Analysis of mRNA COVID-19 Vaccine Uptake Among Immunocompromised Individuals in a Large US Health System

Key Points

Question  What is the uptake of messenger RNA (mRNA) COVID-19 vaccine among immunocompromised individuals, and what factors are associated with receiving at least 4 doses?

Findings  In this cohort study of 42 697 patients in a large US integrated delivery network, only 41% of immunocompromised individuals had received 4 doses of mRNA COVID-19 vaccine and only 1% had received 5 doses as of August 6, 2022, consistent with US Centers for Disease Control and Prevention (CDC) recommendations for this population at the time. Younger adults, Hispanic and non-Hispanic Black adults, and individuals receiving high-dose corticosteroids were less likely to receive at least 4 doses.

Meaning  These findings suggest that adherence to CDC mRNA monovalent COVID-19 booster dose recommendations among immunocompromised individuals was low, suggesting that targeted and tailored efforts to improve booster dose uptake among immunocompromised individuals are warranted.

Importance  Immunocompromised individuals are at increased risk for severe outcomes due to SARS-CoV-2 infection. Given the varying and complex nature of COVID-19 vaccination recommendations, it is important to understand COVID-19 vaccine uptake in this vulnerable population.

Objective  To assess mRNA COVID-19 vaccine uptake and factors associated with uptake among immunocompromised individuals from December 14, 2020, through August 6, 2022.

Design, Setting, and Participants  This cohort study was conducted with patients of Kaiser Permanente Southern California (KPSC), an integrated health care system in the US. The study included patients aged 18 years or older who were immunocompromised (individuals with an immunocompromising condition or patients who received immunosuppressive medications in the year prior to December 14, 2020) and still met criteria for being immunocompromised 1 year later.

Exposures  Age, sex, self-identified race and ethnicity, prior positive COVID-19 test result, immunocompromising condition, immunomodulating medication, comorbidities, health care utilization, and neighborhood median income.

Main Outcomes and Measures  Outcomes were the number of doses of mRNA COVID-19 vaccine received and the factors associated with receipt of at least 4 doses, estimated by hazard ratios (HRs) and 95% Wald CIs via Cox proportional hazards regression. Statistical analyses were conducted between August 9 and 23, 2022.

Results  Overall, 42 697 immunocompromised individuals met the study eligibility criteria. Among these, 18 789 (44.0%) were aged 65 years or older; 20 061 (47.0%) were women and 22 635 (53.0%) were men. With regard to race and ethnicity, 4295 participants (10.1%) identified as Asian or Pacific Islander, 5174 (12.1%) as Black, 14 289 (33.5%) as Hispanic, and 17 902 (41.9%) as White. As of the end of the study period and after accounting for participant censoring due to death or disenrollment from the KPSC health plan, 78.0% of immunocompromised individuals had received a third dose of mRNA COVID-19 vaccine. Only 41.0% had received a fourth dose, which corresponds to a primary series and a monovalent booster dose for immunocompromised individuals. Uptake of a fifth dose was only 0.9% following the US Centers for Disease Control and Prevention (CDC) recommendation to receive a second monovalent booster (ie, fifth dose). Adults aged 65 years or older (HR, 3.95 [95% CI, 3.70-4.22]) were more likely to receive at least 4 doses compared with those aged 18 to 44 years or 45 to 64 years (2.52 [2.36-2.69]). Hispanic and non-Hispanic Black adults (HR, 0.77 [95% CI, 0.74-0.80] and 0.82 [0.78-0.87], respectively, compared with non-Hispanic White adults), individuals with prior documented SARS-CoV-2 infection (0.71 [0.62-0.81] compared with those without), and individuals receiving high-dose corticosteroids (0.88 [0.81-0.95] compared with those who were not) were less likely to receive at least 4 doses.

Conclusions and Relevance  These findings suggest that adherence to CDC mRNA monovalent COVID-19 booster dose recommendations among immunocompromised individuals was low. Given the increased risk for severe COVID-19 in this vulnerable population and the well-established additional protection afforded by booster doses, targeted and tailored efforts to ensure that immunocompromised individuals remain up to date with COVID-19 booster dose recommendations are warranted.

