Pathways to COVID-19 vaccine initiation: The roles of medical mistrust, conspiracy beliefs, hesitancy, and confidence among black young adults.

Pathways to COVID-19 Vaccine Initiation: The Roles of Medical Mistrust, Conspiracy Beliefs, Hesitancy, and Confidence among Black Young Adults - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Vaccine . Author manuscript; available in PMC: 2026 Apr 18. Published in final edited form as: Vaccine. 2026 Jan 18;75:128253. doi: 10.1016/j.vaccine.2026.128253 Search in PMC Search in PubMed View in NLM Catalog Add to search Pathways to COVID-19 Vaccine Initiation: The Roles of Medical Mistrust, Conspiracy Beliefs, Hesitancy, and Confidence among Black Young Adults Ibrahim Yigit Ibrahim Yigit 1 College of Nursing, Florida State University, Tallahassee, Florida, USA. Find articles by Ibrahim Yigit 1, * , Marie C D Stoner Marie C D Stoner 2 Research Triangle Institute (RTI) International, Women’s Global Health Imperative, Berkeley, USA Find articles by Marie C D Stoner 2 , Kathryn E Muessig Kathryn E Muessig 1 College of Nursing, Florida State University, Tallahassee, Florida, USA. 3 Institute on Digital Health and Innovation, College of Nursing, Florida State University, Tallahassee, Florida, USA. Find articles by Kathryn E Muessig 1, 3 , Lisa B Hightow-Weidman Lisa B Hightow-Weidman 1 College of Nursing, Florida State University, Tallahassee, Florida, USA. 3 Institute on Digital Health and Innovation, College of Nursing, Florida State University, Tallahassee, Florida, USA. Find articles by Lisa B Hightow-Weidman 1, 3 , Henna Budhwani Henna Budhwani 1 College of Nursing, Florida State University, Tallahassee, Florida, USA. 3 Institute on Digital Health and Innovation, College of Nursing, Florida State University, Tallahassee, Florida, USA. Find articles by Henna Budhwani 1, 3 Author information Article notes Copyright and License information 1 College of Nursing, Florida State University, Tallahassee, Florida, USA. 2 Research Triangle Institute (RTI) International, Women’s Global Health Imperative, Berkeley, USA 3 Institute on Digital Health and Innovation, College of Nursing, Florida State University, Tallahassee, Florida, USA. * Corresponding Author, Ibrahim Yigit, Florida State University College of Nursing, Vivian M. Duxbury Hall, 98 Varsity Way, Tallahassee, Florida 32306-4310; [email protected] Issue date 2026 Mar 7. PMC Copyright notice PMCID: PMC13088946  NIHMSID: NIHMS2159228  PMID: 41548529 The publisher's version of this article is available at Vaccine Abstract Medical mistrust, stemming from historical and contemporary inequalities in healthcare, poses a major barrier to vaccination, particularly among Black communities in the southern U.S. While medical mistrust is known to influence vaccine uptake, the underlying psychological mechanisms, such as conspiracy beliefs and attitudinal factors like vaccine hesitancy and confidence, are not well understood. This cross-sectional analysis used baseline data from the Tough Talks-COVID randomized controlled trial (N=360), conducted among Black young adults (ages 18–29) in Alabama, Georgia, and North Carolina between March and June 2023, who had not completed the primary COVID-19 vaccine series at screening. Participants completed validated measures of medical mistrust, vaccine-related conspiracy beliefs, vaccine hesitancy, vaccine confidence, and COVID-19 vaccine initiation (ever receipt of ≥1 dose at baseline). Serial mediation models specifying a theoretically informed ordering (medical mistrust, vaccine-related conspiracy beliefs, vaccine hesitancy or vaccine confidence, and COVID-19 vaccine initiation) were tested adjusting for age, sex, and state. Medical mistrust was significantly associated with lower odds of COVID-19 vaccine initiation (B=−.63, AOR=.53, p<.001). Serial mediation analyses revealed two significant indirect associations: (1) Greater medical mistrust was associated with stronger endorsement of vaccine-related conspiracy beliefs, which were linked to increased vaccine hesitancy, resulting in lower vaccine initiation (B=−.26, CI[−.463, −.127]); and (2) Greater medical mistrust was associated with stronger vaccine-related conspiracy beliefs, which were associated with reduced vaccine confidence; higher vaccine confidence was associated with higher vaccine initiation, yielding an overall negative indirect association (B = −.35, CI[−.591, −.191]). Findings highlight critical psychological mechanisms through which medical mistrust may undermine COVID-19 vaccine initiation in under-vaccinated Black young adults. Addressing mistrust and countering conspiracy beliefs while