Low Rates of Co-Administration of Respiratory Vaccines Across the United States: Experiences from a Large Vaccination Ecosystem

1. Introduction

Simultaneous vaccine administration, or co-administration, is the delivery of more than one vaccine using different syringes and anatomic sites at the same clinic visit. [1] Co-administration is considered an important strategy for increasing vaccination coverage across populations. [2,3] With only rare exceptions, co-administered vaccines have similar immunogenicity and adverse event rates compared with vaccines administered alone. [4,5,6] Recommendations from the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) support co-administration of most indicated vaccines and explicitly endorse co-administration of vaccines intended to protect against respiratory viruses (e.g., influenza, respiratory syncytial virus [RSV], and COVID-19) in people of all ages. [7,8]

Despite the extensive data supporting the safety and efficacy of co-administered vaccines and the recommendations from the CDC, missed opportunities for co-administration are prevalent in routine clinical practice. [9,10,11] Studies show that caregiver, patient, and provider concerns about co-administration are common. [12,13] However, more data are needed to identify motivators of co-administration acceptance and hesitance in order to guide interventions that may increase vaccine uptake across the lifespan. These interventions are particularly crucial for vulnerable populations who have lower vaccine coverage rates despite being at higher risk for complications from vaccine-preventable illnesses. [14,15,16,17,18] The importance of understanding vaccine uptake in this context is underscored by the 2023-2024 respiratory virus season marking a critical juncture in vaccine delivery, representing the first season when vaccines against influenza, COVID-19, and RSV were simultaneously available for adults aged 60 years and older. This unique opportunity for comprehensive respiratory virus protection through co-administration occurred against the backdrop of ongoing concerns about concurrent circulation of multiple respiratory pathogens (i.e. the ‘tripledemic’).

To better characterize rates of co-administration and potential missed opportunities, this study leveraged data from a large vaccine ecosystem that provides end-to-end vaccine management for more than 5000 clinics located in 43 states across the United States. The objectives of this study were to (1) describe the frequency of co-administration of COVID-19, influenza, or RSV vaccines within the large vaccine ecosystem during the 2022-2023 respiratory virus season and (2) determine whether sociodemographic factors and clinic attributes contribute to co-administration of these vaccines within that same vaccine ecosystem.

2. Methods

2.1. Study Design

This retrospective, observational study analyzed data from a large, end-to-end vaccine ecosystem (VaxCare LLC, Orlando, Florida). This vaccination network has been previously described and includes more than 5000 active clinic sites across more than 40 US states. In 2023, the more than 17,000 providers in this network administered approximately 4 million vaccines. [19] Through the ecosystem’s automated technology platform, which is integrated with clinic electronic health records (EHR) systems, vaccine encounters are documented, billed to insurance, and reimbursed, resulting in a robust repository of vaccination information. Providers and clinics within this ecosystem can select the vaccines they would like to offer to their patient populations. Vaccine inventory is continuously monitored and replenished, making vaccines available for immediate access at the time of the patient visit.

This study included data from active patients, defined as those who were eligible for vaccination with at least one of three respiratory vaccines (COVID-19, influenza, and RSV), had a clinic visit between July 1, 2022 and June 1, 2023, and received one or more of those vaccine(s) during the study period. Active patients were categorized according to the number and types of those vaccines received.

The study was approved by the University of Louisville Institutional Review Board [23.0719]. Data were provided by the VaxCare data science team and all identifiers removed. The IRB waived the requirement for informed consent due to the retrospective review of de-identified data.

2.2. Statistical Analysis

Demographic and clinic data for the overall population and age-group subpopulations are presented as percentages of their respective totals. Statistical analyses were performed to compare characteristics among active patients who received 1 respiratory vaccine with those who received at least 2 respiratory vaccines at a single visit (co-administration). Additionally, characteristics for patients who received co-administered vaccines were compared for those who received 2 vaccines and those who received at least 3 vaccines at a single visit. Frequencies and percentages were used to summarize categorical variables. Characteristics were statistically compared between the two groups using Chi-squared tests. P values of <.05 were considered statistically significant. Analyses were performed using SAS 9.4 software (SAS Institute Inc., Cary, North Carolina).

3. Results

3.1. Study Population

The vaccine ecosystem had a total of 1,850,269 patients who were vaccinated with any vaccine, and of them, 1,233,349 (67%) received one or more respiratory vaccines during the study period (Figure 1). Of the study population, 40.5% were 65 years or older, and 56.4% were women. Most patients were covered by commercial insurance (53%) or Medicare (39.9%), with a smaller proportion covered by Medicaid or the Vaccines for Children (VFC) program. The most common clinic sites for care were internal medicine (33.9%), pediatric (33.1%), and family medicine (25.1%).

Within the vaccination ecosystem, clinics are categorized based on their annual vaccination volume: highest (>10,000 vaccines annually), extra high (between 2001 and 10,000 vaccines annually), high (9999 to 2000 vaccines annually), medium (401 to 2001 vaccines annually), and low (≤400 vaccines annually). Clinics in the highest volume bracket are typically health system clinics and provided vaccines to nearly one-quarter of the study population.

