures. In addition, none of the patients exhibited wheals greater than 5 mm on their forearm within 15 minutes of the percutaneous skin prick testing for the COVID-19 vaccine but all displayed a valid greater than 5-mm wheal to the positive histamine control and a 0-mm wheal to the negative saline control. Some patients did have wheals less than 5 mm at the vaccine administration site, but these patients did not have symptoms that met the criteria for immediate (type 1) hypersensitivity based on Gell and Coombs classification. Similarly, none of the patients who underwent allergy testing exhibited symptoms of immediate allergic hypersensitivity after intradermal allergy testing was performed. All patients had a valid less than 1-mm wheal from the negative saline control but no vaccine wheal greater than 1 mm was observed on the patients’ forearms. Two patients had minor symptoms such as mild redness and slight itchiness associated with the intradermal skin testing, but no wheals greater than or equal to 5 mm or type 1 hypersensitivity reactions were observed. Two patients in the cohort previously tolerated PEG 3350 with no allergic reaction issues and had no known allergy to PEG, whereas the remainder of the cohort had never taken any PEG 3350 products and also did not have a known allergy to PEG. Previous research has shown there is a high rate of false-positive intradermal skin test results during PEG skin testing, proven by subsequent negative PEG oral challenge results.19 Patients were offered an oral challenge using PEG 3350 if they still expressed concerns about allergy to PEG despite negative COVID-19 vaccine allergy testing. None of the patients in the study elected to undergo an oral challenge to PEG. Nine patients (69.2%) in the study cohort opted to be skin tested for possible allergic reactions to the vaccine. Of these, 8 went on to receive at least one dose of a COVID-19 vaccine series. We found that 4 individuals (30.8%) eventually completed either the Pfizer-BioNTech or Moderna COVID-19 vaccine series; 3 (23.0%) only received the first dose, and 1 (7.7%) received the Johnson & Johnson COVID-19 vaccine. Although most patients elected to receive the vaccine after negative allergy testing, 5 of 13 (38.5%) declined the COVID-19 vaccine. In total, 8 patients (61.5%) initiated COVID-19 vaccination, but none of the 4 patients who refused allergy testing received the vaccine. DISCUSSION No patients requested allergy testing for the COVID-19 vaccine at the allergy practice until August 2021, after the government-imposed mandate initiated the demand for COVID-19 vaccine skin testing, even though the vaccine had been available since December 2020. The first date when a patient presented for COVID-19 vaccine allergy concerns was August 17, 2021, the day after former New York State Governor Andrew Cuomo issued the COVID-19 vaccination mandate policy for employees at all hospitals and long-term care facilities on August 16, 2021. Figure 1 shows how the number of patients seeking allergy testing for the COVID-19 vaccine increased as the vaccination mandate deadline of September 27 was nearing. Most patients presented to the practice in September and October, before the September 27th healthcare worker and October 29th city employee vaccination deadline. This increased demand for COVID-19 vaccine allergy testing is likely related to the COVID-19 vaccination mandates in New York State because no patients requested COVID-19 vaccine allergy testing in the months before the mandate, nor in the months that followed (November through December 2021). All 13 of the patients who presented to the office because of apprehension about the COVID vaccine also expressed concerns about the NY state vaccination mandate.FIGURE 1: Timeline of the COVID-19 vaccination mandate in New York State and the patients in the study presenting to the medical center.No patients in the study had a positive allergy testing result to skin prick or intradermal administration of the Pfizer-BioNTech COVID-19 mRNA vaccine. The negative results of allergy testing were sufficient to convince most patients (8 of 9) who requested COVID-19 allergy testing. However, of the 13 patients who expressed concerns about the COVID-19 vaccine, 4 declined to undergo allergy testing and did not thereafter initiate the COVID-19 vaccination series. These patients most likely established that they would not perform allergy testing or receive the COVID-19 vaccine before presenting for a visit, possibly because of personal beliefs, such as distrust of vaccines, perceived infringement on personal liberties, or contempt for government mandates in addition to the abovementioned patient-reported concerns regarding vaccine safety when patients were interviewed. Although 8 patients eventually received at least one dose of a COVID-19 vaccine, one of the patients remained hesitant even though no allergic hypersensitivity responses were elicited during allergy skin testing. These individuals seeking a medical exemption from the employee vaccination mandate by using numerous unorthodox approaches can create a dilemma. Physicians may become skeptical about issuing medical exemptions for patients, with pertinent issues such as severe allergic reactions to the COVID-19 vaccines or one of its components, who genuinely require an exemption from the vaccine for their employers. Furthermore, employers and the government may become suspicious of exemptions if individuals exploit the accommodations by providing falsified information to maneuver around the mandate. In addition, accommodations at work for individuals who do not truly need them, such as weekly COVID-19 polymerase chain reaction testing, can unnecessarily burden healthcare professionals and medical laboratories. This can consume valuable time and resources for individuals who may be ill and infected with COVID-19. Moreover, exemption from the vaccine with accommodations to work remotely or take a leave of absence can create strain on hospitals, police departments, and other vital community organizations by placing additional hardships on employees who were vaccinated and did not request an exemption. A significant limitation of this study is the limited sample size and the inability to perform an oral challenge using PEG 3350 (MiraLAX®) secondary to patient refusal to test for possible allergic reactions caused by PEG. In addition, the allergy skin testing was performed using only the Pfizer-BioNTech COVID-19 vaccine; future studies should be performed using the Moderna and Johnson & Johnson vaccines with an increased sample size. Furthermore, the study relies on data collected from a single allergy practice located in New York State, limiting the generalizability of insights gained to other US states and territories as well as to other countries. Ideally, future research surrounding allergy testing for mandated employee vaccination would recruit patients from multiple locations to account for regional differences that may contribute to hesitancy associated with the COVID-19 vaccine. Nevertheless, the results of this study can guide allergists and immunologists in their evaluation of the patients before and after COVID-19 vaccine administration. David Li, BS Three Village Allergy and Asthma PLLC South Setauket, New York Weill Cornell Medical College New York, New YorkDennis L. Caruana, BS Yale University School of Medicine New Haven, ConnecticutAnthony M. Szema, MD Three Village Allergy and Asthma PLLC South Setauket, New York Departments of Medicine and Occupational Medicine Epidemiology, and Prevention Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Hempstead, New York Department of Technology and Society College of Engineering and Applied Sciences Stony Brook University Stony Brook, New York