Best Practices for Implementation of an Employee Health COVID-19 Vaccine Clinic - A Model for Future Pandemic Preparedness.

OBJECTIVES: To determine best practices from two large-scale, academic medical centers' employee coronavirus-19 (COVID-19) vaccination clinics and apply them to create scalable modules for rapid administration of 10,000 vaccinations. METHODS: The weekly number of COVID-19 vaccine doses administered was captured. Processes were compared to determine best practices, which informed the scalable financial model. RESULTS: Within the first 3 months, >60,000 COVID-19 vaccine doses were administered, and 70% of employees were fully vaccinated in 4 months with >95% by the vaccine mandate deadline. The estimated cost of delivering one dose was $29.95 ($299,505/10,000) compared to $35-$39/dose when delivered by an onsite retail pharmacy. CONCLUSION: Successful, safe, and rapid delivery of >60,000 COVID-19 vaccine doses in 3 months is practical and scalable. Learnings go beyond COVID-19 and can be applied to future outbreaks/pandemics.

Emerging heterologous mRNA-based booster strategies within the COVID-19 vaccine landscape.

Messenger RNA (mRNA)-based vaccine platforms used for the development of mRNA-1273 and BNT162b2 have provided a robust adaptable approach to offer protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, as variants of concern (VoCs), such as omicron and associated sub-variants, emerge, boosting strategies must also adapt to keep pace with the changing landscape. Heterologous vaccination regimens involving the administration of booster vaccines different than the primary vaccination series offer a practical, effective, and safe approach to continue to reduce the global burden of coronavirus disease 2019 (COVID-19). To understand the immunogenicity, effectiveness, and safety of heterologous mRNA-based vaccination strategies, relevant clinical and real-world observational studies were identified and summarized. Overall, heterologous boosting strategies with mRNA-based vaccines that are currently available and those in development will play an important global role in protecting individuals from COVID-19 caused by emerging VoCs.

Vaccine development

The Center for Biologics Evaluation and Research, established by the FDA in 1987, has rigorously evaluated the use of vaccines in the United States for the past 35 years.1,2 The details of vaccine evaluation are well documented in the Code of Federal Regulations (Title 21), and FDA guidance documents that form the "Bible" for vaccine manufacturers (known as sponsors) to follow.3 The guiding principles for vaccine evaluation can be summed up in 3 words-safety, efficacy, and quality. Vaccine development first begins in the laboratory, where the goal of basic research is to understand the complex interactions between pathogens and their human hosts and to generate the knowledge and technology essential for developing a vaccine candidate.5 In advancing the development of a vaccine candidate, scientists build on the extensive research accumulated from the development of more than 80 vaccines currently licensed in the United States and elsewhere while also accessing new technological advances, including improvements in adjuvants and the development of mRNA technology, used in several COVID-19 vaccines.6-8 Preclinical testing in nonhumans Before any vaccine is tested in humans, preclinical research, involving animal studies (eg, with rodents or nonhuman primates) and/or in vitro testing is required. All human studies are required to be conducted under Good Clinical Practice (GCP) regulations established by the FDA as well as the Declaration of Helsinki, a statement of ethical principles for medical research first written in 1964.11,12 The safety and human rights of study participants are rigorously enforced in every clinical trial through well-defined processes for informed consent, study oversight, and protection of privacy. Most vaccines have been required to have a prelicensure safety database of at least 3000 participants vaccinated with the dosing regimen intended for licensure.13 Assessment of safety in 3000 individuals allows for a 95% chance of detecting the occurrence of more common adverse events in 1 in 1000 participants (the "rule of 3").14 The COVID-19 trials for mRNA vacci nes for adults were considerably larger (> 15,000 and > 13,000 vaccine recipients followed for safety);subsequent studies to authorize use in children aged 6 months to 4 to 5 years involved several thousand children followed for a median of 2 months.7,8,15,16 Clinical trials for other vaccines have included safet y data on more than 5900 infants for the pen-tavalent DTaP, IPV, Hib-combina-tion vaccine, more than 7000 infants and toddlers for 3 pneumococcal conjugate vaccines, and more than 15,000 children and young adults (8-26 years) for 3 HPV vaccines.17-19 The FDA may request a larger safety database if a possible safety signal is identified or in response to new information from other vaccines.

Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age.

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-µg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo. RESULTS: On the basis of safety and immunogenicity results in part 1 of the trial, the 25-µg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-µg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-µg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant. CONCLUSIONS: Two 25-µg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).

Factors Associated With COVID-19 Vaccine Receipt by Health Care Personnel at a Major Academic Hospital During the First Months of Vaccine Availability.