strengthening vaccine confidence may support vaccine initiation efforts in Black communities. Keywords: Vaccine initiation, Conspiracies, Hesitancy, Confidence, Minority, Young Adults INTRODUCTION The global outbreak of COVID-19 in early 2020 marked an unprecedented public health crisis, resulting in millions of deaths and disrupting nearly every aspect of daily life [ 1 ]. In response, the rapid development and deployment of COVID-19 vaccines were hailed as a major scientific breakthrough [ 2 ], offering hope for containment of the virus and a path toward social and economic recovery. Vaccines have proven highly effective in reducing severe illness, hospitalization, and death [ 3 ]; however, vaccine uptake has varied widely across populations, leaving critical gaps in community-level protection. While some individuals remain unvaccinated due to limited access or structural barriers, others experience doubts or negative attitudes toward vaccines (a phenomenon referred to as vaccine hesitancy) which may or may not result in delayed or refused vaccination [ 4 , 5 ]. National data and regional estimates continue to show concerning levels of under-vaccination for COVID-19 among specific groups, including young adults and racial minorities in the southern United States (U.S.); for instance, nearly one-third of young adults in some southern states have not initiated the primary COVID-19 vaccine series [ 6 – 9 ]. Poor vaccination coverage for COVID-19 underscores the urgent need to understand the complex psychosocial drivers of vaccine behavior to effectively address disparities and strengthen public health preparedness. A growing body of research identifies multiple factors contributing to suboptimal vaccination, including misinformation, structural barriers, and most notably, vaccine hesitancy [ 4 , 5 ]. Among these, one critical barrier to COVID-19 vaccination behavior may be medical mistrust [ 10 , 11 ], defined as the suspicion or lack of trust in health care systems and medical professionals, particularly as it relates to one’s racial or ethnic group (i.e., group-based medical mistrust) [ 11 – 13 ]. Medical mistrust is rooted in historical and contemporary experiences of racism, discrimination, and unethical medical practices that disproportionately impact communities of color, particularly Black communities [ 14 , 15 ]. Not surprisingly, this mistrust has been linked to lower engagement in preventive health behaviors, including vaccination [ 16 – 18 ]. For example, existing studies have shown that higher levels of medical mistrust are associated with a lower likelihood of receiving vaccines, including COVID-19 and human papillomavirus (HPV) vaccines [ 10 , 11 ], reduced intention to get vaccinated [ 19 ], or greater vaccine hesitancy [ 20 , 21 ]. Theoretical frameworks such as the Health Belief Model [ 22 ] and the Theory of Planned Behavior [ 23 ] suggest that perceived benefits of health behaviors and related cognitive factors are central to decision-making. Given that trust in healthcare providers and healthcare systems can influence the perceived benefits of health behaviors, elucidating the role of medical mistrust on COVID-19 vaccination is important for addressing disparities in vaccine initiation. Yet, few studies have integrated these theoretical models to empirically test serial pathways that connect mistrust, vaccine-related beliefs, and behavioral outcomes within marginalized populations. Medical mistrust may influence vaccination behavior not only directly but also through its impact on various mechanisms, particularly cognitive beliefs. In this context, especially during or after the COVID-19 pandemic, increased attention has been given to conspiracy beliefs, such as the notion that vaccines cause more harm than good or are used for population control, in understanding non-vaccination behaviors, including lower vaccination intention, acceptance, or vaccination [ 24 – 27 ]. From a health communication perspective, medical mistrust may also influence which sources are perceived as credible, thereby influencing exposure to and acceptance of misinformation and conspiratorial narratives. Prior evidence suggests that Black-oriented media ecosystems and culturally grounded messaging strategies can meaningfully affect COVID-19 information environments and vaccine-related attitudes among Black audiences [ 28 , 29 ]. In addition, experimental work indicates that exposure to mediated discrimination cues can heighten medical mistrust among Black audiences, underscoring how communication environments can contribute to downstream mistrust and related beliefs [ 30 ]. These conspiracy