Immunocompromised individuals (ie, persons with immunocompromising conditions or who are taking immunosuppressive medications) are at increased risk for severe COVID-19.¹ Additionally, immunocompromised individuals often mount weaker immune responses to vaccines and experience higher rates of vaccine failure compared with immunocompetent individuals.^2-5 The US Food and Drug Administration (FDA) and the US Centers for Disease Control and Prevention (CDC) have progressively amended COVID-19 vaccine authorizations and recommendations to include additional doses of COVID-19 vaccine for immunocompromised individuals.^6,7 Following the 2-dose mRNA recommendation in December 2020, the CDC Advisory Committee on Immunization Practices recommended in August 2021 that individuals with immunocompromising conditions who had received any mRNA vaccine should receive a third dose as part of their primary series.⁶ In September 2021, an mRNA monovalent booster dose administered 6 months or more after completion of a primary series of BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) was recommended for certain high-risk individuals, including immunocompromised individuals. For immunocompromised individuals, this booster dose corresponded to a fourth dose to follow the recommended 3-dose primary series in this population. In October 2021, the booster recommendation was expanded to recipients of any mRNA vaccine and the interval between completion of a primary series and receipt of a first booster dose was shortened to at least 5 months after completion of a primary series. In February 2022, the recommended interval between a 3-dose primary series and receipt of a first booster (ie, fourth) dose was again shortened for immunocompromised individuals, this time to at least 3 months after completion of a primary series. In March 2022, the CDC announced that immunocompromised individuals could receive a second mRNA monovalent booster of COVID-19 vaccine (ie, a fifth dose) at least 4 months after receiving their first booster (ie, their fourth dose). In May 2022, this recommendation was revised to specify that immunocompromised individuals should receive a second booster (ie, fifth dose).

Given the rapid pace of changing COVID-19 vaccination guidelines over the last 2 years, there has been considerable confusion about what constitutes being up to date with COVID-19 vaccination in the US, especially for immunocompromised individuals.⁸ However, there are few data describing vaccine uptake in the immunocompromised population. Nonadherence to COVID-19 vaccine recommendations in this subpopulation has important public health implications. For example, a recent CDC analysis showed that roughly 1 in 8 COVID-19–related hospitalizations occur in immunocompromised individuals.⁹ We analyzed uptake of mRNA monovalent COVID-19 vaccines among immunocompromised individuals and identified factors associated with uptake in this population using data from a large US integrated delivery system.

This cohort study was approved by the Kaiser Permanente Southern California (KPSC) Institutional Review Board with a waiver of the Health Insurance Portability and Accountability Act and informed consent, as the data-only research activities were determined to pose minimal risk. This study conformed to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

Kaiser Permanente Southern California is a large integrated US health care system with more than 4.7 million members in Southern California, which is generally representative of the socioeconomic, racial, and ethnic diversity of the area’s population.¹⁰ The KPSC integrated electronic health record system includes data for members across all settings of care. Care delivered to members outside of the KPSC system is captured through reimbursement claims.

Kaiser Permanente Southern California members aged 18 years or older who were immunocompromised were included in this retrospective cohort study. Participants were required to have at least 1 year of health plan membership (45-day gap allowed) to determine comorbidities and medical history.

Immunocompromised status was defined as having an immunocompromising condition in the year prior to the study start date (December 14, 2020, which corresponded to the date the first doses of COVID-19 vaccine were administered to KPSC members) or receiving immunosuppressive medications as of the study start date (defined as having an outpatient dispense that included December 14, 2020, or an inpatient administration 90 days or less prior to December 14, 2020). In addition, to be included, 1 of these same 2 criteria (having an immunocompromising condition in the year prior or receiving immunosuppressive medication) also had to be met 1 year later (December 14, 2021).

Identification of immunocompromising conditions and medications was based on an algorithm from a previous study.¹¹ The algorithm uses International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes to identify patients with evidence of hematologic malignancy, HIV/AIDS, or intrinsic immunocompromising conditions associated with (1) at least 1 inpatient diagnosis code, (2) 2 separate encounters not occurring on the same day in the outpatient (including virtual visits) or emergency department setting, or (3) a combination of these settings (eg, 1 emergency department encounter and 1 virtual visit; eTable 1 in Supplement 1). In addition, patients listed on the solid organ or hematopoietic stem cell registries or individuals with evidence of being prescribed systemic immunosuppressive medications were classified as immunocompromised. Immunosuppressive medications included chemotherapy, immunomodulators, tumor necrosis factor-α (TNF-α) antagonists, and systemic steroids (≥20 mg/d prednisone equivalent; eTables 1 and 2 in Supplement 1). Days’ supply was assumed to be 90 days for long-acting immunosuppressive medications such as infliximab.