Importance: Several COVID-19 vaccines have been authorized in the US, yet preliminary evidence suggests high levels of vaccine hesitancy and wide racial, ethnic, and socioeconomic disparities in uptake. Objective: To assess COVID-19 vaccine acceptance among health care personnel (HCP) during the first 4 months of availability in a large academic hospital, compare acceptance with previously measured vaccine hesitancy, and describe racial, ethnic, and socioeconomic disparities in vaccine uptake. Design, Setting, and Participants: This cross-sectional study included 12 610 HCP who were offered COVID-19 vaccination at a major academic hospital in Philadelphia between December 16, 2020, and April 16, 2021. Exposures: For each HCP, data were collected on occupational category, age, sex, race and ethnicity (Asian or Pacific Islander, Black or African American [Black], Hispanic, White, and multiracial), and social vulnerability index (SVI) at the zip code of residence. Main Outcomes and Measures: Vaccine uptake by HCP at the employee vaccination clinic. Results: The study population included 4173 men (34.8%) and 7814 women (65.2%) (623 without data). A total of 1480 were Asian or Pacific Islander (12.4%); 2563 (21.6%), Black; 452 (3.8%), Hispanic; 7086 (59.6%), White; and 192 (1.6%), multiracial; 717 had no data for race and ethnicity. The mean (SD) age was 40.9 (12.4) years, and 9573 (76.0%) received at least 1 vaccine dose during the first 4 months of vaccine availability. Adjusted for age, sex, job position, and SVI, Black (relative risk [RR], 0.69; 95% CI, 0.66-0.72) and multiracial (RR, 0.80; 95% CI, 0.73-0.89) HCP were less likely to receive vaccine compared with White HCP. When stratified by job position, Black nurses (n = 189; 62.8%), Black HCP with some patient contact (n = 466; 49.9%), and Black HCP with no patient contact (n = 636; 56.3%) all had lower vaccine uptake compared with their White and Asian or Pacific Islander counterparts. Similarly, multiracial HCP with some (n = 26; 52.0%) or no (n = 48; 58.5%) patient contact had lower vaccine uptake. In contrast, Black physicians were just as likely to receive the vaccine as physicians of other racial and ethnic groups. Conclusions and Relevance: In this cross-sectional study, more than two-thirds of HCP at a large academic hospital in Philadelphia received a COVID-19 vaccine within 4 months of vaccine availability. Although racial, ethnic, and socioeconomic disparities were seen in vaccine uptake, no such disparities were found among physicians. Better understanding of factors driving these disparities may help improve uptake.

Coronavirus disease 2019 (COVID-19) vaccine hesitancy among physicians, physician assistants, nurse practitioners, and nurses in two academic hospitals in Philadelphia.

OBJECTIVE: To evaluate coronavirus disease 2019 (COVID-19) vaccine hesitancy among healthcare personnel (HCP) with significant clinical exposure to COVID-19 at 2 large, academic hospitals in Philadelphia, Pennsylvania. DESIGN, SETTING, AND PARTICIPANTS: HCP were surveyed in November-December 2020 about their intention to receive the COVID-19 vaccine. METHODS: The survey measured the intent among HCP to receive a COVID-19 vaccine, timing of vaccination, and reasons for or against vaccination. Among patient-facing HCP, multivariate regression evaluated the associations between healthcare positions (medical doctor, nurse practitioner or physician assistant, and registered nurse) and vaccine hesitancy (intending to decline, delay, or were unsure about vaccination), adjusting for demographic characteristics, reasons why or why not to receive the vaccine, and prior receipt of routine vaccines. RESULTS: Among 5,929 HCP (2,253 medical doctors [MDs] and doctors of osteopathy [DOs], 582 nurse practitioners [NPs], 158 physician assistants [PAs], and 2,936 nurses), a higher proportion of nurses (47.3%) were COVID-vaccine hesitant compared with 30.0% of PAs and NPs and 13.1% of MDs and DOs. The most common reasons for vaccine hesitancy included concerns about side effects, the newness of the vaccines, and lack of vaccine knowledge. Regardless of position, Black HCP were more hesitant than White HCP (odds ratio [OR], ∼5) and females were more hesitant than males (OR, ∼2). CONCLUSIONS: Although most clinical HCP intended to receive a COVID-19 vaccine, intention varied by healthcare position. Consistent with other studies, hesitancy was also significantly associated with race or ethnicity across all positions. These results highlight the importance of understanding and effectively addressing reasons for hesitancy, especially among frontline HCP who are at increased risk of COVID exposure and play a critical role in recommending vaccines to patients.

Racial/Ethnic Differences in COVID-19 Vaccine Hesitancy Among Health Care Workers in 2 Large Academic Hospitals.