beliefs can be fueled by general mistrust (also conceptualized as a conspiracy mentality), and social environments with high mistrust can also fuel conspiracy beliefs [ 13 , 31 , 32 ]. Individuals with high levels of medical mistrust may thus be more likely to believe that vaccines are unsafe, ineffective, or part of a broader effort to harm marginalized communities [ 17 , 33 – 35 ]. Endorsement of these conspiracy beliefs has been consistently associated with greater vaccine hesitancy [ 36 – 39 ]. This resulting psychological barrier diminishes trust not only in vaccines themselves but also in the institutions promoting vaccination. Therefore, examining theoretically specified serial pathways—specifically how medical mistrust is associated with vaccine-related conspiracy beliefs, which are associated with vaccine hesitancy or lower vaccine confidence, and with COVID-19 vaccine initiation—may offer critical insights into the behavioral processes driving vaccine decisions. This analytical approach addresses an existing gap in the literature by clarifying the psychological mechanisms through which mistrust translates into behavior, rather than examining these factors in isolation. This line of inquiry becomes even more pressing when considering the racial context, particularly the experiences of Black communities. Lived experiences which include racism in clinical encounters, structural inequalities, and cultural narratives of exploitation can intensify medical mistrust [ 14 , 16 , 40 , 41 ], and affect how individuals interpret and respond to vaccine-related information. These sociocultural dynamics may also influence the extent to which conspiracy beliefs take hold and how vaccine hesitancy or confidence manifests in vaccination behavior. However, research simultaneously examining these mechanisms within the same explanatory framework remains limited, particularly among Black young adults in the southern U.S., where structural inequities and historical mistrust continue to affect health behaviors. In this study, we aim to examine the mediating mechanisms linking medical mistrust to COVID-19 vaccine initiation behavior among Black young adults living in Alabama (AL), Georgia (GA), and North Carolina (NC). Using baseline data from the Tough Talks-COVID (TT-C) randomized controlled trial (RCT), we tested a serial mediation model to examine whether vaccine-related conspiracy beliefs and vaccine hesitancy or confidence mediate the relationship between medical mistrust and COVID-19 vaccine initiation. By elucidating these pathways, this study can contribute to a deeper understanding of the psychological and sociocultural barriers to vaccination in historically marginalized communities, with important implications for individual and public health interventions aimed at improving vaccine initiation and trust in healthcare systems. METHODS Parent Study The TT-C study ( NCT05490329 ), a RCT evaluating a digital health intervention to reduce COVID-19 vaccine hesitancy, was conducted between March and June 2023 in AL, GA, and NC among Black young adults. Details of the RCT have been published previously [ 42 ], with a brief summary provided below. The study received Institutional Review Board approval from the University of North Carolina at Chapel Hill, the University of Alabama at Birmingham (IRB #21-1746), and Florida State University (STUDY00003617). All participants provided informed consent prior to enrollment. Data, Participants, and Procedures Participants were young adults aged 18 to 29 who met the following eligibility criteria: 1) self-identified as Black; 2) fluent in English; 3) resided in AL, GA, or NC; 4) able to provide written informed consent; 5) had personal smartphone access, and 6) had not completed the full primary COVID-19 vaccination series (excluding booster doses). However, vaccination status was assessed through self-reported surveys at baseline, and some participants who initially met eligibility criteria later reported receiving additional doses (e.g., booster or subsequent series) between screening and baseline data collection. Recruitment for the parent TT-C trial used a multi-pronged approach (free and paid social media advertising, dissemination through national organizations including historically Black colleges and universities, and outreach through community partners) to maximize reach across Black young adults in the three states [ 42 ]. For the present analysis, we focused on baseline data collected through self-reported surveys prior to the implementation of the intervention. Accordingly, the present analysis compares participants who reported no