In KPSC, all members were eligible for COVID-19 vaccines at no cost based on FDA approval or emergency use authorization. Vaccination data, including the date and type of each COVID-19 vaccine dose, were captured within the electronic health record system if provided at a KPSC site or via the California Immunization Registry if administered outside KPSC. We excluded doses recorded as received prior to the initial emergency use authorization of mRNA COVID-19 vaccines on December 14, 2020 (ie, our study start date).

To simplify interpretation and ensure consistent definitions of the term fully vaccinated, analyses were restricted to individuals who received only mRNA vaccines. Individuals who received non-mRNA vaccines were excluded; however, the frequency of those receiving non-mRNA vaccines was reported for completeness. Doses of mRNA vaccine were counted as administered if a subsequent dose occurred at least 14 days after the previous dose. Individuals were considered unvaccinated if they never received a COVID-19 vaccine of any kind. Patients were censored at the time of death or disenrollment from the KPSC health plan.

Patient and clinical characteristics by vaccination status were compared using the χ² test for categorical variables and the Fisher exact test for binary variables. P values were 2 sided, and statistical significance was set at P = .05. Hazard ratios (HRs) and 95% Wald CIs to identify characteristics associated with receipt of 4 doses of mRNA monovalent COVID-19 vaccine (which corresponds to a primary series and a booster dose for immunocompromised individuals) were estimated using a Cox proportional hazards regression model. Factors included in the model were as follows: age (18-44, 45-64, or ≥65 years); sex (men vs women); self-identified race and ethnicity (Hispanic; non-Hispanic Asian or Pacific Islander, non-Hispanic Black, or non-Hispanic White [hereafter, Asian or Pacific Islander, Black, or White, respectively], other [American Indian or Alaska Native, multiple races, or other race or ethnicity], or unknown); prior positive COVID-19 test result (ever vs never); responses to indicators (yes vs no) for each category of immunocompromise (history of organ transplant, congenital immunodeficiencies, asplenia/hyposplenia, HIV/AIDS, leukemia, lymphoma, or receipt of chemotherapy, immunomodulating medication, high-dose corticosteroids, or TNF-α antagonists; eTable 2 in Supplement 1); comorbidities (yes vs no; congestive heart failure, cerebrovascular disease, diabetes); health care utilization (count of outpatient, emergency department, and inpatient encounters in the year prior to index); and neighborhood median income (per $10 000). To account for whether individuals were eligible to receive mRNA monovalent COVID-19 booster doses based on the timing of receipt of their last dose, we examined uptake among the subset who were eligible to receive a fourth or fifth dose based on CDC-recommended intervals between doses at the time.

All analyses were performed using SAS Enterprise guide, version 8.2 (SAS Institute Inc). Statistical analyses were performed from August 9 to 23, 2022.

Of 3 133 341 KPSC members aged 18 years or older with at least 1 year of health plan membership on December 14, 2020, 44 529 (1.4%) met our study definition of immunocompromised. Of these 44 529 individuals, 1832 (4.1%) received at least 1 dose of non-mRNA COVID-19 vaccine and were excluded. Among the 42 697 individuals included in the final analysis cohort, 18 789 (44.0%) were aged 65 years or older; 20 061 (47.0%) were women and 22 635 (53.0%) were men (Table 1). With regard to race and ethnicity, 4295 participants (10.1%) identified as Asian or Pacific Islander, 5174 (12.1%) as Black, 14 289 (33.5%) as Hispanic, and 17 902 (41.9%) as White. With regard to vaccination, 4503 individuals (10.6%) were unvaccinated, 36 606 (85.7%) received a single monovalent mRNA product (BNT162b2 or mRNA-1273 [Moderna]), and 1588 (3.7%) received a combination of the 2 monovalent mRNA vaccines. While most mRNA doses were compliant with vaccine recommendation timelines, 59 patients (0.1%) received a fourth dose prior to September 1, 2021 (the date of the CDC recommendation to do so), and 78 patients (0.2%) received a fifth dose prior to March 1, 2022 (the date of the CDC recommendation to make a fifth dose available), and were included in analyses.