IMPORTANCE: Significant differences in hesitancy to receive COVID-19 vaccination by race/ethnicity have been observed in several settings. Racial/ethnic differences in COVID-19 vaccine hesitancy among health care workers (HCWs), who face occupational and community exposure to COVID-19, have not been well described. OBJECTIVE: To assess hesitancy to COVID-19 vaccination among HCWs across different racial/ethnic groups and assess factors associated with vaccine hesitancy. DESIGN, SETTING, AND PARTICIPANTS: This survey study was conducted among HCWs from 2 large academic hospitals (ie, a children's hospital and an adult hospital) over a 3-week period in November and December 2020. Eligible participants were HCWs with and without direct patient contact. A 3-step hierarchical multivariable logistic regression was used to evaluate associations between race/ethnicity and vaccine hesitancy controlling for demographic characteristics, employment characteristics, COVID-19 exposure risk, and being up to date with routine vaccinations. Data were analyzed from February through March 2021. MAIN OUTCOMES AND MEASURES: Vaccine hesitancy, defined as not planning on, being unsure about, or planning to delay vaccination, served as the outcome. RESULTS: Among 34 865 HCWs eligible for this study, 12 034 individuals (34.5%) completed the survey and 10 871 individuals (32.2%) completed the survey and reported their race/ethnicity. Among 10 866 of these HCWs with data on sex, 8362 individuals (76.9%) were women, and among 10 833 HCWs with age data, 5923 individuals (54.5%) were younger than age 40 years. (Percentages for demographic and clinical characteristics are among the number of respondents for each type of question.) There were 8388 White individuals (77.2%), 882 Black individuals (8.1%), 845 Asian individuals (7.8%), and 449 individuals with other or mixed race/ethnicity (4.1%), and there were 307 Hispanic or Latino individuals (2.8%). Vaccine hesitancy was highest among Black HCWs (732 individuals [83.0%]) and Hispanic or Latino HCWs (195 individuals [63.5%]) (P < .001). Among 5440 HCWs with vaccine hesitancy, reasons given for hesitancy included concerns about side effects (4737 individuals [87.1%]), newness of the vaccine (4306 individuals [79.2%]), and lack of vaccine knowledge (4091 individuals [75.2%]). The adjusted odds ratio (aOR) for vaccine hesitancy was 4.98 (95% CI, 4.11-6.03) among Black HCWs, 2.10 (95% CI, 1.63-2.70) among Hispanic or Latino HCWs, 1.48 (95% CI, 1.21-1.82) among HCWs with other or mixed race/ethnicity, and 1.47 (95% CI, 1.26-1.71) among Asian HCWs compared with White HCWs (P < .001). The aOR was decreased among Black HCWs when adjusting for employment characteristics and COVID-19 exposure risk (aOR, 4.87; 95% CI, 3.96-6.00; P < .001) and being up to date with prior vaccines (aOR, 4.48; 95% CI, 3.62-5.53; P < .001) but not among HCWs with other racial/ethnic backgrounds. CONCLUSIONS AND RELEVANCE: This study found that vaccine hesitancy before the authorization of the COVID-19 vaccine was increased among Black, Hispanic or Latino, and Asian HCWs compared with White HCWs. These findings suggest that interventions focused on addressing vaccine hesitancy among HCWs are needed.

Perspectives on the receipt of a COVID-19 vaccine: A survey of employees in two large hospitals in Philadelphia.

BACKGROUND: Health care personnel have been identified by the ACIP as a priority group for COVID-19 vaccination. We conducted a survey in November-December 2020 at two large, academic hospitals in Philadelphia to evaluate the intention of hospital employees to be vaccinated. METHODS: The survey was sent electronically to all employees (clinical and nonclinical staff) at a children's hospital and an adult hospital. The survey was voluntary and confidential. Questions focused on plans to receive a COVID-19 vaccine when available, reasons why employees would/would not get vaccinated, when employees planned to be vaccinated, vaccine safety and efficacy features that would be acceptable, and past history of receipt of other vaccines by the employee and family. Responses were analyzed using univariate and multiple logistic regression methods. RESULTS: A total of 12,034 hospital employees completed the survey (a 34.5% response rate). Overall, 63.7% of employees reported that they planned to receive a COVID-19 vaccine, 26.3% were unsure, and 10.0% did not plan to be vaccinated. Over 80% of those unsure or unwilling to be vaccinated expressed concerns about vaccine side effects and the vaccines' newness. In multivariable logistic regression, persons planning to take a COVID-19 vaccine were more likely to be older, male, more educated, Asian or White, up-to-date on vaccinations, without direct patient contact, and tested for COVID-19 in the past. No significant difference in intention to be vaccinated was found between those with higher versus lower levels of exposure to COVID-19 patients or the number of previous exposures to patients with COVID-19. CONCLUSIONS: While the majority of hospital employees are planning to receive a COVID-19 vaccine, many are unsure or not planning to do so. Further education of hospital employees about the safety, efficacy, and value of the currently available COVID-19 vaccines is critical to vaccine acceptance in this population.