prior COVID-19 vaccination at baseline with those who reported having received at least one dose (i.e., vaccine initiation) within this under-vaccinated sample. Measures Medical Mistrust We assessed medical mistrust using the 12-item Group-Based Medical Mistrust Scale [ 12 ], which evaluates suspicion toward healthcare systems and providers based on one’s racial or ethnic identity. Participants responded to items on a 5-point Likert scale ranging from strongly disagree to strongly agree. Sample items include, “People of my race or ethnic group cannot trust doctors and health care workers” and “Doctors and health care workers do not take the medical complaints of people of my race or ethnic group seriously.” A total score was calculated ranging from 12 to 60, with higher scores indicating greater levels of medical mistrust. In the current study, Cronbach’s alpha was .87. Vaccine-related Conspiracy Beliefs Vaccine-related conspiracy beliefs were assessed using six items (e.g., “Vaccine safety data are often fabricated” and “People are deceived into thinking that vaccines are safe”) adapted from the Vaccine Conspiracy Beliefs Scale [ 43 ]. Items were rated on a 4-point Likert scale ranging from strongly disagree to strongly agree. We calculated a mean score by averaging responses across the six items, with higher scores indicating stronger endorsement of vaccine-related conspiracy beliefs. In the current study, the scale demonstrated excellent internal consistency (Cronbach’s alpha = .90). Vaccine Hesitancy Vaccine hesitancy was assessed using nine items from the Vaccine Hesitancy Scale [ 44 ], with responses rated on a 5-point Likert scale ranging from strongly disagree to strongly agree. Sample items include “New vaccines carry more risks than older vaccines” and “Getting vaccines is a good way to protect myself from disease.” Positively worded items were reverse coded, and a composite score was calculated by averaging all item responses, with higher scores indicating greater vaccine hesitancy. The scale showed strong internal consistency in this study (Cronbach’s alpha = .89). Vaccine Confidence Vaccine confidence was measured using six items (e.g., “Vaccines are safe” and “If I do not get vaccinated I may get a disease and cause others to get the disease”) adapted from the Vaccine Confidence Scale (VCS) [ 45 ]. Participants responded to items on a 5-point Likert scale ranging from strongly disagree to strongly agree, with higher scores indicating greater vaccine confidence. In the current study, Cronbach’s alpha was .84. Self-reported Vaccine Initiation for COVID-19 COVID-19 vaccination status was assessed with the question, “Have you ever received a COVID-19 vaccine?” with response options of 0 = No and 1 = Yes. For the present analyses, this item operationalized COVID-19 vaccine initiation (ever receipt of ≥1 dose). In addition, participants were asked to report the number of COVID-19 vaccine doses they had received. This information was used for descriptive purposes to provide a more detailed understanding of vaccination patterns within the sample. For ease of reference, sample items and response options for the study measures are summarized in Supplementary Table S1 . Data Analyses We calculated descriptive statistics for all participants. A correlation analysis was conducted to examine relationships between the study variables. Next, we tested serial mediation models specifying a theory-informed ordering to examine whether medical mistrust was associated with vaccine-related conspiracy beliefs, which was associated with vaccine hesitancy or vaccine confidence, which was associated with COVID-19 vaccine initiation. We utilized the SPSS PROCESS macro (Model 6) with 95% percentile confidence intervals (CI) based on 5,000 bootstrapped resamples [ 46 ]. A serial mediation (indirect) effect was considered significant if the CI did not include zero. Given the cross-sectional nature of the data, the indirect effects are interpreted as statistical decompositions of associations consistent with the specified ordering, rather than evidence of temporal precedence or causal mediation. The sample size (N = 360) exceeded the recommended minimum of 200 participants for detecting medium indirect effects in mediation analyses with adequate power [ 47 ], supporting the robustness of the statistical tests. All analyses were cross-sectional, adjusting for age, sex, and state. As sensitivity analyses, we re-estimated both serial models with an expanded covariate set to evaluate robustness to socio-economic and access-related factors: we first added insurance status (uninsured vs. any insured) and