3.2. Co-Administration of Respiratory Vaccines

Of those with a respiratory vaccine, most active patients in the study population (n=1,182,767; 95.9%) received a single vaccine only (no co-administration). Only 50,582 active patients (4.1%) received 2 or more co-administered respiratory vaccines.

3.3. Differences in Characteristics Between Cohorts

Across all subgroups studied, co-administration rates were substantially lower than single-vaccination rates. The subgroup with the highest co-administration rate was the population of active patients vaccinated at health department sites (13.4%), followed by those with VFC coverage (5.9%), with Medicaid coverage (5.5%), receiving vaccines at the highest-volume clinics (5.2%), and aged 51 to 64 years (5.0%).

The differences in subgroup distribution were compared between the co-administration and no co-administration cohorts are shown in Table 1. The distribution of patient ages, patient genders, insurance types, clinic types, and clinic vaccine volumes were significantly different between the cohorts receiving co-administration vs no co-administration (all P<0.0001). The largest differences between the co-administration and no co-administration cohorts were by clinic specialty, with higher proportions of patients vaccinated at health departments receiving co-administered vaccines (between-group difference, +18.1 percentage points) and lower proportions of patients vaccinated in pediatric clinics receiving co-administered vaccines (−9.0 percentage points). When the distribution of active patients by clinic vaccine volume was compared between cohorts, the differences between the co-administration and no co-administration cohort became increasingly disparate with decreasing vaccine volume, from +7.0 percentage points in the highest-volume clinics to −5.2 percentage points in low-volume clinics. Additionally, compared with the no co-administration cohort, the co-administration cohort had higher proportions of patients aged 51-64 years (between-group difference, +4.3 percentage points) and lower proportions of patients 65 years or older (−5.2 percentage points).

3.4. Co-Administration by Vaccine Types

In the co-administration cohort, the most commonly co-administered respiratory vaccines were influenza and COVID-19 (91.3%). In addition, 5.4% of co-administration events included influenza and RSV, and 2.5% of co-administration events included RSV and COVID-19 vaccines. Only 0.7% of patients in the co-administration cohort received all 3 respiratory vaccines simultaneously.

The co-administered vaccine combinations were evaluated by age group, gender, insurance type, specialty type, and clinic vaccination volume. In general, adults 51 years and older received more co-administered influenza and RSV vaccines than patients in other age groups. Co-administered influenza and COVID-19 were the only combination used in those aged 6 months to 2 years and predominated in people aged 3 to 50 years.

3.5. Co-Administration by Number of Co-Administered Vaccines

Significantly more patients received 2 co-administered vaccines (99.3%) than >2 co-administered vaccines (0.7%). Most individuals receiving 3 co-administered vaccines were aged 51-64 years (67.5%) or 65 years and older (31.2%) and were vaccinated in clinics administering at least 2001 vaccines annually (extra-high or highest volume; 73.2%) (Table 2). The distribution of patients receiving two versus more than two co-administered vaccines differed significantly by age group, insurance type, specialty type, and clinic vaccination volume (all P <0.001). There was no statistically significant difference between the gender of those who received two or more than two co-administered vaccines (P = 0.299).

4. Discussion

In this study of a large, nationwide vaccine ecosystem, we found low rates of co-administration of respiratory vaccines. Despite the CDC recommendations for respiratory vaccines co-administration, fewer than 5% of vaccine visits included multiple vaccines, potentially indicating persistent missed opportunities for optimizing vaccination delivery in real-world clinical settings. To our knowledge, this is the first large study to examine vaccine co-administration in health clinics across multiple states and a wide range of clinic types and sizes.

The underutilization of co-administration represents a critical gap in adult immunization delivery, particularly given evidence supporting the safety, immunogenicity, and operational benefits of administering multiple vaccines simultaneously. Studies of influenza, COVID-19, and RSV vaccines have consistently shown that co-administration does not compromise immune responses or increase serious adverse events, supporting broader implementation in routine practice. [4,5,6] Co-administering vaccines reduces the number of healthcare visits required and addresses barriers such as limited patient access and clinic capacity constraints. [3]

Our findings indicate that respiratory vaccine co-administration is more common and feasible among certain demographic groups and care settings. Middle-aged adults (51-64 years), women, commercially insured patients, and those vaccinated in primary care clinics and health departments were more likely to receive co-administered vaccines. These patterns are unlikely to be due to chance and likely reflect systematic differences in vaccination practices or patient preferences across different population segments. For example, differences in co-administration rates may be related to employee immunization or preventive health initiatives in the workplace among commercially insured and middle-aged adults, differences in health care–seeking behaviors between genders, and stronger vaccination infrastructure in high-volume clinics. [20,21]