At the end of the study period, 26 303 of 42 697 immunocompromised patients (61.6%) had received 3 or fewer doses of mRNA monovalent vaccine and 16 000 (37.5%) had received 4 doses. Further, 394 (0.9%) had received 5 doses of mRNA monovalent vaccine as was recommended by CDC at the time of study conduct (Table 1).

When examining cumulative uptake over time, 78.0% of immunocompromised individuals had received a third dose by the end of the study period (approximately 1 year after the CDC recommendation in August 2021 for immunocompromised individuals to receive a 3-dose primary series). Fourth-dose uptake was slower, reaching only 14.0% coverage by April 2022 (>6 months after CDC recommendation for immunocompromised individuals to receive a fourth dose [ie, first booster]) and 41.0% by August 2022 (almost 1 year after the same recommendation). Uptake of a fifth dose was only 0.9% following the CDC recommendation to receive a second mRNA monovalent booster (ie, fifth dose) (Figure).

Of the 31 122 individuals who had received a third dose at least 3 months before the end of the study (and were therefore eligible for a fourth dose), 14 730 (47.3%) had received a fourth dose. Likewise, among 13 054 individuals who had received a fourth dose at least 4 months prior to the end of the study (and were therefore eligible for a fifth dose), 391 (3.0%) had received a fifth dose. Thus, the results were not markedly different after accounting for booster dose eligibility.

In multivariable Cox proportional hazards regression analyses, adults aged 65 years or older (HR, 3.95 [95% CI, 3.70-4.22]) were more likely to receive at least 4 doses compared with those aged 18 to 44 years and 45 to 64 years (HR, 2.52 [95% CI, 2.36-2.69]). Black and Hispanic adults (HR, 0.82 [95% CI, 0.78-0.87] and HR, 0.77 [95% CI, 0.74-0.80], respectively, compared with White adults), individuals with prior documented SARS-CoV-2 infection (HR, 0.71 [95% CI, 0.62-0.81] compared with those without), and individuals receiving high-dose corticosteroids (HR, 0.88 [95% CI, 0.81-0.95] compared with those who were not) were less likely to receive at least 4 doses of mRNA monovalent COVID-19 vaccine. Some types of immunocompromising conditions were associated with a higher likelihood of receiving a fourth dose, including those who previously received an organ transplant (HR, 1.36 [95% CI, 1.29-1.44]), those with a congenital immunodeficiency (HR, 1.09 [95% CI, 1.01-1.18]) or HIV/AIDS (1.69 [1.58-1.80]), or individuals receiving chemotherapy (HR, 1.07 [95% CI, 1.01-1.12]), immunomodulating medications (HR, 1.22 [95% CI, 1.16-1.28]), or TNF-α antagonists (HR, 1.28 [95% CI, 1.19-1.37]) (Table 2).

As of August 6, 2022, merely 0.9% of immunocompromised individuals within the large KPSC integrated health care system in this cohort study had received 5 doses of mRNA monovalent COVID-19 vaccine as was recommended by the CDC for this high-risk population. Only 41.0% had received 4 mRNA monovalent doses, which corresponds to a primary series and a booster dose for immunocompromised individuals. Vaccination rates with COVID-19 mRNA vaccines are higher in California than in the US as a whole; thus, these estimates are therefore likely the upper bound of uptake nationwide. Given the vulnerability of this population to develop severe COVID-19 and the well-established additional protection afforded by booster doses,^2,6,12-15 these data are a call to action for practitioners and public health officials alike to devise efforts to improve mRNA COVID-19 booster dose coverage.