then added insurance plus education level and household income (modeled as ordered categories). RESULTS Descriptive Statistics Descriptive statistics are presented in Table 1 . The sample included 360 participants, with a mean age of 23.72 years (SD=3.42; range=18–29). The majority identified as female (n=299, 83.1%). Approximately one-third of participants (n=119, 33.5%) reported no prior COVID-19 vaccination (no initiation), while the remaining participants (n=236, 66.5%) had received at least one dose. Specifically, 11.4% (n=27) had received one dose, 57.6% (n=136) two doses, 29.7% (n=70) three doses, and 1.3% (n=3) four doses. Table 1. Descriptive Statistics Variables N % State Alabama 67 18.6 Georgia 160 44.4 North Carolina 133 36.9 Sex at birth Male 61 16.9 Female 299 83.1 Ethnicity Hispanic 16 4.4 Non-Hispanic 344 95.6 Insurance No insurance 42 11.7 Private 170 47.2 Public 126 35.0 Do not know 16 4.4 Prefer not to answer 6 1.7 Education level 9 th to 12 th grade, no diploma 16 4.4 High school graduate or GED completed 88 24.4 Some college level/technical/vocational degree 131 36.4 Bachelor’s degree 88 24.4 Other advanced degree (Master’s, Doctoral degree) 34 9.4 Prefer not to answer 3 0.8 Total household income Less than $15,000 70 19.4 $15,000–$19,999 36 10.0 $20,000–$24,999 20 5.6 $25,000–$34,999 48 13.3 $35,000–$49,999 63 17.5 $50,000–$74,999 46 12.8 $75,000–$99,999 25 6.9 $100,000 and above 18 5.0 Do not know 23 6.4 Prefer not to answer 11 3.1 Vaccination behaviors Have you ever received a COVID-19 vaccine? Yes 236 66.5 No 119 33.5 How many total shots (for COVID-19) have you received? One shot 27 11.4 Two shots 136 57.6 Three shots 70 29.7 Four shots 3 1.3 Variables M(SD) range Age, years 23.72(3.42) 18–29 Medical mistrust 3.39(.72) 1–5 Vaccine-related conspiracy beliefs 2.32(.75) 1–4 Vaccine hesitancy 2.45(.85) 1–5 Vaccine confidence 3.48(.75) 1–5 Open in a new tab Correlation Coefficients As shown in Table 2 , medical mistrust was significantly correlated with vaccine-related conspiracy beliefs (r=.43, p<.001), vaccine hesitancy (r=.42, p<.001), vaccine confidence (r=−.46, p<.001), and COVID-19 vaccine initiation (r=−.19, p<.001). Vaccine-related conspiracy beliefs were also significantly correlated with vaccine hesitancy (r=.70, p<.001), vaccine confidence (r=−.73, p<.001), and COVID-19 vaccine initiation (r=−.49, p<.001). Lastly, vaccine hesitancy and vaccine confidence were significantly correlated with COVID-19 vaccine initiation (r=−.48, p<.001; r=.49, p<.001, respectively). Table 2. Correlations between the Study Variables Variables 1 2 3 4 5 Medical mistrust - Vaccine-related conspiracy beliefs .43 ** - Vaccine hesitancy .42 ** .70 ** - Vaccine confidence −.46 ** −.73 ** −.87 ** - COVID-19 vaccination −.19 ** −.49 ** −.48 ** −.49 ** - Open in a new tab ** p<.001. Serial Mediation Models We conducted two serial mediation analyses to examine theoretically specified indirect associations between medical mistrust and COVID-19 vaccine initiation through vaccine-related conspiracy beliefs and either vaccine hesitancy or vaccine confidence, while adjusting for age, sex, and state. In the first serial mediation model (see Figure 1 ), the total effect of medical mistrust (the effect when the mediator variables are not in the model) on COVID-19 vaccine initiation was significant (B=−.63, Adjusted Odds Ratio [AOR]=.53, SE=.17, p<.001). The serial indirect effect was also significant (B=−.26, SE=.08, CI[−.463, −.127]), suggesting that higher medical mistrust was significantly associated with greater vaccine-related conspiracy beliefs (B=.48, SE=.05, p<.001), which was significantly associated with higher vaccine hesitancy (B=.65, SE=.05, p<.001), and lower likelihood of COVID-19 vaccine initiation (B=−.85, AOR=.43, SE=.22, p<.001). Figure 1. Serial mediation of medical mistrust on COVID-19 vaccine initiation through vaccine-related conspiracy beliefs and vaccine hesitancy. Open in a new tab ***p<.001. The values in parentheses reflect coefficients (direct effects) after the mediator variables are in the model. Next, we tested a second serial mediation model depicted in Figure 2 . Similarly, the total effect of medical mistrust on COVID-19 vaccine initiation was significant (B=−.63, AOR=.53, SE=.17, p<.001). The serial indirect effect was also significant (B=−.35, SE=.10, CI[−.591, −.191]), consistent with the specified ordering in which higher medical mistrust was significantly associated with greater vaccine-related conspiracy beliefs (B=.48, SE=.05, p<.001), which was significantly associated with lower vaccine confidence (B=−.64, SE=.04, p<.001), and higher