The higher rates of co-administration observed in specific settings—such as high-volume clinics, health departments, and among Medicare recipients —underscore the critical role that infrastructure and system supports play in optimizing vaccine delivery. Studies have consistently shown that implementing standing orders, integrated vaccination records, clinician reminders, and care coordinator support can substantially increase vaccine uptake relative to routine care. [22] Clinics with standing orders streamline workflows by authorizing non-provider staff to assess vaccine eligibility and administer vaccines without direct clinician involvement, a practice endorsed by the CDC and ACIP. [23] Similarly, centralized immunization registries and care coordinators facilitate the timely identification of vaccination needs and enable delivery of multiple vaccines during a single encounter. [24] These systems-level interventions may reduce missed opportunities for co-administration and promote efficient use of healthcare resources. In the analysis of Medicare claims data examining the extent of COVID-19 and influenza vaccine administration among older adults, Harris and colleagues observed that racial and ethnic differences in coadministration rates may be more related to access and awareness than to vaccine acceptance itself. Their findings further support attention to structural barriers and operational attention in order to impact vaccine acceptance and resultant co-administration. [25]

Conversely, lower co-administration rates among pediatric clinics, Medicaid and VFC beneficiaries, and low-volume sites suggest potential systemic barriers to vaccine co-administration. For example, vaccine coverage among Medicaid recipients is often hindered by low reimbursement rates and administrative burdens—state Medicaid typically pays less than Medicare or private insurance, potentially discouraging providers from stocking and administering vaccines. [26] Similarly, data show that VFC-eligible children receive vaccines at lower rates than their privately insured peers, reflecting potential structural and organizational challenges. [15] The disparities in co-administration by clinical setting and insurance type highlight areas where targeted interventions—such as improved provider training and streamlined clinic workflows—may help close the co-administration gap. In addition, policy changes that address low vaccine reimbursement rates in Medicaid and other public programs may be necessary to ensure providers are adequately supported to stock and provide commonly co-administered respiratory vaccines. Finally, differences in provider training and knowledge regarding contraindications could also explain the observed patterns. Vaccine co-administration may be enhanced through provider training, with a focus on vaccine safety, co-administration reassurance, and strategies for patient and caregiver counseling on co-administration to reduce vaccine hesitancy. [27]

Further research into the causes of low co-administration rates and disparities in co-administration are needed. Future research should explore patient and provider perceptions of co-administration through qualitative studies. Additionally, the feasibility and acceptability of workflow redesign to incorporate co-administration protocols should be evaluated. Cost-effectiveness analyses examining the impact of improved co-administration on healthcare utilization and disease prevention are also warranted.

This study has limitations that are inherent to its retrospective design, which limits inferential analyses. Additionally, reliance on patient EHR data may incompletely capture patient demographics or vaccinations received outside the ecosystem (e.g., at pharmacies, workplaces, or community events). Lack of race and ethnicity data prevents analysis of disparities across these different groups, but the large sample size helps inform overall co-administration trends, which are likely robust across various ethnic and racial groups. Finally, the dataset did not include information about contraindications, prior vaccinations, and provider-level decision making, so true eligibility for co-administration was not calculated. VaxCare clinics provide vaccines on-site in clinics thereby facilitating access. Although patients can access vaccines through other routes (e.g., other clinics, pharmacies), the ability to seamlessly access co-administered vaccines increase co-administration opportunities and likely influence co-administration rates. The purpose of this study, however, is to report what has occurred in these clinics and serve as a baseline for improvement opportunities. The results also provide the chance to see co-administration rates under what could be considered as a best access opportunity. The exceptionally large sample size of over 1.2 million individuals allowed us to capture real-world vaccination practices across various demographics and settings, enhancing the external validity of the findings. Strengths of this study include the large sample size, geographic diversity, and real world settings which capture actual clinical practice patterns.

In conclusion, this study highlights the possibility of missed opportunities for co-administration of respiratory vaccines in the United States and identifies population- and clinic-level factors associated with higher uptake. Notable disparities across age groups, gender, insurance types, specialty types, and vaccination volume demonstrate that both patient- and systems-level influences, such as access to care, provider practices, and clinic guidelines, shape co-administration patterns. Enhancing co-administration practices could improve vaccine coverage, reduce preventable illnesses, and streamline healthcare delivery.

Future efforts should focus on targeted interventions, including policy changes to address insurance-related disparities, expanding co-administration coverage across payer types, and implementing provider training programs to build confidence in co-administration practices across specialties. Additional research is needed to explore disparities by socioeconomic status, geographic regions, and race and ethnicity. Studies investigating short-term sequalae (e.g., adverse events) and long-term metrics (e.g., vaccine effectiveness, seroconversion, and the need for booster doses) could support efforts to increase co-administration rates by reassuring both patients and providers. Pilot studies on clinic workflow redesign such as standing orders and integration of co-administration, coupled with cost-effectiveness analyses, could provide critical insights for improving vaccine coverage and optimizing resource use in diverse health care settings.