Reasons for low uptake of fourth and fifth (ie, booster) doses in immunocompromised individuals are not entirely clear. It is possible that vaccine hesitancy among immunocompromised individuals could explain our findings and may stem from multiple sources in this population. Most COVID-19 vaccine clinical trials excluded patients with immunocompromising conditions—which may have contributed to safety concerns in this population.¹⁶ Based on our findings, however, vaccine hesitancy seems unlikely to be a primary driver for low booster dose uptake among immunocompromised individuals. Namely, immunocompromised individuals had high and rapid uptake of second and third doses of COVID-19 vaccines. Early in the pandemic, immunocompromised individuals were prioritized for vaccination; in KPSC, by August 2021, 85.0% of immunocompromised patients had received at least 2 doses—a number that rose to 89.0% to 90.0% by the end of 2021. Third-dose uptake had also reached high levels (78.0%) by August 2022. Recommendations for the third dose of mRNA monovalent vaccine to be given to immunocompromised patients as a primary series dose, however, occurred in a similar time frame as did recommendations for the general population to receive a third dose as a booster. This timing, along with the complexity of COVID-19 vaccine recommendations for immunocompromised individuals, likely caused confusion among both the lay and medical communities about how a third dose should be used in the immunocompromised population. Specifically, many immunocompromised patients may have failed to realize that recommendations for immunocompromised individuals were different than that of the general population—as dialogue about a third dose given as a “booster” in the general population tended to dominate discussions in the medical community and in the press.⁸ Our data support this, showing that COVID-19 vaccine uptake among immunocompromised individuals was high for second and third doses but particularly lagged for fourth and fifth doses. This likely reflects confusion about COVID-19 vaccine recommendations for immunocompromised individuals and how to accurately define the primary series, booster doses, and being up to date for this high-risk population.

Other reasons for low uptake of fourth and fifth doses in immunocompromised individuals beyond confusion about vaccine recommendations for this subpopulation, however, are possible. For example, the need for additional doses among immunocompromised individuals may have been misinterpreted as lack of vaccine effectiveness in this population, particularly given early reports of lower efficacy among some groups of immunocompromised individuals compared with those who were immunocompetent.^3,17,18 Moreover, during the Omicron wave, it became clear that COVID-19 vaccines had reduced effectiveness against SARS-CoV-2 infection and symptomatic disease, which could have lessened confidence in COVID-19 vaccination.^19,20 This possibility was compounded by overall “pandemic fatigue,” which could have also contributed to lower-than-expected uptake of booster doses.²¹ Additionally, the increasing availability of antivirals and monoclonal antibodies as both prophylaxis and treatment for COVID-19 may have reduced urgency to get vaccinated. Additional research to help pinpoint the reasons behind low uptake of booster doses in immunocompromised individuals is warranted.

Data to date have shown that a booster dose is critical for improving protection against a spectrum of COVID-19 outcomes, especially against Omicron and its sublineages.^2,12-15 For immunocompromised individuals, the fourth dose constitutes the first booster dose; thus, low fourth-dose uptake in this population translates to low booster coverage in a population at high risk of severe illness. In addition, a fourth dose of mRNA monovalent vaccine has been shown to increase protection across a spectrum of COVID-19 outcomes in the general population, including severe disease. A study in Israel among adults aged 60 years or older reported a 2-fold lower rate of confirmed infection for those who received 4 doses of mRNA monovalent COVID-19 vaccine compared with those who received only 3, although the durability of this increased protection against infection appeared short-lived. Protection against severe illness after 4 doses, however, was 3.5 times higher compared with those who received only 3 doses and was maintained through at least 6 weeks.²² A study conducted in a Canadian population compared long-term care residents who received 4 doses with those who received only 3 doses and found 19.0%, 31.0%, and 40.0% relative increases in vaccine effectiveness against any SARS-CoV-2 infection, symptomatic infection, and severe illness, respectively.²³ In addition, a few small studies have evaluated the level of protection among individuals with autoimmune disease¹⁷ and history of organ transplantation^24-26 and showed a benefit of additional booster doses in these high-risk populations.

In our predictive model, younger adults, Black and Hispanic individuals (compared with Asian or Pacific Islander or White individuals), those with prior SARS-CoV-2 infection, those taking high-dose corticosteroids, those with fewer outpatient encounters in the prior year, and those with congestive heart failure or uncontrolled diabetes (hemoglobin A_1c ≥7.5% [to convert to proportion of total hemoglobin, multiply by 0.01]) were less likely to receive at least 4 doses of mRNA COVID-19 vaccine. Similar disparities in overall COVID-19 vaccine uptake by age, race, and ethnicity—namely, that younger and racial and ethnic minority populations also tend to have lower overall rates of COVID-19 vaccination—have been described.^27,28 These findings suggest that younger and racial and ethnic minority immunocompromised individuals would benefit from vaccine uptake interventions.