likelihood of COVID-19 vaccine initiation (B=1.15, AOR=3.16, SE=.28, p<.001). Figure 2. Serial mediation of medical mistrust on COVID-19 vaccine initiation through vaccine-related conspiracy beliefs and vaccine confidence. Open in a new tab ***p<.001. The values in parentheses reflect coefficients (direct effects) after the mediator variables are in the model. Sensitivity analyses incorporating insurance alone and then insurance plus education and household income yielded substantively similar serial indirect associations ( Supplementary Table S2 ). DISCUSSION This study examined the mechanisms linking medical mistrust to COVID-19 vaccine initiation behavior among Black young adults in the southern U.S. Consistent with previous literature, our findings demonstrate that higher levels of medical mistrust are significantly associated with lower COVID-19 vaccine initiation [ 10 , 11 , 20 ]. Importantly, this relationship was characterized by indirect associations involving vaccine-related conspiracy beliefs, vaccine hesitancy, and vaccine confidence, illustrating how medical mistrust may affect COVID-19 vaccine initiation through specific belief patterns and attitudinal pathways. Given that the parent trial enrolled individuals who had not completed the primary series at screening, these findings should be interpreted as mechanisms of initiation within an under-vaccinated sample rather than determinants of vaccination uptake or series completion in the general population. In this context, the results suggest that the need to address not only the root causes of medical mistrust but also the downstream cognitive and emotional responses it generates, in order to effectively promote vaccine initiation in this population. One important finding from this study is that medical mistrust was associated with greater vaccine-related conspiracy beliefs, which were associated with higher vaccine hesitancy, reducing the likelihood of COVID-19 vaccine initiation. This pathway highlights how mistrust in the healthcare system does not operate in isolation but can activate broader belief systems that question the legitimacy, intentions, and safety of vaccines (i.e., conspiracy beliefs). In this model, vaccine hesitancy emerges as a behavioral manifestation of these beliefs, reflecting not only doubts about vaccine efficacy and safety but also broader concerns related to personal vulnerability and societal risk. The significant associations along each step of the pathway were consistent with a pattern of associations in which higher mistrust co-occurred with higher conspiracy beliefs and hesitancy, reducing the likelihood of COVID-19 vaccine initiation. This finding aligns with previous research showing that conspiracy beliefs are a major barrier to vaccination uptake by fueling vaccine hesitancy [ 25 , 26 ], particularly when rooted in historical and ongoing medical mistrust among Black communities, who often perceive healthcare systems as discriminatory or exploitative. These findings also build upon prior analysis using the same dataset [ 48 ], where higher levels of medical mistrust and discrimination in medical settings were associated with lower likelihood of ever receiving a COVID-19 vaccine. In that study, mistrust and discrimination were prevalent even among those who had received at least one vaccine, suggesting that vaccine behaviors cannot be fully understood without accounting for underlying attitudes. By identifying conspiracy beliefs and vaccine hesitancy as key psychological mechanisms, the current study extends this work and contributes to our understanding of how mistrust translates into vaccine avoidance. In the second serial mediation model, we examined an alternative specification in which vaccine confidence, rather than vaccine hesitancy, served as the second mediator. The data supported a significant serial indirect effect: greater medical mistrust was associated with stronger conspiracy beliefs, which were associated with lower vaccine confidence. Then, vaccine confidence was linked to increased likelihood of COVID-19 vaccine initiation. Although vaccine confidence was a positive predictor of vaccine initiation, the overall indirect effect of medical mistrust on COVID-19 vaccine initiation behavior remained negative, operating through its influence on conspiracy beliefs and diminished vaccine confidence. This finding underscores the importance of positive belief structures, such as trust in the efficacy and safety of vaccines, as facilitators of vaccine behavior. Unlike hesitancy, which reflects doubt or concern, confidence may represent a more proactive psychological state, characterized by a strong belief in the protective value of vaccines. Notably, in this sample, vaccine hesitancy and vaccine confidence were strongly inversely related, suggesting considerable empirical overlap between these constructs. This raises the possibility that they reflect opposite valences of a broader underlying vaccination attitude, consistent with conceptualizations in which confidence is a core component/antecedent of vaccine hesitancy [ 49 , 50 ]. Accordingly, we interpret the hesitancy and confidence models as complementary specifications of attitudinal pathways consistent with our conceptual framing, rather than as evidence of two fully independent mechanisms. Examining them separately may still be useful for intervention design because hesitancy- versus confidence-oriented strategies may differ in emphasis (e.g., reducing concerns versus strengthening perceived benefits and trust). These findings suggest that rebuilding trust through culturally responsive communication and community-driven outreach may help enhance vaccine confidence, even in the face of entrenched medical mistrust. In line with this, uptake-focused communication that counters conspiratorial narratives while strengthening culturally credible routes to vaccine confidence may be especially relevant [ 28 , 29 ]. Accordingly, improving vaccination initiation may benefit from a dual emphasis: addressing conspiracy beliefs and hesitation while also actively fostering vaccine confidence, particularly among Black young adults who have been historically marginalized or mistreated by healthcare systems. Importantly, the indirect pathways observed in these models align with our conceptual framing of how medical mistrust may co-occur with vaccine-related conspiracy beliefs and downstream vaccine attitudes in ways that are linked to COVID-19 vaccine initiation. At the same time, these patterns should be interpreted with appropriate caution, as the present findings cannot establish the direction of effects or confirm that the proposed ordering reflects how these processes unfold over time. It is therefore plausible that medical mistrust and conspiracy beliefs mutually reinforce one another, or that broader vaccine attitudes may affect both mistrust and conspiracy endorsement. In this sense, our serial models are best understood as theory-consistent decompositions of associations that are informative for hypothesis generation and intervention targeting, rather than definitive evidence of temporal mediation. Future research using longitudinal designs and repeated measurement can help clarify the sequencing and potential reciprocity among these constructs, particularly in under-vaccinated Black young adult populations. Despite the strengths of this study, including a notable sample of Black young adults in underrepresented southern states and use of theoretically grounded serial mediation models, limitations warrant consideration. First, the cross-sectional design prevents causal inference and leaves open the possibility of bidirectionality. For example, it is plausible that endorsement of conspiracy beliefs may not only stem from medical mistrust but also contribute to its deepening by validating suspicions and fostering increased skepticism toward healthcare institutions [ 51 – 53 ]. Longitudinal studies are needed to clarify the temporal ordering and potential reciprocal relationships among these variables, particularly between medical mistrust and vaccine-related conspiracy beliefs. Second, vaccination status was assessed through self-report, which may be vulnerable to recall bias or social desirability effects, although prior research suggests reasonable validity for self-reports of COVID-19 vaccination [ 54 , 55 ]. Additionally, eligibility criteria required participants to be insufficiently vaccinated against COVID-19 at screening. As a result, the measure of COVID-19 vaccination status compares individuals who were completely unvaccinated to those who had received at least one dose but were not fully vaccinated according to current guidelines. This limits our ability to distinguish between fully vaccinated and partially vaccinated individuals and may introduce selection bias. Consequently, findings related to COVID-19 vaccination status should be interpreted within the context of this restricted sample and may not generalize to populations with a broader range of vaccination behaviors. In particular, these results should not be assumed to reflect determinants of primary-series completion or booster uptake, which may involve partially distinct barriers and facilitators. Third, the sample was predominantly