The findings of this cohort study are subject to limitations. The selection criteria for immunocompromised individuals were based on ICD-10 codes associated with immunocompromising diagnoses and receipt of immunosuppressive medications. Although this is a previously used algorithm,^2,12 it may not perfectly capture the dynamic nature of immunocompromised status. To reduce bias and ensure that all individuals in our study were truly immunocompromised, we required the study participants to meet the definition of immunocompromised at 2 different time points 1 year apart. Furthermore, factors associated with low vaccine uptake were limited to the variables in the electronic health record, which may not adequately capture key social or clinical determinants of vaccine uptake. While there may be differences by type of immunocompromise that influence vaccine uptake, we did not have a sufficient sample size to perform analysis stratified by type of immunocompromising condition. Previous literature has described varying seroconversion rates based on the type of immunocompromising conditions,¹⁸ and the perception of risk of severe COVID-19 may vary by type of immunocompromise.

Our results highlight a substantial gap in adherence to CDC recommendations for mRNA monovalent COVID-19 booster doses among immunocompromised individuals in a large, sociodemographically diverse population. Given the vulnerability of this population to develop severe COVID-19, a renewed focus on targeted and tailored efforts to ensure that immunocompromised individuals remain up to date with continuously evolving COVID-19 booster dose recommendations is warranted at this stage of the pandemic.

Accepted for Publication: November 25, 2022.

Published: January 20, 2023. doi:10.1001/jamanetworkopen.2022.51833

Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2023 Tartof SY et al. JAMA Network Open.

Corresponding Author: Sara Y. Tartof, PhD, MPH, Department of Research and Evaluation, Kaiser Permanente Southern California, 100 S Los Robles, 2nd Floor, Pasadena, CA 91101 (sara.y.tartof@kp.org).

Author Contributions: Mr Slezak and Ms Hong had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Tartof, Slezak, Puzniak, Frankland, Ogun, Simmons, Zamparo, Jodar, McLaughlin.

Acquisition, analysis, or interpretation of data: Tartof, Slezak, Hong, Frankland, Xie, Ackerson, Takhar, Tseng, McLaughlin.

Drafting of the manuscript: Tartof, Puzniak, Frankland, Ackerson, McLaughlin.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Tartof, Slezak, Hong, Frankland, Xie.

Obtained funding: Tartof, Zamparo, Jodar, McLaughlin.

Administrative, technical, or material support: Tartof, Puzniak, Frankland, Ackerson, Takhar, Ogun, Simmons, Zamparo, McLaughlin.

Supervision: Tartof, Puzniak, Ackerson, Zamparo, Tseng, Jodar, McLaughlin.

Conflict of Interest Disclosures: Dr Tartof reported receiving grants paid to Kaiser Permanente Southern California (KPSC) from Pfizer during the conduct of the study and from Genentech and GlaxoSmithKline outside the submitted work. Mr Slezak reported receiving funding paid to KPSC from Pfizer during the conduct of the study and from ALK outside the submitted work. Dr Puzniak reported receiving personal fees from Pfizer during the conduct of the study. Ms Hong reported receiving grants paid to KPSC from Pfizer during the conduct of the study. Mr Frankland reported owning stock in AbbVie, CVS Health, and Regeneron Pharmaceuticals and previously owning stock in Pfizer, Viatris, Biogen, and Gilead Sciences outside the submitted work. Dr Ackerson reported receiving grants paid to KPSC from Pfizer during the conduct of this study and from Pfizer, Moderna, GlaxoSmithKline, Dynavax Technologies, Genentech, Novavax, Seqirus, and Novartis outside the submitted work. Mr Takhar reported receiving grants from Pfizer during the conduct of the study. Dr Ogun reported receiving grants paid to KPSC from Pfizer during the conduct of the study. Ms Simmons reported receiving grants paid to KPSC from Pfizer during the conduct of the study and grants paid to KPSC from Dynavax Technologies, the US Centers for Disease Control and Prevention, and GlaxoSmithKline outside the submitted work. Ms Zamparo reported being a full-time employee of Pfizer during the conduct of the study. Dr Tseng reported receiving grants paid to KPSC from Moderna during the conduct of the study and outside the submitted work. Dr Jodar reported receiving a salary and stock from Pfizer during the conduct of the study. Dr McLaughlin reported receiving a salary and stock from Pfizer during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was sponsored by Pfizer.

Role of the Funder/Sponsor: The design and conduct of the study were led and developed by KPSC but approved by Pfizer. KPSC led the collection, management, analysis, and interpretation of the data. KPSC and Pfizer participated in the preparation, review, or approval of the manuscript. KPSC and Pfizer participated in the decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2.