female, with over 83% of participants identifying as female. This imbalance likely reflects well-documented challenges in recruiting and retaining men, particularly Black men, into health research, including prevention-focused studies that rely on remote or online recruitment and participation [ 56 , 57 ]. Although the parent study implemented broad, multi-channel recruitment [ 42 ], male participation remained limited. Accordingly, while sex was statistically controlled for, the generalizability of these findings to Black young men may be constrained, and future research should incorporate more targeted, relationship-based, and male-centered recruitment strategies and settings. For example, partnering with trusted, male-serving community venues and networks (e.g., barbershops, workplaces, sports clubs, community centers), using culturally congruent recruiters and community gatekeepers, and reducing participation burden through clear, non-directive study communication, flexible logistics (e.g., transportation support), and referral-based (“snowball”) outreach have the potential to improve representation of male participants [ 56 – 58 ]. Additionally, although sensitivity analyses adjusting for insurance, education, and income produced materially similar conclusions, residual confounding by unmeasured access-to-care and structural factors remains possible. Finally, while this study focused on vaccine-specific conspiracy beliefs, broader conspiracy mentalities or political orientations were not assessed. Future work could examine how these factors intersect with medical mistrust to influence health decisions. In conclusion, our findings highlight the critical role of medical mistrust and related belief systems in understanding COVID-19 vaccine initiation (ever vs. never vaccinated) among Black young adults in the southern U.S. These findings emphasize that improving vaccine initiation in marginalized communities requires more than disseminating factual information; it necessitates efforts to build and restore trust, acknowledge historical harms, and directly engage with the belief systems that erode vaccine confidence and the perceived credibility of health information sources. Thus, public health strategies aimed at COVID-19 vaccine initiation among under vaccinated Black young adults may benefit culturally tailored interventions that address not only structural barriers, but also cognitive and emotional barriers rooted in lived experiences of racial injustice. Overall, these findings suggest that addressing medical mistrust and vaccine-related misinformation while strengthening vaccine confidence may help support COVID-19 vaccine initiation and reduce persistent disparities in COVID-19 vaccination. Supplementary Material Supplementary Material NIHMS2159228-supplement-Supplementary_Material.docx (17KB, docx) Funding Research reported in this publication was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number R01MD016834. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Footnotes Statements and Declarations Disclosure of Potential Conflicts of Interest The authors have no relevant financial or non-financial interests to disclose. Clinical Trials Number : NCT05490329 CRediT Authorship Contribution Statement Conceptualization: [Ibrahim Yigit], [Lisa B. Hightow-Weidman], [Henna Budhwani]; Methodology: [Ibrahim Yigit]; Formal analysis and investigation: [Ibrahim Yigit]; Writing - original draft preparation: [Ibrahim Yigit]; Writing - review and editing: [Marie C. D. Stoner], [Kathryn E. Muessig], [Lisa B. Hightow-Weidman], [Henna Budhwani]; Funding acquisition: [Lisa B. Hightow-Weidman], [Henna Budhwani]; Supervision: [Lisa B. Hightow-Weidman], [Henna Budhwani]. Compliance with Ethical Standards Ethics approval The study received Institutional Review Board approval from the University of North Carolina at Chapel Hill, the University of Alabama at Birmingham (IRB #21-1746), and Florida State University (STUDY00003617). Informed Consent Informed consent was obtained from all participants prior to enrollment. Data Availability Statement The data that support the findings of this study are available from the Co-PIs of the study upon reasonable request. References 1. 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[ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. Supplementary Materials Supplementary Material NIHMS2159228-supplement-Supplementary_Material.docx (17KB, docx) Data Availability Statement The data that support the findings of this study are available from the Co-PIs of the study upon reasonable request. 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